CHICAGO – Tweaking the R-CHOP recipe to substitute bortezomib for vincristine may bring clinical benefit to patients with newly diagnosed mantle cell lymphoma who are ineligible for bone marrow transplant.

In a randomized phase III trial in patients with MCL who could not undergo bone marrow transplant due to age or comorbidities, those patients who received a combination of rituximab, doxorubicin, bortezomib (Velcade), cyclophosphamide, and prednisone (the VR-CAP regimen) had significantly better progression-free survival than did patients treated with R-CHOP, the same regimen but with vincristine instead of bortezomib.

The VR-CAP regimen "could be considered a new standard of care for newly diagnosed mantle cell lymphoma patients not considered for intensive treatment and bone marrow transplant," Dr. Franco Cavalli reported at the annual meeting of the American Society of Clinical Oncology.

The bortezomib-containing regimen was associated with more grade 3 or 4 toxicities than standard R-CHOP, but adverse events were manageable, and most patients in each study arm were able to stay on chemotherapy for all prescribed cycles, said Dr. Cavalli of the Oncology Institute of Southern Switzerland, Bellinzona.

R-CHOP is a standard frontline therapy for patients with MCL who are deemed to be ineligible for intensive therapy and/or bone marrow transplant. But the regimen offers only limited progression-free survival (PFS) in this population, Dr. Cavalli said.

Because bortezomib is approved for the treatment of relapsed MCL in the United States and 53 other nations, the authors investigated whether it could improve outcomes when given to patients with newly diagnosed disease.

The LYM-3002 trial was a phase III study conducted at 128 centers in 28 countries in Europe, Asia, the Americas, and Africa. Patients with newly diagnosed MCL stage II-IV, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and who were ineligible or not considered for bone marrow transplant, were randomized to receive either R-CHOP or VR-CAP. In R-CHOP, vincristine 1.4 mg/m² was delivered to a maximum of 2 mg intravenously on day 1 of each cycle. In VR-CAP, bortezomib 1.3 mg/m² was delivered via intravenous infusion on days 1, 4, 8, and 11 of each cycle. Patients were assigned to receive at least six cycles of therapy, with an additional two cycles possible if investigator-assessed responses were first documented at the end of cycle 6.

A total of 487 patients (244 assigned to R-CHOP and 243 to VR-CAP) were included in the intention-to-treat analysis.

At a median follow-up of 40 months, median PFS, the primary endpoint, was 24.7 months in the VR-CAP arm, compared with 14.4 months for R-CHOP (hazard ratio, 0.63; P less than .001), as judged by an independent review committee. Investigator-rated PFS was 30.7 months vs. 16.1 months, respectively (HR, 0.51; P less than .001).

Clinical responses according to International Working Group revised response criteria for malignant lymphoma included overall response rates (complete response, complete unconfirmed response, and partial response) of 90% in the R-CHOP–treated patients and 92% in those who received VR-CAP.

However, there was a higher proportion of combined complete response and complete unconfirmed response in the VR-CAP group: 42% for R-CHOP vs. 53% for VR-CAP (odds ratio, 1.69; P = .007).

Median time to response was also shorter with VR-CAP (1.6 vs. 1.4 months; HR, 1.54; P less than .001).

Independent reviewer-rated median time-to-progression was 16.1 months for R-CHOP vs. 30.5 months for VR-CAP (HR, 0.58; P less than .001). Median time to next therapy was 24.8 vs. 44.5 months, respectively (HR, 0.50; P less than .001), and median treatment-free interval was 20.5 vs. 40.6 months (HR, 0.50; P less than .001).

Median overall survival was 56.3 months among R-CHOP–treated patients, vs. not reached among VR-CAP–treated patients.

Grade 3 or higher drug-related adverse events occurred in 85% and 93% of patients, respectively. The events were considered serious in 21% of R-CHOP–treated patients and in 33% of VR-CAP–treated patients. In all, 7% of patients on R-CHOP and 9% of those on VR-CAP discontinued therapy because of adverse events.

Grade 3 adverse events were more frequent with VR-CAP and included neutropenia, leukopenia, lymphopenia, and thrombocytopenia, the last of which occurred in 6% of patients on R-CHOP, compared with 57% for VR-CAP. Despite this difference, however, rates of grade 3 or higher bleeding were similar between the groups, occurring in 1.2% and 1.7%, respectively.

The invited discussant, Dr. Michael E. Williams, chief of hematology/oncology at the University of Virginia Cancer Center, Charlottesville, commented that the study provides proof of principle "that if you add an active single agent and substitute bortezomib for vincristine, which would appear to be a less active agent, that you can certainly improve PFS significantly."

Dr. Williams said that it remains to be seen, however, whether, as Dr. Cavalli suggested, certain treatment strategies could be used to lower the incidence of drug-related adverse events and improve PFS rates further, such as the use of subcutaneous rather than intravenous bortezomib, different dosing schedules, or rituximab in the maintenance phase.

The study was supported by Janssen Global Services and Millennium. Dr. Cavalli disclosed receiving travel support for attending the ASCO annual meeting, but reported having no other conflicts of interest. Dr. Williams disclosed consulting/advising for Millennium and receiving research funding from Janssen and Millennium.

CHICAGO – Tweaking the R-CHOP recipe to substitute bortezomib for vincristine may bring clinical benefit to patients with newly diagnosed mantle cell lymphoma who are ineligible for bone marrow transplant.

In a randomized phase III trial in patients with MCL who could not undergo bone marrow transplant due to age or comorbidities, those patients who received a combination of rituximab, doxorubicin, bortezomib (Velcade), cyclophosphamide, and prednisone (the VR-CAP regimen) had significantly better progression-free survival than did patients treated with R-CHOP, the same regimen but with vincristine instead of bortezomib.

The VR-CAP regimen "could be considered a new standard of care for newly diagnosed mantle cell lymphoma patients not considered for intensive treatment and bone marrow transplant," Dr. Franco Cavalli reported at the annual meeting of the American Society of Clinical Oncology.

The bortezomib-containing regimen was associated with more grade 3 or 4 toxicities than standard R-CHOP, but adverse events were manageable, and most patients in each study arm were able to stay on chemotherapy for all prescribed cycles, said Dr. Cavalli of the Oncology Institute of Southern Switzerland, Bellinzona.

R-CHOP is a standard frontline therapy for patients with MCL who are deemed to be ineligible for intensive therapy and/or bone marrow transplant. But the regimen offers only limited progression-free survival (PFS) in this population, Dr. Cavalli said.

Because bortezomib is approved for the treatment of relapsed MCL in the United States and 53 other nations, the authors investigated whether it could improve outcomes when given to patients with newly diagnosed disease.

The LYM-3002 trial was a phase III study conducted at 128 centers in 28 countries in Europe, Asia, the Americas, and Africa. Patients with newly diagnosed MCL stage II-IV, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and who were ineligible or not considered for bone marrow transplant, were randomized to receive either R-CHOP or VR-CAP. In R-CHOP, vincristine 1.4 mg/m² was delivered to a maximum of 2 mg intravenously on day 1 of each cycle. In VR-CAP, bortezomib 1.3 mg/m² was delivered via intravenous infusion on days 1, 4, 8, and 11 of each cycle. Patients were assigned to receive at least six cycles of therapy, with an additional two cycles possible if investigator-assessed responses were first documented at the end of cycle 6.

A total of 487 patients (244 assigned to R-CHOP and 243 to VR-CAP) were included in the intention-to-treat analysis.

At a median follow-up of 40 months, median PFS, the primary endpoint, was 24.7 months in the VR-CAP arm, compared with 14.4 months for R-CHOP (hazard ratio, 0.63; P less than .001), as judged by an independent review committee. Investigator-rated PFS was 30.7 months vs. 16.1 months, respectively (HR, 0.51; P less than .001).

Clinical responses according to International Working Group revised response criteria for malignant lymphoma included overall response rates (complete response, complete unconfirmed response, and partial response) of 90% in the R-CHOP–treated patients and 92% in those who received VR-CAP.

However, there was a higher proportion of combined complete response and complete unconfirmed response in the VR-CAP group: 42% for R-CHOP vs. 53% for VR-CAP (odds ratio, 1.69; P = .007).

Median time to response was also shorter with VR-CAP (1.6 vs. 1.4 months; HR, 1.54; P less than .001).

Independent reviewer-rated median time-to-progression was 16.1 months for R-CHOP vs. 30.5 months for VR-CAP (HR, 0.58; P less than .001). Median time to next therapy was 24.8 vs. 44.5 months, respectively (HR, 0.50; P less than .001), and median treatment-free interval was 20.5 vs. 40.6 months (HR, 0.50; P less than .001).

Median overall survival was 56.3 months among R-CHOP–treated patients, vs. not reached among VR-CAP–treated patients.

Grade 3 or higher drug-related adverse events occurred in 85% and 93% of patients, respectively. The events were considered serious in 21% of R-CHOP–treated patients and in 33% of VR-CAP–treated patients. In all, 7% of patients on R-CHOP and 9% of those on VR-CAP discontinued therapy because of adverse events.

Grade 3 adverse events were more frequent with VR-CAP and included neutropenia, leukopenia, lymphopenia, and thrombocytopenia, the last of which occurred in 6% of patients on R-CHOP, compared with 57% for VR-CAP. Despite this difference, however, rates of grade 3 or higher bleeding were similar between the groups, occurring in 1.2% and 1.7%, respectively.

The invited discussant, Dr. Michael E. Williams, chief of hematology/oncology at the University of Virginia Cancer Center, Charlottesville, commented that the study provides proof of principle "that if you add an active single agent and substitute bortezomib for vincristine, which would appear to be a less active agent, that you can certainly improve PFS significantly."

Dr. Williams said that it remains to be seen, however, whether, as Dr. Cavalli suggested, certain treatment strategies could be used to lower the incidence of drug-related adverse events and improve PFS rates further, such as the use of subcutaneous rather than intravenous bortezomib, different dosing schedules, or rituximab in the maintenance phase.

The study was supported by Janssen Global Services and Millennium. Dr. Cavalli disclosed receiving travel support for attending the ASCO annual meeting, but reported having no other conflicts of interest. Dr. Williams disclosed consulting/advising for Millennium and receiving research funding from Janssen and Millennium.

CHICAGO – Tweaking the R-CHOP recipe to substitute bortezomib for vincristine may bring clinical benefit to patients with newly diagnosed mantle cell lymphoma who are ineligible for bone marrow transplant.

In a randomized phase III trial in patients with MCL who could not undergo bone marrow transplant due to age or comorbidities, those patients who received a combination of rituximab, doxorubicin, bortezomib (Velcade), cyclophosphamide, and prednisone (the VR-CAP regimen) had significantly better progression-free survival than did patients treated with R-CHOP, the same regimen but with vincristine instead of bortezomib.

The VR-CAP regimen "could be considered a new standard of care for newly diagnosed mantle cell lymphoma patients not considered for intensive treatment and bone marrow transplant," Dr. Franco Cavalli reported at the annual meeting of the American Society of Clinical Oncology.

The bortezomib-containing regimen was associated with more grade 3 or 4 toxicities than standard R-CHOP, but adverse events were manageable, and most patients in each study arm were able to stay on chemotherapy for all prescribed cycles, said Dr. Cavalli of the Oncology Institute of Southern Switzerland, Bellinzona.

R-CHOP is a standard frontline therapy for patients with MCL who are deemed to be ineligible for intensive therapy and/or bone marrow transplant. But the regimen offers only limited progression-free survival (PFS) in this population, Dr. Cavalli said.

Because bortezomib is approved for the treatment of relapsed MCL in the United States and 53 other nations, the authors investigated whether it could improve outcomes when given to patients with newly diagnosed disease.

The LYM-3002 trial was a phase III study conducted at 128 centers in 28 countries in Europe, Asia, the Americas, and Africa. Patients with newly diagnosed MCL stage II-IV, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and who were ineligible or not considered for bone marrow transplant, were randomized to receive either R-CHOP or VR-CAP. In R-CHOP, vincristine 1.4 mg/m² was delivered to a maximum of 2 mg intravenously on day 1 of each cycle. In VR-CAP, bortezomib 1.3 mg/m² was delivered via intravenous infusion on days 1, 4, 8, and 11 of each cycle. Patients were assigned to receive at least six cycles of therapy, with an additional two cycles possible if investigator-assessed responses were first documented at the end of cycle 6.

A total of 487 patients (244 assigned to R-CHOP and 243 to VR-CAP) were included in the intention-to-treat analysis.

At a median follow-up of 40 months, median PFS, the primary endpoint, was 24.7 months in the VR-CAP arm, compared with 14.4 months for R-CHOP (hazard ratio, 0.63; P less than .001), as judged by an independent review committee. Investigator-rated PFS was 30.7 months vs. 16.1 months, respectively (HR, 0.51; P less than .001).

Clinical responses according to International Working Group revised response criteria for malignant lymphoma included overall response rates (complete response, complete unconfirmed response, and partial response) of 90% in the R-CHOP–treated patients and 92% in those who received VR-CAP.

However, there was a higher proportion of combined complete response and complete unconfirmed response in the VR-CAP group: 42% for R-CHOP vs. 53% for VR-CAP (odds ratio, 1.69; P = .007).

Median time to response was also shorter with VR-CAP (1.6 vs. 1.4 months; HR, 1.54; P less than .001).

Independent reviewer-rated median time-to-progression was 16.1 months for R-CHOP vs. 30.5 months for VR-CAP (HR, 0.58; P less than .001). Median time to next therapy was 24.8 vs. 44.5 months, respectively (HR, 0.50; P less than .001), and median treatment-free interval was 20.5 vs. 40.6 months (HR, 0.50; P less than .001).

Median overall survival was 56.3 months among R-CHOP–treated patients, vs. not reached among VR-CAP–treated patients.

Grade 3 or higher drug-related adverse events occurred in 85% and 93% of patients, respectively. The events were considered serious in 21% of R-CHOP–treated patients and in 33% of VR-CAP–treated patients. In all, 7% of patients on R-CHOP and 9% of those on VR-CAP discontinued therapy because of adverse events.

Grade 3 adverse events were more frequent with VR-CAP and included neutropenia, leukopenia, lymphopenia, and thrombocytopenia, the last of which occurred in 6% of patients on R-CHOP, compared with 57% for VR-CAP. Despite this difference, however, rates of grade 3 or higher bleeding were similar between the groups, occurring in 1.2% and 1.7%, respectively.

The invited discussant, Dr. Michael E. Williams, chief of hematology/oncology at the University of Virginia Cancer Center, Charlottesville, commented that the study provides proof of principle "that if you add an active single agent and substitute bortezomib for vincristine, which would appear to be a less active agent, that you can certainly improve PFS significantly."

Dr. Williams said that it remains to be seen, however, whether, as Dr. Cavalli suggested, certain treatment strategies could be used to lower the incidence of drug-related adverse events and improve PFS rates further, such as the use of subcutaneous rather than intravenous bortezomib, different dosing schedules, or rituximab in the maintenance phase.

The study was supported by Janssen Global Services and Millennium. Dr. Cavalli disclosed receiving travel support for attending the ASCO annual meeting, but reported having no other conflicts of interest. Dr. Williams disclosed consulting/advising for Millennium and receiving research funding from Janssen and Millennium.

Known also as the common daisy or English daisy, Bellis perennis is a perennial plant belonging to the Asteraceae or Compositae (aster, daisy, or sunflower) family. Native to Europe and North Africa, it has been used in traditional medicine in Europe since the Middle Ages to treat bruises, broken bones, muscle pain, cutaneous wounds, and rheumatism. Other skin applications include eczema, boils, inflammation, and purulent skin disease. In addition, B. perennis has been used in folk medicine to treat upper respiratory tract infections, gastritis, stomachache, diarrhea, bleeding, rheumatism, common colds, and headache (Pharm. Biol. 2014 March 12 [Epub ahead of print]; Pharm. Biol. 2012;50:1031-7; Chem. Pharm. Bull. [Tokyo] 2008;56:559-68; Chem. Pharm. Bull. [Tokyo] 2011;59:889-95; Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Chemistry

Courtesy Wikimedia Commons/Gareth Davidson Bitplane/Creative Commons License

B. perennis roots and flowers have been shown to contain several important bioactive constituents, including triterpene saponins, anthocyanins, flavonoids, polysaccharides, and polyacetylenes (Chem. Pharm. Bull. [Tokyo] 2008;56:559-68; SOFW J. 2005;131:40-9). In 2008, Morikawa et al. identified newly isolated triterpene saponins in B. perennis. These compounds, labeled as perennisosides I-VII, exhibited inhibitory activity on serum triglyceride elevation in olive oil–treated mice (J. Nat. Prod. 2008;71:828-35). That same year, Yoshikawa et al. isolated six new acylated oleanane-type triterpene oligoglycosides (perennisaponins A-F) from the flowers of B. perennis in addition to 14 saponins, 9 flavonoids, and 2 glycosides (Chem. Pharm. Bull. [Tokyo] 2008;56:559-68).

In 2011, Morikawa et al. isolated five new triterpene saponins (perennisosides VIII-XII) from the methanolic extract of B. perennis flowers. The extract was shown to suppress gastric emptying in olive oil–laded mice (Chem. Pharm. Bull. [Tokyo] 2011;59:889-95).

Early in 2014, Pehlivan et al. used bioassay-guided fractionation and isolation procedures to isolate an oleanane-type saponin from B. perennis that exhibited antitumor activity, the first such finding associated with B. perennis flowers. Tumor inhibition of 99% was achieved by the most active fraction at 3,000 mg/L (Pharm. Biol. 2014 March 12 [Epub ahead of print]).

Wound-healing capacity

In 2012, Karakas et al. studied the wound-healing activity displayed by the dried flowers of B. perennis in 12 male adult Wistar albino rats over a 30-day period. Six wounds were introduced onto each animal, with two treated topically once a day with a hydrophilic ointment containing an n-butanol fraction of B. perennis, two treated daily with the ointment minus the B. perennis fraction, and two untreated wounds used as control. Statistically significant differences were noted with 100% wound closure in the B. perennis group, 87% in the control group, and 85% in the other treatment group. The investigators concluded that their findings represented the first scientific confirmation supporting the traditional usage of B. perennis for wound healing. They noted that the topical administration of an ointment formulated with an n-butanol fraction of B. perennis flowers exhibits wound healing activity without inducing scars in a circular excision wound model in rats (Pharm. Biol. 2012;50:1031-7).

Antimicrobial activity against gram-positive and gram-negative bacteria, as well as anticancer activity against human leukemia cells in vitro, has also been associated with B. perennis (Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Skin-lightening activity

Extracts of B. perennis are included in the product Belides that has been combined in a formulation with emblica and licorice for use as a skin-lightening agent. In 2010, Costa et al. conducted a monoblind clinical study to assess the clinical efficacy of the combination of Belides, emblica, and licorice 7%, compared with hydroquinone 2% for the treatment of epidermal or mixed melasma in 56 women aged 18-60 years. Subjects (ranging from Fitzpatrick skin type I to IV) exclusively used an SPF 35 sunscreen for 60 days before being selected for either the herbal combination cream treatment, applied twice daily, or the hydroquinone group, applied nightly.

Depigmentation was observed in 78.3% of the herbal combination group and 88.9% of the hydroquinone group, among the 23 volunteers in the herbal group and 27 in the hydroquinone group who completed the study. No statistically significant differences were found between the treatment regimens in ameliorating melasma, but fewer adverse cutaneous reactions were associated with the herbal treatment. The investigators found the combination of Belides, emblica, and licorice to be a safe and effective option for treating melasma (An. Bras. Dermatol. 2010;85:613-20). Previously, Belides was shown to be nearly twice as active as arbutin and an effective skin-lightening agent in a pilot study with human volunteers (SOFW J. 2005;131:40-9; Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Conclusion

The roots and flowers of B. perennis have been used for many years in traditional medicine to treat various conditions, including skin disorders. While modern scientific interest has been piqued, the current body of evidence is meager. Much more research is necessary to determine the potential role of topical B. perennis in the dermatologic armamentarium. But recent data and the history of traditional use suggest that such research is warranted.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

Known also as the common daisy or English daisy, Bellis perennis is a perennial plant belonging to the Asteraceae or Compositae (aster, daisy, or sunflower) family. Native to Europe and North Africa, it has been used in traditional medicine in Europe since the Middle Ages to treat bruises, broken bones, muscle pain, cutaneous wounds, and rheumatism. Other skin applications include eczema, boils, inflammation, and purulent skin disease. In addition, B. perennis has been used in folk medicine to treat upper respiratory tract infections, gastritis, stomachache, diarrhea, bleeding, rheumatism, common colds, and headache (Pharm. Biol. 2014 March 12 [Epub ahead of print]; Pharm. Biol. 2012;50:1031-7; Chem. Pharm. Bull. [Tokyo] 2008;56:559-68; Chem. Pharm. Bull. [Tokyo] 2011;59:889-95; Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Chemistry

Courtesy Wikimedia Commons/Gareth Davidson Bitplane/Creative Commons License

B. perennis roots and flowers have been shown to contain several important bioactive constituents, including triterpene saponins, anthocyanins, flavonoids, polysaccharides, and polyacetylenes (Chem. Pharm. Bull. [Tokyo] 2008;56:559-68; SOFW J. 2005;131:40-9). In 2008, Morikawa et al. identified newly isolated triterpene saponins in B. perennis. These compounds, labeled as perennisosides I-VII, exhibited inhibitory activity on serum triglyceride elevation in olive oil–treated mice (J. Nat. Prod. 2008;71:828-35). That same year, Yoshikawa et al. isolated six new acylated oleanane-type triterpene oligoglycosides (perennisaponins A-F) from the flowers of B. perennis in addition to 14 saponins, 9 flavonoids, and 2 glycosides (Chem. Pharm. Bull. [Tokyo] 2008;56:559-68).

In 2011, Morikawa et al. isolated five new triterpene saponins (perennisosides VIII-XII) from the methanolic extract of B. perennis flowers. The extract was shown to suppress gastric emptying in olive oil–laded mice (Chem. Pharm. Bull. [Tokyo] 2011;59:889-95).

Early in 2014, Pehlivan et al. used bioassay-guided fractionation and isolation procedures to isolate an oleanane-type saponin from B. perennis that exhibited antitumor activity, the first such finding associated with B. perennis flowers. Tumor inhibition of 99% was achieved by the most active fraction at 3,000 mg/L (Pharm. Biol. 2014 March 12 [Epub ahead of print]).

Wound-healing capacity

In 2012, Karakas et al. studied the wound-healing activity displayed by the dried flowers of B. perennis in 12 male adult Wistar albino rats over a 30-day period. Six wounds were introduced onto each animal, with two treated topically once a day with a hydrophilic ointment containing an n-butanol fraction of B. perennis, two treated daily with the ointment minus the B. perennis fraction, and two untreated wounds used as control. Statistically significant differences were noted with 100% wound closure in the B. perennis group, 87% in the control group, and 85% in the other treatment group. The investigators concluded that their findings represented the first scientific confirmation supporting the traditional usage of B. perennis for wound healing. They noted that the topical administration of an ointment formulated with an n-butanol fraction of B. perennis flowers exhibits wound healing activity without inducing scars in a circular excision wound model in rats (Pharm. Biol. 2012;50:1031-7).

Antimicrobial activity against gram-positive and gram-negative bacteria, as well as anticancer activity against human leukemia cells in vitro, has also been associated with B. perennis (Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Skin-lightening activity

Extracts of B. perennis are included in the product Belides that has been combined in a formulation with emblica and licorice for use as a skin-lightening agent. In 2010, Costa et al. conducted a monoblind clinical study to assess the clinical efficacy of the combination of Belides, emblica, and licorice 7%, compared with hydroquinone 2% for the treatment of epidermal or mixed melasma in 56 women aged 18-60 years. Subjects (ranging from Fitzpatrick skin type I to IV) exclusively used an SPF 35 sunscreen for 60 days before being selected for either the herbal combination cream treatment, applied twice daily, or the hydroquinone group, applied nightly.

Depigmentation was observed in 78.3% of the herbal combination group and 88.9% of the hydroquinone group, among the 23 volunteers in the herbal group and 27 in the hydroquinone group who completed the study. No statistically significant differences were found between the treatment regimens in ameliorating melasma, but fewer adverse cutaneous reactions were associated with the herbal treatment. The investigators found the combination of Belides, emblica, and licorice to be a safe and effective option for treating melasma (An. Bras. Dermatol. 2010;85:613-20). Previously, Belides was shown to be nearly twice as active as arbutin and an effective skin-lightening agent in a pilot study with human volunteers (SOFW J. 2005;131:40-9; Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Conclusion

The roots and flowers of B. perennis have been used for many years in traditional medicine to treat various conditions, including skin disorders. While modern scientific interest has been piqued, the current body of evidence is meager. Much more research is necessary to determine the potential role of topical B. perennis in the dermatologic armamentarium. But recent data and the history of traditional use suggest that such research is warranted.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

Known also as the common daisy or English daisy, Bellis perennis is a perennial plant belonging to the Asteraceae or Compositae (aster, daisy, or sunflower) family. Native to Europe and North Africa, it has been used in traditional medicine in Europe since the Middle Ages to treat bruises, broken bones, muscle pain, cutaneous wounds, and rheumatism. Other skin applications include eczema, boils, inflammation, and purulent skin disease. In addition, B. perennis has been used in folk medicine to treat upper respiratory tract infections, gastritis, stomachache, diarrhea, bleeding, rheumatism, common colds, and headache (Pharm. Biol. 2014 March 12 [Epub ahead of print]; Pharm. Biol. 2012;50:1031-7; Chem. Pharm. Bull. [Tokyo] 2008;56:559-68; Chem. Pharm. Bull. [Tokyo] 2011;59:889-95; Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Chemistry

Courtesy Wikimedia Commons/Gareth Davidson Bitplane/Creative Commons License

B. perennis roots and flowers have been shown to contain several important bioactive constituents, including triterpene saponins, anthocyanins, flavonoids, polysaccharides, and polyacetylenes (Chem. Pharm. Bull. [Tokyo] 2008;56:559-68; SOFW J. 2005;131:40-9). In 2008, Morikawa et al. identified newly isolated triterpene saponins in B. perennis. These compounds, labeled as perennisosides I-VII, exhibited inhibitory activity on serum triglyceride elevation in olive oil–treated mice (J. Nat. Prod. 2008;71:828-35). That same year, Yoshikawa et al. isolated six new acylated oleanane-type triterpene oligoglycosides (perennisaponins A-F) from the flowers of B. perennis in addition to 14 saponins, 9 flavonoids, and 2 glycosides (Chem. Pharm. Bull. [Tokyo] 2008;56:559-68).

In 2011, Morikawa et al. isolated five new triterpene saponins (perennisosides VIII-XII) from the methanolic extract of B. perennis flowers. The extract was shown to suppress gastric emptying in olive oil–laded mice (Chem. Pharm. Bull. [Tokyo] 2011;59:889-95).

Early in 2014, Pehlivan et al. used bioassay-guided fractionation and isolation procedures to isolate an oleanane-type saponin from B. perennis that exhibited antitumor activity, the first such finding associated with B. perennis flowers. Tumor inhibition of 99% was achieved by the most active fraction at 3,000 mg/L (Pharm. Biol. 2014 March 12 [Epub ahead of print]).

Wound-healing capacity

In 2012, Karakas et al. studied the wound-healing activity displayed by the dried flowers of B. perennis in 12 male adult Wistar albino rats over a 30-day period. Six wounds were introduced onto each animal, with two treated topically once a day with a hydrophilic ointment containing an n-butanol fraction of B. perennis, two treated daily with the ointment minus the B. perennis fraction, and two untreated wounds used as control. Statistically significant differences were noted with 100% wound closure in the B. perennis group, 87% in the control group, and 85% in the other treatment group. The investigators concluded that their findings represented the first scientific confirmation supporting the traditional usage of B. perennis for wound healing. They noted that the topical administration of an ointment formulated with an n-butanol fraction of B. perennis flowers exhibits wound healing activity without inducing scars in a circular excision wound model in rats (Pharm. Biol. 2012;50:1031-7).

Antimicrobial activity against gram-positive and gram-negative bacteria, as well as anticancer activity against human leukemia cells in vitro, has also been associated with B. perennis (Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Skin-lightening activity

Extracts of B. perennis are included in the product Belides that has been combined in a formulation with emblica and licorice for use as a skin-lightening agent. In 2010, Costa et al. conducted a monoblind clinical study to assess the clinical efficacy of the combination of Belides, emblica, and licorice 7%, compared with hydroquinone 2% for the treatment of epidermal or mixed melasma in 56 women aged 18-60 years. Subjects (ranging from Fitzpatrick skin type I to IV) exclusively used an SPF 35 sunscreen for 60 days before being selected for either the herbal combination cream treatment, applied twice daily, or the hydroquinone group, applied nightly.

Depigmentation was observed in 78.3% of the herbal combination group and 88.9% of the hydroquinone group, among the 23 volunteers in the herbal group and 27 in the hydroquinone group who completed the study. No statistically significant differences were found between the treatment regimens in ameliorating melasma, but fewer adverse cutaneous reactions were associated with the herbal treatment. The investigators found the combination of Belides, emblica, and licorice to be a safe and effective option for treating melasma (An. Bras. Dermatol. 2010;85:613-20). Previously, Belides was shown to be nearly twice as active as arbutin and an effective skin-lightening agent in a pilot study with human volunteers (SOFW J. 2005;131:40-9; Lim, T.K. Edible Medicinal and Non-Medicinal Plants. Springer: Dordrecht, 2014, pp. 204-11).

Conclusion

The roots and flowers of B. perennis have been used for many years in traditional medicine to treat various conditions, including skin disorders. While modern scientific interest has been piqued, the current body of evidence is meager. Much more research is necessary to determine the potential role of topical B. perennis in the dermatologic armamentarium. But recent data and the history of traditional use suggest that such research is warranted.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at pdnews@frontlinemedcom.com.

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at pdnews@frontlinemedcom.com.

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at pdnews@frontlinemedcom.com.

CHICAGO – A novel, externally worn device for the treatment of extraesophageal reflux proved effective, safe, and well tolerated in a multicenter clinical trial.

"Given the poor response to PPI [proton-pump inhibitors] therapy in many patients with extraesophageal reflux, this device may be an alternative form of treating this difficult disorder," Dr. Michael F. Vaezi said in a presentation of the study findings at the annual Digestive Disease Week.

Extraesophageal reflux (EER) affects more than 15 million Americans. The cost of care is estimated to be in excess of $50 billion annually, most of which goes for PPIs, which are overused and generally not effective in treating this common disorder, observed Dr. Vaezi, professor of medicine at Vanderbilt University, Nashville, Tenn.

EER is caused by reflux of gastroduodenal contents into the laryngopharynx, resulting in a range of symptoms including chronic cough, postnasal drip, throat clearing, hoarseness, and a sensation of a lump in the throat.

The investigational device, known as the Reza-Band, is an individually fitted upper esophageal sphincter assist device to be worn at bedtime. It is designed to apply slight pressure to the cricoid cartilage area sufficient to increase the intraluminal pressure of the upper esophageal sphincter to 20 mm Hg. In earlier studies, this modest increase in pressure eliminated pharyngeal reflux without affecting normal activities such as swallowing and belching.

Dr. Vaezi reported on 47 patients with EER treated with the upper esophageal assist device at four medical centers. Their mean age was 50 years, with an average body mass index of 26.1 kg/m². Three-quarters of patients were on PPI therapy, which they felt to be ineffective.

The primary study endpoint was the change in Reflux Symptom Index scores from baseline through week 4 of nighttime use of the assist device. The median score improved from 27 at baseline to 14 at week 2 and 12 at week 4. That translated to a mean 54% reduction. A total of 86% of subjects were deemed to have experienced treatment success as defined by at least a 25% improvement in their symptom score; 30% of participants showed a greater than 75% improvement.

Treatment side effects were few, mild, and brief, consisting chiefly of skin irritation from the device’s Velcro strap. No one withdrew from the study.

The Reza-Band device was developed by gastroenterologists at the Medical College of Wisconsin, Milwaukee. Dr. Vaezi said he and his coinvestigators decided to formally investigate the device because "we were intrigued and impressed by the fact that it has helped so many patients."

"For me, it’s a welcome development," Dr. Vaezi added. "Just anecdotally, many patients in the study wanted to know how they could purchase this device. It’s really welcome in an area [in which] we don’t have many therapeutic options."

Still, he noted, it’s probably a good idea for device users to continue to keep a couple of bricks under the head of the bed, in accord with standard medical advice.

Future plans include a sham-controlled study designed to assess the device’s true benefit over placebo therapy; this will be an important study because EER is known to have a substantial placebo response rate, he continued. Also, plans are afoot for a safety study assessing whether the device has any clinically meaningful impact upon intraocular pressure.

The study was supported by Somna Therapeutics, which is developing the device. Dr. Vaezi reported having no financial relationship with the company.

bjancin@frontlinemedcom.com

CHICAGO – A novel, externally worn device for the treatment of extraesophageal reflux proved effective, safe, and well tolerated in a multicenter clinical trial.

"Given the poor response to PPI [proton-pump inhibitors] therapy in many patients with extraesophageal reflux, this device may be an alternative form of treating this difficult disorder," Dr. Michael F. Vaezi said in a presentation of the study findings at the annual Digestive Disease Week.

Extraesophageal reflux (EER) affects more than 15 million Americans. The cost of care is estimated to be in excess of $50 billion annually, most of which goes for PPIs, which are overused and generally not effective in treating this common disorder, observed Dr. Vaezi, professor of medicine at Vanderbilt University, Nashville, Tenn.

EER is caused by reflux of gastroduodenal contents into the laryngopharynx, resulting in a range of symptoms including chronic cough, postnasal drip, throat clearing, hoarseness, and a sensation of a lump in the throat.

The investigational device, known as the Reza-Band, is an individually fitted upper esophageal sphincter assist device to be worn at bedtime. It is designed to apply slight pressure to the cricoid cartilage area sufficient to increase the intraluminal pressure of the upper esophageal sphincter to 20 mm Hg. In earlier studies, this modest increase in pressure eliminated pharyngeal reflux without affecting normal activities such as swallowing and belching.

Dr. Vaezi reported on 47 patients with EER treated with the upper esophageal assist device at four medical centers. Their mean age was 50 years, with an average body mass index of 26.1 kg/m². Three-quarters of patients were on PPI therapy, which they felt to be ineffective.

The primary study endpoint was the change in Reflux Symptom Index scores from baseline through week 4 of nighttime use of the assist device. The median score improved from 27 at baseline to 14 at week 2 and 12 at week 4. That translated to a mean 54% reduction. A total of 86% of subjects were deemed to have experienced treatment success as defined by at least a 25% improvement in their symptom score; 30% of participants showed a greater than 75% improvement.

Treatment side effects were few, mild, and brief, consisting chiefly of skin irritation from the device’s Velcro strap. No one withdrew from the study.

The Reza-Band device was developed by gastroenterologists at the Medical College of Wisconsin, Milwaukee. Dr. Vaezi said he and his coinvestigators decided to formally investigate the device because "we were intrigued and impressed by the fact that it has helped so many patients."

"For me, it’s a welcome development," Dr. Vaezi added. "Just anecdotally, many patients in the study wanted to know how they could purchase this device. It’s really welcome in an area [in which] we don’t have many therapeutic options."

Still, he noted, it’s probably a good idea for device users to continue to keep a couple of bricks under the head of the bed, in accord with standard medical advice.

Future plans include a sham-controlled study designed to assess the device’s true benefit over placebo therapy; this will be an important study because EER is known to have a substantial placebo response rate, he continued. Also, plans are afoot for a safety study assessing whether the device has any clinically meaningful impact upon intraocular pressure.

The study was supported by Somna Therapeutics, which is developing the device. Dr. Vaezi reported having no financial relationship with the company.

bjancin@frontlinemedcom.com

CHICAGO – A novel, externally worn device for the treatment of extraesophageal reflux proved effective, safe, and well tolerated in a multicenter clinical trial.

"Given the poor response to PPI [proton-pump inhibitors] therapy in many patients with extraesophageal reflux, this device may be an alternative form of treating this difficult disorder," Dr. Michael F. Vaezi said in a presentation of the study findings at the annual Digestive Disease Week.

Extraesophageal reflux (EER) affects more than 15 million Americans. The cost of care is estimated to be in excess of $50 billion annually, most of which goes for PPIs, which are overused and generally not effective in treating this common disorder, observed Dr. Vaezi, professor of medicine at Vanderbilt University, Nashville, Tenn.

EER is caused by reflux of gastroduodenal contents into the laryngopharynx, resulting in a range of symptoms including chronic cough, postnasal drip, throat clearing, hoarseness, and a sensation of a lump in the throat.

The investigational device, known as the Reza-Band, is an individually fitted upper esophageal sphincter assist device to be worn at bedtime. It is designed to apply slight pressure to the cricoid cartilage area sufficient to increase the intraluminal pressure of the upper esophageal sphincter to 20 mm Hg. In earlier studies, this modest increase in pressure eliminated pharyngeal reflux without affecting normal activities such as swallowing and belching.

Dr. Vaezi reported on 47 patients with EER treated with the upper esophageal assist device at four medical centers. Their mean age was 50 years, with an average body mass index of 26.1 kg/m². Three-quarters of patients were on PPI therapy, which they felt to be ineffective.

The primary study endpoint was the change in Reflux Symptom Index scores from baseline through week 4 of nighttime use of the assist device. The median score improved from 27 at baseline to 14 at week 2 and 12 at week 4. That translated to a mean 54% reduction. A total of 86% of subjects were deemed to have experienced treatment success as defined by at least a 25% improvement in their symptom score; 30% of participants showed a greater than 75% improvement.

Treatment side effects were few, mild, and brief, consisting chiefly of skin irritation from the device’s Velcro strap. No one withdrew from the study.

The Reza-Band device was developed by gastroenterologists at the Medical College of Wisconsin, Milwaukee. Dr. Vaezi said he and his coinvestigators decided to formally investigate the device because "we were intrigued and impressed by the fact that it has helped so many patients."

"For me, it’s a welcome development," Dr. Vaezi added. "Just anecdotally, many patients in the study wanted to know how they could purchase this device. It’s really welcome in an area [in which] we don’t have many therapeutic options."

Still, he noted, it’s probably a good idea for device users to continue to keep a couple of bricks under the head of the bed, in accord with standard medical advice.

Future plans include a sham-controlled study designed to assess the device’s true benefit over placebo therapy; this will be an important study because EER is known to have a substantial placebo response rate, he continued. Also, plans are afoot for a safety study assessing whether the device has any clinically meaningful impact upon intraocular pressure.

The study was supported by Somna Therapeutics, which is developing the device. Dr. Vaezi reported having no financial relationship with the company.

bjancin@frontlinemedcom.com

Antihemophilic factor

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Eloctate) to treat children and adults with hemophilia A.

Efmoroctocog alfa is intended to reduce the frequency of injections required to prevent or reduce the occurrence of bleeding in patients with hemophilia A.

The FDA approved efmoroctocog alfa based on results of the phase 3 A-LONG trial, which were reported last year.

The trial included 165 male patients age 12 or older.

Patients who received individualized prophylaxis with efmoroctocog alfa every 3 to 5 days reduced their annualized bleeding rate by 92% compared with patients who received episodic treatment.

Patients who received weekly prophylaxis with efmoroctocog alfa reduced their annualized bleeding rate by 76% compared to patients who received episodic treatment.

Overall, 1 injection of efmoroctocog alfa resolved 87.3% of bleeding episodes.

None of the patients in the study developed neutralizing antibodies, and there were no serious adverse events related to efmoroctocog alfa.

The study was published online in Blood last November.

Efmoroctocog alfa consists of the coagulation factor VIII molecule linked to an Fc protein fragment found in antibodies, which confers the product with a longer half-life than recombinant factor VIII.

Efmoroctocog alfa is specifically indicated for the control and prevention of bleeding episodes, the management of bleeding during surgical procedures, and prophylaxis against bleeding episodes.

The approval of efmoroctocog alfa fills an unmet medical need, according to Johnny Mahlangu, MD, of the Haemophilia Comprehensive Care Centre at the University of Witwatersrand in Johannesburg, South Africa.

He explained that the fusion protein allows patients with hemophilia A to go for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes.

The product, which received orphan drug designation by the FDA, is manufactured by Biogen Idec, Inc, of Cambridge, Massachusetts.

Full prescribing information is available on the drug website.

Antihemophilic factor

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Eloctate) to treat children and adults with hemophilia A.

Efmoroctocog alfa is intended to reduce the frequency of injections required to prevent or reduce the occurrence of bleeding in patients with hemophilia A.

The FDA approved efmoroctocog alfa based on results of the phase 3 A-LONG trial, which were reported last year.

The trial included 165 male patients age 12 or older.

Patients who received individualized prophylaxis with efmoroctocog alfa every 3 to 5 days reduced their annualized bleeding rate by 92% compared with patients who received episodic treatment.

Patients who received weekly prophylaxis with efmoroctocog alfa reduced their annualized bleeding rate by 76% compared to patients who received episodic treatment.

Overall, 1 injection of efmoroctocog alfa resolved 87.3% of bleeding episodes.

None of the patients in the study developed neutralizing antibodies, and there were no serious adverse events related to efmoroctocog alfa.

The study was published online in Blood last November.

Efmoroctocog alfa consists of the coagulation factor VIII molecule linked to an Fc protein fragment found in antibodies, which confers the product with a longer half-life than recombinant factor VIII.

Efmoroctocog alfa is specifically indicated for the control and prevention of bleeding episodes, the management of bleeding during surgical procedures, and prophylaxis against bleeding episodes.

The approval of efmoroctocog alfa fills an unmet medical need, according to Johnny Mahlangu, MD, of the Haemophilia Comprehensive Care Centre at the University of Witwatersrand in Johannesburg, South Africa.

He explained that the fusion protein allows patients with hemophilia A to go for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes.

The product, which received orphan drug designation by the FDA, is manufactured by Biogen Idec, Inc, of Cambridge, Massachusetts.

Full prescribing information is available on the drug website.

Antihemophilic factor

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Eloctate) to treat children and adults with hemophilia A.

Efmoroctocog alfa is intended to reduce the frequency of injections required to prevent or reduce the occurrence of bleeding in patients with hemophilia A.

The FDA approved efmoroctocog alfa based on results of the phase 3 A-LONG trial, which were reported last year.

The trial included 165 male patients age 12 or older.

Patients who received individualized prophylaxis with efmoroctocog alfa every 3 to 5 days reduced their annualized bleeding rate by 92% compared with patients who received episodic treatment.

Patients who received weekly prophylaxis with efmoroctocog alfa reduced their annualized bleeding rate by 76% compared to patients who received episodic treatment.

Overall, 1 injection of efmoroctocog alfa resolved 87.3% of bleeding episodes.

None of the patients in the study developed neutralizing antibodies, and there were no serious adverse events related to efmoroctocog alfa.

The study was published online in Blood last November.

Efmoroctocog alfa consists of the coagulation factor VIII molecule linked to an Fc protein fragment found in antibodies, which confers the product with a longer half-life than recombinant factor VIII.

Efmoroctocog alfa is specifically indicated for the control and prevention of bleeding episodes, the management of bleeding during surgical procedures, and prophylaxis against bleeding episodes.

The approval of efmoroctocog alfa fills an unmet medical need, according to Johnny Mahlangu, MD, of the Haemophilia Comprehensive Care Centre at the University of Witwatersrand in Johannesburg, South Africa.

He explained that the fusion protein allows patients with hemophilia A to go for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes.

The product, which received orphan drug designation by the FDA, is manufactured by Biogen Idec, Inc, of Cambridge, Massachusetts.

Full prescribing information is available on the drug website.

Vial of Soliris

Credit: Globovision

The manufacturer of the recently approved eculizumab (Soliris) issued a voluntary US recall on June 2 of a single affected lot of the drug, although it included 8 additional lots in the recall.

The manufacturer, Alexion Pharmaceuticals, found visible particulates in the 300 mg/30 mL concentrated solution for intravenous infusion, which could cause an immune reaction and blood clots in patients receiving the drug.

The single affected Soliris lot, distributed in the US only, is #1007A. Also included in the U.S. recall are lots 10002-1, 00006-1, 10003A, 10004A, 10005A, 10005AR, 10006A, and 10008A.

All lots in the recall were manufactured using the same process component.

Alexion believes it has identified the part of the process that has resulted in the visible particles in the solution and has changed the process component.

An earlier recall of eculizumab, also for particulate matter, occurred in December 2013.

Alexion does not anticipate any interruption to the patient supply of eculizumab.

Eculizumab recently received full US Food and Drug Administration (FDA) approval to treat adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS). It had received accelerated approval for this indication in 2011.

Eculizumab is also FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria.

For more information on the recall, visit the company website.

Healthcare professionals and patients should report adverse events or side effects related to Soliris to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

Vial of Soliris

Credit: Globovision

The manufacturer of the recently approved eculizumab (Soliris) issued a voluntary US recall on June 2 of a single affected lot of the drug, although it included 8 additional lots in the recall.

The manufacturer, Alexion Pharmaceuticals, found visible particulates in the 300 mg/30 mL concentrated solution for intravenous infusion, which could cause an immune reaction and blood clots in patients receiving the drug.

The single affected Soliris lot, distributed in the US only, is #1007A. Also included in the U.S. recall are lots 10002-1, 00006-1, 10003A, 10004A, 10005A, 10005AR, 10006A, and 10008A.

All lots in the recall were manufactured using the same process component.

Alexion believes it has identified the part of the process that has resulted in the visible particles in the solution and has changed the process component.

An earlier recall of eculizumab, also for particulate matter, occurred in December 2013.

Alexion does not anticipate any interruption to the patient supply of eculizumab.

Eculizumab recently received full US Food and Drug Administration (FDA) approval to treat adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS). It had received accelerated approval for this indication in 2011.

Eculizumab is also FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria.

For more information on the recall, visit the company website.

Healthcare professionals and patients should report adverse events or side effects related to Soliris to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

Vial of Soliris

Credit: Globovision

The manufacturer of the recently approved eculizumab (Soliris) issued a voluntary US recall on June 2 of a single affected lot of the drug, although it included 8 additional lots in the recall.

The manufacturer, Alexion Pharmaceuticals, found visible particulates in the 300 mg/30 mL concentrated solution for intravenous infusion, which could cause an immune reaction and blood clots in patients receiving the drug.

The single affected Soliris lot, distributed in the US only, is #1007A. Also included in the U.S. recall are lots 10002-1, 00006-1, 10003A, 10004A, 10005A, 10005AR, 10006A, and 10008A.

All lots in the recall were manufactured using the same process component.

Alexion believes it has identified the part of the process that has resulted in the visible particles in the solution and has changed the process component.

An earlier recall of eculizumab, also for particulate matter, occurred in December 2013.

Alexion does not anticipate any interruption to the patient supply of eculizumab.

Eculizumab recently received full US Food and Drug Administration (FDA) approval to treat adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS). It had received accelerated approval for this indication in 2011.

Eculizumab is also FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria.

For more information on the recall, visit the company website.

Healthcare professionals and patients should report adverse events or side effects related to Soliris to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

Newly synthesized proteins

Credit: Lu Wei

By cataloging more than 18,000 proteins, scientists have produced an “almost-complete” inventory of the human proteome.

They discovered protein fragments encoded by DNA outside of currently known genes and found that many known genes have become non-functional.

They also described an important function for messenger RNA (mRNA) and showed that protein profiles could predict drug sensitivity.

The team reported their findings in Nature.

They also made the information freely available in ProteomicsDB. This database includes information on the types, distribution, and abundance of proteins in various cells, tissues, and body fluids.

Through their protein cataloguing, the researchers showed that each mRNA determines the number of protein copies to be produced by a cell. And this “copying key” is specific to each protein.

“It appears that every mRNA molecule knows the unit amount for its protein so it knows whether to produce 10, 100, or 1000 copies,” said study author Bernhard Küster, PhD, of Technische Universitaet Muenchen in Germany.

“Since we now know this ratio for a large number of proteins, we can infer protein abundance from mRNA abundance in just about every tissue, and vice versa.”

The researchers were also surprised to discover hundreds of protein fragments that are encoded by DNA outside of currently known genes. The team believes these “new” proteins may possess novel biological properties and functions that could be exploited for therapeutic purposes.

On the other hand, Dr Küster and his colleagues have been unable to locate roughly 2000 proteins that should exist, according to the gene map. The team also found evidence suggesting that many known genes have become non-functional.

“We might be watching evolution in action here,” Dr Küster said. “The human organism deactivates superfluous genes and tests new gene prototypes at the same time.”

That being the case, the researchers noted that it might never be possible to determine exactly how many proteins there are in the human body.

Lastly, Dr Küster and his colleagues confirmed the findings of previous studies, which showed that specific protein patterns can predict the efficacy of a given drug.

The team evaluated 24 cancer drugs and found their effectiveness against 35 cancer cell lines was strongly correlated with their protein profiles.

“This edges us a little bit closer to the individualized treatment of patients,” Dr Küster said. “If we knew the protein profile of a tumor in detail, we might be able to administer drugs in a more targeted way.”

Newly synthesized proteins

Credit: Lu Wei

By cataloging more than 18,000 proteins, scientists have produced an “almost-complete” inventory of the human proteome.

They discovered protein fragments encoded by DNA outside of currently known genes and found that many known genes have become non-functional.

They also described an important function for messenger RNA (mRNA) and showed that protein profiles could predict drug sensitivity.

The team reported their findings in Nature.

They also made the information freely available in ProteomicsDB. This database includes information on the types, distribution, and abundance of proteins in various cells, tissues, and body fluids.

Through their protein cataloguing, the researchers showed that each mRNA determines the number of protein copies to be produced by a cell. And this “copying key” is specific to each protein.

“It appears that every mRNA molecule knows the unit amount for its protein so it knows whether to produce 10, 100, or 1000 copies,” said study author Bernhard Küster, PhD, of Technische Universitaet Muenchen in Germany.

“Since we now know this ratio for a large number of proteins, we can infer protein abundance from mRNA abundance in just about every tissue, and vice versa.”

The researchers were also surprised to discover hundreds of protein fragments that are encoded by DNA outside of currently known genes. The team believes these “new” proteins may possess novel biological properties and functions that could be exploited for therapeutic purposes.

On the other hand, Dr Küster and his colleagues have been unable to locate roughly 2000 proteins that should exist, according to the gene map. The team also found evidence suggesting that many known genes have become non-functional.

“We might be watching evolution in action here,” Dr Küster said. “The human organism deactivates superfluous genes and tests new gene prototypes at the same time.”

That being the case, the researchers noted that it might never be possible to determine exactly how many proteins there are in the human body.

Lastly, Dr Küster and his colleagues confirmed the findings of previous studies, which showed that specific protein patterns can predict the efficacy of a given drug.

The team evaluated 24 cancer drugs and found their effectiveness against 35 cancer cell lines was strongly correlated with their protein profiles.

“This edges us a little bit closer to the individualized treatment of patients,” Dr Küster said. “If we knew the protein profile of a tumor in detail, we might be able to administer drugs in a more targeted way.”

Newly synthesized proteins

Credit: Lu Wei

By cataloging more than 18,000 proteins, scientists have produced an “almost-complete” inventory of the human proteome.

They discovered protein fragments encoded by DNA outside of currently known genes and found that many known genes have become non-functional.

They also described an important function for messenger RNA (mRNA) and showed that protein profiles could predict drug sensitivity.

The team reported their findings in Nature.

They also made the information freely available in ProteomicsDB. This database includes information on the types, distribution, and abundance of proteins in various cells, tissues, and body fluids.

Through their protein cataloguing, the researchers showed that each mRNA determines the number of protein copies to be produced by a cell. And this “copying key” is specific to each protein.

“It appears that every mRNA molecule knows the unit amount for its protein so it knows whether to produce 10, 100, or 1000 copies,” said study author Bernhard Küster, PhD, of Technische Universitaet Muenchen in Germany.

“Since we now know this ratio for a large number of proteins, we can infer protein abundance from mRNA abundance in just about every tissue, and vice versa.”

The researchers were also surprised to discover hundreds of protein fragments that are encoded by DNA outside of currently known genes. The team believes these “new” proteins may possess novel biological properties and functions that could be exploited for therapeutic purposes.

On the other hand, Dr Küster and his colleagues have been unable to locate roughly 2000 proteins that should exist, according to the gene map. The team also found evidence suggesting that many known genes have become non-functional.

“We might be watching evolution in action here,” Dr Küster said. “The human organism deactivates superfluous genes and tests new gene prototypes at the same time.”

That being the case, the researchers noted that it might never be possible to determine exactly how many proteins there are in the human body.

Lastly, Dr Küster and his colleagues confirmed the findings of previous studies, which showed that specific protein patterns can predict the efficacy of a given drug.

The team evaluated 24 cancer drugs and found their effectiveness against 35 cancer cell lines was strongly correlated with their protein profiles.

“This edges us a little bit closer to the individualized treatment of patients,” Dr Küster said. “If we knew the protein profile of a tumor in detail, we might be able to administer drugs in a more targeted way.”

It has been 2 months since we implemented an electronic health record. I’ve made peace with it, but it is oh so far from perfect. Around the office, tempers are flared and people are grumpy. There are threats to quit by staff and doctors alike. Chaotic accurately describes what the first few weeks were like.

For a week, I had a greatly thinned schedule, but was pretty much back up to my usual 15-minute follow-up schedule by week 3. This meant, frankly, that if I did not want my patients to be waiting for hours beyond their appointment time, shortcuts had to be made. And 2 months in, the trend continues. I am definitely not able to dutifully fill out each and every blank that meaningful use requires me to fill out. There is just not enough time to document every follow-up patient’s family history and surgical history all over again. If you thought pointing-and-clicking were going to make life much easier for you, think again.

The issue is that the electronic record, rather than being a blank space, is essentially pages and pages of blanks to be filled out. So instead of freely typing as the patient jumps from, say, the history of their present illness to their family history to their systems review back to their present illness – because as we all know, our patients do not tell their stories in a nice linear fashion – I find myself having to interrupt the patient as I find the right blank on the right page.

Another sore point for me, and of course this issue predates the EHR, is that I don’t like having to reduce my patients to codes. I understand that codes are useful, but they can also be limiting and, frankly, idiotic. For example, Medicare in Rhode Island will no longer reimburse for zoledronic acid for patients coded as 733.00 (Osteoporosis NOS), but will cover if a patient is coded as 733.01 (postmenopausal/senile osteoporosis). I would like to know who came up with that rule and how they came up with it.

Codes also fall short of really capturing what a patient looks like. One lupus patient can look quite different from the next. Some of my patients are extremely sick and have complicated histories that have taken many months to piece together, and those four digits just do not capture that complexity and absolutely do not do justice to the patient. Patients do not fit neatly into boxes, so why must we be forced to make them fit?

It is not all bad. There are definitely a number of things that I appreciate about having an EHR.

I like being able to access patient records from home. It makes call a lot easier when you have the ability to look up a patient, know what meds they’re on, and document what you did for them over the weekend.

I like being able to hand the patient a document at the end of the visit outlining what we talked about. Although composing this definitely slows me down, it is helpful for some of the more forgetful patients in our panel who cannot be expected to remember their instructions for tapering their prednisone or that methotrexate is taken weekly, not daily.

I like that our system has a homunculus and will automatically calculate the Clinical Disease Activity Index for me and track down the patient’s progress. The system is too new for me to use this functionality, but I look forward to trying it out.

I like being able to electronically prescribe meds. The med list can get cluttered with old medications that the patient is not taking anymore (how often do patients change NSAIDs or go from gabapentin to cyclobenzaprine to amitriptyline?), and it can get quite confusing, but I’m sure in the long run it will make life much easier. When I fill out the blasted prior authorization forms, I will now be able to check on a single screen what generic drugs the patient has failed.

I must admit that the forthcoming Medicare penalty for not having an EHR was a big motivator for us to get on board. In the end, though, it shouldn’t be about avoiding penalties. It should be about providing better-quality care. And once most doctors are on board and Medicare has access to measurable data, I fervently hope that the data shows us that all of this pain was worth it.

Dr. Chan practices rheumatology in Pawtucket, R.I.

It has been 2 months since we implemented an electronic health record. I’ve made peace with it, but it is oh so far from perfect. Around the office, tempers are flared and people are grumpy. There are threats to quit by staff and doctors alike. Chaotic accurately describes what the first few weeks were like.

For a week, I had a greatly thinned schedule, but was pretty much back up to my usual 15-minute follow-up schedule by week 3. This meant, frankly, that if I did not want my patients to be waiting for hours beyond their appointment time, shortcuts had to be made. And 2 months in, the trend continues. I am definitely not able to dutifully fill out each and every blank that meaningful use requires me to fill out. There is just not enough time to document every follow-up patient’s family history and surgical history all over again. If you thought pointing-and-clicking were going to make life much easier for you, think again.

The issue is that the electronic record, rather than being a blank space, is essentially pages and pages of blanks to be filled out. So instead of freely typing as the patient jumps from, say, the history of their present illness to their family history to their systems review back to their present illness – because as we all know, our patients do not tell their stories in a nice linear fashion – I find myself having to interrupt the patient as I find the right blank on the right page.

Another sore point for me, and of course this issue predates the EHR, is that I don’t like having to reduce my patients to codes. I understand that codes are useful, but they can also be limiting and, frankly, idiotic. For example, Medicare in Rhode Island will no longer reimburse for zoledronic acid for patients coded as 733.00 (Osteoporosis NOS), but will cover if a patient is coded as 733.01 (postmenopausal/senile osteoporosis). I would like to know who came up with that rule and how they came up with it.

Codes also fall short of really capturing what a patient looks like. One lupus patient can look quite different from the next. Some of my patients are extremely sick and have complicated histories that have taken many months to piece together, and those four digits just do not capture that complexity and absolutely do not do justice to the patient. Patients do not fit neatly into boxes, so why must we be forced to make them fit?

It is not all bad. There are definitely a number of things that I appreciate about having an EHR.

I like being able to access patient records from home. It makes call a lot easier when you have the ability to look up a patient, know what meds they’re on, and document what you did for them over the weekend.

I like being able to hand the patient a document at the end of the visit outlining what we talked about. Although composing this definitely slows me down, it is helpful for some of the more forgetful patients in our panel who cannot be expected to remember their instructions for tapering their prednisone or that methotrexate is taken weekly, not daily.

I like that our system has a homunculus and will automatically calculate the Clinical Disease Activity Index for me and track down the patient’s progress. The system is too new for me to use this functionality, but I look forward to trying it out.

I like being able to electronically prescribe meds. The med list can get cluttered with old medications that the patient is not taking anymore (how often do patients change NSAIDs or go from gabapentin to cyclobenzaprine to amitriptyline?), and it can get quite confusing, but I’m sure in the long run it will make life much easier. When I fill out the blasted prior authorization forms, I will now be able to check on a single screen what generic drugs the patient has failed.

I must admit that the forthcoming Medicare penalty for not having an EHR was a big motivator for us to get on board. In the end, though, it shouldn’t be about avoiding penalties. It should be about providing better-quality care. And once most doctors are on board and Medicare has access to measurable data, I fervently hope that the data shows us that all of this pain was worth it.

Dr. Chan practices rheumatology in Pawtucket, R.I.

It has been 2 months since we implemented an electronic health record. I’ve made peace with it, but it is oh so far from perfect. Around the office, tempers are flared and people are grumpy. There are threats to quit by staff and doctors alike. Chaotic accurately describes what the first few weeks were like.

For a week, I had a greatly thinned schedule, but was pretty much back up to my usual 15-minute follow-up schedule by week 3. This meant, frankly, that if I did not want my patients to be waiting for hours beyond their appointment time, shortcuts had to be made. And 2 months in, the trend continues. I am definitely not able to dutifully fill out each and every blank that meaningful use requires me to fill out. There is just not enough time to document every follow-up patient’s family history and surgical history all over again. If you thought pointing-and-clicking were going to make life much easier for you, think again.

The issue is that the electronic record, rather than being a blank space, is essentially pages and pages of blanks to be filled out. So instead of freely typing as the patient jumps from, say, the history of their present illness to their family history to their systems review back to their present illness – because as we all know, our patients do not tell their stories in a nice linear fashion – I find myself having to interrupt the patient as I find the right blank on the right page.

Another sore point for me, and of course this issue predates the EHR, is that I don’t like having to reduce my patients to codes. I understand that codes are useful, but they can also be limiting and, frankly, idiotic. For example, Medicare in Rhode Island will no longer reimburse for zoledronic acid for patients coded as 733.00 (Osteoporosis NOS), but will cover if a patient is coded as 733.01 (postmenopausal/senile osteoporosis). I would like to know who came up with that rule and how they came up with it.

Codes also fall short of really capturing what a patient looks like. One lupus patient can look quite different from the next. Some of my patients are extremely sick and have complicated histories that have taken many months to piece together, and those four digits just do not capture that complexity and absolutely do not do justice to the patient. Patients do not fit neatly into boxes, so why must we be forced to make them fit?

It is not all bad. There are definitely a number of things that I appreciate about having an EHR.

I like being able to access patient records from home. It makes call a lot easier when you have the ability to look up a patient, know what meds they’re on, and document what you did for them over the weekend.

I like being able to hand the patient a document at the end of the visit outlining what we talked about. Although composing this definitely slows me down, it is helpful for some of the more forgetful patients in our panel who cannot be expected to remember their instructions for tapering their prednisone or that methotrexate is taken weekly, not daily.

I like that our system has a homunculus and will automatically calculate the Clinical Disease Activity Index for me and track down the patient’s progress. The system is too new for me to use this functionality, but I look forward to trying it out.

I like being able to electronically prescribe meds. The med list can get cluttered with old medications that the patient is not taking anymore (how often do patients change NSAIDs or go from gabapentin to cyclobenzaprine to amitriptyline?), and it can get quite confusing, but I’m sure in the long run it will make life much easier. When I fill out the blasted prior authorization forms, I will now be able to check on a single screen what generic drugs the patient has failed.

I must admit that the forthcoming Medicare penalty for not having an EHR was a big motivator for us to get on board. In the end, though, it shouldn’t be about avoiding penalties. It should be about providing better-quality care. And once most doctors are on board and Medicare has access to measurable data, I fervently hope that the data shows us that all of this pain was worth it.

Dr. Chan practices rheumatology in Pawtucket, R.I.

Drug release in a cancer cell

Credit: PNAS

Biomedical engineers have reported that daisy-shaped, nanoscale structures can deliver a cocktail of drugs directly to cancer cells.

The “nanodaisies” effectively delivered a 2-drug combination in a range of cell lines, including the leukemia cell line HL-60.

The drug-delivery vehicles also proved effective in a mouse model of lung cancer.

Zhen Gu, PhD, of North Carolina State University and the University of North Carolina at Chapel Hill, and his colleagues detailed these results in Biomaterials.

“We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” Dr Gu said.

“And based on in vitro tests in 9 different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian, and brain cancers.”

To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side.

The researchers directly link the anticancer drug camptothecin (CPT) onto the shorter strands and introduce the anticancer drug doxorubicin (Dox) into the solution.

PEG is hydrophilic, but CPT and Dox are hydrophobic. As a result, the CPT and Dox cluster together in the solution, wrapping the PEG around themselves. This results in a daisy-shaped drug cocktail, only 50 nanometers in diameter, that can (in theory) be injected into a cancer patient.

Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. In fact, one of the reasons the researchers chose to use PEG is because it has chemical properties that prolong the life of the drugs in the bloodstream. Once in a cancer cell, the drugs are released.

“Both drugs attack the cell’s nucleus but via different mechanisms,” said study author Wanyi Tai, PhD, who was previously a researcher in Dr Gu’s lab but is now at the University of Washington in Seattle.

“Combined, the drugs are more effective than either drug is by itself,” Dr Gu added. “We are very optimistic about this technique and are hoping to begin preclinical testing in the near future.”

Drug release in a cancer cell

Credit: PNAS

Biomedical engineers have reported that daisy-shaped, nanoscale structures can deliver a cocktail of drugs directly to cancer cells.

The “nanodaisies” effectively delivered a 2-drug combination in a range of cell lines, including the leukemia cell line HL-60.

The drug-delivery vehicles also proved effective in a mouse model of lung cancer.

Zhen Gu, PhD, of North Carolina State University and the University of North Carolina at Chapel Hill, and his colleagues detailed these results in Biomaterials.

“We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” Dr Gu said.

“And based on in vitro tests in 9 different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian, and brain cancers.”

To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side.

The researchers directly link the anticancer drug camptothecin (CPT) onto the shorter strands and introduce the anticancer drug doxorubicin (Dox) into the solution.

PEG is hydrophilic, but CPT and Dox are hydrophobic. As a result, the CPT and Dox cluster together in the solution, wrapping the PEG around themselves. This results in a daisy-shaped drug cocktail, only 50 nanometers in diameter, that can (in theory) be injected into a cancer patient.

Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. In fact, one of the reasons the researchers chose to use PEG is because it has chemical properties that prolong the life of the drugs in the bloodstream. Once in a cancer cell, the drugs are released.

“Both drugs attack the cell’s nucleus but via different mechanisms,” said study author Wanyi Tai, PhD, who was previously a researcher in Dr Gu’s lab but is now at the University of Washington in Seattle.

“Combined, the drugs are more effective than either drug is by itself,” Dr Gu added. “We are very optimistic about this technique and are hoping to begin preclinical testing in the near future.”

Drug release in a cancer cell

Credit: PNAS

Biomedical engineers have reported that daisy-shaped, nanoscale structures can deliver a cocktail of drugs directly to cancer cells.

The “nanodaisies” effectively delivered a 2-drug combination in a range of cell lines, including the leukemia cell line HL-60.

The drug-delivery vehicles also proved effective in a mouse model of lung cancer.

Zhen Gu, PhD, of North Carolina State University and the University of North Carolina at Chapel Hill, and his colleagues detailed these results in Biomaterials.

“We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” Dr Gu said.

“And based on in vitro tests in 9 different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian, and brain cancers.”

To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side.

The researchers directly link the anticancer drug camptothecin (CPT) onto the shorter strands and introduce the anticancer drug doxorubicin (Dox) into the solution.

PEG is hydrophilic, but CPT and Dox are hydrophobic. As a result, the CPT and Dox cluster together in the solution, wrapping the PEG around themselves. This results in a daisy-shaped drug cocktail, only 50 nanometers in diameter, that can (in theory) be injected into a cancer patient.

Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. In fact, one of the reasons the researchers chose to use PEG is because it has chemical properties that prolong the life of the drugs in the bloodstream. Once in a cancer cell, the drugs are released.

“Both drugs attack the cell’s nucleus but via different mechanisms,” said study author Wanyi Tai, PhD, who was previously a researcher in Dr Gu’s lab but is now at the University of Washington in Seattle.

“Combined, the drugs are more effective than either drug is by itself,” Dr Gu added. “We are very optimistic about this technique and are hoping to begin preclinical testing in the near future.”