Abstaining from the consumption of tap water at health care facilities can dramatically reduce the risk of Mycobacterium abscessus infections among patients and staff, according to a new study published in Clinical Infectious Diseases.

“Outbreaks of [M. abscessus] and other rapidly growing mycobacteria are common and have been associated with colonized plumbing systems in commercial buildings and health care facilities,” wrote the authors, led by Arthur W. Baker, MD, MPH, of Duke University, Durham, N.C., adding that “Infections due to M. abscessus are difficult to diagnose and typically require months of therapy using multiple antibiotics” (Clin Infect Dis. 2017 Jan 10. doi: 10.1093/cid/ciw877).

nikkytok/Thinkstock

[email protected]

Abstaining from the consumption of tap water at health care facilities can dramatically reduce the risk of Mycobacterium abscessus infections among patients and staff, according to a new study published in Clinical Infectious Diseases.

“Outbreaks of [M. abscessus] and other rapidly growing mycobacteria are common and have been associated with colonized plumbing systems in commercial buildings and health care facilities,” wrote the authors, led by Arthur W. Baker, MD, MPH, of Duke University, Durham, N.C., adding that “Infections due to M. abscessus are difficult to diagnose and typically require months of therapy using multiple antibiotics” (Clin Infect Dis. 2017 Jan 10. doi: 10.1093/cid/ciw877).

nikkytok/Thinkstock

[email protected]

Abstaining from the consumption of tap water at health care facilities can dramatically reduce the risk of Mycobacterium abscessus infections among patients and staff, according to a new study published in Clinical Infectious Diseases.

“Outbreaks of [M. abscessus] and other rapidly growing mycobacteria are common and have been associated with colonized plumbing systems in commercial buildings and health care facilities,” wrote the authors, led by Arthur W. Baker, MD, MPH, of Duke University, Durham, N.C., adding that “Infections due to M. abscessus are difficult to diagnose and typically require months of therapy using multiple antibiotics” (Clin Infect Dis. 2017 Jan 10. doi: 10.1093/cid/ciw877).

nikkytok/Thinkstock

[email protected]

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

SEATTLE – Zika virus RNA lingered longer in semen than in any other body fluid but was cleared by 95% of men after 3 months, according to investigators from the Centers for Disease Control and Prevention.

The findings support the agency’s recommendation that men abstain from sex or use a condom for 6 months after coming down with symptoms. There had been concern following case reports of two men with semen positive for Zika RNA beyond 180 days, but further study supported the recommendation.

Many wondered if 6 months was too short, creating “a lot of anxiety and some confusion. It was good to find that [6 months is fine],” said senior CDC epidemiologist and lead investigator Gabriela Paz-Bailey, MD. “Based on our findings, late detection seems rare,” and the longest any infectious virus has been found in semen is 69 days.

The investigation team collected body fluids for 6 months from 150 patients in Puerto Rico who had confirmed Zika infection. Samples included semen samples from 55 men and vaginal secretions from 95 women in the study. Most of the participants presented to a hospital with symptoms, but some were household contacts who didn’t remember symptoms until asked.

“We found that two out of every three people who have evidence of infection reported symptoms,” which was higher than what was expected for an infection thought to be asymptomatic in many who remembered symptoms only when drilled by persistent epidemiologists. “You have to ask the questions,” Dr. Paz-Bailey said at the annual Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The samples were tested by reverse transcriptase polymerase chain reaction to see how long viral RNA stayed in various body fluids. Urine often is used to screen patients for Zika RNA, but the team found that virus evidence lasts longer in serum. While half of patients still had Zika RNA in their serum 2 weeks after symptom onset, and 5% were positive after about 2 months, urine was positive for Zika RNA in half of patients for only about a week. After 39 days, only 5% had RNA in their urine.

“It was thought that you could detect the virus more often in urine. We found the opposite. This is new. Serum may be a superior diagnostic specimen compared to urine,” Dr. Paz-Bailey said.

Additionally, RNA was found in semen longer than any other fluid, with about half of men positive after a month and 5% at about 3 months. The maximum for detection of Zika RNA in semen was 125 days. Meanwhile, RNA was largely undetectable in saliva and vaginal fluids after a week.

Until now, the 6-month window for men has been based on case reports and cross-sectional observations, mostly of travelers returning to the United States. The new findings bolster the 6-month abstinence or condom use recommendation but also support advice that women avoid pregnancy for 2 months following symptom onset, although the evidence for a 2-month window in women isn’t as strong.

The serum findings “suggest that the risk of intrauterine transmission ... is small” in women trying to conceive toward the end of the 2-month period, but “we will continue to monitor women of reproductive age to inform evaluations of these recommendations,” Dr. Paz-Bailey and her colleagues said in a report published after the presentation (N Engl J Med. 2017 Feb 14. doi: 10.1056/NEJMoa1613108).

It’s unclear if finding Zika RNA in body fluids means that there’s still active virus that can be transmitted. The team is plating out their specimens to see if they grow live virus.

The results are from an interim analysis. CDC plans to recruit at least 300 people into the study.

Dr. Paz-Bailey had no relevant financial disclosures. CDC funded the work.

[email protected]

SEATTLE – Zika virus RNA lingered longer in semen than in any other body fluid but was cleared by 95% of men after 3 months, according to investigators from the Centers for Disease Control and Prevention.

The findings support the agency’s recommendation that men abstain from sex or use a condom for 6 months after coming down with symptoms. There had been concern following case reports of two men with semen positive for Zika RNA beyond 180 days, but further study supported the recommendation.

Many wondered if 6 months was too short, creating “a lot of anxiety and some confusion. It was good to find that [6 months is fine],” said senior CDC epidemiologist and lead investigator Gabriela Paz-Bailey, MD. “Based on our findings, late detection seems rare,” and the longest any infectious virus has been found in semen is 69 days.

The investigation team collected body fluids for 6 months from 150 patients in Puerto Rico who had confirmed Zika infection. Samples included semen samples from 55 men and vaginal secretions from 95 women in the study. Most of the participants presented to a hospital with symptoms, but some were household contacts who didn’t remember symptoms until asked.

“We found that two out of every three people who have evidence of infection reported symptoms,” which was higher than what was expected for an infection thought to be asymptomatic in many who remembered symptoms only when drilled by persistent epidemiologists. “You have to ask the questions,” Dr. Paz-Bailey said at the annual Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The samples were tested by reverse transcriptase polymerase chain reaction to see how long viral RNA stayed in various body fluids. Urine often is used to screen patients for Zika RNA, but the team found that virus evidence lasts longer in serum. While half of patients still had Zika RNA in their serum 2 weeks after symptom onset, and 5% were positive after about 2 months, urine was positive for Zika RNA in half of patients for only about a week. After 39 days, only 5% had RNA in their urine.

“It was thought that you could detect the virus more often in urine. We found the opposite. This is new. Serum may be a superior diagnostic specimen compared to urine,” Dr. Paz-Bailey said.

Additionally, RNA was found in semen longer than any other fluid, with about half of men positive after a month and 5% at about 3 months. The maximum for detection of Zika RNA in semen was 125 days. Meanwhile, RNA was largely undetectable in saliva and vaginal fluids after a week.

Until now, the 6-month window for men has been based on case reports and cross-sectional observations, mostly of travelers returning to the United States. The new findings bolster the 6-month abstinence or condom use recommendation but also support advice that women avoid pregnancy for 2 months following symptom onset, although the evidence for a 2-month window in women isn’t as strong.

The serum findings “suggest that the risk of intrauterine transmission ... is small” in women trying to conceive toward the end of the 2-month period, but “we will continue to monitor women of reproductive age to inform evaluations of these recommendations,” Dr. Paz-Bailey and her colleagues said in a report published after the presentation (N Engl J Med. 2017 Feb 14. doi: 10.1056/NEJMoa1613108).

It’s unclear if finding Zika RNA in body fluids means that there’s still active virus that can be transmitted. The team is plating out their specimens to see if they grow live virus.

The results are from an interim analysis. CDC plans to recruit at least 300 people into the study.

Dr. Paz-Bailey had no relevant financial disclosures. CDC funded the work.

[email protected]

SEATTLE – Zika virus RNA lingered longer in semen than in any other body fluid but was cleared by 95% of men after 3 months, according to investigators from the Centers for Disease Control and Prevention.

The findings support the agency’s recommendation that men abstain from sex or use a condom for 6 months after coming down with symptoms. There had been concern following case reports of two men with semen positive for Zika RNA beyond 180 days, but further study supported the recommendation.

Many wondered if 6 months was too short, creating “a lot of anxiety and some confusion. It was good to find that [6 months is fine],” said senior CDC epidemiologist and lead investigator Gabriela Paz-Bailey, MD. “Based on our findings, late detection seems rare,” and the longest any infectious virus has been found in semen is 69 days.

The investigation team collected body fluids for 6 months from 150 patients in Puerto Rico who had confirmed Zika infection. Samples included semen samples from 55 men and vaginal secretions from 95 women in the study. Most of the participants presented to a hospital with symptoms, but some were household contacts who didn’t remember symptoms until asked.

“We found that two out of every three people who have evidence of infection reported symptoms,” which was higher than what was expected for an infection thought to be asymptomatic in many who remembered symptoms only when drilled by persistent epidemiologists. “You have to ask the questions,” Dr. Paz-Bailey said at the annual Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The samples were tested by reverse transcriptase polymerase chain reaction to see how long viral RNA stayed in various body fluids. Urine often is used to screen patients for Zika RNA, but the team found that virus evidence lasts longer in serum. While half of patients still had Zika RNA in their serum 2 weeks after symptom onset, and 5% were positive after about 2 months, urine was positive for Zika RNA in half of patients for only about a week. After 39 days, only 5% had RNA in their urine.

“It was thought that you could detect the virus more often in urine. We found the opposite. This is new. Serum may be a superior diagnostic specimen compared to urine,” Dr. Paz-Bailey said.

Additionally, RNA was found in semen longer than any other fluid, with about half of men positive after a month and 5% at about 3 months. The maximum for detection of Zika RNA in semen was 125 days. Meanwhile, RNA was largely undetectable in saliva and vaginal fluids after a week.

Until now, the 6-month window for men has been based on case reports and cross-sectional observations, mostly of travelers returning to the United States. The new findings bolster the 6-month abstinence or condom use recommendation but also support advice that women avoid pregnancy for 2 months following symptom onset, although the evidence for a 2-month window in women isn’t as strong.

The serum findings “suggest that the risk of intrauterine transmission ... is small” in women trying to conceive toward the end of the 2-month period, but “we will continue to monitor women of reproductive age to inform evaluations of these recommendations,” Dr. Paz-Bailey and her colleagues said in a report published after the presentation (N Engl J Med. 2017 Feb 14. doi: 10.1056/NEJMoa1613108).

It’s unclear if finding Zika RNA in body fluids means that there’s still active virus that can be transmitted. The team is plating out their specimens to see if they grow live virus.

The results are from an interim analysis. CDC plans to recruit at least 300 people into the study.

Dr. Paz-Bailey had no relevant financial disclosures. CDC funded the work.

[email protected]

HOUSTON – Even when patients on an oral anticoagulant have the dreaded complication of an intracerebral hemorrhage, resumption of their oral anticoagulation regimen appears to produce the best midterm outcomes, based on a meta-analysis of data from more than 1,000 patients collected in three observational studies.

Resumption of oral anticoagulation therapy (OAT) is a “major dilemma” when managing patients who developed an intracerebral hemorrhage (ICH) while on OAT, said Alessandro Biffi, MD, explaining why he performed this meta-analysis that he presented at the International Stroke Conference sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

HOUSTON – Even when patients on an oral anticoagulant have the dreaded complication of an intracerebral hemorrhage, resumption of their oral anticoagulation regimen appears to produce the best midterm outcomes, based on a meta-analysis of data from more than 1,000 patients collected in three observational studies.

Resumption of oral anticoagulation therapy (OAT) is a “major dilemma” when managing patients who developed an intracerebral hemorrhage (ICH) while on OAT, said Alessandro Biffi, MD, explaining why he performed this meta-analysis that he presented at the International Stroke Conference sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

HOUSTON – Even when patients on an oral anticoagulant have the dreaded complication of an intracerebral hemorrhage, resumption of their oral anticoagulation regimen appears to produce the best midterm outcomes, based on a meta-analysis of data from more than 1,000 patients collected in three observational studies.

Resumption of oral anticoagulation therapy (OAT) is a “major dilemma” when managing patients who developed an intracerebral hemorrhage (ICH) while on OAT, said Alessandro Biffi, MD, explaining why he performed this meta-analysis that he presented at the International Stroke Conference sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

For patients with newly diagnosed mantle cell lymphoma, duration and quality of response were superior with a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) when compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), based on a post hoc analysis of the randomized, phase III LYM-3002 trial.

The difference was especially evident among patients who had a low- or medium-risk mantle cell lymphoma international prognostic index, Gregor Verhoef, MD, of University Hospital Leuven (Belgium) and his associates wrote in Haematologica.

In LYM-3002, 487 patients with newly diagnosed stage II-IV mantle cell lymphoma received six to eight 21-day cycles of intravenous VR-CAP or R-CHOP. Although overall response rates were similar for both groups, VR-CAP was associated with better duration of response and progression-free survival (PFS) and extended time to next treatment. To further explore these differences, the post hoc analysis stratified outcomes by response categories and analyzed depth of response based on computed tomography (CT) scans. Patients had a median age of about 65 years, and most were white males with stage-IV disease at diagnosis and an Eastern Cooperative Oncology Group performance status of 1 (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.152496).The superiority of VR-CAP held up across response categories. Complete responders to VR-CAP had more than twice the median PFS as did complete responders to R-CHOP (40.9 vs. 19.8 months; hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; P = .004). Among partial responders, median PFS was 17.1 vs. 11.7 months, respectively (HR, 0.62; 95% CI, 0.43-0.89; P = .01). Respective median duration of overall response was 42.1 months for VR-CAP vs. 18.5 months among complete responders (HR, 0.42; P less than .001), and 20.2 vs. 9.6 months among partial responders (HR, 0.57; P = .006).

Median time to next treatment also favored VR-CAP over R-CHOP among both complete responders (not evaluable vs. 26.6 months; HR, 0.42; P less than .001) and partial responders (35.3 vs. 24.3 months; HR, 0.57; P = .006), the researchers said. Further, CT scans showed that proportionally more patients in each response category became lesion-negative on VR-CAP than on R-CHOP. Among complete responders, rates of lesion negativity were 72% and 59%, respectively. Among partial responders, rates were 48% and 28%.

The effects of VR-CAP were most evident among patients with a low or medium-risk mantle cell lymphoma international prognostic index. Perhaps high-risk status signifies more rapidly proliferative disease, which negates the deeper responses with VR-CAP, compared with R-CHOP, they added.

The LYM-3002 study was supported by Janssen Research & Development and Millennium Pharmaceuticals. Dr. Verhoef had no disclosures. Nine coinvestigators disclosed ties to Janssen, Roche, GlaxoSmithKline, and several other pharmaceutical companies.

For patients with newly diagnosed mantle cell lymphoma, duration and quality of response were superior with a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) when compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), based on a post hoc analysis of the randomized, phase III LYM-3002 trial.

The difference was especially evident among patients who had a low- or medium-risk mantle cell lymphoma international prognostic index, Gregor Verhoef, MD, of University Hospital Leuven (Belgium) and his associates wrote in Haematologica.

In LYM-3002, 487 patients with newly diagnosed stage II-IV mantle cell lymphoma received six to eight 21-day cycles of intravenous VR-CAP or R-CHOP. Although overall response rates were similar for both groups, VR-CAP was associated with better duration of response and progression-free survival (PFS) and extended time to next treatment. To further explore these differences, the post hoc analysis stratified outcomes by response categories and analyzed depth of response based on computed tomography (CT) scans. Patients had a median age of about 65 years, and most were white males with stage-IV disease at diagnosis and an Eastern Cooperative Oncology Group performance status of 1 (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.152496).The superiority of VR-CAP held up across response categories. Complete responders to VR-CAP had more than twice the median PFS as did complete responders to R-CHOP (40.9 vs. 19.8 months; hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; P = .004). Among partial responders, median PFS was 17.1 vs. 11.7 months, respectively (HR, 0.62; 95% CI, 0.43-0.89; P = .01). Respective median duration of overall response was 42.1 months for VR-CAP vs. 18.5 months among complete responders (HR, 0.42; P less than .001), and 20.2 vs. 9.6 months among partial responders (HR, 0.57; P = .006).

Median time to next treatment also favored VR-CAP over R-CHOP among both complete responders (not evaluable vs. 26.6 months; HR, 0.42; P less than .001) and partial responders (35.3 vs. 24.3 months; HR, 0.57; P = .006), the researchers said. Further, CT scans showed that proportionally more patients in each response category became lesion-negative on VR-CAP than on R-CHOP. Among complete responders, rates of lesion negativity were 72% and 59%, respectively. Among partial responders, rates were 48% and 28%.

The effects of VR-CAP were most evident among patients with a low or medium-risk mantle cell lymphoma international prognostic index. Perhaps high-risk status signifies more rapidly proliferative disease, which negates the deeper responses with VR-CAP, compared with R-CHOP, they added.

The LYM-3002 study was supported by Janssen Research & Development and Millennium Pharmaceuticals. Dr. Verhoef had no disclosures. Nine coinvestigators disclosed ties to Janssen, Roche, GlaxoSmithKline, and several other pharmaceutical companies.

For patients with newly diagnosed mantle cell lymphoma, duration and quality of response were superior with a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) when compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), based on a post hoc analysis of the randomized, phase III LYM-3002 trial.

The difference was especially evident among patients who had a low- or medium-risk mantle cell lymphoma international prognostic index, Gregor Verhoef, MD, of University Hospital Leuven (Belgium) and his associates wrote in Haematologica.

In LYM-3002, 487 patients with newly diagnosed stage II-IV mantle cell lymphoma received six to eight 21-day cycles of intravenous VR-CAP or R-CHOP. Although overall response rates were similar for both groups, VR-CAP was associated with better duration of response and progression-free survival (PFS) and extended time to next treatment. To further explore these differences, the post hoc analysis stratified outcomes by response categories and analyzed depth of response based on computed tomography (CT) scans. Patients had a median age of about 65 years, and most were white males with stage-IV disease at diagnosis and an Eastern Cooperative Oncology Group performance status of 1 (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.152496).The superiority of VR-CAP held up across response categories. Complete responders to VR-CAP had more than twice the median PFS as did complete responders to R-CHOP (40.9 vs. 19.8 months; hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; P = .004). Among partial responders, median PFS was 17.1 vs. 11.7 months, respectively (HR, 0.62; 95% CI, 0.43-0.89; P = .01). Respective median duration of overall response was 42.1 months for VR-CAP vs. 18.5 months among complete responders (HR, 0.42; P less than .001), and 20.2 vs. 9.6 months among partial responders (HR, 0.57; P = .006).

Median time to next treatment also favored VR-CAP over R-CHOP among both complete responders (not evaluable vs. 26.6 months; HR, 0.42; P less than .001) and partial responders (35.3 vs. 24.3 months; HR, 0.57; P = .006), the researchers said. Further, CT scans showed that proportionally more patients in each response category became lesion-negative on VR-CAP than on R-CHOP. Among complete responders, rates of lesion negativity were 72% and 59%, respectively. Among partial responders, rates were 48% and 28%.

The effects of VR-CAP were most evident among patients with a low or medium-risk mantle cell lymphoma international prognostic index. Perhaps high-risk status signifies more rapidly proliferative disease, which negates the deeper responses with VR-CAP, compared with R-CHOP, they added.

The LYM-3002 study was supported by Janssen Research & Development and Millennium Pharmaceuticals. Dr. Verhoef had no disclosures. Nine coinvestigators disclosed ties to Janssen, Roche, GlaxoSmithKline, and several other pharmaceutical companies.

Oral anticoagulation with warfarin is used for the treatment and prevention of a variety of thrombotic disorders, including deep venous thrombosis (DVT), pulmonary embolism (PE), stroke prevention in atrial fibrillation (AF) and atrial flutter, and other hypercoagulable conditions. Although a mainstay in the treatment for these conditions, warfarin requires close monitoring due to its narrow therapeutic range, extensive drug and dietary interactions, and dosage variability among patients.¹ Patients outside the therapeutic range are at risk of having a thrombotic or bleeding event that could lead to hospitalization or fatality.¹ To reduce the risk of these events, patients on warfarin are managed by dose adjustment based on the international normalized ratio (INR). Research has shown that patients on warfarin in pharmacist-managed specialty anticoagulation clinics have more consistent monitoring and lower rates of adverse events (AEs) compared with traditional physician or nurse clinics.^2-6 Management through these clinics can be achieved through office visits or telephone visits.

There are advantages and disadvantages to each model of anticoagulation management for patients.Telephone clinics provide time and cost savings, increased access to care, and convenience. However, disadvantages include missed phone calls or inability to contact the patient, difficulty for the patient to hear the provider’s instructions over the phone, and patient unavailability when a critical INR is of concern. Office visits are beneficial in that providers can provide both written and verbal instruction to patients, perform visual or physical patient assessments, and provide timely care if needed. Disadvantages of office visits may include long wait times and inconvenience for patients who live far away.

Telephone anticoagulation clinics have been evaluated for their efficacy and cost-effectiveness in several studies.^5,7,8 However, few studies are available that compare patient outcomes between office visits and telephone visits. Two prior studies comparing groups of anticoagulation patients managed by telephone or by office visit concluded that there is no difference in outcomes between the 2 management models.^9,10 However, a retrospective study by Stoudenmire and colleagues examined extreme INR values (≤ 1.5 or ≥ 4.5) in each management model and found that telephone clinic patients have a significant increase in extreme INR values but no difference in AEs between the 2 management models.¹¹

The VA North Texas Health Care System (VANTHCS) includes a major medical center, 3 outlying medical facilities, and 5 community-based outpatient clinics (CBOCs). A centralized pharmacist-managed anticoagulation clinic is used to manage more than 2,500 VANTHCS anticoagulation patients. To meet the National Patient Safety Goal measures and provide consistent management across the system, all anticoagulation patients from CBOCs and medical facilities are enrolled in the clinic.¹² To facilitate access to care, many patients transitioned from office visits to telephone visits. It was essential to evaluate the transition of patients from office to telephone visits to ensure continued stability and continuity of care across both models. The objective of this study was to determine whether a difference in anticoagulation outcomes exists when patients are transitioned from office to telephone visits.

Methods

The VANTHCS anticoagulation clinic policy for office visits requires that patients arrive at the Dallas VAMC 2 hours before their appointment for INR lab draw. During the office visit, the anticoagulation pharmacist evaluates the INR and pertinent changes since the previous visit. The patient is provided verbal instructions and a written dosage adjustment card. Telephone clinic protocol is similar to office visits with a few exceptions. Any patient, regardless of INR stability, may be enrolled in the telephone clinic as long as the patient provides consent and has a working telephone with voice mail. Patients enrolled in the telephone clinic access blood draws at the nearest VA facility and are given a questionnaire that includes pertinent questions asked during an office visit. Anticoagulation pharmacists evaluate the questionnaire and INR then contact the patient within 1 business day to provide the patient with instructions. If a patient fails to answer the telephone, the anticoagulation pharmacist leaves a voicemail message.

Study Design

This retrospective study was conducted by chart review using Computerized Patient Record System (CPRS) at VANTHCS on patients who met inclusion criteria between January 1, 2011 and May 31, 2014, and it was approved by the institutional review board and research and development committee. The study included patients aged ≥ 18 years on warfarin therapy managed by the VANTHCS anticoagulation clinic who were previously managed in office visits for ≥ 180 days before the telephone transition, then in telephone visits for another ≥ 180 days. Only INR values obtained through the VANTHCS anticoagulation clinic were assessed.

Patients were excluded from the study if they were not managed by the VANTHCS anticoagulation clinic or received direct oral anticoagulants (DOACs). The INR values were excluded if they were nonclinic related INR values (ie, results reported that do not reflect management by the anticoagulation clinic), the first INR after hospitalization, or INRs obtained during the first month of initial warfarin treatment for a patient.

For all patients included in the study, demographic information, goal INR range (2 to 3 or 2.5 to 3.5), indication for warfarin therapy, and duration of warfarin therapy (defined as the first prescription filled for warfarin at the VA) were obtained. Individual INR values were obtained for each patient during the period of investigation and type of visit (office or telephone) for each INR drawn was specified. Any major bleeding or thrombotic events (bleed requiring an emergency department [ED] visit, hospitalization, vitamin K administration, blood transfusion, and/or warfarin therapy hold/discontinuation) were documented. Procedures and number of hospitalizations also during the investigation were recorded.

The primary outcomes measures evaluated INRs for time in therapeutic range (TTR) using the Rosendaal method and percentage of INRs within range.¹³ The therapeutic range was either 2 to 3 or 2.5 to 3.5 (the “strict range” for INR management). Because many patients fluctuate around the strict range and it is common to avoid therapy adjustment based on slightly elevated or lower values, a “nonstrict” range (1.8 to 3.2 or 2.3 to 3.7) also was evaluated.¹⁴ The secondary outcomes examined differences between the 2 management models in rates of major AEs, including thrombosis and major bleeding events as defined earlier.Frequencies, percentages, and other descriptive statistics were used to describe nominal data. A paired t test was used to compare TTR of patients transitioned from office to telephone visits. A P value of < .05 was used for statistical significance.

Results

A total of 111 patients met inclusion criteria (Table 1). Most patients were elderly males with AF or atrial flutter as their primary indication for warfarin therapy. No statistically significant difference was found for percentage INRs in strict range (56.8% in office vs 56.9% in telephone, P = .98) or TTR (65.9% in office vs 62.72% in telephone, P = .23) for patients who transitioned from office to telephone visits (Table 2). Similar results were found within the nonstrict range.

In examining safety, 5 major AEs occurred. One patient had 2 thrombotic pulmonary embolism events. This patient had a history of nonadherence with warfarin therapy. Three major bleeding events occurred (2 in the telephone group and 1 in the office group). Two bleeding events led to ED visits, and 1 event led to hospitalization. Although 43% of patients had a procedure during the study period, only a portion of patients received bridging with low-molecular-weight heparin (LMWH). None of the 3 reported bleeding events discovered during the study were associated with recent LMWH use. No events were fatal (Table 3).

Discussion

This study demonstrates that patients transitioned from office to telephone visits for warfarin management will have no significant change in their TTR. Additionally, patients had similar rates of major AEs before and after transition, although there were few events overall.

Previous research comparing anticoagulation outcomes in telephone vs office visits also has described outcomes to be similar between these 2 management models. Wittkowsky and colleagues examined 2 university-affiliated clinics to evaluate warfarin outcomes and AEs in patients in each management model (office vs telephone) and found no difference in outcomes between the 2 management models.⁹

Staresinic and colleagues designed a prospective study of 192 patients to evaluate TTR and AEs of the 2 management models at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin.¹⁰ This study found no difference between the 2 groups in percentage of time maintained within INR range or AEs and concluded that the telephone model was effective for anticoagulant management.

A retrospective study by Stoudenmire and colleagues evaluated office vs telephone management effects on extreme INR values (≤ 1.5 or ≥ 4.5), TTR, and AEs.¹¹ This study found overall TTR and AEs to be similar between groups, but the telephone clinic had a 2-fold increase in extreme INR values compared with the office clinic.¹¹

The current study differs from the previously discussed studies in that it evaluated outcomes for the same patients before and after the transition to telephone. This study did not exclude specific patients from telephone clinic. In the Wittkowsky study, patients were enrolled in the telephone clinic based on criteria such as patient disability or living long distances from the clinic.⁹ Additionally, in the current study, patients transitioned to telephone visits did not have scheduled office visits for anticoagulation management. In contrast, patients in the Staresinic study had routine anticoagulation office visits every 3 months, thus it was not a true telephone-only clinic.¹⁰

This study’s findings support prior studies’ findings that telephone clinics are acceptable for anticoagulation management. Furthermore, safety does not seem to be affected when transitioning patients, although there were few AEs to review. Providers can use telephone clinics to potentially decrease cost and facilitate access to care for patients.

Limitations

Patients were required to be in office and telephone for a sequential 6 months, and this may have produced selection biases toward patients who adhered to appointments and who were on long-term warfarin therapy. Many patients that were excluded from the study transitioned back and forth between the 2 management models. Due to the retrospective nature of this study, the authors were unable to control for all confounding variables. Patients also were not randomly assigned to be transitioned from office to telephone. Although a strength of this study was the limited telephone clinic selection criteria, there may be a few individual situations in which the pharmacist’s clinical judgment influenced the transition to the telephone clinic, creating selection bias.

There may be time bias present as clinical guidelines, providers, and clinic population size differed over the study period and might have influenced management. The population of VA patients was mainly elderly males; therefore, the study results may not be applicable to other populations. Last, the results of the study are reflective of the VANTHCS clinic structure and may not be applicable to other clinic designs.

Conclusion

Veterans in a pharmacist-managed anticoagulation clinic experienced the same outcomes in terms of TTR and major AEs when transitioned from the traditional face-to-face office visits to telephone visits. The study supports the safety and efficacy of transitioning patients from a pharmacist-managed anticoagulation office clinic to telephone clinic.

Oral anticoagulation with warfarin is used for the treatment and prevention of a variety of thrombotic disorders, including deep venous thrombosis (DVT), pulmonary embolism (PE), stroke prevention in atrial fibrillation (AF) and atrial flutter, and other hypercoagulable conditions. Although a mainstay in the treatment for these conditions, warfarin requires close monitoring due to its narrow therapeutic range, extensive drug and dietary interactions, and dosage variability among patients.¹ Patients outside the therapeutic range are at risk of having a thrombotic or bleeding event that could lead to hospitalization or fatality.¹ To reduce the risk of these events, patients on warfarin are managed by dose adjustment based on the international normalized ratio (INR). Research has shown that patients on warfarin in pharmacist-managed specialty anticoagulation clinics have more consistent monitoring and lower rates of adverse events (AEs) compared with traditional physician or nurse clinics.^2-6 Management through these clinics can be achieved through office visits or telephone visits.

There are advantages and disadvantages to each model of anticoagulation management for patients.Telephone clinics provide time and cost savings, increased access to care, and convenience. However, disadvantages include missed phone calls or inability to contact the patient, difficulty for the patient to hear the provider’s instructions over the phone, and patient unavailability when a critical INR is of concern. Office visits are beneficial in that providers can provide both written and verbal instruction to patients, perform visual or physical patient assessments, and provide timely care if needed. Disadvantages of office visits may include long wait times and inconvenience for patients who live far away.

Telephone anticoagulation clinics have been evaluated for their efficacy and cost-effectiveness in several studies.^5,7,8 However, few studies are available that compare patient outcomes between office visits and telephone visits. Two prior studies comparing groups of anticoagulation patients managed by telephone or by office visit concluded that there is no difference in outcomes between the 2 management models.^9,10 However, a retrospective study by Stoudenmire and colleagues examined extreme INR values (≤ 1.5 or ≥ 4.5) in each management model and found that telephone clinic patients have a significant increase in extreme INR values but no difference in AEs between the 2 management models.¹¹

The VA North Texas Health Care System (VANTHCS) includes a major medical center, 3 outlying medical facilities, and 5 community-based outpatient clinics (CBOCs). A centralized pharmacist-managed anticoagulation clinic is used to manage more than 2,500 VANTHCS anticoagulation patients. To meet the National Patient Safety Goal measures and provide consistent management across the system, all anticoagulation patients from CBOCs and medical facilities are enrolled in the clinic.¹² To facilitate access to care, many patients transitioned from office visits to telephone visits. It was essential to evaluate the transition of patients from office to telephone visits to ensure continued stability and continuity of care across both models. The objective of this study was to determine whether a difference in anticoagulation outcomes exists when patients are transitioned from office to telephone visits.

Methods

The VANTHCS anticoagulation clinic policy for office visits requires that patients arrive at the Dallas VAMC 2 hours before their appointment for INR lab draw. During the office visit, the anticoagulation pharmacist evaluates the INR and pertinent changes since the previous visit. The patient is provided verbal instructions and a written dosage adjustment card. Telephone clinic protocol is similar to office visits with a few exceptions. Any patient, regardless of INR stability, may be enrolled in the telephone clinic as long as the patient provides consent and has a working telephone with voice mail. Patients enrolled in the telephone clinic access blood draws at the nearest VA facility and are given a questionnaire that includes pertinent questions asked during an office visit. Anticoagulation pharmacists evaluate the questionnaire and INR then contact the patient within 1 business day to provide the patient with instructions. If a patient fails to answer the telephone, the anticoagulation pharmacist leaves a voicemail message.

Study Design

This retrospective study was conducted by chart review using Computerized Patient Record System (CPRS) at VANTHCS on patients who met inclusion criteria between January 1, 2011 and May 31, 2014, and it was approved by the institutional review board and research and development committee. The study included patients aged ≥ 18 years on warfarin therapy managed by the VANTHCS anticoagulation clinic who were previously managed in office visits for ≥ 180 days before the telephone transition, then in telephone visits for another ≥ 180 days. Only INR values obtained through the VANTHCS anticoagulation clinic were assessed.

Patients were excluded from the study if they were not managed by the VANTHCS anticoagulation clinic or received direct oral anticoagulants (DOACs). The INR values were excluded if they were nonclinic related INR values (ie, results reported that do not reflect management by the anticoagulation clinic), the first INR after hospitalization, or INRs obtained during the first month of initial warfarin treatment for a patient.

For all patients included in the study, demographic information, goal INR range (2 to 3 or 2.5 to 3.5), indication for warfarin therapy, and duration of warfarin therapy (defined as the first prescription filled for warfarin at the VA) were obtained. Individual INR values were obtained for each patient during the period of investigation and type of visit (office or telephone) for each INR drawn was specified. Any major bleeding or thrombotic events (bleed requiring an emergency department [ED] visit, hospitalization, vitamin K administration, blood transfusion, and/or warfarin therapy hold/discontinuation) were documented. Procedures and number of hospitalizations also during the investigation were recorded.

The primary outcomes measures evaluated INRs for time in therapeutic range (TTR) using the Rosendaal method and percentage of INRs within range.¹³ The therapeutic range was either 2 to 3 or 2.5 to 3.5 (the “strict range” for INR management). Because many patients fluctuate around the strict range and it is common to avoid therapy adjustment based on slightly elevated or lower values, a “nonstrict” range (1.8 to 3.2 or 2.3 to 3.7) also was evaluated.¹⁴ The secondary outcomes examined differences between the 2 management models in rates of major AEs, including thrombosis and major bleeding events as defined earlier.Frequencies, percentages, and other descriptive statistics were used to describe nominal data. A paired t test was used to compare TTR of patients transitioned from office to telephone visits. A P value of < .05 was used for statistical significance.

Results

A total of 111 patients met inclusion criteria (Table 1). Most patients were elderly males with AF or atrial flutter as their primary indication for warfarin therapy. No statistically significant difference was found for percentage INRs in strict range (56.8% in office vs 56.9% in telephone, P = .98) or TTR (65.9% in office vs 62.72% in telephone, P = .23) for patients who transitioned from office to telephone visits (Table 2). Similar results were found within the nonstrict range.

In examining safety, 5 major AEs occurred. One patient had 2 thrombotic pulmonary embolism events. This patient had a history of nonadherence with warfarin therapy. Three major bleeding events occurred (2 in the telephone group and 1 in the office group). Two bleeding events led to ED visits, and 1 event led to hospitalization. Although 43% of patients had a procedure during the study period, only a portion of patients received bridging with low-molecular-weight heparin (LMWH). None of the 3 reported bleeding events discovered during the study were associated with recent LMWH use. No events were fatal (Table 3).

Discussion

This study demonstrates that patients transitioned from office to telephone visits for warfarin management will have no significant change in their TTR. Additionally, patients had similar rates of major AEs before and after transition, although there were few events overall.

Previous research comparing anticoagulation outcomes in telephone vs office visits also has described outcomes to be similar between these 2 management models. Wittkowsky and colleagues examined 2 university-affiliated clinics to evaluate warfarin outcomes and AEs in patients in each management model (office vs telephone) and found no difference in outcomes between the 2 management models.⁹

Staresinic and colleagues designed a prospective study of 192 patients to evaluate TTR and AEs of the 2 management models at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin.¹⁰ This study found no difference between the 2 groups in percentage of time maintained within INR range or AEs and concluded that the telephone model was effective for anticoagulant management.

A retrospective study by Stoudenmire and colleagues evaluated office vs telephone management effects on extreme INR values (≤ 1.5 or ≥ 4.5), TTR, and AEs.¹¹ This study found overall TTR and AEs to be similar between groups, but the telephone clinic had a 2-fold increase in extreme INR values compared with the office clinic.¹¹

The current study differs from the previously discussed studies in that it evaluated outcomes for the same patients before and after the transition to telephone. This study did not exclude specific patients from telephone clinic. In the Wittkowsky study, patients were enrolled in the telephone clinic based on criteria such as patient disability or living long distances from the clinic.⁹ Additionally, in the current study, patients transitioned to telephone visits did not have scheduled office visits for anticoagulation management. In contrast, patients in the Staresinic study had routine anticoagulation office visits every 3 months, thus it was not a true telephone-only clinic.¹⁰

This study’s findings support prior studies’ findings that telephone clinics are acceptable for anticoagulation management. Furthermore, safety does not seem to be affected when transitioning patients, although there were few AEs to review. Providers can use telephone clinics to potentially decrease cost and facilitate access to care for patients.

Limitations

Patients were required to be in office and telephone for a sequential 6 months, and this may have produced selection biases toward patients who adhered to appointments and who were on long-term warfarin therapy. Many patients that were excluded from the study transitioned back and forth between the 2 management models. Due to the retrospective nature of this study, the authors were unable to control for all confounding variables. Patients also were not randomly assigned to be transitioned from office to telephone. Although a strength of this study was the limited telephone clinic selection criteria, there may be a few individual situations in which the pharmacist’s clinical judgment influenced the transition to the telephone clinic, creating selection bias.

There may be time bias present as clinical guidelines, providers, and clinic population size differed over the study period and might have influenced management. The population of VA patients was mainly elderly males; therefore, the study results may not be applicable to other populations. Last, the results of the study are reflective of the VANTHCS clinic structure and may not be applicable to other clinic designs.

Conclusion

Veterans in a pharmacist-managed anticoagulation clinic experienced the same outcomes in terms of TTR and major AEs when transitioned from the traditional face-to-face office visits to telephone visits. The study supports the safety and efficacy of transitioning patients from a pharmacist-managed anticoagulation office clinic to telephone clinic.

Oral anticoagulation with warfarin is used for the treatment and prevention of a variety of thrombotic disorders, including deep venous thrombosis (DVT), pulmonary embolism (PE), stroke prevention in atrial fibrillation (AF) and atrial flutter, and other hypercoagulable conditions. Although a mainstay in the treatment for these conditions, warfarin requires close monitoring due to its narrow therapeutic range, extensive drug and dietary interactions, and dosage variability among patients.¹ Patients outside the therapeutic range are at risk of having a thrombotic or bleeding event that could lead to hospitalization or fatality.¹ To reduce the risk of these events, patients on warfarin are managed by dose adjustment based on the international normalized ratio (INR). Research has shown that patients on warfarin in pharmacist-managed specialty anticoagulation clinics have more consistent monitoring and lower rates of adverse events (AEs) compared with traditional physician or nurse clinics.^2-6 Management through these clinics can be achieved through office visits or telephone visits.

There are advantages and disadvantages to each model of anticoagulation management for patients.Telephone clinics provide time and cost savings, increased access to care, and convenience. However, disadvantages include missed phone calls or inability to contact the patient, difficulty for the patient to hear the provider’s instructions over the phone, and patient unavailability when a critical INR is of concern. Office visits are beneficial in that providers can provide both written and verbal instruction to patients, perform visual or physical patient assessments, and provide timely care if needed. Disadvantages of office visits may include long wait times and inconvenience for patients who live far away.

Telephone anticoagulation clinics have been evaluated for their efficacy and cost-effectiveness in several studies.^5,7,8 However, few studies are available that compare patient outcomes between office visits and telephone visits. Two prior studies comparing groups of anticoagulation patients managed by telephone or by office visit concluded that there is no difference in outcomes between the 2 management models.^9,10 However, a retrospective study by Stoudenmire and colleagues examined extreme INR values (≤ 1.5 or ≥ 4.5) in each management model and found that telephone clinic patients have a significant increase in extreme INR values but no difference in AEs between the 2 management models.¹¹

The VA North Texas Health Care System (VANTHCS) includes a major medical center, 3 outlying medical facilities, and 5 community-based outpatient clinics (CBOCs). A centralized pharmacist-managed anticoagulation clinic is used to manage more than 2,500 VANTHCS anticoagulation patients. To meet the National Patient Safety Goal measures and provide consistent management across the system, all anticoagulation patients from CBOCs and medical facilities are enrolled in the clinic.¹² To facilitate access to care, many patients transitioned from office visits to telephone visits. It was essential to evaluate the transition of patients from office to telephone visits to ensure continued stability and continuity of care across both models. The objective of this study was to determine whether a difference in anticoagulation outcomes exists when patients are transitioned from office to telephone visits.

Methods

The VANTHCS anticoagulation clinic policy for office visits requires that patients arrive at the Dallas VAMC 2 hours before their appointment for INR lab draw. During the office visit, the anticoagulation pharmacist evaluates the INR and pertinent changes since the previous visit. The patient is provided verbal instructions and a written dosage adjustment card. Telephone clinic protocol is similar to office visits with a few exceptions. Any patient, regardless of INR stability, may be enrolled in the telephone clinic as long as the patient provides consent and has a working telephone with voice mail. Patients enrolled in the telephone clinic access blood draws at the nearest VA facility and are given a questionnaire that includes pertinent questions asked during an office visit. Anticoagulation pharmacists evaluate the questionnaire and INR then contact the patient within 1 business day to provide the patient with instructions. If a patient fails to answer the telephone, the anticoagulation pharmacist leaves a voicemail message.

Study Design

This retrospective study was conducted by chart review using Computerized Patient Record System (CPRS) at VANTHCS on patients who met inclusion criteria between January 1, 2011 and May 31, 2014, and it was approved by the institutional review board and research and development committee. The study included patients aged ≥ 18 years on warfarin therapy managed by the VANTHCS anticoagulation clinic who were previously managed in office visits for ≥ 180 days before the telephone transition, then in telephone visits for another ≥ 180 days. Only INR values obtained through the VANTHCS anticoagulation clinic were assessed.

Patients were excluded from the study if they were not managed by the VANTHCS anticoagulation clinic or received direct oral anticoagulants (DOACs). The INR values were excluded if they were nonclinic related INR values (ie, results reported that do not reflect management by the anticoagulation clinic), the first INR after hospitalization, or INRs obtained during the first month of initial warfarin treatment for a patient.

For all patients included in the study, demographic information, goal INR range (2 to 3 or 2.5 to 3.5), indication for warfarin therapy, and duration of warfarin therapy (defined as the first prescription filled for warfarin at the VA) were obtained. Individual INR values were obtained for each patient during the period of investigation and type of visit (office or telephone) for each INR drawn was specified. Any major bleeding or thrombotic events (bleed requiring an emergency department [ED] visit, hospitalization, vitamin K administration, blood transfusion, and/or warfarin therapy hold/discontinuation) were documented. Procedures and number of hospitalizations also during the investigation were recorded.

The primary outcomes measures evaluated INRs for time in therapeutic range (TTR) using the Rosendaal method and percentage of INRs within range.¹³ The therapeutic range was either 2 to 3 or 2.5 to 3.5 (the “strict range” for INR management). Because many patients fluctuate around the strict range and it is common to avoid therapy adjustment based on slightly elevated or lower values, a “nonstrict” range (1.8 to 3.2 or 2.3 to 3.7) also was evaluated.¹⁴ The secondary outcomes examined differences between the 2 management models in rates of major AEs, including thrombosis and major bleeding events as defined earlier.Frequencies, percentages, and other descriptive statistics were used to describe nominal data. A paired t test was used to compare TTR of patients transitioned from office to telephone visits. A P value of < .05 was used for statistical significance.

Results

A total of 111 patients met inclusion criteria (Table 1). Most patients were elderly males with AF or atrial flutter as their primary indication for warfarin therapy. No statistically significant difference was found for percentage INRs in strict range (56.8% in office vs 56.9% in telephone, P = .98) or TTR (65.9% in office vs 62.72% in telephone, P = .23) for patients who transitioned from office to telephone visits (Table 2). Similar results were found within the nonstrict range.

In examining safety, 5 major AEs occurred. One patient had 2 thrombotic pulmonary embolism events. This patient had a history of nonadherence with warfarin therapy. Three major bleeding events occurred (2 in the telephone group and 1 in the office group). Two bleeding events led to ED visits, and 1 event led to hospitalization. Although 43% of patients had a procedure during the study period, only a portion of patients received bridging with low-molecular-weight heparin (LMWH). None of the 3 reported bleeding events discovered during the study were associated with recent LMWH use. No events were fatal (Table 3).

Discussion

This study demonstrates that patients transitioned from office to telephone visits for warfarin management will have no significant change in their TTR. Additionally, patients had similar rates of major AEs before and after transition, although there were few events overall.

Previous research comparing anticoagulation outcomes in telephone vs office visits also has described outcomes to be similar between these 2 management models. Wittkowsky and colleagues examined 2 university-affiliated clinics to evaluate warfarin outcomes and AEs in patients in each management model (office vs telephone) and found no difference in outcomes between the 2 management models.⁹

Staresinic and colleagues designed a prospective study of 192 patients to evaluate TTR and AEs of the 2 management models at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin.¹⁰ This study found no difference between the 2 groups in percentage of time maintained within INR range or AEs and concluded that the telephone model was effective for anticoagulant management.

A retrospective study by Stoudenmire and colleagues evaluated office vs telephone management effects on extreme INR values (≤ 1.5 or ≥ 4.5), TTR, and AEs.¹¹ This study found overall TTR and AEs to be similar between groups, but the telephone clinic had a 2-fold increase in extreme INR values compared with the office clinic.¹¹

The current study differs from the previously discussed studies in that it evaluated outcomes for the same patients before and after the transition to telephone. This study did not exclude specific patients from telephone clinic. In the Wittkowsky study, patients were enrolled in the telephone clinic based on criteria such as patient disability or living long distances from the clinic.⁹ Additionally, in the current study, patients transitioned to telephone visits did not have scheduled office visits for anticoagulation management. In contrast, patients in the Staresinic study had routine anticoagulation office visits every 3 months, thus it was not a true telephone-only clinic.¹⁰

This study’s findings support prior studies’ findings that telephone clinics are acceptable for anticoagulation management. Furthermore, safety does not seem to be affected when transitioning patients, although there were few AEs to review. Providers can use telephone clinics to potentially decrease cost and facilitate access to care for patients.

Limitations

Patients were required to be in office and telephone for a sequential 6 months, and this may have produced selection biases toward patients who adhered to appointments and who were on long-term warfarin therapy. Many patients that were excluded from the study transitioned back and forth between the 2 management models. Due to the retrospective nature of this study, the authors were unable to control for all confounding variables. Patients also were not randomly assigned to be transitioned from office to telephone. Although a strength of this study was the limited telephone clinic selection criteria, there may be a few individual situations in which the pharmacist’s clinical judgment influenced the transition to the telephone clinic, creating selection bias.

There may be time bias present as clinical guidelines, providers, and clinic population size differed over the study period and might have influenced management. The population of VA patients was mainly elderly males; therefore, the study results may not be applicable to other populations. Last, the results of the study are reflective of the VANTHCS clinic structure and may not be applicable to other clinic designs.

Conclusion

Veterans in a pharmacist-managed anticoagulation clinic experienced the same outcomes in terms of TTR and major AEs when transitioned from the traditional face-to-face office visits to telephone visits. The study supports the safety and efficacy of transitioning patients from a pharmacist-managed anticoagulation office clinic to telephone clinic.

As warmer temperatures herald the arrival of pesky mosquitoes, researchers are feverishly working on several promising vaccines against Zika, a virus notorious for infecting humans through this insect’s bite.

The speed and debilitating effects of last year’s Zika outbreak in the Western Hemisphere prompted a sprint to develop a vaccine. Just a little more than a year after the pandemic was declared a global health emergency, a handful of candidates are undergoing preliminary testing in humans.

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

As warmer temperatures herald the arrival of pesky mosquitoes, researchers are feverishly working on several promising vaccines against Zika, a virus notorious for infecting humans through this insect’s bite.

The speed and debilitating effects of last year’s Zika outbreak in the Western Hemisphere prompted a sprint to develop a vaccine. Just a little more than a year after the pandemic was declared a global health emergency, a handful of candidates are undergoing preliminary testing in humans.

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

As warmer temperatures herald the arrival of pesky mosquitoes, researchers are feverishly working on several promising vaccines against Zika, a virus notorious for infecting humans through this insect’s bite.

The speed and debilitating effects of last year’s Zika outbreak in the Western Hemisphere prompted a sprint to develop a vaccine. Just a little more than a year after the pandemic was declared a global health emergency, a handful of candidates are undergoing preliminary testing in humans.

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Nearly one-quarter of patients with long-standing rheumatoid arthritis who participated in a recent survey reported that their diets affect their RA symptoms.

Of 217 participants with a median disease duration of 17 years, 52 (24%) reported that certain foods either improve or worsen symptoms. Foods most commonly associated with improved symptoms were blueberries (11.1%), fish (10.9%), and spinach; foods most commonly associated with exacerbated symptoms were desserts (12.7%) and soda with sugar (12.4%, ), Sara K. Tedeschi, MD, of Brigham and Women’s Hospital, Boston, and her colleagues reported online in Arthritis Care & Research.

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Nearly one-quarter of patients with long-standing rheumatoid arthritis who participated in a recent survey reported that their diets affect their RA symptoms.

Of 217 participants with a median disease duration of 17 years, 52 (24%) reported that certain foods either improve or worsen symptoms. Foods most commonly associated with improved symptoms were blueberries (11.1%), fish (10.9%), and spinach; foods most commonly associated with exacerbated symptoms were desserts (12.7%) and soda with sugar (12.4%, ), Sara K. Tedeschi, MD, of Brigham and Women’s Hospital, Boston, and her colleagues reported online in Arthritis Care & Research.

Povareshka/Thinkstock

[email protected]

Nearly one-quarter of patients with long-standing rheumatoid arthritis who participated in a recent survey reported that their diets affect their RA symptoms.

Of 217 participants with a median disease duration of 17 years, 52 (24%) reported that certain foods either improve or worsen symptoms. Foods most commonly associated with improved symptoms were blueberries (11.1%), fish (10.9%), and spinach; foods most commonly associated with exacerbated symptoms were desserts (12.7%) and soda with sugar (12.4%, ), Sara K. Tedeschi, MD, of Brigham and Women’s Hospital, Boston, and her colleagues reported online in Arthritis Care & Research.

Povareshka/Thinkstock

[email protected]

A friend of mine recently fell and sustained a complex wrist fracture. She is more than a month post injury, and her forearm, with all its external hardware, looks like an 11-year-old’s science project gone horribly wrong. As she related the story of her fall, the surgery, and her recovery, she mentioned that, since the surgery, she has had four follow-up visits, none of them with the same provider.

Two visits were with nurse practitioners and two with physicians’ assistants. Each of the folks that she saw was pleasant and courteous and appeared genuinely concerned about how she was doing. From a purely economic standpoint, I can understand why a surgeon feels he can be more productive in the operating room than when he is doing follow-ups in the office. Personally, I would have preferred to have at least a quick look at my handiwork. What I found most troubling, however, was the fact that my friend’s injury hadn’t received even the smallest dose of continuity during her recovery.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

A friend of mine recently fell and sustained a complex wrist fracture. She is more than a month post injury, and her forearm, with all its external hardware, looks like an 11-year-old’s science project gone horribly wrong. As she related the story of her fall, the surgery, and her recovery, she mentioned that, since the surgery, she has had four follow-up visits, none of them with the same provider.

Two visits were with nurse practitioners and two with physicians’ assistants. Each of the folks that she saw was pleasant and courteous and appeared genuinely concerned about how she was doing. From a purely economic standpoint, I can understand why a surgeon feels he can be more productive in the operating room than when he is doing follow-ups in the office. Personally, I would have preferred to have at least a quick look at my handiwork. What I found most troubling, however, was the fact that my friend’s injury hadn’t received even the smallest dose of continuity during her recovery.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

A friend of mine recently fell and sustained a complex wrist fracture. She is more than a month post injury, and her forearm, with all its external hardware, looks like an 11-year-old’s science project gone horribly wrong. As she related the story of her fall, the surgery, and her recovery, she mentioned that, since the surgery, she has had four follow-up visits, none of them with the same provider.

Two visits were with nurse practitioners and two with physicians’ assistants. Each of the folks that she saw was pleasant and courteous and appeared genuinely concerned about how she was doing. From a purely economic standpoint, I can understand why a surgeon feels he can be more productive in the operating room than when he is doing follow-ups in the office. Personally, I would have preferred to have at least a quick look at my handiwork. What I found most troubling, however, was the fact that my friend’s injury hadn’t received even the smallest dose of continuity during her recovery.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].