Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

DENVER – Distal embolic protection using a filter device during primary PCI for acute MI significantly reduced the incidence of the no-reflow phenomenon and serious adverse events in the randomized VAMPIRE 3 trial.

The reason VAMPIRE 3 (Vacuum Aspiration Thrombus Removal) was a positive trial when other studies of distal embolic protection during coronary intervention have failed was that VAMPIRE 3 targeted a high-risk, high-benefit population: the subset of acute MI patients with attenuated, high-risk coronary plaque identified by intravascular ultrasound, Kiyoshi Hibi, MD, explained at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

Also, the filter device used in the trial was easily deployed and problem free, which doesn’t appear to be true of distal protection devices used in some earlier trials.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Hibi K. TCT 2017

DENVER – Distal embolic protection using a filter device during primary PCI for acute MI significantly reduced the incidence of the no-reflow phenomenon and serious adverse events in the randomized VAMPIRE 3 trial.

The reason VAMPIRE 3 (Vacuum Aspiration Thrombus Removal) was a positive trial when other studies of distal embolic protection during coronary intervention have failed was that VAMPIRE 3 targeted a high-risk, high-benefit population: the subset of acute MI patients with attenuated, high-risk coronary plaque identified by intravascular ultrasound, Kiyoshi Hibi, MD, explained at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

Also, the filter device used in the trial was easily deployed and problem free, which doesn’t appear to be true of distal protection devices used in some earlier trials.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Hibi K. TCT 2017

DENVER – Distal embolic protection using a filter device during primary PCI for acute MI significantly reduced the incidence of the no-reflow phenomenon and serious adverse events in the randomized VAMPIRE 3 trial.

The reason VAMPIRE 3 (Vacuum Aspiration Thrombus Removal) was a positive trial when other studies of distal embolic protection during coronary intervention have failed was that VAMPIRE 3 targeted a high-risk, high-benefit population: the subset of acute MI patients with attenuated, high-risk coronary plaque identified by intravascular ultrasound, Kiyoshi Hibi, MD, explained at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

Also, the filter device used in the trial was easily deployed and problem free, which doesn’t appear to be true of distal protection devices used in some earlier trials.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Hibi K. TCT 2017

Lab mouse

Researchers say they have found a way to target the oncogenic transcription factor MYB in acute myeloid leukemia (AML).

By inducing the expression of a peptide in mouse models of AML, the researchers were able to prevent MYB from promoting leukemia growth.

In fact, the team observed AML regression with no harmful impact on the function of normal cells.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described these findings in Cancer Cell.

“MYB is a dream target in cancer research because it’s involved in so many cancers,” Dr Vakoc said. “In leukemia, it’s special because we know from previous research that, by targeting MYB, you can get AML not just to stop growing but actually to regress.”

With the current research, Dr Vakoc and his colleagues discovered how to selectively target MYB.

First, the researchers found that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID.

Specifically, the MYB transactivation domain binds to the TAF12/TAF4 histone-fold domain (HFD) heterodimer. TAF12 and TAF4 are subunits of TFIID.

Based on this finding, the researchers hypothesized that “a minimal HFD fragment of TAF4 would be an ideal probe for blocking MYB function, since this peptide binds with high affinity and specificity to the TAF12 HFD.”

The team thought the peptide would form an ineffective complex with TAF12 and MYB, interfering with the endogenous MYB-TFIID interaction.

In in vitro experiments, TAF4-HFD expression inhibited AML growth and blast colony formation, induced differentiation, and destabilized MYB protein.

For their in vivo experiments, the researchers transduced RN2 cells with a dox-inducible TAF4-HFD retroviral vector and transplanted the cells in mice.

The team observed “marked” AML regression and prolonged survival in these mice compared to controls.

While the peptide is not itself a drug, Dr Vakoc said its action could be replicated by a drug.

“It’s a concept we’re now discussing with the pharmaceutical industry,” he said. “It is going to take lots of work before it can result in a medicine leukemia patients might take. But we’re excited about this new approach because MYB is such an important player in many cancers and, until now, has eluded efforts to selectively target it.”

Lab mouse

Researchers say they have found a way to target the oncogenic transcription factor MYB in acute myeloid leukemia (AML).

By inducing the expression of a peptide in mouse models of AML, the researchers were able to prevent MYB from promoting leukemia growth.

In fact, the team observed AML regression with no harmful impact on the function of normal cells.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described these findings in Cancer Cell.

“MYB is a dream target in cancer research because it’s involved in so many cancers,” Dr Vakoc said. “In leukemia, it’s special because we know from previous research that, by targeting MYB, you can get AML not just to stop growing but actually to regress.”

With the current research, Dr Vakoc and his colleagues discovered how to selectively target MYB.

First, the researchers found that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID.

Specifically, the MYB transactivation domain binds to the TAF12/TAF4 histone-fold domain (HFD) heterodimer. TAF12 and TAF4 are subunits of TFIID.

Based on this finding, the researchers hypothesized that “a minimal HFD fragment of TAF4 would be an ideal probe for blocking MYB function, since this peptide binds with high affinity and specificity to the TAF12 HFD.”

The team thought the peptide would form an ineffective complex with TAF12 and MYB, interfering with the endogenous MYB-TFIID interaction.

In in vitro experiments, TAF4-HFD expression inhibited AML growth and blast colony formation, induced differentiation, and destabilized MYB protein.

For their in vivo experiments, the researchers transduced RN2 cells with a dox-inducible TAF4-HFD retroviral vector and transplanted the cells in mice.

The team observed “marked” AML regression and prolonged survival in these mice compared to controls.

While the peptide is not itself a drug, Dr Vakoc said its action could be replicated by a drug.

“It’s a concept we’re now discussing with the pharmaceutical industry,” he said. “It is going to take lots of work before it can result in a medicine leukemia patients might take. But we’re excited about this new approach because MYB is such an important player in many cancers and, until now, has eluded efforts to selectively target it.”

Lab mouse

Researchers say they have found a way to target the oncogenic transcription factor MYB in acute myeloid leukemia (AML).

By inducing the expression of a peptide in mouse models of AML, the researchers were able to prevent MYB from promoting leukemia growth.

In fact, the team observed AML regression with no harmful impact on the function of normal cells.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described these findings in Cancer Cell.

“MYB is a dream target in cancer research because it’s involved in so many cancers,” Dr Vakoc said. “In leukemia, it’s special because we know from previous research that, by targeting MYB, you can get AML not just to stop growing but actually to regress.”

With the current research, Dr Vakoc and his colleagues discovered how to selectively target MYB.

First, the researchers found that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID.

Specifically, the MYB transactivation domain binds to the TAF12/TAF4 histone-fold domain (HFD) heterodimer. TAF12 and TAF4 are subunits of TFIID.

Based on this finding, the researchers hypothesized that “a minimal HFD fragment of TAF4 would be an ideal probe for blocking MYB function, since this peptide binds with high affinity and specificity to the TAF12 HFD.”

The team thought the peptide would form an ineffective complex with TAF12 and MYB, interfering with the endogenous MYB-TFIID interaction.

In in vitro experiments, TAF4-HFD expression inhibited AML growth and blast colony formation, induced differentiation, and destabilized MYB protein.

For their in vivo experiments, the researchers transduced RN2 cells with a dox-inducible TAF4-HFD retroviral vector and transplanted the cells in mice.

The team observed “marked” AML regression and prolonged survival in these mice compared to controls.

While the peptide is not itself a drug, Dr Vakoc said its action could be replicated by a drug.

“It’s a concept we’re now discussing with the pharmaceutical industry,” he said. “It is going to take lots of work before it can result in a medicine leukemia patients might take. But we’re excited about this new approach because MYB is such an important player in many cancers and, until now, has eluded efforts to selectively target it.”

© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”

Safety

The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”

Safety

The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”

Safety

The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

Photo courtesy of Janssen

New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).

It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.

But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.

Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.

The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.

These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.

With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.

Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.

The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.

The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.

“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.

“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”

Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.

The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.

Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”

The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.

“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.

Photo courtesy of Janssen

New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).

It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.

But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.

Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.

The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.

These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.

With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.

Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.

The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.

The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.

“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.

“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”

Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.

The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.

Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”

The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.

“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.

Photo courtesy of Janssen

New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).

It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.

But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.

Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.

The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.

These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.

With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.

Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.

The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.

The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.

“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.

“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”

Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.

The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.

Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”

The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.

“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.

A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm. The patient reached complete cervical dilation after artificial rupture of membranes and oxytocin augmentation. After four hours of pushing, there has been minimal descent of the fetal vertex beyond +1 station with significant caput succedaneum. Her physician decides to proceed with cesarean delivery.^2,3 What antibiotics should be administered prior to incision to reduce postoperative infection?

The CDC reports that nearly 1.3 million cesarean deliveries were performed in the United States in 2015, which represents about a third of all births.⁴ C-section is the most common major surgical procedure performed in this country and is associated with an infection rate five to 10 times that of vaginal delivery.^5,6 Pregnancy-associated infection, particularly during delivery, is a significant risk and the fourth most common cause of maternal death in the United States.⁵

The current standard of care in cesarean delivery is antibiotic prophylaxis (often a first-generation cephalosporin) prior to skin incision.⁷ The majority of c-sections performed are nonelective, and of these, postoperative infections occur in 12% of women who receive standard prophylaxis.^8,9 A small, single-center design trial suggested that azithromycin adjunctive therapy expands antibiotic coverage to Ureaplasma species, resulting in a lower risk for postoperative infection.¹⁰

This study evaluated the use of azithromycin adjunctive therapy, in addition to standard antibiotic prophylaxis, to reduce the risk for postoperative infections in women receiving nonelective c-sections.

STUDY SUMMARY

Reduced infections up to 6 weeks post–c-section

A multicenter, randomized, double-blind trial conducted in 14 hospitals in the United States evaluated the effect of a one-time dose of azithromycin (500 mg IV) on post­cesarean infections. Women with a singleton pregnancy of at least 24 weeks’ gestation were eligible for inclusion if they required nonelective cesarean delivery during labor or at least four hours after membrane rupture. Patients were excluded if they had a known azithromycin allergy, subsequent vaginal delivery, azithromycin use within the week prior to randomization, extensive hepatic or renal dysfunction, a known history of prolonged QT interval, or substantial electrolyte abnormalities. Patients were eligible even if they were receiving other antibiotics for a positive group B Streptococcus screening.¹

All patients (N = 2,013) were treated with standard antibiotic prophylaxis (most often cefazolin), according to individual institution protocols. The women were randomized to receive either an azithromycin 500 mg/250 mL IV infusion (n = 1,019) or an identical placebo IV infusion (n = 994) within one hour of the procedure. The primary outcome was a composite endpoint of endometritis, wound infection, or other infections occurring up to six weeks after the c-section. Secondary outcomes included neonatal death, sepsis, and other neonatal and maternal complications.¹

Patients in the placebo group had a higher rate of smoking during pregnancy; the researchers found no other significant differences.¹

Results. The primary composite outcome occurred less frequently in the azithromycin group than in the placebo group (6.1% vs 12.0%; relative risk [RR], 0.51; number needed to treat [NNT], 17). When the researchers looked at the individual elements of the primary composite outcome, two had significant reductions versus placebo. Endometritis (3.8% vs 6.1%; RR, 0.62; NNT, 43) and wound infections (2.4% vs 6.6%; RR, 0.35; NNT, 24) occurred significantly less frequently, but there was no difference for other infections (0.3% vs 0.6%; RR, 0.49).

Serious maternal adverse events were also lower in the treatment group than in the control group (1.5% vs 2.9%; RR, 0.5; NNT, 71). There was no difference in composite secondary neonatal outcomes, including death and serious complications (14.3% vs 13.6%; RR, 1.05).¹

 

 

WHAT’S NEW

Fewer infections without more adverse events

This study showed that adding azithromycin to standard antibiotic prophylaxis within one hour of a c-section reduces post–cesarean delivery infection rates without increasing the risk for maternal or neonatal adverse events.

CAVEATS

Caution with prolonged QT

While azithromycin was efficacious and well tolerated in the study, not every patient can take it. Patients with a previous drug reaction or allergy should avoid it, and experts advise prescribing it with caution for patients who have (or are at increased risk for) a prolonged QT interval, including those on other QT-prolonging medications.

Of note, women with scheduled c-sections and those with chorioamnionitis or another infection requiring postpartum antibiotics were excluded from this study. Thus, it is unknown if azithromycin use decreases complications in these patients.

CHALLENGES TO IMPLEMENTATION

Drug availability is key

Nonelective c-sections are performed based on many factors, including a nonreassuring fetal heart rate. In many of these cases, speed of cesarean delivery may mean the difference between positive and negative outcomes. Availability of azithromycin on labor and delivery floors for timely administration within one hour of the procedure is important.

Additionally, azithromycin has known QT prolongation risks.¹¹ While the baseline QT interval is not known for many healthy young women, this should be considered when azithromycin is utilized in combination with other medications that may prolong the QT interval.

ACKNOWLEDGEMENT

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

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[12]:762-764).

A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm. The patient reached complete cervical dilation after artificial rupture of membranes and oxytocin augmentation. After four hours of pushing, there has been minimal descent of the fetal vertex beyond +1 station with significant caput succedaneum. Her physician decides to proceed with cesarean delivery.^2,3 What antibiotics should be administered prior to incision to reduce postoperative infection?

The CDC reports that nearly 1.3 million cesarean deliveries were performed in the United States in 2015, which represents about a third of all births.⁴ C-section is the most common major surgical procedure performed in this country and is associated with an infection rate five to 10 times that of vaginal delivery.^5,6 Pregnancy-associated infection, particularly during delivery, is a significant risk and the fourth most common cause of maternal death in the United States.⁵

The current standard of care in cesarean delivery is antibiotic prophylaxis (often a first-generation cephalosporin) prior to skin incision.⁷ The majority of c-sections performed are nonelective, and of these, postoperative infections occur in 12% of women who receive standard prophylaxis.^8,9 A small, single-center design trial suggested that azithromycin adjunctive therapy expands antibiotic coverage to Ureaplasma species, resulting in a lower risk for postoperative infection.¹⁰

This study evaluated the use of azithromycin adjunctive therapy, in addition to standard antibiotic prophylaxis, to reduce the risk for postoperative infections in women receiving nonelective c-sections.

STUDY SUMMARY

Reduced infections up to 6 weeks post–c-section

A multicenter, randomized, double-blind trial conducted in 14 hospitals in the United States evaluated the effect of a one-time dose of azithromycin (500 mg IV) on post­cesarean infections. Women with a singleton pregnancy of at least 24 weeks’ gestation were eligible for inclusion if they required nonelective cesarean delivery during labor or at least four hours after membrane rupture. Patients were excluded if they had a known azithromycin allergy, subsequent vaginal delivery, azithromycin use within the week prior to randomization, extensive hepatic or renal dysfunction, a known history of prolonged QT interval, or substantial electrolyte abnormalities. Patients were eligible even if they were receiving other antibiotics for a positive group B Streptococcus screening.¹

All patients (N = 2,013) were treated with standard antibiotic prophylaxis (most often cefazolin), according to individual institution protocols. The women were randomized to receive either an azithromycin 500 mg/250 mL IV infusion (n = 1,019) or an identical placebo IV infusion (n = 994) within one hour of the procedure. The primary outcome was a composite endpoint of endometritis, wound infection, or other infections occurring up to six weeks after the c-section. Secondary outcomes included neonatal death, sepsis, and other neonatal and maternal complications.¹

Patients in the placebo group had a higher rate of smoking during pregnancy; the researchers found no other significant differences.¹

Results. The primary composite outcome occurred less frequently in the azithromycin group than in the placebo group (6.1% vs 12.0%; relative risk [RR], 0.51; number needed to treat [NNT], 17). When the researchers looked at the individual elements of the primary composite outcome, two had significant reductions versus placebo. Endometritis (3.8% vs 6.1%; RR, 0.62; NNT, 43) and wound infections (2.4% vs 6.6%; RR, 0.35; NNT, 24) occurred significantly less frequently, but there was no difference for other infections (0.3% vs 0.6%; RR, 0.49).

Serious maternal adverse events were also lower in the treatment group than in the control group (1.5% vs 2.9%; RR, 0.5; NNT, 71). There was no difference in composite secondary neonatal outcomes, including death and serious complications (14.3% vs 13.6%; RR, 1.05).¹

 

 

WHAT’S NEW

Fewer infections without more adverse events

This study showed that adding azithromycin to standard antibiotic prophylaxis within one hour of a c-section reduces post–cesarean delivery infection rates without increasing the risk for maternal or neonatal adverse events.

CAVEATS

Caution with prolonged QT

While azithromycin was efficacious and well tolerated in the study, not every patient can take it. Patients with a previous drug reaction or allergy should avoid it, and experts advise prescribing it with caution for patients who have (or are at increased risk for) a prolonged QT interval, including those on other QT-prolonging medications.

Of note, women with scheduled c-sections and those with chorioamnionitis or another infection requiring postpartum antibiotics were excluded from this study. Thus, it is unknown if azithromycin use decreases complications in these patients.

CHALLENGES TO IMPLEMENTATION

Drug availability is key

Nonelective c-sections are performed based on many factors, including a nonreassuring fetal heart rate. In many of these cases, speed of cesarean delivery may mean the difference between positive and negative outcomes. Availability of azithromycin on labor and delivery floors for timely administration within one hour of the procedure is important.

Additionally, azithromycin has known QT prolongation risks.¹¹ While the baseline QT interval is not known for many healthy young women, this should be considered when azithromycin is utilized in combination with other medications that may prolong the QT interval.

ACKNOWLEDGEMENT

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

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[12]:762-764).

A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm. The patient reached complete cervical dilation after artificial rupture of membranes and oxytocin augmentation. After four hours of pushing, there has been minimal descent of the fetal vertex beyond +1 station with significant caput succedaneum. Her physician decides to proceed with cesarean delivery.^2,3 What antibiotics should be administered prior to incision to reduce postoperative infection?

The CDC reports that nearly 1.3 million cesarean deliveries were performed in the United States in 2015, which represents about a third of all births.⁴ C-section is the most common major surgical procedure performed in this country and is associated with an infection rate five to 10 times that of vaginal delivery.^5,6 Pregnancy-associated infection, particularly during delivery, is a significant risk and the fourth most common cause of maternal death in the United States.⁵

The current standard of care in cesarean delivery is antibiotic prophylaxis (often a first-generation cephalosporin) prior to skin incision.⁷ The majority of c-sections performed are nonelective, and of these, postoperative infections occur in 12% of women who receive standard prophylaxis.^8,9 A small, single-center design trial suggested that azithromycin adjunctive therapy expands antibiotic coverage to Ureaplasma species, resulting in a lower risk for postoperative infection.¹⁰

This study evaluated the use of azithromycin adjunctive therapy, in addition to standard antibiotic prophylaxis, to reduce the risk for postoperative infections in women receiving nonelective c-sections.

STUDY SUMMARY

Reduced infections up to 6 weeks post–c-section

A multicenter, randomized, double-blind trial conducted in 14 hospitals in the United States evaluated the effect of a one-time dose of azithromycin (500 mg IV) on post­cesarean infections. Women with a singleton pregnancy of at least 24 weeks’ gestation were eligible for inclusion if they required nonelective cesarean delivery during labor or at least four hours after membrane rupture. Patients were excluded if they had a known azithromycin allergy, subsequent vaginal delivery, azithromycin use within the week prior to randomization, extensive hepatic or renal dysfunction, a known history of prolonged QT interval, or substantial electrolyte abnormalities. Patients were eligible even if they were receiving other antibiotics for a positive group B Streptococcus screening.¹

All patients (N = 2,013) were treated with standard antibiotic prophylaxis (most often cefazolin), according to individual institution protocols. The women were randomized to receive either an azithromycin 500 mg/250 mL IV infusion (n = 1,019) or an identical placebo IV infusion (n = 994) within one hour of the procedure. The primary outcome was a composite endpoint of endometritis, wound infection, or other infections occurring up to six weeks after the c-section. Secondary outcomes included neonatal death, sepsis, and other neonatal and maternal complications.¹

Patients in the placebo group had a higher rate of smoking during pregnancy; the researchers found no other significant differences.¹

Results. The primary composite outcome occurred less frequently in the azithromycin group than in the placebo group (6.1% vs 12.0%; relative risk [RR], 0.51; number needed to treat [NNT], 17). When the researchers looked at the individual elements of the primary composite outcome, two had significant reductions versus placebo. Endometritis (3.8% vs 6.1%; RR, 0.62; NNT, 43) and wound infections (2.4% vs 6.6%; RR, 0.35; NNT, 24) occurred significantly less frequently, but there was no difference for other infections (0.3% vs 0.6%; RR, 0.49).

Serious maternal adverse events were also lower in the treatment group than in the control group (1.5% vs 2.9%; RR, 0.5; NNT, 71). There was no difference in composite secondary neonatal outcomes, including death and serious complications (14.3% vs 13.6%; RR, 1.05).¹

 

 

WHAT’S NEW

Fewer infections without more adverse events

This study showed that adding azithromycin to standard antibiotic prophylaxis within one hour of a c-section reduces post–cesarean delivery infection rates without increasing the risk for maternal or neonatal adverse events.

CAVEATS

Caution with prolonged QT

While azithromycin was efficacious and well tolerated in the study, not every patient can take it. Patients with a previous drug reaction or allergy should avoid it, and experts advise prescribing it with caution for patients who have (or are at increased risk for) a prolonged QT interval, including those on other QT-prolonging medications.

Of note, women with scheduled c-sections and those with chorioamnionitis or another infection requiring postpartum antibiotics were excluded from this study. Thus, it is unknown if azithromycin use decreases complications in these patients.

CHALLENGES TO IMPLEMENTATION

Drug availability is key

Nonelective c-sections are performed based on many factors, including a nonreassuring fetal heart rate. In many of these cases, speed of cesarean delivery may mean the difference between positive and negative outcomes. Availability of azithromycin on labor and delivery floors for timely administration within one hour of the procedure is important.

Additionally, azithromycin has known QT prolongation risks.¹¹ While the baseline QT interval is not known for many healthy young women, this should be considered when azithromycin is utilized in combination with other medications that may prolong the QT interval.

ACKNOWLEDGEMENT

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

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[12]:762-764).

The Checklist to Prevent MRSA Surgical Site Infections study is an interventional trial recruiting veteran patients who are undergoing or have undergone cardiac surgery or total joint arthroplasty.

The Department of Veteran Affairs has previously implemented the VA MRSA Prevention Initiative, which successfully reduced patient-to-patient MRSA transmission; however, this initiative does not prevent most MRSA surgical site infections, which are spread differently. The VA has developed a new checklist which will be tested in this study aimed at reducing MRSA surgical site infections (SSIs), and will be implemented at 10 VA medical centers.

[email protected]

The Checklist to Prevent MRSA Surgical Site Infections study is an interventional trial recruiting veteran patients who are undergoing or have undergone cardiac surgery or total joint arthroplasty.

The Department of Veteran Affairs has previously implemented the VA MRSA Prevention Initiative, which successfully reduced patient-to-patient MRSA transmission; however, this initiative does not prevent most MRSA surgical site infections, which are spread differently. The VA has developed a new checklist which will be tested in this study aimed at reducing MRSA surgical site infections (SSIs), and will be implemented at 10 VA medical centers.

[email protected]

The Checklist to Prevent MRSA Surgical Site Infections study is an interventional trial recruiting veteran patients who are undergoing or have undergone cardiac surgery or total joint arthroplasty.

The Department of Veteran Affairs has previously implemented the VA MRSA Prevention Initiative, which successfully reduced patient-to-patient MRSA transmission; however, this initiative does not prevent most MRSA surgical site infections, which are spread differently. The VA has developed a new checklist which will be tested in this study aimed at reducing MRSA surgical site infections (SSIs), and will be implemented at 10 VA medical centers.

[email protected]

GENEVA – Omalizumab for treatment of chronic spontaneous urticaria brings about a profound improvement in angioedema-related quality of life, a widely underappreciated dimension of the impairment caused by this disease, Karsten Weller, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Weller K et al. EADV Congress 2017.

GENEVA – Omalizumab for treatment of chronic spontaneous urticaria brings about a profound improvement in angioedema-related quality of life, a widely underappreciated dimension of the impairment caused by this disease, Karsten Weller, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Weller K et al. EADV Congress 2017.

GENEVA – Omalizumab for treatment of chronic spontaneous urticaria brings about a profound improvement in angioedema-related quality of life, a widely underappreciated dimension of the impairment caused by this disease, Karsten Weller, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Weller K et al. EADV Congress 2017.

In my December 2017 editorial, I presented a values-based roundup of the year. That column explained the criteria for the selections of the most right and most wrong in 2017 in terms of 3 ethical theories: utilitarianism, deontology, and virtue ethics. December featured the good in federal practice. This month, the editorial turns to the bad in federal practice.

Sadly, there were far more candidates for the ethical worst of 2017 in the DoD, VA, and PHS than those of us dedicated to federal service would wish to see. Unfortunately, this reflects both the current state of our society and the nature of the human condition.

On Sunday morning, November 5, 2017, near my hometown of San Antonio, Texas, a gunman in military gear and firearms murdered 26 people who were worshipping at a rural Baptist church. The context of this horrific offense simultaneously mocked the fidelity of our armed forces and a religious faith that in many forms has been a foundation of our nation. Leading forensic mental health experts advise against using the name of mass murderers to avoid perversely glorifying them, and I will adopt that wise convention here.¹

Soon after the massacre, news organizations reported that the perpetrator had served in the Air Force, stationed in my adopted home of New Mexico. The shooter had been given a bad conduct discharge after a court-martial in 2012 found him guilty of brutally assaulting his then current wife and their child.² More than 1 military law expert has opined that perhaps the discharge should have been dishonorable, given the brutality of the conduct, although whether that verdict would have made it more likely, the crime was reported is not certain.

The day following the mass shooting, the Air Force euphemistically acknowledged that it had made an “error,” “mistake,” in not reporting the attacker’s violent history to the federal database, which tracks such offenders to prevent them from lawfully purchasing a weapon. These words and others, such as blunder and failure, used in the media do an injustice to the worshippers’ lives lost that ill-fated morning.³

I must stop here and emphasize as strongly as possible that the selection of this attack is in no way meant to demonize the Air Force as an agency or any individual serving in it. In fact, further investigation suggested that all branches of the armed forces did not fulfill their reporting obligations under the law. Nor am I making the unprovable claim, as some politicians have hinted, that if the Air Force had followed its procedure and policy, the shooter would never have taken 26 innocent lives. Although I note that this is exactly the assumption driving a number of lawsuits brought by the victims’ families against the Air Force for its failure to follow its rules.

Rather, I chose this terrible incident because of its universality and generalizability as a paradigm of what philosopher Hannah Arendt called the banality of evil. As she wrote in her book Eichmann in Jerusalem, “There is a strange interdependence between thoughtlessness and evil.”⁴ Although the law must deem the attack a capital crime, ethics should see it as a the ripple effect of hundreds of small moral failures of dozens of individuals and the system that neither inspired nor held them accountable for taking routine tasks as morally serious. An Office of Special Investigations officer told CNN, “The system as it is now is personality dependent, which is obviously irresponsible and broken,” noting that accurate recording of case details depends on the discretion of individual case workers.⁵

Those federal workers are no better or worse than any of us. This bloody tragedy that might be dismissed as an administrative oversight powerfully demonstrates that even the smallest task matters greatly. It is the systemic, long-standing, repeated nature of the DoD’s improper reporting of servicemen and women that makes this action ethically problematic and warrants my selection as the worst event of 2018.

Major newspapers on November 7 carried a report from the Associated Press with a damning headline, “Pentagon has known of crime reporting lapses for 20 years.”⁶ National Public Radio reported that several Inspector General investigations had documented that over this period the DoD was not regularly reporting violent offenses to the National Criminal Information Center database as mandated. A Fordham law professor and gun regulation specialist quoted on the program zeroed in on an absence of accountability as the leadership flaw that permitted rank and file staff to ignore their protocols. “It’s a ‘who’s watching the watchers’ kind of issue,” he said. “There is no oversight over the Air Force or over the FBI that demands that these regulatory obligations are actually followed through with.”⁷

Finally, after the tragedy, it was discovered that the Air Force had not just 1 but 2 chances to prevent the gunman from future firearm purchases. The shooter had escaped from a psychiatric facility—his status in the psychiatric hospital was unclear—but it is known that he was admitted after he had smuggled weapons onto the base and threatened to kill his commanders. His hospitalization should have been reported to the national database, which would have raised a red flag when he tried to buy guns.⁸

Each of the hundreds of prosaic decisions that indirectly contributed to the Texas shooting was borne of a juggernaut of small compromises from procrustean bureaucratic leadership at the top to mindless conformity at the bottom: a breach all 3 ethical theories. Even if 1 unfiled report leads to no untoward outcome, it is clear that for utilitarianism, it is safer and sounder public policy to take lawful steps to prevent individuals with violent pasts and the potential to kill others from purchasing firearms. Deontologically, whether by omission or commission, not reporting such individuals violates the duty of veracity, as it withholds the truth from those who have a right to possess it. Finally, for this horror to be possible, many people had to not act with integrity, accountability, and trustworthiness.

Many may criticize my a choice to begin the new year so inauspiciously drawing attention to ethical failures and such a malicious crime. I would counter this criticism with the contention that a sober analysis of serious moral lapses in terms of the ethical theory introduced last month is a most salutatory welcome to 2018. So as we embark upon a new year in federal practice, let us strive not only for clinical expertise and administrative efficiency, but also for moral excellence.

In my December 2017 editorial, I presented a values-based roundup of the year. That column explained the criteria for the selections of the most right and most wrong in 2017 in terms of 3 ethical theories: utilitarianism, deontology, and virtue ethics. December featured the good in federal practice. This month, the editorial turns to the bad in federal practice.

Sadly, there were far more candidates for the ethical worst of 2017 in the DoD, VA, and PHS than those of us dedicated to federal service would wish to see. Unfortunately, this reflects both the current state of our society and the nature of the human condition.

On Sunday morning, November 5, 2017, near my hometown of San Antonio, Texas, a gunman in military gear and firearms murdered 26 people who were worshipping at a rural Baptist church. The context of this horrific offense simultaneously mocked the fidelity of our armed forces and a religious faith that in many forms has been a foundation of our nation. Leading forensic mental health experts advise against using the name of mass murderers to avoid perversely glorifying them, and I will adopt that wise convention here.¹

Soon after the massacre, news organizations reported that the perpetrator had served in the Air Force, stationed in my adopted home of New Mexico. The shooter had been given a bad conduct discharge after a court-martial in 2012 found him guilty of brutally assaulting his then current wife and their child.² More than 1 military law expert has opined that perhaps the discharge should have been dishonorable, given the brutality of the conduct, although whether that verdict would have made it more likely, the crime was reported is not certain.

The day following the mass shooting, the Air Force euphemistically acknowledged that it had made an “error,” “mistake,” in not reporting the attacker’s violent history to the federal database, which tracks such offenders to prevent them from lawfully purchasing a weapon. These words and others, such as blunder and failure, used in the media do an injustice to the worshippers’ lives lost that ill-fated morning.³

I must stop here and emphasize as strongly as possible that the selection of this attack is in no way meant to demonize the Air Force as an agency or any individual serving in it. In fact, further investigation suggested that all branches of the armed forces did not fulfill their reporting obligations under the law. Nor am I making the unprovable claim, as some politicians have hinted, that if the Air Force had followed its procedure and policy, the shooter would never have taken 26 innocent lives. Although I note that this is exactly the assumption driving a number of lawsuits brought by the victims’ families against the Air Force for its failure to follow its rules.

Rather, I chose this terrible incident because of its universality and generalizability as a paradigm of what philosopher Hannah Arendt called the banality of evil. As she wrote in her book Eichmann in Jerusalem, “There is a strange interdependence between thoughtlessness and evil.”⁴ Although the law must deem the attack a capital crime, ethics should see it as a the ripple effect of hundreds of small moral failures of dozens of individuals and the system that neither inspired nor held them accountable for taking routine tasks as morally serious. An Office of Special Investigations officer told CNN, “The system as it is now is personality dependent, which is obviously irresponsible and broken,” noting that accurate recording of case details depends on the discretion of individual case workers.⁵

Those federal workers are no better or worse than any of us. This bloody tragedy that might be dismissed as an administrative oversight powerfully demonstrates that even the smallest task matters greatly. It is the systemic, long-standing, repeated nature of the DoD’s improper reporting of servicemen and women that makes this action ethically problematic and warrants my selection as the worst event of 2018.

Major newspapers on November 7 carried a report from the Associated Press with a damning headline, “Pentagon has known of crime reporting lapses for 20 years.”⁶ National Public Radio reported that several Inspector General investigations had documented that over this period the DoD was not regularly reporting violent offenses to the National Criminal Information Center database as mandated. A Fordham law professor and gun regulation specialist quoted on the program zeroed in on an absence of accountability as the leadership flaw that permitted rank and file staff to ignore their protocols. “It’s a ‘who’s watching the watchers’ kind of issue,” he said. “There is no oversight over the Air Force or over the FBI that demands that these regulatory obligations are actually followed through with.”⁷

Finally, after the tragedy, it was discovered that the Air Force had not just 1 but 2 chances to prevent the gunman from future firearm purchases. The shooter had escaped from a psychiatric facility—his status in the psychiatric hospital was unclear—but it is known that he was admitted after he had smuggled weapons onto the base and threatened to kill his commanders. His hospitalization should have been reported to the national database, which would have raised a red flag when he tried to buy guns.⁸

Each of the hundreds of prosaic decisions that indirectly contributed to the Texas shooting was borne of a juggernaut of small compromises from procrustean bureaucratic leadership at the top to mindless conformity at the bottom: a breach all 3 ethical theories. Even if 1 unfiled report leads to no untoward outcome, it is clear that for utilitarianism, it is safer and sounder public policy to take lawful steps to prevent individuals with violent pasts and the potential to kill others from purchasing firearms. Deontologically, whether by omission or commission, not reporting such individuals violates the duty of veracity, as it withholds the truth from those who have a right to possess it. Finally, for this horror to be possible, many people had to not act with integrity, accountability, and trustworthiness.

Many may criticize my a choice to begin the new year so inauspiciously drawing attention to ethical failures and such a malicious crime. I would counter this criticism with the contention that a sober analysis of serious moral lapses in terms of the ethical theory introduced last month is a most salutatory welcome to 2018. So as we embark upon a new year in federal practice, let us strive not only for clinical expertise and administrative efficiency, but also for moral excellence.

In my December 2017 editorial, I presented a values-based roundup of the year. That column explained the criteria for the selections of the most right and most wrong in 2017 in terms of 3 ethical theories: utilitarianism, deontology, and virtue ethics. December featured the good in federal practice. This month, the editorial turns to the bad in federal practice.

Sadly, there were far more candidates for the ethical worst of 2017 in the DoD, VA, and PHS than those of us dedicated to federal service would wish to see. Unfortunately, this reflects both the current state of our society and the nature of the human condition.

On Sunday morning, November 5, 2017, near my hometown of San Antonio, Texas, a gunman in military gear and firearms murdered 26 people who were worshipping at a rural Baptist church. The context of this horrific offense simultaneously mocked the fidelity of our armed forces and a religious faith that in many forms has been a foundation of our nation. Leading forensic mental health experts advise against using the name of mass murderers to avoid perversely glorifying them, and I will adopt that wise convention here.¹

Soon after the massacre, news organizations reported that the perpetrator had served in the Air Force, stationed in my adopted home of New Mexico. The shooter had been given a bad conduct discharge after a court-martial in 2012 found him guilty of brutally assaulting his then current wife and their child.² More than 1 military law expert has opined that perhaps the discharge should have been dishonorable, given the brutality of the conduct, although whether that verdict would have made it more likely, the crime was reported is not certain.

The day following the mass shooting, the Air Force euphemistically acknowledged that it had made an “error,” “mistake,” in not reporting the attacker’s violent history to the federal database, which tracks such offenders to prevent them from lawfully purchasing a weapon. These words and others, such as blunder and failure, used in the media do an injustice to the worshippers’ lives lost that ill-fated morning.³

I must stop here and emphasize as strongly as possible that the selection of this attack is in no way meant to demonize the Air Force as an agency or any individual serving in it. In fact, further investigation suggested that all branches of the armed forces did not fulfill their reporting obligations under the law. Nor am I making the unprovable claim, as some politicians have hinted, that if the Air Force had followed its procedure and policy, the shooter would never have taken 26 innocent lives. Although I note that this is exactly the assumption driving a number of lawsuits brought by the victims’ families against the Air Force for its failure to follow its rules.

Rather, I chose this terrible incident because of its universality and generalizability as a paradigm of what philosopher Hannah Arendt called the banality of evil. As she wrote in her book Eichmann in Jerusalem, “There is a strange interdependence between thoughtlessness and evil.”⁴ Although the law must deem the attack a capital crime, ethics should see it as a the ripple effect of hundreds of small moral failures of dozens of individuals and the system that neither inspired nor held them accountable for taking routine tasks as morally serious. An Office of Special Investigations officer told CNN, “The system as it is now is personality dependent, which is obviously irresponsible and broken,” noting that accurate recording of case details depends on the discretion of individual case workers.⁵

Those federal workers are no better or worse than any of us. This bloody tragedy that might be dismissed as an administrative oversight powerfully demonstrates that even the smallest task matters greatly. It is the systemic, long-standing, repeated nature of the DoD’s improper reporting of servicemen and women that makes this action ethically problematic and warrants my selection as the worst event of 2018.

Major newspapers on November 7 carried a report from the Associated Press with a damning headline, “Pentagon has known of crime reporting lapses for 20 years.”⁶ National Public Radio reported that several Inspector General investigations had documented that over this period the DoD was not regularly reporting violent offenses to the National Criminal Information Center database as mandated. A Fordham law professor and gun regulation specialist quoted on the program zeroed in on an absence of accountability as the leadership flaw that permitted rank and file staff to ignore their protocols. “It’s a ‘who’s watching the watchers’ kind of issue,” he said. “There is no oversight over the Air Force or over the FBI that demands that these regulatory obligations are actually followed through with.”⁷

Finally, after the tragedy, it was discovered that the Air Force had not just 1 but 2 chances to prevent the gunman from future firearm purchases. The shooter had escaped from a psychiatric facility—his status in the psychiatric hospital was unclear—but it is known that he was admitted after he had smuggled weapons onto the base and threatened to kill his commanders. His hospitalization should have been reported to the national database, which would have raised a red flag when he tried to buy guns.⁸

Each of the hundreds of prosaic decisions that indirectly contributed to the Texas shooting was borne of a juggernaut of small compromises from procrustean bureaucratic leadership at the top to mindless conformity at the bottom: a breach all 3 ethical theories. Even if 1 unfiled report leads to no untoward outcome, it is clear that for utilitarianism, it is safer and sounder public policy to take lawful steps to prevent individuals with violent pasts and the potential to kill others from purchasing firearms. Deontologically, whether by omission or commission, not reporting such individuals violates the duty of veracity, as it withholds the truth from those who have a right to possess it. Finally, for this horror to be possible, many people had to not act with integrity, accountability, and trustworthiness.

Many may criticize my a choice to begin the new year so inauspiciously drawing attention to ethical failures and such a malicious crime. I would counter this criticism with the contention that a sober analysis of serious moral lapses in terms of the ethical theory introduced last month is a most salutatory welcome to 2018. So as we embark upon a new year in federal practice, let us strive not only for clinical expertise and administrative efficiency, but also for moral excellence.

Shampoo is a staple in hair grooming that is ever-evolving along with cultural trends. The global shampoo market is expected to reach an estimated value of $25.73 billion by 2019. A major driver of this upward trend in market growth is the increasing demand for natural and organic hair shampoos.¹ Society today has a growing fixation on healthy living practices, and as of late, the ingredients in shampoos and other cosmetic products have become one of the latest targets in the health-consciousness craze. In the age of the Internet where information—and misinformation—is widely accessible and dispersed, the general public often strives to self-educate on specialized matters that are out of their expertise. As a result, individuals have developed an aversion to using certain shampoos out of fear that the ingredients, often referred to as “chemicals” by patients due to their complex names, are unnatural and therefore unhealthy.^1,2 Product developers are working to meet the demand by reformulating shampoos with labels that indicate sulfate free or paraben free, despite the lack of proof that these formulations are an improvement over traditional approaches to hair health. Additionally, alternative methods of cleansing the hair and scalp, also known as the no-shampoo or “no-poo” method, have begun to gain popularity.^2,3

It is essential that dermatologists acknowledge the concerns that their patients have about common shampoo ingredients to dispel the myths that may misinform patient decision-making. This article reviews the controversy surrounding the use of sulfates and parabens in shampoos as well as commonly used shampoo alternatives. Due to the increased prevalence of dry hair shafts in the skin of color population, especially black women, this group is particularly interested in products that will minimize breakage and dryness of the hair. To that end, this population has great interest in the removal of chemical ingredients that may cause damage to the hair shafts, despite the lack of data to support sulfates and paraben damage to hair shafts or scalp skin. Blogs and uninformed hairstylists may propagate these beliefs in a group of consumers who are desperate for new approaches to hair fragility and breakage.

Surfactants and Sulfates

The cleansing ability of a shampoo depends on the surface activity of its detergents. Surface-active ingredients, or surfactants, reduce the surface tension between water and dirt, thus facilitating the removal of environmental dirt from the hair and scalp,⁴ which is achieved by a molecular structure containing both a hydrophilic and a lipophilic group. Sebum and dirt are bound by the lipophilic ends of the surfactant, becoming the center of a micelle structure with the hydrophilic molecule ends pointing outward. Dirt particles become water soluble and are removed from the scalp and hair shaft upon rinsing with water.⁴

Surfactants are classified according to the electric charge of the hydrophilic polar group as either anionic, cationic, amphoteric (zwitterionic), or nonionic.⁵ Each possesses different hair conditioning and cleansing qualities, and multiple surfactants are used in shampoos in differing ratios to accommodate different hair types. In most shampoos, the base consists of anionic and amphoteric surfactants. Depending on individual product requirements, nonionic and cationic surfactants are used to either modify the effects of the surfactants or as conditioning agents.^4,5

One subcategory of surfactants that receives much attention is the group of anionic surfactants known as sulfates. Sulfates, particularly sodium lauryl sulfate (SLS), recently have developed a negative reputation as cosmetic ingredients, as reports from various unscientific sources have labeled them as hazardous to one’s health; SLS has been described as a skin and scalp irritant, has been linked to cataract formation, and has even been wrongly labeled as carcinogenic.⁶ The origins of some of these claims are not clear, though they likely arose from the misinterpretation of complex scientific studies that are easily accessible to laypeople. The link between SLS and ocular irritation or cataract formation is a good illustration of this unsubstantiated fear. A study by Green et al⁷ showed that corneal exposure to extremely high concentrations of SLS following physical or chemical damage to the eye can result in a slowed healing process. The results of this study have since been wrongly quoted to state that SLS-containing products lead to blindness or severe corneal damage.⁸ A different study tested for possible ocular irritation in vivo by submerging the lens of an eye into a 20% SLS solution, which accurately approximates the concentration of SLS in rinse-off consumer products.⁹ However, to achieve ocular irritation, the eyes of laboratory animals were exposed to SLS constantly for 14 days, which would not occur in practical use.⁹ Similarly, a third study achieved cataract formation in a laboratory only by immersing the lens of an eye into a highly concentrated solution of SLS.¹⁰ Such studies are not appropriate representations of how SLS-containing products are used by consumers and have unfortunately been vulnerable to misinterpretation by the general public.

There is no known study that has shown SLS to be carcinogenic. One possible origin of this idea may be from the wrongful interpretation of studies that used SLS as a vehicle substance to test agents that were deemed to be carcinogenic.¹¹ Another possible source of the idea that SLS is carcinogenic comes from its association with 1,4-dioxane, a by-product of the synthesis of certain sulfates such as sodium laureth sulfate due to a process known as ethoxylation.^6,12 Although SLS does not undergo this process in its formation and is not linked to 1,4-dioxane, there is potential for cross-contamination of SLS with 1,4-dioxane, which cannot be overlooked. 1,4-Dioxane is classified as “possibly carcinogenic to humans (Group 2B)” by the International Agency for Research on Cancer,¹³ but screening of SLS for this substance prior to its use in commercial products is standard.

Sulfates are inexpensive detergents that are responsible for lather formation in shampoos as well as in many household cleaning agents.⁵ Sulfates, similar to all anionic surfactants, are characterized by a negatively charged hydrophilic polar group. The best-known and most commonly used anionic surfactants are sulfated fatty alcohols, alkyl sulfates, and their polyethoxylated analogues alkyl ether sulfates.^5,6 Sodium lauryl sulfate (also known as sodium laurilsulfate or sodium dodecyl sulfate) is the most common of them all, found in shampoo and conditioner formulations. Ammonium lauryl sulfate and sodium laureth sulfate are other sulfates commonly used in shampoos and household cleansing products. Sodium lauryl sulfate is a nonvolatile, water-soluble compound. Its partition coefficient (P₀), a measure of a substance’s hydrophilic or lipophilic nature, is low at 1.6, making it a rather hydrophilic substance.⁶ Hydrophilic substances tend to have low bioaccumulation profiles in the body. Additionally, SLS is readily biodegradable. It can be derived from both synthetic and naturally occurring sources; for example, palm kernel oil, petrolatum, and coconut oil are all sources of lauric acid, the starting ingredient used to synthesize SLS. Sodium lauryl sulfate is created by reacting lauryl alcohol with sulfur trioxide gas, followed by neutralization with sodium carbonate (also a naturally occurring compound).⁶ Sodium lauryl sulfate and other sulfate-containing shampoos widely replaced the usage of traditional soaps formulated from animal or vegetable fats, as these latter formations created a film of insoluble calcium salts on the hair strands upon contact with water, resulting in tangled, dull-appearing hair.⁵ Additionally, sulfates were preferred to the alkaline pH of traditional soap, which can be harsh on hair strands and cause irritation of the skin and mucous membranes.¹⁴ Because they are highly water soluble, sulfates enable the formulation of clear shampoos. They exhibit remarkable cleaning properties and lather formation.^5,14

Because sulfates are potent surfactants, they can remove dirt and debris as well as naturally produced healthy oils from the hair and scalp. As a result, sulfates can leave the hair feeling dry and stripped of moisture.^4,5 Sulfates are used as the primary detergents in the formulation of deep-cleaning shampoos, which are designed for people who accumulate a heavy buildup of dirt, sebum, and debris from frequent use of styling products. Due to their potent detergency, these shampoos typically are not used on a daily basis but rather at longer intervals.¹⁵ A downside to sulfates is that they can have cosmetically unpleasant properties, which can be compensated for by including appropriate softening additives in shampoo formulations.⁴ A number of anionic surfactants such as olefin sulfonate, alkyl sulfosuccinate, acyl peptides, and alkyl ether carboxylates are well tolerated by the skin and are used together with other anionic and amphoteric surfactants to optimize shampoo properties. Alternatively, sulfate-free shampoos are cleansers compounded by the removal of the anionic group and switched for surfactants with less detergency.^4,5

Preservatives and Parabens

Parabens refer to a group of esters of 4-hydroxybenzoic acid commonly used as preservatives in foods, pharmaceuticals, and cosmetics whose widespread use dates back to 1923.¹⁶ Concerns over the presence of parabens in shampoos and other cosmetics have been raised by patients for their reputed estrogenic and antiandrogenic effects and suspected involvement in carcinogenesis via endocrine modulation.^16,17 In in vitro studies done on yeast assays, parabens have shown weak estrogenic activity that increases in proportion to both the length and increased branching of the alkyl side chains in the paraben’s molecular structure.¹⁸ They are 10,000-fold less potent than 17β-estradiol. In in vivo animal studies, parabens show weak estrogenic activity and are 100,000-fold less potent than 17β-estradiol.¹⁸ 4-Hydroxybenzoic acid, a common metabolite, showed no estrogenic activity when tested both in vitro and in vivo.¹⁹ Some concerning research has implicated a link between parabens used in underarm cosmetics, such as deodorants and antiperspirants, and breast cancer¹⁶; however, the studies have been conflicting, and there is simply not enough data to assert that parabens cause breast cancer.

The Cosmetic Ingredient Review expert panel first reviewed parabens in 1984 and concluded that “methylparaben, ethylparaben, propylparaben, and butylparaben are safe as cosmetic ingredients in the present practices of use.”²⁰ They extended this statement to include isopropylparaben and isobutylparaben in a later review.²¹ In 2005, the Scientific Committee on Consumer Products (now known as the Scientific Committee for Consumer Safety) in Europe stated that methylparaben and ethylparaben can be used at levels up to 0.4% in products.²² This decision was reached due to reports of decreased sperm counts and testosterone levels in male juvenile rats exposed to these parabens; however, these reults were not successfully replicated in larger studies.^16,22 In 2010, the Scientific Committee for Consumer Safety revisited its stance on parabens, and they then revised their recommendations to say that concentrations of propylparaben and butylparaben should not exceed concentrations of 0.19%, based on “the conservative choice for the calculation of the [Margin-of-Safety] of butyl- and propylparaben.”²³ However, in 2011 the use of propylparaben and butylparaben was banned in Denmark for cosmetic products used in children 3 years or younger,¹⁶ and the European Commission subsequently amended their directive in 2014, banning isopropylparaben, isobutylparaben, phenylparaben, benzylparaben, and pentylparaben due to lack of data available to evaluate the human risk of these products.²⁴

Contrary to the trends in Europe, there currently are no regulations against the use of parabens in shampoos or other cosmetics in the United States. The American Cancer Society found that there is no evidence to suggest that the current levels of parabens in cosmetic products (eg, antiperspirants) increase one’s risk of breast cancer.²⁵ Parabens are readily absorbed into the body both transdermally and through ingestion but also are believed to be rapidly transformed into harmless and nonspecific metabolites; they are readily metabolized by the liver and excreted in urine, and there is no measured accumulation in tissues.¹⁷

Parabens continue to be the most widely used preservatives in personal care products, usually in conjunction with other preservatives. Parabens are good biocides; short-chain esters (eg, methylparabens, ethylparabens) are effective against gram-positive bacteria and are weakly effective against gram-negative bacteria. Long-chain paraben esters (eg, propylparabens, butylparabens) are effective against mold and yeast. The addition of other preservatives creates a broad spectrum of antimicrobial defense in consumer products. Other preservatives include formaldehyde releasers or phenoxyethanol, as well as chelating agents such as EDTA, which improve the stability of these cosmetic products when exposed to air.¹⁶ Parabens are naturally occurring substances found in foods such as blueberries, barley, strawberries, yeast, olives, and grapes. As a colorless, odorless, and inexpensive substance, their use has been heavily favored in cosmetic and food products.¹⁶

Shampoo Alternatives and the No-Poo Method

Although research has not demonstrated any long-term danger to using shampoo, certain chemicals found in shampoos have the potential to irritate the scalp. Commonly cited allergens in shampoos include cocamidopropyl betaine, propylene glycol, vitamin E (tocopherol), parabens, and benzophenones.⁵ Additionally, the rising use of formaldehyde-releasing preservatives and isothiazolinones due to mounting pressures to move away from parabens has led to an increase in cases of allergic contact dermatitis (ACD).¹⁶ However, the irritability (rather than allergenicity) of these substances often is established during patch testing, a method of detecting delayed-type allergic reactions, which is important to note because patch testing requires a substance to be exposed to the skin for 24 to 48 hours, whereas exposure to shampoo ingredients may last a matter of minutes at most and occur in lesser concentrations because the ingredients are diluted by water in the rinsing process. Given these differences, it is unlikely that a patient would develop a true allergic response from regular shampoo use. Nevertheless, in patients who are already sensitized, exposure could conceivably trigger ACD, and patients must be cognizant of the composition of their shampoos.¹⁶

The no-poo method refers to the avoidance of commercial shampoo products when cleansing the hair and scalp and encompasses different methods of cleansing the hair, such as the use of household items (eg, baking soda, apple cider vinegar [ACV]), the use of conditioners to wash the hair (also known as conditioner-only washing or co-washing), treating the scalp with tea tree oil, or simply rinsing the hair with water. Proponents of the no-poo method believe that abstaining from shampoo use leads to healthier hair, retained natural oils, and less exposure to supposedly dangerous chemicals such as parabens or sulfates.^2,3,26-28 However, there are no known studies in the literature that assess or support the hypotheses of the no-poo method.

Baking Soda and ACV
Baking soda (sodium bicarbonate) is a substance commonly found in the average household. It has been used in toothpaste formulas and cosmetic products and is known for its acid-neutralizing properties. Baking soda has been shown to have some antifungal and viricidal properties through an unknown mechanism of action.²⁸ It has gained popularity for its use as a means of reducing the appearance of excessive greasiness of the hair shafts. Users also have reported that when washing their hair with baking soda, they are able to achieve a clean scalp and hair that feels soft to the touch.^2,3,26,27,29 Despite these reports, users must beware of using baking soda without adequately diluting it with water. Baking soda is a known alkaline irritant.^26,30 With a pH of 9, baking soda causes the cuticle layer of the hair fiber to open, increasing the capacity for water absorption. Water penetrates the scales that open, breaking the hydrogen bonds of the keratin molecule.³¹ Keratin is a spiral helical molecule that keeps its shape due to hydrogen, disulfide, and ionic bonds, as well as Van der Waals force.³⁰ Hydrolysis of these bonds due to exposure to baking soda lowers the elasticity of the hair and increases the negative electrical net charge of the hair fiber surface, which leads to increased friction between fibers, cuticle damage, hair fragility, and fiber breakage.^32,33

Apple cider vinegar is an apple-derived acetic acid solution with a pH ranging from 3.1 to 5.²⁸ The pH range of ACV is considered to be ideal for hair by no-poo proponents, as it is similar to the natural pH of the scalp. Its acidic properties are responsible for its antimicrobial abilities, particularly its effectiveness against gram-negative bacteria.³⁰ The acetic acid of ACV can partially interrupt oil interfaces, which contributes to its mild ability to remove product residue and scalp buildup from the hair shaft; the acetic acid also tightens the cuticles on hair fibers.³³ Apple cider vinegar is used as a means of cleansing the hair and scalp by no-poo proponents^2,3,26; other uses for ACV include using it as a rinse following washing and/or conditioning of the hair or as a means of preserving color in color-treated hair. There also is evidence that ACV may have antifungal properties.²⁸ However, consumers must be aware that if it is not diluted in water, ACV may be too caustic for direct application to the hair and may lead to damage; it can be irritating to eyes, mucus membranes, and acutely inflamed skin. Also, vinegar rinses used on processed or chemically damaged hair may lead to increased hair fragility.^2,3

Hair fibers have a pH of 3.67, while the scalp has a pH between 4.5 and 6.2. This slightly acidic film acts as a barrier to viruses, bacteria, and other potential contaminants.³³ Studies have shown that the pH of skin increases in proportion to the pH of the cleanser used.³⁴ Therefore, due to the naturally acidic pH of the scalp, acid-balanced shampoos generally are recommended. Shampoos should not have a pH higher than 5.5, as hair shafts can swell due to alkalinization, which can be prevented by pH balancing the shampoo through the addition of an acidic substance (eg, glycolic acid, citric acid) to lower the pH down to approximately 5.5. Apple cider vinegar often is used for this purpose. However, one study revealed that 82% of shampoos already have an acidic pH.³⁴

Conditioner-Only Washing (Co-washing)
Conditioner-only washing, or co-washing, is a widely practiced method of hair grooming. It is popular among individuals who find that commercial shampoos strip too much of the natural hair oils away, leaving the hair rough or unmanageable. Co-washing is not harmful to the hair; however, the molecular structure and function of a conditioner and that of a shampoo are very different.^5,35,36 Conditioners are not formulated to remove dirt and buildup in the hair but rather to add substances to the hair, and thus cannot provide extensive cleansing of the hair and scalp; therefore, it is inappropriate to use co-washing as a replacement for shampooing. Quaternary conditioning agents are an exception because they contain amphoteric detergents comprised of both anionic and cationic groups, which allow them both the ability to remove dirt and sebum with its anionic group, typically found in shampoos, as well as the ability to coat and condition the hair due to the high affinity of the cationic group for the negatively charged hair fibers.^36,37 Amphoteric detergents are commonly found in 2-in-1 conditioning cleansers, among other ingredients, such as hydrolyzed animal proteins that temporarily plug surface defects on the hair fiber, and dimethicone, a synthetic oil that creates a thin film over the hair shaft, increasing shine and manageability. Of note, these conditioning shampoos are ideal for individuals with minimal product buildup on the hair and scalp and are not adequate scalp cleansers for individuals who either wash their hair infrequently or who regularly use hairstyling products.^36,37

Tea Tree Oil
Tea tree oil is an essential oil extracted from the Melaleuca alternifolia plant of the Myrtaceae family. It is native to the coast of northeastern Australia. A holy grail of natural cosmetics, tea tree oil is widely known for its antiviral, antifungal, and antiseptic properties.³⁸ Although not used as a stand-alone cleanser, it is often added to a number of cosmetic products, including shampoos and co-washes. Although deemed safe for topical use, it has been shown to be quite toxic when ingested. Symptoms of ingestion include nausea, vomiting, hallucinations, and coma. The common concern with tea tree oil is its ability to cause ACD. In particular, it is believed that the oxidation products of tea tree oil are allergenic rather than the tea tree oil itself. The evaluation of tea tree oil as a potential contact allergen has been quite difficult; it consists of more than 100 distinct compounds and is often mislabeled, or does not meet the guidelines of the International Organization for Standardization. Nonetheless, the prevalence of ACD due to tea tree oil is low (approximately 1.4%). Despite its low prevalence, tea tree oil should remain in the differential as an ACD-inducing agent. Patch testing with the patient’s supply of tea tree oil is advised when possible.³⁸

Conclusion

It is customary that the ingredients used in shampoos undergo periodic testing and monitoring to assure the safety of their use. Although it is encouraging that patients are proactive in their efforts to stay abreast of the literature, it is still important that cosmetic scientists, dermatologists, and other experts remain at the forefront of educating the public about these substances. Not doing so can result in the propagation of misinformation and unnecessary fears, which can lead to the adaptation of unhygienic or even unsafe hair care practices. As dermatologists, we must ensure that patients are educated about the benefits and hazards of off-label use of household ingredients to the extent that evidence-based medicine permits. Patients must be informed that not all synthetic substances are harmful, and likewise not all naturally occurring substances are safe.

Shampoo is a staple in hair grooming that is ever-evolving along with cultural trends. The global shampoo market is expected to reach an estimated value of $25.73 billion by 2019. A major driver of this upward trend in market growth is the increasing demand for natural and organic hair shampoos.¹ Society today has a growing fixation on healthy living practices, and as of late, the ingredients in shampoos and other cosmetic products have become one of the latest targets in the health-consciousness craze. In the age of the Internet where information—and misinformation—is widely accessible and dispersed, the general public often strives to self-educate on specialized matters that are out of their expertise. As a result, individuals have developed an aversion to using certain shampoos out of fear that the ingredients, often referred to as “chemicals” by patients due to their complex names, are unnatural and therefore unhealthy.^1,2 Product developers are working to meet the demand by reformulating shampoos with labels that indicate sulfate free or paraben free, despite the lack of proof that these formulations are an improvement over traditional approaches to hair health. Additionally, alternative methods of cleansing the hair and scalp, also known as the no-shampoo or “no-poo” method, have begun to gain popularity.^2,3

It is essential that dermatologists acknowledge the concerns that their patients have about common shampoo ingredients to dispel the myths that may misinform patient decision-making. This article reviews the controversy surrounding the use of sulfates and parabens in shampoos as well as commonly used shampoo alternatives. Due to the increased prevalence of dry hair shafts in the skin of color population, especially black women, this group is particularly interested in products that will minimize breakage and dryness of the hair. To that end, this population has great interest in the removal of chemical ingredients that may cause damage to the hair shafts, despite the lack of data to support sulfates and paraben damage to hair shafts or scalp skin. Blogs and uninformed hairstylists may propagate these beliefs in a group of consumers who are desperate for new approaches to hair fragility and breakage.

Surfactants and Sulfates

The cleansing ability of a shampoo depends on the surface activity of its detergents. Surface-active ingredients, or surfactants, reduce the surface tension between water and dirt, thus facilitating the removal of environmental dirt from the hair and scalp,⁴ which is achieved by a molecular structure containing both a hydrophilic and a lipophilic group. Sebum and dirt are bound by the lipophilic ends of the surfactant, becoming the center of a micelle structure with the hydrophilic molecule ends pointing outward. Dirt particles become water soluble and are removed from the scalp and hair shaft upon rinsing with water.⁴

Surfactants are classified according to the electric charge of the hydrophilic polar group as either anionic, cationic, amphoteric (zwitterionic), or nonionic.⁵ Each possesses different hair conditioning and cleansing qualities, and multiple surfactants are used in shampoos in differing ratios to accommodate different hair types. In most shampoos, the base consists of anionic and amphoteric surfactants. Depending on individual product requirements, nonionic and cationic surfactants are used to either modify the effects of the surfactants or as conditioning agents.^4,5

One subcategory of surfactants that receives much attention is the group of anionic surfactants known as sulfates. Sulfates, particularly sodium lauryl sulfate (SLS), recently have developed a negative reputation as cosmetic ingredients, as reports from various unscientific sources have labeled them as hazardous to one’s health; SLS has been described as a skin and scalp irritant, has been linked to cataract formation, and has even been wrongly labeled as carcinogenic.⁶ The origins of some of these claims are not clear, though they likely arose from the misinterpretation of complex scientific studies that are easily accessible to laypeople. The link between SLS and ocular irritation or cataract formation is a good illustration of this unsubstantiated fear. A study by Green et al⁷ showed that corneal exposure to extremely high concentrations of SLS following physical or chemical damage to the eye can result in a slowed healing process. The results of this study have since been wrongly quoted to state that SLS-containing products lead to blindness or severe corneal damage.⁸ A different study tested for possible ocular irritation in vivo by submerging the lens of an eye into a 20% SLS solution, which accurately approximates the concentration of SLS in rinse-off consumer products.⁹ However, to achieve ocular irritation, the eyes of laboratory animals were exposed to SLS constantly for 14 days, which would not occur in practical use.⁹ Similarly, a third study achieved cataract formation in a laboratory only by immersing the lens of an eye into a highly concentrated solution of SLS.¹⁰ Such studies are not appropriate representations of how SLS-containing products are used by consumers and have unfortunately been vulnerable to misinterpretation by the general public.

There is no known study that has shown SLS to be carcinogenic. One possible origin of this idea may be from the wrongful interpretation of studies that used SLS as a vehicle substance to test agents that were deemed to be carcinogenic.¹¹ Another possible source of the idea that SLS is carcinogenic comes from its association with 1,4-dioxane, a by-product of the synthesis of certain sulfates such as sodium laureth sulfate due to a process known as ethoxylation.^6,12 Although SLS does not undergo this process in its formation and is not linked to 1,4-dioxane, there is potential for cross-contamination of SLS with 1,4-dioxane, which cannot be overlooked. 1,4-Dioxane is classified as “possibly carcinogenic to humans (Group 2B)” by the International Agency for Research on Cancer,¹³ but screening of SLS for this substance prior to its use in commercial products is standard.

Sulfates are inexpensive detergents that are responsible for lather formation in shampoos as well as in many household cleaning agents.⁵ Sulfates, similar to all anionic surfactants, are characterized by a negatively charged hydrophilic polar group. The best-known and most commonly used anionic surfactants are sulfated fatty alcohols, alkyl sulfates, and their polyethoxylated analogues alkyl ether sulfates.^5,6 Sodium lauryl sulfate (also known as sodium laurilsulfate or sodium dodecyl sulfate) is the most common of them all, found in shampoo and conditioner formulations. Ammonium lauryl sulfate and sodium laureth sulfate are other sulfates commonly used in shampoos and household cleansing products. Sodium lauryl sulfate is a nonvolatile, water-soluble compound. Its partition coefficient (P₀), a measure of a substance’s hydrophilic or lipophilic nature, is low at 1.6, making it a rather hydrophilic substance.⁶ Hydrophilic substances tend to have low bioaccumulation profiles in the body. Additionally, SLS is readily biodegradable. It can be derived from both synthetic and naturally occurring sources; for example, palm kernel oil, petrolatum, and coconut oil are all sources of lauric acid, the starting ingredient used to synthesize SLS. Sodium lauryl sulfate is created by reacting lauryl alcohol with sulfur trioxide gas, followed by neutralization with sodium carbonate (also a naturally occurring compound).⁶ Sodium lauryl sulfate and other sulfate-containing shampoos widely replaced the usage of traditional soaps formulated from animal or vegetable fats, as these latter formations created a film of insoluble calcium salts on the hair strands upon contact with water, resulting in tangled, dull-appearing hair.⁵ Additionally, sulfates were preferred to the alkaline pH of traditional soap, which can be harsh on hair strands and cause irritation of the skin and mucous membranes.¹⁴ Because they are highly water soluble, sulfates enable the formulation of clear shampoos. They exhibit remarkable cleaning properties and lather formation.^5,14

Because sulfates are potent surfactants, they can remove dirt and debris as well as naturally produced healthy oils from the hair and scalp. As a result, sulfates can leave the hair feeling dry and stripped of moisture.^4,5 Sulfates are used as the primary detergents in the formulation of deep-cleaning shampoos, which are designed for people who accumulate a heavy buildup of dirt, sebum, and debris from frequent use of styling products. Due to their potent detergency, these shampoos typically are not used on a daily basis but rather at longer intervals.¹⁵ A downside to sulfates is that they can have cosmetically unpleasant properties, which can be compensated for by including appropriate softening additives in shampoo formulations.⁴ A number of anionic surfactants such as olefin sulfonate, alkyl sulfosuccinate, acyl peptides, and alkyl ether carboxylates are well tolerated by the skin and are used together with other anionic and amphoteric surfactants to optimize shampoo properties. Alternatively, sulfate-free shampoos are cleansers compounded by the removal of the anionic group and switched for surfactants with less detergency.^4,5

Preservatives and Parabens

Parabens refer to a group of esters of 4-hydroxybenzoic acid commonly used as preservatives in foods, pharmaceuticals, and cosmetics whose widespread use dates back to 1923.¹⁶ Concerns over the presence of parabens in shampoos and other cosmetics have been raised by patients for their reputed estrogenic and antiandrogenic effects and suspected involvement in carcinogenesis via endocrine modulation.^16,17 In in vitro studies done on yeast assays, parabens have shown weak estrogenic activity that increases in proportion to both the length and increased branching of the alkyl side chains in the paraben’s molecular structure.¹⁸ They are 10,000-fold less potent than 17β-estradiol. In in vivo animal studies, parabens show weak estrogenic activity and are 100,000-fold less potent than 17β-estradiol.¹⁸ 4-Hydroxybenzoic acid, a common metabolite, showed no estrogenic activity when tested both in vitro and in vivo.¹⁹ Some concerning research has implicated a link between parabens used in underarm cosmetics, such as deodorants and antiperspirants, and breast cancer¹⁶; however, the studies have been conflicting, and there is simply not enough data to assert that parabens cause breast cancer.

The Cosmetic Ingredient Review expert panel first reviewed parabens in 1984 and concluded that “methylparaben, ethylparaben, propylparaben, and butylparaben are safe as cosmetic ingredients in the present practices of use.”²⁰ They extended this statement to include isopropylparaben and isobutylparaben in a later review.²¹ In 2005, the Scientific Committee on Consumer Products (now known as the Scientific Committee for Consumer Safety) in Europe stated that methylparaben and ethylparaben can be used at levels up to 0.4% in products.²² This decision was reached due to reports of decreased sperm counts and testosterone levels in male juvenile rats exposed to these parabens; however, these reults were not successfully replicated in larger studies.^16,22 In 2010, the Scientific Committee for Consumer Safety revisited its stance on parabens, and they then revised their recommendations to say that concentrations of propylparaben and butylparaben should not exceed concentrations of 0.19%, based on “the conservative choice for the calculation of the [Margin-of-Safety] of butyl- and propylparaben.”²³ However, in 2011 the use of propylparaben and butylparaben was banned in Denmark for cosmetic products used in children 3 years or younger,¹⁶ and the European Commission subsequently amended their directive in 2014, banning isopropylparaben, isobutylparaben, phenylparaben, benzylparaben, and pentylparaben due to lack of data available to evaluate the human risk of these products.²⁴

Contrary to the trends in Europe, there currently are no regulations against the use of parabens in shampoos or other cosmetics in the United States. The American Cancer Society found that there is no evidence to suggest that the current levels of parabens in cosmetic products (eg, antiperspirants) increase one’s risk of breast cancer.²⁵ Parabens are readily absorbed into the body both transdermally and through ingestion but also are believed to be rapidly transformed into harmless and nonspecific metabolites; they are readily metabolized by the liver and excreted in urine, and there is no measured accumulation in tissues.¹⁷

Parabens continue to be the most widely used preservatives in personal care products, usually in conjunction with other preservatives. Parabens are good biocides; short-chain esters (eg, methylparabens, ethylparabens) are effective against gram-positive bacteria and are weakly effective against gram-negative bacteria. Long-chain paraben esters (eg, propylparabens, butylparabens) are effective against mold and yeast. The addition of other preservatives creates a broad spectrum of antimicrobial defense in consumer products. Other preservatives include formaldehyde releasers or phenoxyethanol, as well as chelating agents such as EDTA, which improve the stability of these cosmetic products when exposed to air.¹⁶ Parabens are naturally occurring substances found in foods such as blueberries, barley, strawberries, yeast, olives, and grapes. As a colorless, odorless, and inexpensive substance, their use has been heavily favored in cosmetic and food products.¹⁶

Shampoo Alternatives and the No-Poo Method

Although research has not demonstrated any long-term danger to using shampoo, certain chemicals found in shampoos have the potential to irritate the scalp. Commonly cited allergens in shampoos include cocamidopropyl betaine, propylene glycol, vitamin E (tocopherol), parabens, and benzophenones.⁵ Additionally, the rising use of formaldehyde-releasing preservatives and isothiazolinones due to mounting pressures to move away from parabens has led to an increase in cases of allergic contact dermatitis (ACD).¹⁶ However, the irritability (rather than allergenicity) of these substances often is established during patch testing, a method of detecting delayed-type allergic reactions, which is important to note because patch testing requires a substance to be exposed to the skin for 24 to 48 hours, whereas exposure to shampoo ingredients may last a matter of minutes at most and occur in lesser concentrations because the ingredients are diluted by water in the rinsing process. Given these differences, it is unlikely that a patient would develop a true allergic response from regular shampoo use. Nevertheless, in patients who are already sensitized, exposure could conceivably trigger ACD, and patients must be cognizant of the composition of their shampoos.¹⁶

The no-poo method refers to the avoidance of commercial shampoo products when cleansing the hair and scalp and encompasses different methods of cleansing the hair, such as the use of household items (eg, baking soda, apple cider vinegar [ACV]), the use of conditioners to wash the hair (also known as conditioner-only washing or co-washing), treating the scalp with tea tree oil, or simply rinsing the hair with water. Proponents of the no-poo method believe that abstaining from shampoo use leads to healthier hair, retained natural oils, and less exposure to supposedly dangerous chemicals such as parabens or sulfates.^2,3,26-28 However, there are no known studies in the literature that assess or support the hypotheses of the no-poo method.

Baking Soda and ACV
Baking soda (sodium bicarbonate) is a substance commonly found in the average household. It has been used in toothpaste formulas and cosmetic products and is known for its acid-neutralizing properties. Baking soda has been shown to have some antifungal and viricidal properties through an unknown mechanism of action.²⁸ It has gained popularity for its use as a means of reducing the appearance of excessive greasiness of the hair shafts. Users also have reported that when washing their hair with baking soda, they are able to achieve a clean scalp and hair that feels soft to the touch.^2,3,26,27,29 Despite these reports, users must beware of using baking soda without adequately diluting it with water. Baking soda is a known alkaline irritant.^26,30 With a pH of 9, baking soda causes the cuticle layer of the hair fiber to open, increasing the capacity for water absorption. Water penetrates the scales that open, breaking the hydrogen bonds of the keratin molecule.³¹ Keratin is a spiral helical molecule that keeps its shape due to hydrogen, disulfide, and ionic bonds, as well as Van der Waals force.³⁰ Hydrolysis of these bonds due to exposure to baking soda lowers the elasticity of the hair and increases the negative electrical net charge of the hair fiber surface, which leads to increased friction between fibers, cuticle damage, hair fragility, and fiber breakage.^32,33

Apple cider vinegar is an apple-derived acetic acid solution with a pH ranging from 3.1 to 5.²⁸ The pH range of ACV is considered to be ideal for hair by no-poo proponents, as it is similar to the natural pH of the scalp. Its acidic properties are responsible for its antimicrobial abilities, particularly its effectiveness against gram-negative bacteria.³⁰ The acetic acid of ACV can partially interrupt oil interfaces, which contributes to its mild ability to remove product residue and scalp buildup from the hair shaft; the acetic acid also tightens the cuticles on hair fibers.³³ Apple cider vinegar is used as a means of cleansing the hair and scalp by no-poo proponents^2,3,26; other uses for ACV include using it as a rinse following washing and/or conditioning of the hair or as a means of preserving color in color-treated hair. There also is evidence that ACV may have antifungal properties.²⁸ However, consumers must be aware that if it is not diluted in water, ACV may be too caustic for direct application to the hair and may lead to damage; it can be irritating to eyes, mucus membranes, and acutely inflamed skin. Also, vinegar rinses used on processed or chemically damaged hair may lead to increased hair fragility.^2,3

Hair fibers have a pH of 3.67, while the scalp has a pH between 4.5 and 6.2. This slightly acidic film acts as a barrier to viruses, bacteria, and other potential contaminants.³³ Studies have shown that the pH of skin increases in proportion to the pH of the cleanser used.³⁴ Therefore, due to the naturally acidic pH of the scalp, acid-balanced shampoos generally are recommended. Shampoos should not have a pH higher than 5.5, as hair shafts can swell due to alkalinization, which can be prevented by pH balancing the shampoo through the addition of an acidic substance (eg, glycolic acid, citric acid) to lower the pH down to approximately 5.5. Apple cider vinegar often is used for this purpose. However, one study revealed that 82% of shampoos already have an acidic pH.³⁴

Conditioner-Only Washing (Co-washing)
Conditioner-only washing, or co-washing, is a widely practiced method of hair grooming. It is popular among individuals who find that commercial shampoos strip too much of the natural hair oils away, leaving the hair rough or unmanageable. Co-washing is not harmful to the hair; however, the molecular structure and function of a conditioner and that of a shampoo are very different.^5,35,36 Conditioners are not formulated to remove dirt and buildup in the hair but rather to add substances to the hair, and thus cannot provide extensive cleansing of the hair and scalp; therefore, it is inappropriate to use co-washing as a replacement for shampooing. Quaternary conditioning agents are an exception because they contain amphoteric detergents comprised of both anionic and cationic groups, which allow them both the ability to remove dirt and sebum with its anionic group, typically found in shampoos, as well as the ability to coat and condition the hair due to the high affinity of the cationic group for the negatively charged hair fibers.^36,37 Amphoteric detergents are commonly found in 2-in-1 conditioning cleansers, among other ingredients, such as hydrolyzed animal proteins that temporarily plug surface defects on the hair fiber, and dimethicone, a synthetic oil that creates a thin film over the hair shaft, increasing shine and manageability. Of note, these conditioning shampoos are ideal for individuals with minimal product buildup on the hair and scalp and are not adequate scalp cleansers for individuals who either wash their hair infrequently or who regularly use hairstyling products.^36,37

Tea Tree Oil
Tea tree oil is an essential oil extracted from the Melaleuca alternifolia plant of the Myrtaceae family. It is native to the coast of northeastern Australia. A holy grail of natural cosmetics, tea tree oil is widely known for its antiviral, antifungal, and antiseptic properties.³⁸ Although not used as a stand-alone cleanser, it is often added to a number of cosmetic products, including shampoos and co-washes. Although deemed safe for topical use, it has been shown to be quite toxic when ingested. Symptoms of ingestion include nausea, vomiting, hallucinations, and coma. The common concern with tea tree oil is its ability to cause ACD. In particular, it is believed that the oxidation products of tea tree oil are allergenic rather than the tea tree oil itself. The evaluation of tea tree oil as a potential contact allergen has been quite difficult; it consists of more than 100 distinct compounds and is often mislabeled, or does not meet the guidelines of the International Organization for Standardization. Nonetheless, the prevalence of ACD due to tea tree oil is low (approximately 1.4%). Despite its low prevalence, tea tree oil should remain in the differential as an ACD-inducing agent. Patch testing with the patient’s supply of tea tree oil is advised when possible.³⁸

Conclusion

It is customary that the ingredients used in shampoos undergo periodic testing and monitoring to assure the safety of their use. Although it is encouraging that patients are proactive in their efforts to stay abreast of the literature, it is still important that cosmetic scientists, dermatologists, and other experts remain at the forefront of educating the public about these substances. Not doing so can result in the propagation of misinformation and unnecessary fears, which can lead to the adaptation of unhygienic or even unsafe hair care practices. As dermatologists, we must ensure that patients are educated about the benefits and hazards of off-label use of household ingredients to the extent that evidence-based medicine permits. Patients must be informed that not all synthetic substances are harmful, and likewise not all naturally occurring substances are safe.

Shampoo is a staple in hair grooming that is ever-evolving along with cultural trends. The global shampoo market is expected to reach an estimated value of $25.73 billion by 2019. A major driver of this upward trend in market growth is the increasing demand for natural and organic hair shampoos.¹ Society today has a growing fixation on healthy living practices, and as of late, the ingredients in shampoos and other cosmetic products have become one of the latest targets in the health-consciousness craze. In the age of the Internet where information—and misinformation—is widely accessible and dispersed, the general public often strives to self-educate on specialized matters that are out of their expertise. As a result, individuals have developed an aversion to using certain shampoos out of fear that the ingredients, often referred to as “chemicals” by patients due to their complex names, are unnatural and therefore unhealthy.^1,2 Product developers are working to meet the demand by reformulating shampoos with labels that indicate sulfate free or paraben free, despite the lack of proof that these formulations are an improvement over traditional approaches to hair health. Additionally, alternative methods of cleansing the hair and scalp, also known as the no-shampoo or “no-poo” method, have begun to gain popularity.^2,3

It is essential that dermatologists acknowledge the concerns that their patients have about common shampoo ingredients to dispel the myths that may misinform patient decision-making. This article reviews the controversy surrounding the use of sulfates and parabens in shampoos as well as commonly used shampoo alternatives. Due to the increased prevalence of dry hair shafts in the skin of color population, especially black women, this group is particularly interested in products that will minimize breakage and dryness of the hair. To that end, this population has great interest in the removal of chemical ingredients that may cause damage to the hair shafts, despite the lack of data to support sulfates and paraben damage to hair shafts or scalp skin. Blogs and uninformed hairstylists may propagate these beliefs in a group of consumers who are desperate for new approaches to hair fragility and breakage.

Surfactants and Sulfates

The cleansing ability of a shampoo depends on the surface activity of its detergents. Surface-active ingredients, or surfactants, reduce the surface tension between water and dirt, thus facilitating the removal of environmental dirt from the hair and scalp,⁴ which is achieved by a molecular structure containing both a hydrophilic and a lipophilic group. Sebum and dirt are bound by the lipophilic ends of the surfactant, becoming the center of a micelle structure with the hydrophilic molecule ends pointing outward. Dirt particles become water soluble and are removed from the scalp and hair shaft upon rinsing with water.⁴

Surfactants are classified according to the electric charge of the hydrophilic polar group as either anionic, cationic, amphoteric (zwitterionic), or nonionic.⁵ Each possesses different hair conditioning and cleansing qualities, and multiple surfactants are used in shampoos in differing ratios to accommodate different hair types. In most shampoos, the base consists of anionic and amphoteric surfactants. Depending on individual product requirements, nonionic and cationic surfactants are used to either modify the effects of the surfactants or as conditioning agents.^4,5

One subcategory of surfactants that receives much attention is the group of anionic surfactants known as sulfates. Sulfates, particularly sodium lauryl sulfate (SLS), recently have developed a negative reputation as cosmetic ingredients, as reports from various unscientific sources have labeled them as hazardous to one’s health; SLS has been described as a skin and scalp irritant, has been linked to cataract formation, and has even been wrongly labeled as carcinogenic.⁶ The origins of some of these claims are not clear, though they likely arose from the misinterpretation of complex scientific studies that are easily accessible to laypeople. The link between SLS and ocular irritation or cataract formation is a good illustration of this unsubstantiated fear. A study by Green et al⁷ showed that corneal exposure to extremely high concentrations of SLS following physical or chemical damage to the eye can result in a slowed healing process. The results of this study have since been wrongly quoted to state that SLS-containing products lead to blindness or severe corneal damage.⁸ A different study tested for possible ocular irritation in vivo by submerging the lens of an eye into a 20% SLS solution, which accurately approximates the concentration of SLS in rinse-off consumer products.⁹ However, to achieve ocular irritation, the eyes of laboratory animals were exposed to SLS constantly for 14 days, which would not occur in practical use.⁹ Similarly, a third study achieved cataract formation in a laboratory only by immersing the lens of an eye into a highly concentrated solution of SLS.¹⁰ Such studies are not appropriate representations of how SLS-containing products are used by consumers and have unfortunately been vulnerable to misinterpretation by the general public.

There is no known study that has shown SLS to be carcinogenic. One possible origin of this idea may be from the wrongful interpretation of studies that used SLS as a vehicle substance to test agents that were deemed to be carcinogenic.¹¹ Another possible source of the idea that SLS is carcinogenic comes from its association with 1,4-dioxane, a by-product of the synthesis of certain sulfates such as sodium laureth sulfate due to a process known as ethoxylation.^6,12 Although SLS does not undergo this process in its formation and is not linked to 1,4-dioxane, there is potential for cross-contamination of SLS with 1,4-dioxane, which cannot be overlooked. 1,4-Dioxane is classified as “possibly carcinogenic to humans (Group 2B)” by the International Agency for Research on Cancer,¹³ but screening of SLS for this substance prior to its use in commercial products is standard.

Sulfates are inexpensive detergents that are responsible for lather formation in shampoos as well as in many household cleaning agents.⁵ Sulfates, similar to all anionic surfactants, are characterized by a negatively charged hydrophilic polar group. The best-known and most commonly used anionic surfactants are sulfated fatty alcohols, alkyl sulfates, and their polyethoxylated analogues alkyl ether sulfates.^5,6 Sodium lauryl sulfate (also known as sodium laurilsulfate or sodium dodecyl sulfate) is the most common of them all, found in shampoo and conditioner formulations. Ammonium lauryl sulfate and sodium laureth sulfate are other sulfates commonly used in shampoos and household cleansing products. Sodium lauryl sulfate is a nonvolatile, water-soluble compound. Its partition coefficient (P₀), a measure of a substance’s hydrophilic or lipophilic nature, is low at 1.6, making it a rather hydrophilic substance.⁶ Hydrophilic substances tend to have low bioaccumulation profiles in the body. Additionally, SLS is readily biodegradable. It can be derived from both synthetic and naturally occurring sources; for example, palm kernel oil, petrolatum, and coconut oil are all sources of lauric acid, the starting ingredient used to synthesize SLS. Sodium lauryl sulfate is created by reacting lauryl alcohol with sulfur trioxide gas, followed by neutralization with sodium carbonate (also a naturally occurring compound).⁶ Sodium lauryl sulfate and other sulfate-containing shampoos widely replaced the usage of traditional soaps formulated from animal or vegetable fats, as these latter formations created a film of insoluble calcium salts on the hair strands upon contact with water, resulting in tangled, dull-appearing hair.⁵ Additionally, sulfates were preferred to the alkaline pH of traditional soap, which can be harsh on hair strands and cause irritation of the skin and mucous membranes.¹⁴ Because they are highly water soluble, sulfates enable the formulation of clear shampoos. They exhibit remarkable cleaning properties and lather formation.^5,14

Because sulfates are potent surfactants, they can remove dirt and debris as well as naturally produced healthy oils from the hair and scalp. As a result, sulfates can leave the hair feeling dry and stripped of moisture.^4,5 Sulfates are used as the primary detergents in the formulation of deep-cleaning shampoos, which are designed for people who accumulate a heavy buildup of dirt, sebum, and debris from frequent use of styling products. Due to their potent detergency, these shampoos typically are not used on a daily basis but rather at longer intervals.¹⁵ A downside to sulfates is that they can have cosmetically unpleasant properties, which can be compensated for by including appropriate softening additives in shampoo formulations.⁴ A number of anionic surfactants such as olefin sulfonate, alkyl sulfosuccinate, acyl peptides, and alkyl ether carboxylates are well tolerated by the skin and are used together with other anionic and amphoteric surfactants to optimize shampoo properties. Alternatively, sulfate-free shampoos are cleansers compounded by the removal of the anionic group and switched for surfactants with less detergency.^4,5

Preservatives and Parabens

Parabens refer to a group of esters of 4-hydroxybenzoic acid commonly used as preservatives in foods, pharmaceuticals, and cosmetics whose widespread use dates back to 1923.¹⁶ Concerns over the presence of parabens in shampoos and other cosmetics have been raised by patients for their reputed estrogenic and antiandrogenic effects and suspected involvement in carcinogenesis via endocrine modulation.^16,17 In in vitro studies done on yeast assays, parabens have shown weak estrogenic activity that increases in proportion to both the length and increased branching of the alkyl side chains in the paraben’s molecular structure.¹⁸ They are 10,000-fold less potent than 17β-estradiol. In in vivo animal studies, parabens show weak estrogenic activity and are 100,000-fold less potent than 17β-estradiol.¹⁸ 4-Hydroxybenzoic acid, a common metabolite, showed no estrogenic activity when tested both in vitro and in vivo.¹⁹ Some concerning research has implicated a link between parabens used in underarm cosmetics, such as deodorants and antiperspirants, and breast cancer¹⁶; however, the studies have been conflicting, and there is simply not enough data to assert that parabens cause breast cancer.

The Cosmetic Ingredient Review expert panel first reviewed parabens in 1984 and concluded that “methylparaben, ethylparaben, propylparaben, and butylparaben are safe as cosmetic ingredients in the present practices of use.”²⁰ They extended this statement to include isopropylparaben and isobutylparaben in a later review.²¹ In 2005, the Scientific Committee on Consumer Products (now known as the Scientific Committee for Consumer Safety) in Europe stated that methylparaben and ethylparaben can be used at levels up to 0.4% in products.²² This decision was reached due to reports of decreased sperm counts and testosterone levels in male juvenile rats exposed to these parabens; however, these reults were not successfully replicated in larger studies.^16,22 In 2010, the Scientific Committee for Consumer Safety revisited its stance on parabens, and they then revised their recommendations to say that concentrations of propylparaben and butylparaben should not exceed concentrations of 0.19%, based on “the conservative choice for the calculation of the [Margin-of-Safety] of butyl- and propylparaben.”²³ However, in 2011 the use of propylparaben and butylparaben was banned in Denmark for cosmetic products used in children 3 years or younger,¹⁶ and the European Commission subsequently amended their directive in 2014, banning isopropylparaben, isobutylparaben, phenylparaben, benzylparaben, and pentylparaben due to lack of data available to evaluate the human risk of these products.²⁴

Contrary to the trends in Europe, there currently are no regulations against the use of parabens in shampoos or other cosmetics in the United States. The American Cancer Society found that there is no evidence to suggest that the current levels of parabens in cosmetic products (eg, antiperspirants) increase one’s risk of breast cancer.²⁵ Parabens are readily absorbed into the body both transdermally and through ingestion but also are believed to be rapidly transformed into harmless and nonspecific metabolites; they are readily metabolized by the liver and excreted in urine, and there is no measured accumulation in tissues.¹⁷

Parabens continue to be the most widely used preservatives in personal care products, usually in conjunction with other preservatives. Parabens are good biocides; short-chain esters (eg, methylparabens, ethylparabens) are effective against gram-positive bacteria and are weakly effective against gram-negative bacteria. Long-chain paraben esters (eg, propylparabens, butylparabens) are effective against mold and yeast. The addition of other preservatives creates a broad spectrum of antimicrobial defense in consumer products. Other preservatives include formaldehyde releasers or phenoxyethanol, as well as chelating agents such as EDTA, which improve the stability of these cosmetic products when exposed to air.¹⁶ Parabens are naturally occurring substances found in foods such as blueberries, barley, strawberries, yeast, olives, and grapes. As a colorless, odorless, and inexpensive substance, their use has been heavily favored in cosmetic and food products.¹⁶

Shampoo Alternatives and the No-Poo Method

Although research has not demonstrated any long-term danger to using shampoo, certain chemicals found in shampoos have the potential to irritate the scalp. Commonly cited allergens in shampoos include cocamidopropyl betaine, propylene glycol, vitamin E (tocopherol), parabens, and benzophenones.⁵ Additionally, the rising use of formaldehyde-releasing preservatives and isothiazolinones due to mounting pressures to move away from parabens has led to an increase in cases of allergic contact dermatitis (ACD).¹⁶ However, the irritability (rather than allergenicity) of these substances often is established during patch testing, a method of detecting delayed-type allergic reactions, which is important to note because patch testing requires a substance to be exposed to the skin for 24 to 48 hours, whereas exposure to shampoo ingredients may last a matter of minutes at most and occur in lesser concentrations because the ingredients are diluted by water in the rinsing process. Given these differences, it is unlikely that a patient would develop a true allergic response from regular shampoo use. Nevertheless, in patients who are already sensitized, exposure could conceivably trigger ACD, and patients must be cognizant of the composition of their shampoos.¹⁶

The no-poo method refers to the avoidance of commercial shampoo products when cleansing the hair and scalp and encompasses different methods of cleansing the hair, such as the use of household items (eg, baking soda, apple cider vinegar [ACV]), the use of conditioners to wash the hair (also known as conditioner-only washing or co-washing), treating the scalp with tea tree oil, or simply rinsing the hair with water. Proponents of the no-poo method believe that abstaining from shampoo use leads to healthier hair, retained natural oils, and less exposure to supposedly dangerous chemicals such as parabens or sulfates.^2,3,26-28 However, there are no known studies in the literature that assess or support the hypotheses of the no-poo method.

Baking Soda and ACV
Baking soda (sodium bicarbonate) is a substance commonly found in the average household. It has been used in toothpaste formulas and cosmetic products and is known for its acid-neutralizing properties. Baking soda has been shown to have some antifungal and viricidal properties through an unknown mechanism of action.²⁸ It has gained popularity for its use as a means of reducing the appearance of excessive greasiness of the hair shafts. Users also have reported that when washing their hair with baking soda, they are able to achieve a clean scalp and hair that feels soft to the touch.^2,3,26,27,29 Despite these reports, users must beware of using baking soda without adequately diluting it with water. Baking soda is a known alkaline irritant.^26,30 With a pH of 9, baking soda causes the cuticle layer of the hair fiber to open, increasing the capacity for water absorption. Water penetrates the scales that open, breaking the hydrogen bonds of the keratin molecule.³¹ Keratin is a spiral helical molecule that keeps its shape due to hydrogen, disulfide, and ionic bonds, as well as Van der Waals force.³⁰ Hydrolysis of these bonds due to exposure to baking soda lowers the elasticity of the hair and increases the negative electrical net charge of the hair fiber surface, which leads to increased friction between fibers, cuticle damage, hair fragility, and fiber breakage.^32,33

Apple cider vinegar is an apple-derived acetic acid solution with a pH ranging from 3.1 to 5.²⁸ The pH range of ACV is considered to be ideal for hair by no-poo proponents, as it is similar to the natural pH of the scalp. Its acidic properties are responsible for its antimicrobial abilities, particularly its effectiveness against gram-negative bacteria.³⁰ The acetic acid of ACV can partially interrupt oil interfaces, which contributes to its mild ability to remove product residue and scalp buildup from the hair shaft; the acetic acid also tightens the cuticles on hair fibers.³³ Apple cider vinegar is used as a means of cleansing the hair and scalp by no-poo proponents^2,3,26; other uses for ACV include using it as a rinse following washing and/or conditioning of the hair or as a means of preserving color in color-treated hair. There also is evidence that ACV may have antifungal properties.²⁸ However, consumers must be aware that if it is not diluted in water, ACV may be too caustic for direct application to the hair and may lead to damage; it can be irritating to eyes, mucus membranes, and acutely inflamed skin. Also, vinegar rinses used on processed or chemically damaged hair may lead to increased hair fragility.^2,3

Hair fibers have a pH of 3.67, while the scalp has a pH between 4.5 and 6.2. This slightly acidic film acts as a barrier to viruses, bacteria, and other potential contaminants.³³ Studies have shown that the pH of skin increases in proportion to the pH of the cleanser used.³⁴ Therefore, due to the naturally acidic pH of the scalp, acid-balanced shampoos generally are recommended. Shampoos should not have a pH higher than 5.5, as hair shafts can swell due to alkalinization, which can be prevented by pH balancing the shampoo through the addition of an acidic substance (eg, glycolic acid, citric acid) to lower the pH down to approximately 5.5. Apple cider vinegar often is used for this purpose. However, one study revealed that 82% of shampoos already have an acidic pH.³⁴

Conditioner-Only Washing (Co-washing)
Conditioner-only washing, or co-washing, is a widely practiced method of hair grooming. It is popular among individuals who find that commercial shampoos strip too much of the natural hair oils away, leaving the hair rough or unmanageable. Co-washing is not harmful to the hair; however, the molecular structure and function of a conditioner and that of a shampoo are very different.^5,35,36 Conditioners are not formulated to remove dirt and buildup in the hair but rather to add substances to the hair, and thus cannot provide extensive cleansing of the hair and scalp; therefore, it is inappropriate to use co-washing as a replacement for shampooing. Quaternary conditioning agents are an exception because they contain amphoteric detergents comprised of both anionic and cationic groups, which allow them both the ability to remove dirt and sebum with its anionic group, typically found in shampoos, as well as the ability to coat and condition the hair due to the high affinity of the cationic group for the negatively charged hair fibers.^36,37 Amphoteric detergents are commonly found in 2-in-1 conditioning cleansers, among other ingredients, such as hydrolyzed animal proteins that temporarily plug surface defects on the hair fiber, and dimethicone, a synthetic oil that creates a thin film over the hair shaft, increasing shine and manageability. Of note, these conditioning shampoos are ideal for individuals with minimal product buildup on the hair and scalp and are not adequate scalp cleansers for individuals who either wash their hair infrequently or who regularly use hairstyling products.^36,37

Tea Tree Oil
Tea tree oil is an essential oil extracted from the Melaleuca alternifolia plant of the Myrtaceae family. It is native to the coast of northeastern Australia. A holy grail of natural cosmetics, tea tree oil is widely known for its antiviral, antifungal, and antiseptic properties.³⁸ Although not used as a stand-alone cleanser, it is often added to a number of cosmetic products, including shampoos and co-washes. Although deemed safe for topical use, it has been shown to be quite toxic when ingested. Symptoms of ingestion include nausea, vomiting, hallucinations, and coma. The common concern with tea tree oil is its ability to cause ACD. In particular, it is believed that the oxidation products of tea tree oil are allergenic rather than the tea tree oil itself. The evaluation of tea tree oil as a potential contact allergen has been quite difficult; it consists of more than 100 distinct compounds and is often mislabeled, or does not meet the guidelines of the International Organization for Standardization. Nonetheless, the prevalence of ACD due to tea tree oil is low (approximately 1.4%). Despite its low prevalence, tea tree oil should remain in the differential as an ACD-inducing agent. Patch testing with the patient’s supply of tea tree oil is advised when possible.³⁸

Conclusion

It is customary that the ingredients used in shampoos undergo periodic testing and monitoring to assure the safety of their use. Although it is encouraging that patients are proactive in their efforts to stay abreast of the literature, it is still important that cosmetic scientists, dermatologists, and other experts remain at the forefront of educating the public about these substances. Not doing so can result in the propagation of misinformation and unnecessary fears, which can lead to the adaptation of unhygienic or even unsafe hair care practices. As dermatologists, we must ensure that patients are educated about the benefits and hazards of off-label use of household ingredients to the extent that evidence-based medicine permits. Patients must be informed that not all synthetic substances are harmful, and likewise not all naturally occurring substances are safe.