There were fewer complications with outpatient unicompartmental knee arthroplasty in a freestanding ambulatory surgery center than in the hospital, according to a review from the University of Tennessee Campbell Clinic, Memphis.

“In carefully selected patients, the ASC [ambulatory surgery center] seems to be a safe alternative to the inpatient hospital setting,” concluded investigators led by led by Marcus Ford, MD, a Campbell Clinic orthopedic surgeon.

He and his colleagues have been doing outpatient unicompartmental knee arthroplasty (UKA) since 2009, and “based on the subjective success,” recently increased the number of total knee, hip, and shoulder arthroplasties performed in their ASC.

They wanted to make sure, however, that their impression of good outpatient UKA results was supported by the data, so they compared outcomes in 48 UKA patients treated at their ASC with 48 treated in the hospital. The operations were done by two surgeons using the same technique and same medial UKA implant.

“Naturally, surgeons select those patients who are deemed physically and mentally capable of succeeding with an accelerated discharge plan” for outpatient service, the investigators wrote. To address that potential selection bias, the team matched their subjects by age and comorbidities.

There was only one minor complication in the outpatient group, a superficial stitch abscess. No patient needed a second operation, and all went home the same day.

It was different on the inpatient side. The average length of stay was 2.9 days, and there were four major complications: a deep venous thrombosis, a pulmonary embolus, an acute postoperative infection, and a periprosthetic fracture. All four required hospital readmission, and two patients needed a second operation.

The report didn’t directly address the reasons for the differences, but Dr. Ford and colleagues did note that they “believe that the ASC allows the surgeon greater direct control of perioperative variables that can impact patient outcome.”

Patients were in their late 50s, on average, and there were more women than men in both groups. The mean American Society of Anesthesiologists physical status classification score was 1.94 and mean body mass index was 34.3 kg/m² in the outpatient group, compared with a mean physical status classification score of 2.08 and mean body mass index of 32.9 kg/m² in the inpatient group. The differences were not statistically significant.

No funding source was reported. The investigators did not report any disclosures.

[email protected]

SOURCE: Ford M et al. Orthop Clin North Am. 2020 Jan;51[1]:1-5. doi: 10.1016/j.ocl.2019.08.001

There were fewer complications with outpatient unicompartmental knee arthroplasty in a freestanding ambulatory surgery center than in the hospital, according to a review from the University of Tennessee Campbell Clinic, Memphis.

“In carefully selected patients, the ASC [ambulatory surgery center] seems to be a safe alternative to the inpatient hospital setting,” concluded investigators led by led by Marcus Ford, MD, a Campbell Clinic orthopedic surgeon.

He and his colleagues have been doing outpatient unicompartmental knee arthroplasty (UKA) since 2009, and “based on the subjective success,” recently increased the number of total knee, hip, and shoulder arthroplasties performed in their ASC.

They wanted to make sure, however, that their impression of good outpatient UKA results was supported by the data, so they compared outcomes in 48 UKA patients treated at their ASC with 48 treated in the hospital. The operations were done by two surgeons using the same technique and same medial UKA implant.

“Naturally, surgeons select those patients who are deemed physically and mentally capable of succeeding with an accelerated discharge plan” for outpatient service, the investigators wrote. To address that potential selection bias, the team matched their subjects by age and comorbidities.

There was only one minor complication in the outpatient group, a superficial stitch abscess. No patient needed a second operation, and all went home the same day.

It was different on the inpatient side. The average length of stay was 2.9 days, and there were four major complications: a deep venous thrombosis, a pulmonary embolus, an acute postoperative infection, and a periprosthetic fracture. All four required hospital readmission, and two patients needed a second operation.

The report didn’t directly address the reasons for the differences, but Dr. Ford and colleagues did note that they “believe that the ASC allows the surgeon greater direct control of perioperative variables that can impact patient outcome.”

Patients were in their late 50s, on average, and there were more women than men in both groups. The mean American Society of Anesthesiologists physical status classification score was 1.94 and mean body mass index was 34.3 kg/m² in the outpatient group, compared with a mean physical status classification score of 2.08 and mean body mass index of 32.9 kg/m² in the inpatient group. The differences were not statistically significant.

No funding source was reported. The investigators did not report any disclosures.

[email protected]

SOURCE: Ford M et al. Orthop Clin North Am. 2020 Jan;51[1]:1-5. doi: 10.1016/j.ocl.2019.08.001

There were fewer complications with outpatient unicompartmental knee arthroplasty in a freestanding ambulatory surgery center than in the hospital, according to a review from the University of Tennessee Campbell Clinic, Memphis.

“In carefully selected patients, the ASC [ambulatory surgery center] seems to be a safe alternative to the inpatient hospital setting,” concluded investigators led by led by Marcus Ford, MD, a Campbell Clinic orthopedic surgeon.

He and his colleagues have been doing outpatient unicompartmental knee arthroplasty (UKA) since 2009, and “based on the subjective success,” recently increased the number of total knee, hip, and shoulder arthroplasties performed in their ASC.

They wanted to make sure, however, that their impression of good outpatient UKA results was supported by the data, so they compared outcomes in 48 UKA patients treated at their ASC with 48 treated in the hospital. The operations were done by two surgeons using the same technique and same medial UKA implant.

“Naturally, surgeons select those patients who are deemed physically and mentally capable of succeeding with an accelerated discharge plan” for outpatient service, the investigators wrote. To address that potential selection bias, the team matched their subjects by age and comorbidities.

There was only one minor complication in the outpatient group, a superficial stitch abscess. No patient needed a second operation, and all went home the same day.

It was different on the inpatient side. The average length of stay was 2.9 days, and there were four major complications: a deep venous thrombosis, a pulmonary embolus, an acute postoperative infection, and a periprosthetic fracture. All four required hospital readmission, and two patients needed a second operation.

The report didn’t directly address the reasons for the differences, but Dr. Ford and colleagues did note that they “believe that the ASC allows the surgeon greater direct control of perioperative variables that can impact patient outcome.”

Patients were in their late 50s, on average, and there were more women than men in both groups. The mean American Society of Anesthesiologists physical status classification score was 1.94 and mean body mass index was 34.3 kg/m² in the outpatient group, compared with a mean physical status classification score of 2.08 and mean body mass index of 32.9 kg/m² in the inpatient group. The differences were not statistically significant.

No funding source was reported. The investigators did not report any disclosures.

[email protected]

SOURCE: Ford M et al. Orthop Clin North Am. 2020 Jan;51[1]:1-5. doi: 10.1016/j.ocl.2019.08.001

Over the years, there has been growing concern about the relationship between physicians and pharmaceutical companies. Many studies have demonstrated that pharmaceutical interactions and incentives can influence physicians’ prescribing habits.^1-3 As a result, many academic centers have adopted policies that attempt to limit the pharmaceutical industry’s influence on faculty and in-training physicians. Although these policies can vary greatly, they generally limit access of pharmaceutical representatives to providers and restrict pharmaceutical samples.^4,5 This policy shift has even been reported in private practice.⁶

At the heart of the matter is the question: What really influences physicians to write a prescription for a particular medication? Is it cost, efficacy, or representatives pushing a product? Prior studies illustrate that generic medications are equivalent to their brand-name counterparts. In fact, current regulations require no more than 5% to 7% difference in bioequivalence.^7-9 Although most generic medications are bioequivalent, it may not be universal.¹⁰

Garrison and Levin¹¹ distributed a survey to US-based prescribers in family practice, psychiatry, and internal medicine and found that prescribers deemed patient response and success as the highest priority when determining which drugs to prescribe. In contrast, drug representatives and free samples only slightly contributed.¹¹ Considering the minimum duration for efficacy of a medication such as an antidepressant vs a topical steroid, this pattern may differ with samples in dermatologic settings. Interestingly, another survey concluded that samples were associated with “sticky” prescribing habits, noting that physicians would prescribe a brand-name medication after using a sample, despite increased cost to the patient.¹² Further, it has been suggested that recipients of free samples may experience increased costs in the long run, which contrasts a stated goal of affordability to patients.^12,13

Physician interaction with pharmaceutical companies begins as early as medical school,¹⁴ with physicians reporting interactions as often as 4 times each month.^14-18 Interactions can include meetings with pharmaceutical representatives, sponsored meals, gifts, continuing medical education sponsorship, funding for travel, pharmaceutical representative speakers, research funding, and drug samples.³

A 2014 study reported that prescribing habits are influenced by the free drug samples provided by nongeneric pharmaceutical companies.¹⁹ Nationally, the number of brand-name and branded generic medications constitute 79% of prescriptions, yet together they only comprise 17% of medications prescribed at an academic medical clinic that does not provide samples. The number of medications with samples being prescribed by dermatologists increased by 15% over 9 years, which may correlate with the wider availability of medication samples, more specifically an increase in branded generic samples.¹⁹ This potential interaction is the reason why institutions question the current influence of pharmaceutical companies. Samples may appear convenient, allowing a patient to test the medication prior to committing; however, with brand-name samples being provided to the physician, he/she may become more inclined to prescribe the branded medication.^12,15,19-22 Because brand-name medications are more expensive than generic medications, this practice can increase the cost of health care.¹³ One study found that over 1 year, the overuse of nongeneric medications led to a loss of potential savings throughout 49 states, equating to $229 million just through Medicaid; interestingly, it was noted that in some states, a maximum reimbursement is set by Medicaid, regardless of whether the generic or branded medication is dispensed. The authors also noted variability in the potential savings by state, which may be a function of the state-by-state maximum reimbursements for certain medications.²³ Another study on oral combination medications estimated Medicare spending on branded drugs relative to the cost if generic combinations had been purchased instead. This study examined branded medications for which the active components were available as over-the-counter (OTC), generic, or same-class generic, and the authors estimated that $925 million could have been saved in 2016 by purchasing a generic substitute.²⁴ The overuse of nongeneric medications when generic alternatives are available becomes an issue that not only financially impacts patients but all taxpayers. However, this pattern may differ if limited only to dermatologic medications, which was not the focus of the prior studies.

To limit conflicts of interest in interactions with the pharmaceutical, medical device, and biotechnology industries, the University of South Florida (USF) Morsani College of Medicine (COM)(Tampa, Florida) implemented its own set of regulations that eliminated in-office pharmaceutical samples, in addition to other restrictions. This study aimed to investigate if there was a change in the prescribing habits of academic dermatologists after their medical school implemented these new policies.

We hypothesized that the number of brand-name drugs prescribed by physicians in the Department of Dermatology & Cutaneous Surgery would change following USF Morsani COM pharmaceutical policy changes. We sought to determine how physician prescribing practices within the Department of Dermatology & Cutaneous Surgery changed following USF Morsani COM pharmaceutical policy changes.

Methods

Data Collection
A retrospective review of medical records was conducted to investigate the effect of the USF Morsani COM pharmaceutical policy changes on physician prescribing practices within the Department of Dermatology & Cutaneous Surgery. Medical records of patients seen for common dermatology diagnoses before (January 1, 2010, to May 30, 2010) and after (August 1, 2011, to December 31, 2011) the pharmaceutical policy changes were reviewed, and all medications prescribed were recorded. Data were collected from medical records within the USF Health electronic medical record system and included visits with each of the department’s 3 attending dermatologists. The diagnoses included in the study—acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, and rosacea—were chosen because in-office samples were available. Prescribing data from the first 100 consecutive medical records were collected from each time period, and a medical record was included only if it contained at least 1 of the following diagnoses: acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, or rosacea. The assessment and plan of each progress note were reviewed, and the exact medication name and associated diagnosis were recorded for each prescription. Subsequently, each medication was reviewed and placed in 1 of 3 categories: brand name, generic, and OTC. The total number of prescriptions for each diagnosis (per visit/note); the specific number of brand, generic, and OTC medications prescribed (per visit/note); and the percentage of brand, generic, and OTC medications prescribed (per visit/note and per diagnosis in total) were calculated. To ensure only intended medications were included, each medication recorded in the medical record note was cross-referenced with the prescribed medication in the electronic medical record. The primary objective of this study was to capture the prescribing physician’s intent as proxied by the pattern of prescription. Thus, changes made in prescriptions after the initial plan—whether insurance related or otherwise—were not relevant to this investigation.

The data were collected to compare the percentage of brand vs generic or OTC prescriptions per diagnosis to see if there was a difference in the prescribing habits before and after the pharmaceutical policy changes. Of note, several other pieces of data were collected from each medical record, including age, race, class of insurance (ie, Medicare, Medicaid, private health maintenance organization, private preferred provider organization), subtype diagnoses, and whether the prescription was new or a refill. The information gathered from the written record on the assessment and plan was verified using prescriptions ordered in the Allscripts electronic record, and any difference was noted. No identifying information that could be used to easily identify study participants was recorded.

Differences in prescribing habits across diagnoses before and after the policy changes were ascertained using a Fisher exact test and were further assessed using a mixed effects ordinal logistic regression model that accounted for within-provider clustering and baseline patient characteristics. An ordinal model was chosen to recognize differences in average cost among brand-name, generic, and OTC medications.

Results

In total, 200 medical records were collected. For the period analyzed before the policy change, 252 brand-name medications were prescribed compared to 231 prescribed for the period analyzed after the policy changes. There was insufficient evidence of an overall difference in brand-name medications prescribed before and after the policy changes (P=.145; Fisher exact test)(Table 1). There also was insufficient evidence of an overall difference in generic prescriptions, which totaled 153 before and 134 after the policy changes (P=.872; Fisher exact test)(Table 2). Over-the-counter prescriptions totaled 49 before and 69 after the policy changes. There was insufficient evidence of an overall difference before and after the policy changes for OTC medications (P=.192; Fisher exact test)(Table 3).

The mixed effects ordinal logistic regression model for the dependent variable—prescription type (branded, generic, or OTC)—showed an odds ratio (OR) of 1.27 for prescribing habits before and after the policy changes (OR, 1.27; 95% confidence interval, 0.97-1.67; P=.08) after accounting for provider and baseline characteristics. Despite the P value exceeding the predefined significance level, the confidence interval suggests anywhere from a 3% decrease, no change, and up to a 67% increase in postpolicy odds relative to the prepolicy odds, with a point estimate of a 27% increase in postpolicy odds over prepolicy odds. As an observational study, this suggests moderate evidence of a change based on the odds after the policy change relative to the odds before implementation (Figure).

Comment

Although some medical institutions are diligently working to limit the potential influence pharmaceutical companies have on physician prescribing habits,^4,5,25 the effect on physician prescribing habits is only now being established.¹⁵ Prior studies^12,19,21 have found evidence that medication samples may lead to overuse of brand-name medications, but these findings do not hold true for the USF dermatologists included in this study, perhaps due to the difference in pharmaceutical company interactions or physicians maintaining prior prescription habits that were unrelated to the policy. Although this study focused on policy changes for in-office samples, prior studies either included other forms of interaction²¹ or did not include samples.²²

Pharmaceutical samples allow patients to try a medication before committing to a long-term course of treatment with a particular medication, which has utility for physicians and patients. Although brand-name prescriptions may cost more, a trial period may assist the patient in deciding whether the medication is worth purchasing. Furthermore, physicians may feel more comfortable prescribing a medication once the individual patient has demonstrated a benefit from the sample, which may be particularly true in a specialty such as dermatology in which many branded topical medications contain a different vehicle than generic formulations, resulting in notable variations in active medication delivery and efficacy. Given the higher cost of branded topical medications, proving efficacy in patients through samples can provide a useful tool to the physician to determine the need for a branded formulation.

The benefits described are subjective but should not be disregarded. Although Hurley et al¹⁹ found that the number of brand-name medications prescribed increases as more samples are given out, our study demonstrated that after eliminating medication samples, there was no significant difference in the percentage of brand-name medications prescribed compared to generic and OTC medications.

Physician education concerning the price of each brand-name medication prescribed in office may be one method of reducing the amount of such prescriptions. Physicians generally are uninformed of the cost of the medications being prescribed²⁶ and may not recognize the financial burden one medication may have compared to its alternative. However, educating physicians will empower them to make the conscious decision to prefer or not prefer a brand-name medication. With some generic medications shown to have a difference in bioequivalence compared to their brand-name counterparts, a physician may find more success prescribing the brand-name medications, regardless of pharmaceutical company influence, which is an alternative solution to policy changes that eliminate samples entirely. Although this study found insufficient evidence that removing samples decreases brand-name medication prescriptions, it is imperative that solutions are established to reduce the country’s increasing burden of medical costs.

Possible shortfalls of this study include the short period of time between which prepolicy data and postpolicy data were collected. It is possible that providers did not have enough time to adjust their prescribing habits or that providers would not have changed a prescribing pattern or preference simply because of a policy change. Future studies could allow a time period greater than 2 years to compare prepolicy and postpolicy prescribing habits, or a future study might make comparisons of prescriber patterns at different institutions that have different policies. Another possible shortfall is that providers and patients were limited to those at the Department of Dermatology & Cutaneous Surgery at the USF Morsani COM. Although this study has found insufficient evidence of a difference in prescribing habits, it may be beneficial to conduct a larger study that encompasses multiple academic institutions with similar policy changes. Most importantly, this study only investigated the influence of in-office pharmaceutical samples on prescribing patterns. This study did not look at the many other ways in which providers may be influenced by pharmaceutical companies, which likely is a significant confounding variable in this study. Continued additional studies that specifically examine other methods through which providers may be influenced would be helpful in further examining the many ways in which physician prescription habits are influenced.

Conclusion

Changes in pharmaceutical policy in 2011 at USF Morsani COM specifically banned in-office samples. The totality of evidence in this study shows modest observational evidence of a change in the postpolicy odds relative to prepolicy odds, but the data also are compatible with no change between prescribing habits before and after the policy changes. Further study is needed to fully understand this relationship.

Over the years, there has been growing concern about the relationship between physicians and pharmaceutical companies. Many studies have demonstrated that pharmaceutical interactions and incentives can influence physicians’ prescribing habits.^1-3 As a result, many academic centers have adopted policies that attempt to limit the pharmaceutical industry’s influence on faculty and in-training physicians. Although these policies can vary greatly, they generally limit access of pharmaceutical representatives to providers and restrict pharmaceutical samples.^4,5 This policy shift has even been reported in private practice.⁶

At the heart of the matter is the question: What really influences physicians to write a prescription for a particular medication? Is it cost, efficacy, or representatives pushing a product? Prior studies illustrate that generic medications are equivalent to their brand-name counterparts. In fact, current regulations require no more than 5% to 7% difference in bioequivalence.^7-9 Although most generic medications are bioequivalent, it may not be universal.¹⁰

Garrison and Levin¹¹ distributed a survey to US-based prescribers in family practice, psychiatry, and internal medicine and found that prescribers deemed patient response and success as the highest priority when determining which drugs to prescribe. In contrast, drug representatives and free samples only slightly contributed.¹¹ Considering the minimum duration for efficacy of a medication such as an antidepressant vs a topical steroid, this pattern may differ with samples in dermatologic settings. Interestingly, another survey concluded that samples were associated with “sticky” prescribing habits, noting that physicians would prescribe a brand-name medication after using a sample, despite increased cost to the patient.¹² Further, it has been suggested that recipients of free samples may experience increased costs in the long run, which contrasts a stated goal of affordability to patients.^12,13

Physician interaction with pharmaceutical companies begins as early as medical school,¹⁴ with physicians reporting interactions as often as 4 times each month.^14-18 Interactions can include meetings with pharmaceutical representatives, sponsored meals, gifts, continuing medical education sponsorship, funding for travel, pharmaceutical representative speakers, research funding, and drug samples.³

A 2014 study reported that prescribing habits are influenced by the free drug samples provided by nongeneric pharmaceutical companies.¹⁹ Nationally, the number of brand-name and branded generic medications constitute 79% of prescriptions, yet together they only comprise 17% of medications prescribed at an academic medical clinic that does not provide samples. The number of medications with samples being prescribed by dermatologists increased by 15% over 9 years, which may correlate with the wider availability of medication samples, more specifically an increase in branded generic samples.¹⁹ This potential interaction is the reason why institutions question the current influence of pharmaceutical companies. Samples may appear convenient, allowing a patient to test the medication prior to committing; however, with brand-name samples being provided to the physician, he/she may become more inclined to prescribe the branded medication.^12,15,19-22 Because brand-name medications are more expensive than generic medications, this practice can increase the cost of health care.¹³ One study found that over 1 year, the overuse of nongeneric medications led to a loss of potential savings throughout 49 states, equating to $229 million just through Medicaid; interestingly, it was noted that in some states, a maximum reimbursement is set by Medicaid, regardless of whether the generic or branded medication is dispensed. The authors also noted variability in the potential savings by state, which may be a function of the state-by-state maximum reimbursements for certain medications.²³ Another study on oral combination medications estimated Medicare spending on branded drugs relative to the cost if generic combinations had been purchased instead. This study examined branded medications for which the active components were available as over-the-counter (OTC), generic, or same-class generic, and the authors estimated that $925 million could have been saved in 2016 by purchasing a generic substitute.²⁴ The overuse of nongeneric medications when generic alternatives are available becomes an issue that not only financially impacts patients but all taxpayers. However, this pattern may differ if limited only to dermatologic medications, which was not the focus of the prior studies.

To limit conflicts of interest in interactions with the pharmaceutical, medical device, and biotechnology industries, the University of South Florida (USF) Morsani College of Medicine (COM)(Tampa, Florida) implemented its own set of regulations that eliminated in-office pharmaceutical samples, in addition to other restrictions. This study aimed to investigate if there was a change in the prescribing habits of academic dermatologists after their medical school implemented these new policies.

We hypothesized that the number of brand-name drugs prescribed by physicians in the Department of Dermatology & Cutaneous Surgery would change following USF Morsani COM pharmaceutical policy changes. We sought to determine how physician prescribing practices within the Department of Dermatology & Cutaneous Surgery changed following USF Morsani COM pharmaceutical policy changes.

Methods

Data Collection
A retrospective review of medical records was conducted to investigate the effect of the USF Morsani COM pharmaceutical policy changes on physician prescribing practices within the Department of Dermatology & Cutaneous Surgery. Medical records of patients seen for common dermatology diagnoses before (January 1, 2010, to May 30, 2010) and after (August 1, 2011, to December 31, 2011) the pharmaceutical policy changes were reviewed, and all medications prescribed were recorded. Data were collected from medical records within the USF Health electronic medical record system and included visits with each of the department’s 3 attending dermatologists. The diagnoses included in the study—acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, and rosacea—were chosen because in-office samples were available. Prescribing data from the first 100 consecutive medical records were collected from each time period, and a medical record was included only if it contained at least 1 of the following diagnoses: acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, or rosacea. The assessment and plan of each progress note were reviewed, and the exact medication name and associated diagnosis were recorded for each prescription. Subsequently, each medication was reviewed and placed in 1 of 3 categories: brand name, generic, and OTC. The total number of prescriptions for each diagnosis (per visit/note); the specific number of brand, generic, and OTC medications prescribed (per visit/note); and the percentage of brand, generic, and OTC medications prescribed (per visit/note and per diagnosis in total) were calculated. To ensure only intended medications were included, each medication recorded in the medical record note was cross-referenced with the prescribed medication in the electronic medical record. The primary objective of this study was to capture the prescribing physician’s intent as proxied by the pattern of prescription. Thus, changes made in prescriptions after the initial plan—whether insurance related or otherwise—were not relevant to this investigation.

The data were collected to compare the percentage of brand vs generic or OTC prescriptions per diagnosis to see if there was a difference in the prescribing habits before and after the pharmaceutical policy changes. Of note, several other pieces of data were collected from each medical record, including age, race, class of insurance (ie, Medicare, Medicaid, private health maintenance organization, private preferred provider organization), subtype diagnoses, and whether the prescription was new or a refill. The information gathered from the written record on the assessment and plan was verified using prescriptions ordered in the Allscripts electronic record, and any difference was noted. No identifying information that could be used to easily identify study participants was recorded.

Differences in prescribing habits across diagnoses before and after the policy changes were ascertained using a Fisher exact test and were further assessed using a mixed effects ordinal logistic regression model that accounted for within-provider clustering and baseline patient characteristics. An ordinal model was chosen to recognize differences in average cost among brand-name, generic, and OTC medications.

Results

In total, 200 medical records were collected. For the period analyzed before the policy change, 252 brand-name medications were prescribed compared to 231 prescribed for the period analyzed after the policy changes. There was insufficient evidence of an overall difference in brand-name medications prescribed before and after the policy changes (P=.145; Fisher exact test)(Table 1). There also was insufficient evidence of an overall difference in generic prescriptions, which totaled 153 before and 134 after the policy changes (P=.872; Fisher exact test)(Table 2). Over-the-counter prescriptions totaled 49 before and 69 after the policy changes. There was insufficient evidence of an overall difference before and after the policy changes for OTC medications (P=.192; Fisher exact test)(Table 3).

The mixed effects ordinal logistic regression model for the dependent variable—prescription type (branded, generic, or OTC)—showed an odds ratio (OR) of 1.27 for prescribing habits before and after the policy changes (OR, 1.27; 95% confidence interval, 0.97-1.67; P=.08) after accounting for provider and baseline characteristics. Despite the P value exceeding the predefined significance level, the confidence interval suggests anywhere from a 3% decrease, no change, and up to a 67% increase in postpolicy odds relative to the prepolicy odds, with a point estimate of a 27% increase in postpolicy odds over prepolicy odds. As an observational study, this suggests moderate evidence of a change based on the odds after the policy change relative to the odds before implementation (Figure).

Comment

Although some medical institutions are diligently working to limit the potential influence pharmaceutical companies have on physician prescribing habits,^4,5,25 the effect on physician prescribing habits is only now being established.¹⁵ Prior studies^12,19,21 have found evidence that medication samples may lead to overuse of brand-name medications, but these findings do not hold true for the USF dermatologists included in this study, perhaps due to the difference in pharmaceutical company interactions or physicians maintaining prior prescription habits that were unrelated to the policy. Although this study focused on policy changes for in-office samples, prior studies either included other forms of interaction²¹ or did not include samples.²²

Pharmaceutical samples allow patients to try a medication before committing to a long-term course of treatment with a particular medication, which has utility for physicians and patients. Although brand-name prescriptions may cost more, a trial period may assist the patient in deciding whether the medication is worth purchasing. Furthermore, physicians may feel more comfortable prescribing a medication once the individual patient has demonstrated a benefit from the sample, which may be particularly true in a specialty such as dermatology in which many branded topical medications contain a different vehicle than generic formulations, resulting in notable variations in active medication delivery and efficacy. Given the higher cost of branded topical medications, proving efficacy in patients through samples can provide a useful tool to the physician to determine the need for a branded formulation.

The benefits described are subjective but should not be disregarded. Although Hurley et al¹⁹ found that the number of brand-name medications prescribed increases as more samples are given out, our study demonstrated that after eliminating medication samples, there was no significant difference in the percentage of brand-name medications prescribed compared to generic and OTC medications.

Physician education concerning the price of each brand-name medication prescribed in office may be one method of reducing the amount of such prescriptions. Physicians generally are uninformed of the cost of the medications being prescribed²⁶ and may not recognize the financial burden one medication may have compared to its alternative. However, educating physicians will empower them to make the conscious decision to prefer or not prefer a brand-name medication. With some generic medications shown to have a difference in bioequivalence compared to their brand-name counterparts, a physician may find more success prescribing the brand-name medications, regardless of pharmaceutical company influence, which is an alternative solution to policy changes that eliminate samples entirely. Although this study found insufficient evidence that removing samples decreases brand-name medication prescriptions, it is imperative that solutions are established to reduce the country’s increasing burden of medical costs.

Possible shortfalls of this study include the short period of time between which prepolicy data and postpolicy data were collected. It is possible that providers did not have enough time to adjust their prescribing habits or that providers would not have changed a prescribing pattern or preference simply because of a policy change. Future studies could allow a time period greater than 2 years to compare prepolicy and postpolicy prescribing habits, or a future study might make comparisons of prescriber patterns at different institutions that have different policies. Another possible shortfall is that providers and patients were limited to those at the Department of Dermatology & Cutaneous Surgery at the USF Morsani COM. Although this study has found insufficient evidence of a difference in prescribing habits, it may be beneficial to conduct a larger study that encompasses multiple academic institutions with similar policy changes. Most importantly, this study only investigated the influence of in-office pharmaceutical samples on prescribing patterns. This study did not look at the many other ways in which providers may be influenced by pharmaceutical companies, which likely is a significant confounding variable in this study. Continued additional studies that specifically examine other methods through which providers may be influenced would be helpful in further examining the many ways in which physician prescription habits are influenced.

Conclusion

Changes in pharmaceutical policy in 2011 at USF Morsani COM specifically banned in-office samples. The totality of evidence in this study shows modest observational evidence of a change in the postpolicy odds relative to prepolicy odds, but the data also are compatible with no change between prescribing habits before and after the policy changes. Further study is needed to fully understand this relationship.

Over the years, there has been growing concern about the relationship between physicians and pharmaceutical companies. Many studies have demonstrated that pharmaceutical interactions and incentives can influence physicians’ prescribing habits.^1-3 As a result, many academic centers have adopted policies that attempt to limit the pharmaceutical industry’s influence on faculty and in-training physicians. Although these policies can vary greatly, they generally limit access of pharmaceutical representatives to providers and restrict pharmaceutical samples.^4,5 This policy shift has even been reported in private practice.⁶

At the heart of the matter is the question: What really influences physicians to write a prescription for a particular medication? Is it cost, efficacy, or representatives pushing a product? Prior studies illustrate that generic medications are equivalent to their brand-name counterparts. In fact, current regulations require no more than 5% to 7% difference in bioequivalence.^7-9 Although most generic medications are bioequivalent, it may not be universal.¹⁰

Garrison and Levin¹¹ distributed a survey to US-based prescribers in family practice, psychiatry, and internal medicine and found that prescribers deemed patient response and success as the highest priority when determining which drugs to prescribe. In contrast, drug representatives and free samples only slightly contributed.¹¹ Considering the minimum duration for efficacy of a medication such as an antidepressant vs a topical steroid, this pattern may differ with samples in dermatologic settings. Interestingly, another survey concluded that samples were associated with “sticky” prescribing habits, noting that physicians would prescribe a brand-name medication after using a sample, despite increased cost to the patient.¹² Further, it has been suggested that recipients of free samples may experience increased costs in the long run, which contrasts a stated goal of affordability to patients.^12,13

Physician interaction with pharmaceutical companies begins as early as medical school,¹⁴ with physicians reporting interactions as often as 4 times each month.^14-18 Interactions can include meetings with pharmaceutical representatives, sponsored meals, gifts, continuing medical education sponsorship, funding for travel, pharmaceutical representative speakers, research funding, and drug samples.³

A 2014 study reported that prescribing habits are influenced by the free drug samples provided by nongeneric pharmaceutical companies.¹⁹ Nationally, the number of brand-name and branded generic medications constitute 79% of prescriptions, yet together they only comprise 17% of medications prescribed at an academic medical clinic that does not provide samples. The number of medications with samples being prescribed by dermatologists increased by 15% over 9 years, which may correlate with the wider availability of medication samples, more specifically an increase in branded generic samples.¹⁹ This potential interaction is the reason why institutions question the current influence of pharmaceutical companies. Samples may appear convenient, allowing a patient to test the medication prior to committing; however, with brand-name samples being provided to the physician, he/she may become more inclined to prescribe the branded medication.^12,15,19-22 Because brand-name medications are more expensive than generic medications, this practice can increase the cost of health care.¹³ One study found that over 1 year, the overuse of nongeneric medications led to a loss of potential savings throughout 49 states, equating to $229 million just through Medicaid; interestingly, it was noted that in some states, a maximum reimbursement is set by Medicaid, regardless of whether the generic or branded medication is dispensed. The authors also noted variability in the potential savings by state, which may be a function of the state-by-state maximum reimbursements for certain medications.²³ Another study on oral combination medications estimated Medicare spending on branded drugs relative to the cost if generic combinations had been purchased instead. This study examined branded medications for which the active components were available as over-the-counter (OTC), generic, or same-class generic, and the authors estimated that $925 million could have been saved in 2016 by purchasing a generic substitute.²⁴ The overuse of nongeneric medications when generic alternatives are available becomes an issue that not only financially impacts patients but all taxpayers. However, this pattern may differ if limited only to dermatologic medications, which was not the focus of the prior studies.

To limit conflicts of interest in interactions with the pharmaceutical, medical device, and biotechnology industries, the University of South Florida (USF) Morsani College of Medicine (COM)(Tampa, Florida) implemented its own set of regulations that eliminated in-office pharmaceutical samples, in addition to other restrictions. This study aimed to investigate if there was a change in the prescribing habits of academic dermatologists after their medical school implemented these new policies.

We hypothesized that the number of brand-name drugs prescribed by physicians in the Department of Dermatology & Cutaneous Surgery would change following USF Morsani COM pharmaceutical policy changes. We sought to determine how physician prescribing practices within the Department of Dermatology & Cutaneous Surgery changed following USF Morsani COM pharmaceutical policy changes.

Methods

Data Collection
A retrospective review of medical records was conducted to investigate the effect of the USF Morsani COM pharmaceutical policy changes on physician prescribing practices within the Department of Dermatology & Cutaneous Surgery. Medical records of patients seen for common dermatology diagnoses before (January 1, 2010, to May 30, 2010) and after (August 1, 2011, to December 31, 2011) the pharmaceutical policy changes were reviewed, and all medications prescribed were recorded. Data were collected from medical records within the USF Health electronic medical record system and included visits with each of the department’s 3 attending dermatologists. The diagnoses included in the study—acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, and rosacea—were chosen because in-office samples were available. Prescribing data from the first 100 consecutive medical records were collected from each time period, and a medical record was included only if it contained at least 1 of the following diagnoses: acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, or rosacea. The assessment and plan of each progress note were reviewed, and the exact medication name and associated diagnosis were recorded for each prescription. Subsequently, each medication was reviewed and placed in 1 of 3 categories: brand name, generic, and OTC. The total number of prescriptions for each diagnosis (per visit/note); the specific number of brand, generic, and OTC medications prescribed (per visit/note); and the percentage of brand, generic, and OTC medications prescribed (per visit/note and per diagnosis in total) were calculated. To ensure only intended medications were included, each medication recorded in the medical record note was cross-referenced with the prescribed medication in the electronic medical record. The primary objective of this study was to capture the prescribing physician’s intent as proxied by the pattern of prescription. Thus, changes made in prescriptions after the initial plan—whether insurance related or otherwise—were not relevant to this investigation.

The data were collected to compare the percentage of brand vs generic or OTC prescriptions per diagnosis to see if there was a difference in the prescribing habits before and after the pharmaceutical policy changes. Of note, several other pieces of data were collected from each medical record, including age, race, class of insurance (ie, Medicare, Medicaid, private health maintenance organization, private preferred provider organization), subtype diagnoses, and whether the prescription was new or a refill. The information gathered from the written record on the assessment and plan was verified using prescriptions ordered in the Allscripts electronic record, and any difference was noted. No identifying information that could be used to easily identify study participants was recorded.

Differences in prescribing habits across diagnoses before and after the policy changes were ascertained using a Fisher exact test and were further assessed using a mixed effects ordinal logistic regression model that accounted for within-provider clustering and baseline patient characteristics. An ordinal model was chosen to recognize differences in average cost among brand-name, generic, and OTC medications.

Results

In total, 200 medical records were collected. For the period analyzed before the policy change, 252 brand-name medications were prescribed compared to 231 prescribed for the period analyzed after the policy changes. There was insufficient evidence of an overall difference in brand-name medications prescribed before and after the policy changes (P=.145; Fisher exact test)(Table 1). There also was insufficient evidence of an overall difference in generic prescriptions, which totaled 153 before and 134 after the policy changes (P=.872; Fisher exact test)(Table 2). Over-the-counter prescriptions totaled 49 before and 69 after the policy changes. There was insufficient evidence of an overall difference before and after the policy changes for OTC medications (P=.192; Fisher exact test)(Table 3).

The mixed effects ordinal logistic regression model for the dependent variable—prescription type (branded, generic, or OTC)—showed an odds ratio (OR) of 1.27 for prescribing habits before and after the policy changes (OR, 1.27; 95% confidence interval, 0.97-1.67; P=.08) after accounting for provider and baseline characteristics. Despite the P value exceeding the predefined significance level, the confidence interval suggests anywhere from a 3% decrease, no change, and up to a 67% increase in postpolicy odds relative to the prepolicy odds, with a point estimate of a 27% increase in postpolicy odds over prepolicy odds. As an observational study, this suggests moderate evidence of a change based on the odds after the policy change relative to the odds before implementation (Figure).

Comment

Although some medical institutions are diligently working to limit the potential influence pharmaceutical companies have on physician prescribing habits,^4,5,25 the effect on physician prescribing habits is only now being established.¹⁵ Prior studies^12,19,21 have found evidence that medication samples may lead to overuse of brand-name medications, but these findings do not hold true for the USF dermatologists included in this study, perhaps due to the difference in pharmaceutical company interactions or physicians maintaining prior prescription habits that were unrelated to the policy. Although this study focused on policy changes for in-office samples, prior studies either included other forms of interaction²¹ or did not include samples.²²

Pharmaceutical samples allow patients to try a medication before committing to a long-term course of treatment with a particular medication, which has utility for physicians and patients. Although brand-name prescriptions may cost more, a trial period may assist the patient in deciding whether the medication is worth purchasing. Furthermore, physicians may feel more comfortable prescribing a medication once the individual patient has demonstrated a benefit from the sample, which may be particularly true in a specialty such as dermatology in which many branded topical medications contain a different vehicle than generic formulations, resulting in notable variations in active medication delivery and efficacy. Given the higher cost of branded topical medications, proving efficacy in patients through samples can provide a useful tool to the physician to determine the need for a branded formulation.

The benefits described are subjective but should not be disregarded. Although Hurley et al¹⁹ found that the number of brand-name medications prescribed increases as more samples are given out, our study demonstrated that after eliminating medication samples, there was no significant difference in the percentage of brand-name medications prescribed compared to generic and OTC medications.

Physician education concerning the price of each brand-name medication prescribed in office may be one method of reducing the amount of such prescriptions. Physicians generally are uninformed of the cost of the medications being prescribed²⁶ and may not recognize the financial burden one medication may have compared to its alternative. However, educating physicians will empower them to make the conscious decision to prefer or not prefer a brand-name medication. With some generic medications shown to have a difference in bioequivalence compared to their brand-name counterparts, a physician may find more success prescribing the brand-name medications, regardless of pharmaceutical company influence, which is an alternative solution to policy changes that eliminate samples entirely. Although this study found insufficient evidence that removing samples decreases brand-name medication prescriptions, it is imperative that solutions are established to reduce the country’s increasing burden of medical costs.

Possible shortfalls of this study include the short period of time between which prepolicy data and postpolicy data were collected. It is possible that providers did not have enough time to adjust their prescribing habits or that providers would not have changed a prescribing pattern or preference simply because of a policy change. Future studies could allow a time period greater than 2 years to compare prepolicy and postpolicy prescribing habits, or a future study might make comparisons of prescriber patterns at different institutions that have different policies. Another possible shortfall is that providers and patients were limited to those at the Department of Dermatology & Cutaneous Surgery at the USF Morsani COM. Although this study has found insufficient evidence of a difference in prescribing habits, it may be beneficial to conduct a larger study that encompasses multiple academic institutions with similar policy changes. Most importantly, this study only investigated the influence of in-office pharmaceutical samples on prescribing patterns. This study did not look at the many other ways in which providers may be influenced by pharmaceutical companies, which likely is a significant confounding variable in this study. Continued additional studies that specifically examine other methods through which providers may be influenced would be helpful in further examining the many ways in which physician prescription habits are influenced.

Conclusion

Changes in pharmaceutical policy in 2011 at USF Morsani COM specifically banned in-office samples. The totality of evidence in this study shows modest observational evidence of a change in the postpolicy odds relative to prepolicy odds, but the data also are compatible with no change between prescribing habits before and after the policy changes. Further study is needed to fully understand this relationship.

A quick search for “antibacterial soap” on many online retailers’ websites will bring up dozens of products, some of which appear to contain an active ingredient that has been banned from the market.

copyright/kosziv/Thinkstock

The website of retail pharmacy giant Walgreens, for example, lists Dial Complete antibacterial soap with the active ingredient triclosan, a chemical the Food and Drug Administration banned along with others in 2017. The agency cited a lack of evidence that the ingredients were more effective than plain soap and water and that they were safe for long-term daily use.

A Dial Complete soap product page on Walgreens’ website lists, as of Feb. 4, 2020, an ingredient that was banned by the FDA.

Yet banned substances such as the triclosan in this Dial soap still commonly appear on online product descriptions, researchers found after searching the National Drug Code Directory and the websites of major online retailers, including Amazon, Walmart, and Target. The health effects of antibacterial ingredients “are very poorly defined,” said Chandler Rundle, MD, first author of the study, which was published in Dermatitis. Dr. Rundle is with the department of dermatology at the University of Colorado at Denver, Aurora.

The label on the back of the Dial soap bottle sold on Walgreens.com states that it “[k]ills more bacteria than ordinary liquid hand soap.” The website displays a close-up graphic of a hand that has been washed with Dial soap and that has fewer bacteria than a hand washed with “Others.” The graphic includes a dramatization disclaimer.

When asked about the product, a Walgreens corporate relations spokesperson checked the soap’s ingredients list they had on file from Dial’s parent company, Henkel North American Consumer Goods.

“I did not see that particular ingredient,” the representative said. Their ingredients list reflected a version of the soap that was updated after the ban. That label differs from Walgreens.com’s product information. The updated, ban-compliant version of the soap contains an alternative antibacterial compound, benzalkonium chloride. The spokesperson wasn’t sure of the source of the incorrect information on the website. Dial did not respond to a request for comment.

The ingredients list for Dial Complete soap on Walgreens.com shows FDA-banned triclosan as the active ingredient.

The 2017 FDA ban restricted the marketing of triclosan and triclocarban along with 17 other ingredients in consumer antibacterial soaps because manufacturers did not provide sufficient data to demonstrate that the ingredients were safe and effective, according to the FDA’s announcement. Independent research also showed that some ingredients worked no better than traditional soap and could create antibacterial-resistant microbes. Regular hand soap “still kills bacteria,” Dr. Rundle said. “The inclusion of an antibacterial substance does not make it better.”

Retailers (such as Walgreens) aren’t required to update their products’ online ingredient lists, which can pose a challenge for people who suffer from skin allergies, said Dr. Rundle. People at risk of having a reaction must read labels to verify the ingredients that are included.

Consumer antibacterial soap products that contain the banned compounds have largely been replaced with stand-ins, such as benzalkonium chloride and chloroxylenol, according to Dr. Rundle’s study. He and other researchers are trying to determine whether those compounds have the same shortcomings. “We’re talking 10-20 years down the line, and we’re worried about things like antibacterial resistance and systemic effects,” Dr. Rundle said.

The FDA has considered a ban on benzalkonium chloride and additional antibacterial ingredients, but in 2016, it granted ban deferrals, pending more research. The agency exchanged letters with the American Cleaning Institute (ACI), a trade association that represents companies, including Henkel. The FDA required that its companies fund research to show that the new antibacterial ingredients are safe and effective. The FDA granted subsequent annual extensions in 2017, 2018, and, most recently, in August 2019 to allow continued research into whether several ingredients are effective in soaps. In its most recent letter to the ACI, the FDA gave a checklist of research tasks to be submitted by July 2020.

The letter from August 2019 stated that the ACI, in its March 2019 progress report, failed to address milestones in studies of health care personnel handwashing for two of the substances. It also referenced the ACI’s lack of funding for the studies and reminded the organization that further deferrals would not be granted unless the ACI can show ongoing progress.

The ACI plans to meet with the FDA to have an in-depth discussion, Brian Sansoni, a spokesperson for the ACI, told Medscape Medical News. The ACI plans to give the FDA data that show the effectiveness of these ingredients over the course of several years, “due to the complexity of what FDA is asking for,” Mr. Sansoni said. “We’re working as diligently as possible to meet FDA requests.”
 

This article first appeared on Medscape.com.

A quick search for “antibacterial soap” on many online retailers’ websites will bring up dozens of products, some of which appear to contain an active ingredient that has been banned from the market.

copyright/kosziv/Thinkstock

The website of retail pharmacy giant Walgreens, for example, lists Dial Complete antibacterial soap with the active ingredient triclosan, a chemical the Food and Drug Administration banned along with others in 2017. The agency cited a lack of evidence that the ingredients were more effective than plain soap and water and that they were safe for long-term daily use.

A Dial Complete soap product page on Walgreens’ website lists, as of Feb. 4, 2020, an ingredient that was banned by the FDA.

Yet banned substances such as the triclosan in this Dial soap still commonly appear on online product descriptions, researchers found after searching the National Drug Code Directory and the websites of major online retailers, including Amazon, Walmart, and Target. The health effects of antibacterial ingredients “are very poorly defined,” said Chandler Rundle, MD, first author of the study, which was published in Dermatitis. Dr. Rundle is with the department of dermatology at the University of Colorado at Denver, Aurora.

The label on the back of the Dial soap bottle sold on Walgreens.com states that it “[k]ills more bacteria than ordinary liquid hand soap.” The website displays a close-up graphic of a hand that has been washed with Dial soap and that has fewer bacteria than a hand washed with “Others.” The graphic includes a dramatization disclaimer.

When asked about the product, a Walgreens corporate relations spokesperson checked the soap’s ingredients list they had on file from Dial’s parent company, Henkel North American Consumer Goods.

“I did not see that particular ingredient,” the representative said. Their ingredients list reflected a version of the soap that was updated after the ban. That label differs from Walgreens.com’s product information. The updated, ban-compliant version of the soap contains an alternative antibacterial compound, benzalkonium chloride. The spokesperson wasn’t sure of the source of the incorrect information on the website. Dial did not respond to a request for comment.

The ingredients list for Dial Complete soap on Walgreens.com shows FDA-banned triclosan as the active ingredient.

The 2017 FDA ban restricted the marketing of triclosan and triclocarban along with 17 other ingredients in consumer antibacterial soaps because manufacturers did not provide sufficient data to demonstrate that the ingredients were safe and effective, according to the FDA’s announcement. Independent research also showed that some ingredients worked no better than traditional soap and could create antibacterial-resistant microbes. Regular hand soap “still kills bacteria,” Dr. Rundle said. “The inclusion of an antibacterial substance does not make it better.”

Retailers (such as Walgreens) aren’t required to update their products’ online ingredient lists, which can pose a challenge for people who suffer from skin allergies, said Dr. Rundle. People at risk of having a reaction must read labels to verify the ingredients that are included.

Consumer antibacterial soap products that contain the banned compounds have largely been replaced with stand-ins, such as benzalkonium chloride and chloroxylenol, according to Dr. Rundle’s study. He and other researchers are trying to determine whether those compounds have the same shortcomings. “We’re talking 10-20 years down the line, and we’re worried about things like antibacterial resistance and systemic effects,” Dr. Rundle said.

The FDA has considered a ban on benzalkonium chloride and additional antibacterial ingredients, but in 2016, it granted ban deferrals, pending more research. The agency exchanged letters with the American Cleaning Institute (ACI), a trade association that represents companies, including Henkel. The FDA required that its companies fund research to show that the new antibacterial ingredients are safe and effective. The FDA granted subsequent annual extensions in 2017, 2018, and, most recently, in August 2019 to allow continued research into whether several ingredients are effective in soaps. In its most recent letter to the ACI, the FDA gave a checklist of research tasks to be submitted by July 2020.

The letter from August 2019 stated that the ACI, in its March 2019 progress report, failed to address milestones in studies of health care personnel handwashing for two of the substances. It also referenced the ACI’s lack of funding for the studies and reminded the organization that further deferrals would not be granted unless the ACI can show ongoing progress.

The ACI plans to meet with the FDA to have an in-depth discussion, Brian Sansoni, a spokesperson for the ACI, told Medscape Medical News. The ACI plans to give the FDA data that show the effectiveness of these ingredients over the course of several years, “due to the complexity of what FDA is asking for,” Mr. Sansoni said. “We’re working as diligently as possible to meet FDA requests.”
 

This article first appeared on Medscape.com.

A quick search for “antibacterial soap” on many online retailers’ websites will bring up dozens of products, some of which appear to contain an active ingredient that has been banned from the market.

copyright/kosziv/Thinkstock

The website of retail pharmacy giant Walgreens, for example, lists Dial Complete antibacterial soap with the active ingredient triclosan, a chemical the Food and Drug Administration banned along with others in 2017. The agency cited a lack of evidence that the ingredients were more effective than plain soap and water and that they were safe for long-term daily use.

A Dial Complete soap product page on Walgreens’ website lists, as of Feb. 4, 2020, an ingredient that was banned by the FDA.

Yet banned substances such as the triclosan in this Dial soap still commonly appear on online product descriptions, researchers found after searching the National Drug Code Directory and the websites of major online retailers, including Amazon, Walmart, and Target. The health effects of antibacterial ingredients “are very poorly defined,” said Chandler Rundle, MD, first author of the study, which was published in Dermatitis. Dr. Rundle is with the department of dermatology at the University of Colorado at Denver, Aurora.

The label on the back of the Dial soap bottle sold on Walgreens.com states that it “[k]ills more bacteria than ordinary liquid hand soap.” The website displays a close-up graphic of a hand that has been washed with Dial soap and that has fewer bacteria than a hand washed with “Others.” The graphic includes a dramatization disclaimer.

When asked about the product, a Walgreens corporate relations spokesperson checked the soap’s ingredients list they had on file from Dial’s parent company, Henkel North American Consumer Goods.

“I did not see that particular ingredient,” the representative said. Their ingredients list reflected a version of the soap that was updated after the ban. That label differs from Walgreens.com’s product information. The updated, ban-compliant version of the soap contains an alternative antibacterial compound, benzalkonium chloride. The spokesperson wasn’t sure of the source of the incorrect information on the website. Dial did not respond to a request for comment.

The ingredients list for Dial Complete soap on Walgreens.com shows FDA-banned triclosan as the active ingredient.

The 2017 FDA ban restricted the marketing of triclosan and triclocarban along with 17 other ingredients in consumer antibacterial soaps because manufacturers did not provide sufficient data to demonstrate that the ingredients were safe and effective, according to the FDA’s announcement. Independent research also showed that some ingredients worked no better than traditional soap and could create antibacterial-resistant microbes. Regular hand soap “still kills bacteria,” Dr. Rundle said. “The inclusion of an antibacterial substance does not make it better.”

Retailers (such as Walgreens) aren’t required to update their products’ online ingredient lists, which can pose a challenge for people who suffer from skin allergies, said Dr. Rundle. People at risk of having a reaction must read labels to verify the ingredients that are included.

Consumer antibacterial soap products that contain the banned compounds have largely been replaced with stand-ins, such as benzalkonium chloride and chloroxylenol, according to Dr. Rundle’s study. He and other researchers are trying to determine whether those compounds have the same shortcomings. “We’re talking 10-20 years down the line, and we’re worried about things like antibacterial resistance and systemic effects,” Dr. Rundle said.

The FDA has considered a ban on benzalkonium chloride and additional antibacterial ingredients, but in 2016, it granted ban deferrals, pending more research. The agency exchanged letters with the American Cleaning Institute (ACI), a trade association that represents companies, including Henkel. The FDA required that its companies fund research to show that the new antibacterial ingredients are safe and effective. The FDA granted subsequent annual extensions in 2017, 2018, and, most recently, in August 2019 to allow continued research into whether several ingredients are effective in soaps. In its most recent letter to the ACI, the FDA gave a checklist of research tasks to be submitted by July 2020.

The letter from August 2019 stated that the ACI, in its March 2019 progress report, failed to address milestones in studies of health care personnel handwashing for two of the substances. It also referenced the ACI’s lack of funding for the studies and reminded the organization that further deferrals would not be granted unless the ACI can show ongoing progress.

The ACI plans to meet with the FDA to have an in-depth discussion, Brian Sansoni, a spokesperson for the ACI, told Medscape Medical News. The ACI plans to give the FDA data that show the effectiveness of these ingredients over the course of several years, “due to the complexity of what FDA is asking for,” Mr. Sansoni said. “We’re working as diligently as possible to meet FDA requests.”
 

This article first appeared on Medscape.com.

Serum levels of neurofilament light (NfL) are elevated as long as 6 years before the clinical onset of multiple sclerosis (MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.

Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
 

Researchers compared presymptomatic and symptomatic samples

With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.

Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.

Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
 

Levels were higher in cases than in controls

About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.

For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.

In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
 

Population included few women

“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.

The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.

The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.

[email protected]

SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.

Serum levels of neurofilament light (NfL) are elevated as long as 6 years before the clinical onset of multiple sclerosis (MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.

Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
 

Researchers compared presymptomatic and symptomatic samples

With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.

Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.

Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
 

Levels were higher in cases than in controls

About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.

For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.

In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
 

Population included few women

“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.

The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.

The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.

[email protected]

SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.

Serum levels of neurofilament light (NfL) are elevated as long as 6 years before the clinical onset of multiple sclerosis (MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.

Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
 

Researchers compared presymptomatic and symptomatic samples

With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.

Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.

Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
 

Levels were higher in cases than in controls

About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.

For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.

In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
 

Population included few women

“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.

The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.

The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.

[email protected]

SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.

There were no major adverse reactions to CRISPR-engineered T cells in three patients with advanced cancer enrolled in a first-in-human trial, according to a report in Science.

[email protected]

SOURCE: Stadtmauer EA et al. Science. 2020 Feb 6. doi: 10.1126/science.aba7365.

There were no major adverse reactions to CRISPR-engineered T cells in three patients with advanced cancer enrolled in a first-in-human trial, according to a report in Science.

[email protected]

SOURCE: Stadtmauer EA et al. Science. 2020 Feb 6. doi: 10.1126/science.aba7365.

There were no major adverse reactions to CRISPR-engineered T cells in three patients with advanced cancer enrolled in a first-in-human trial, according to a report in Science.

[email protected]

SOURCE: Stadtmauer EA et al. Science. 2020 Feb 6. doi: 10.1126/science.aba7365.

A study of lung cancer in younger adults (less than 50 years) has found a recent trend of higher lung cancer rates in women, compared with men. The increase is driven by cases of adenocarcinoma of the lung.

The “emerging pattern of higher lung cancer incidence in young females” is not confined to geographic areas and income levels and “is not fully explained by sex-differences in smoking prevalence,” the authors comment.

Miranda M. Fidler-Benaoudia, PhD, Cancer Control Alberta, Alberta Health Services, Calgary, and colleagues examined lung cancer cases in 40 countries from 1993 to 2012.

They found that the female-to-male incidence rate ratio (IRR) had significantly crossed over from men to women in six countries, including the United States and Canada, and had nonsignificantly crossed over in a further 23 countries.

The research was published online Feb. 5 in the International Journal of Cancer.

These findings “forewarn of a higher lung cancer burden in women than men at older ages in the decades to follow, especially in higher-income settings,” write the authors. They highlight “the need for etiologic studies.”

Historically, lung cancer higher in men

Historically, lung cancer rates have been higher among men than women, owing to the fact that men start smoking in large numbers earlier and smoke at higher rates, the researchers comment.

However, there has been a convergence in lung cancer incidence between men and women. A recent study suggests that, in the United States, the incidence in young women is higher than that in their male counterparts.

To determine the degree to which this phenomenon is occurring globally, the team used national or subnational registry data from Cancer Incidence in Five Continents, volumes VIII–XI.

These included lung and bronchial cancer cases in 40 countries from 1993 to 2012, divided into 5-year periods. Individuals were categorized into 5-year age bands.

In addition, the team used the Global Health Data Exchange to extract data from the Global Burden of Disease Study 2015 and derive country- and sex-specific daily smoking prevalence rates.

The researchers found that among young men and women, there were three patterns in the occurrence of lung cancer between the periods 1993-1997 and 2008-2012:

• A significant crossover from male to female dominance, seen in six countries.
• An insignificant crossover from male to female dominance, found in 23 countries.
• A continued male dominance, observed in 11 countries.

Higher incidence in women in six countries

The six countries with significant crossover from male to female dominance were Canada, Denmark, Germany, New Zealand, the Netherlands, and the United States.

Further analysis showed that, in general, age-specific lung cancer incidence rates decreased in successive male birth cohorts in these six countries. There was more variation across female birth cohorts.

Calculating female-to-male incidence rate ratios, the team found, for example, the IRR increased in New Zealand from 1.0 in the 1953 birth cohort to 1.6 in the 1968 birth cohort for people aged 40-44 years.

In addition, among adults aged 45-49 years in the Netherlands, the IRR rose from 0.7 in those born in the circa 1948 cohort to 1.4 in those from the circa 1958 cohort.

Overall, female-to-male IRRs increased notably among the following groups:

• Individuals aged 30-34 years in Canada, Denmark, and Germany.
• Those aged 40-44 years in Germany, the Netherlands, and the United States.
• Those aged 44-50 years in the Netherlands and the United States.
• Those aged 50-54 years in Canada, Denmark, and New Zealand.

Countries with an insignificant crossover from male to female dominance of lung cancer were located across Africa, the Americas, Asia, Europe, and Oceania.

Again, incidence rates were typically characterized by falling rates of lung cancer among men in more recent birth cohorts, and lung cancer incidence trends were more variable in women.

The team writes: “Of note, the six countries demonstrating a significant crossover are among those considered to be more advanced in the tobacco epidemic.

“Many of the countries where the crossover was insignificant or when there was no crossover are considered to be late adopters of the tobacco epidemic, with the effects of the epidemic on the burden of lung cancer and other smoking-related diseases beginning to manifest more recently, or perhaps yet to come.”

They suggest that low- and middle-resource countries may not follow the tobacco epidemic pattern of high-income countries, and so “we may not see higher lung cancer incidence rates in women than men for the foreseeable future in these countries.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A study of lung cancer in younger adults (less than 50 years) has found a recent trend of higher lung cancer rates in women, compared with men. The increase is driven by cases of adenocarcinoma of the lung.

The “emerging pattern of higher lung cancer incidence in young females” is not confined to geographic areas and income levels and “is not fully explained by sex-differences in smoking prevalence,” the authors comment.

Miranda M. Fidler-Benaoudia, PhD, Cancer Control Alberta, Alberta Health Services, Calgary, and colleagues examined lung cancer cases in 40 countries from 1993 to 2012.

They found that the female-to-male incidence rate ratio (IRR) had significantly crossed over from men to women in six countries, including the United States and Canada, and had nonsignificantly crossed over in a further 23 countries.

The research was published online Feb. 5 in the International Journal of Cancer.

These findings “forewarn of a higher lung cancer burden in women than men at older ages in the decades to follow, especially in higher-income settings,” write the authors. They highlight “the need for etiologic studies.”

Historically, lung cancer higher in men

Historically, lung cancer rates have been higher among men than women, owing to the fact that men start smoking in large numbers earlier and smoke at higher rates, the researchers comment.

However, there has been a convergence in lung cancer incidence between men and women. A recent study suggests that, in the United States, the incidence in young women is higher than that in their male counterparts.

To determine the degree to which this phenomenon is occurring globally, the team used national or subnational registry data from Cancer Incidence in Five Continents, volumes VIII–XI.

These included lung and bronchial cancer cases in 40 countries from 1993 to 2012, divided into 5-year periods. Individuals were categorized into 5-year age bands.

In addition, the team used the Global Health Data Exchange to extract data from the Global Burden of Disease Study 2015 and derive country- and sex-specific daily smoking prevalence rates.

The researchers found that among young men and women, there were three patterns in the occurrence of lung cancer between the periods 1993-1997 and 2008-2012:

• A significant crossover from male to female dominance, seen in six countries.
• An insignificant crossover from male to female dominance, found in 23 countries.
• A continued male dominance, observed in 11 countries.

Higher incidence in women in six countries

The six countries with significant crossover from male to female dominance were Canada, Denmark, Germany, New Zealand, the Netherlands, and the United States.

Further analysis showed that, in general, age-specific lung cancer incidence rates decreased in successive male birth cohorts in these six countries. There was more variation across female birth cohorts.

Calculating female-to-male incidence rate ratios, the team found, for example, the IRR increased in New Zealand from 1.0 in the 1953 birth cohort to 1.6 in the 1968 birth cohort for people aged 40-44 years.

In addition, among adults aged 45-49 years in the Netherlands, the IRR rose from 0.7 in those born in the circa 1948 cohort to 1.4 in those from the circa 1958 cohort.

Overall, female-to-male IRRs increased notably among the following groups:

• Individuals aged 30-34 years in Canada, Denmark, and Germany.
• Those aged 40-44 years in Germany, the Netherlands, and the United States.
• Those aged 44-50 years in the Netherlands and the United States.
• Those aged 50-54 years in Canada, Denmark, and New Zealand.

Countries with an insignificant crossover from male to female dominance of lung cancer were located across Africa, the Americas, Asia, Europe, and Oceania.

Again, incidence rates were typically characterized by falling rates of lung cancer among men in more recent birth cohorts, and lung cancer incidence trends were more variable in women.

The team writes: “Of note, the six countries demonstrating a significant crossover are among those considered to be more advanced in the tobacco epidemic.

“Many of the countries where the crossover was insignificant or when there was no crossover are considered to be late adopters of the tobacco epidemic, with the effects of the epidemic on the burden of lung cancer and other smoking-related diseases beginning to manifest more recently, or perhaps yet to come.”

They suggest that low- and middle-resource countries may not follow the tobacco epidemic pattern of high-income countries, and so “we may not see higher lung cancer incidence rates in women than men for the foreseeable future in these countries.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A study of lung cancer in younger adults (less than 50 years) has found a recent trend of higher lung cancer rates in women, compared with men. The increase is driven by cases of adenocarcinoma of the lung.

The “emerging pattern of higher lung cancer incidence in young females” is not confined to geographic areas and income levels and “is not fully explained by sex-differences in smoking prevalence,” the authors comment.

Miranda M. Fidler-Benaoudia, PhD, Cancer Control Alberta, Alberta Health Services, Calgary, and colleagues examined lung cancer cases in 40 countries from 1993 to 2012.

They found that the female-to-male incidence rate ratio (IRR) had significantly crossed over from men to women in six countries, including the United States and Canada, and had nonsignificantly crossed over in a further 23 countries.

The research was published online Feb. 5 in the International Journal of Cancer.

These findings “forewarn of a higher lung cancer burden in women than men at older ages in the decades to follow, especially in higher-income settings,” write the authors. They highlight “the need for etiologic studies.”

Historically, lung cancer higher in men

Historically, lung cancer rates have been higher among men than women, owing to the fact that men start smoking in large numbers earlier and smoke at higher rates, the researchers comment.

However, there has been a convergence in lung cancer incidence between men and women. A recent study suggests that, in the United States, the incidence in young women is higher than that in their male counterparts.

To determine the degree to which this phenomenon is occurring globally, the team used national or subnational registry data from Cancer Incidence in Five Continents, volumes VIII–XI.

These included lung and bronchial cancer cases in 40 countries from 1993 to 2012, divided into 5-year periods. Individuals were categorized into 5-year age bands.

In addition, the team used the Global Health Data Exchange to extract data from the Global Burden of Disease Study 2015 and derive country- and sex-specific daily smoking prevalence rates.

The researchers found that among young men and women, there were three patterns in the occurrence of lung cancer between the periods 1993-1997 and 2008-2012:

• A significant crossover from male to female dominance, seen in six countries.
• An insignificant crossover from male to female dominance, found in 23 countries.
• A continued male dominance, observed in 11 countries.

Higher incidence in women in six countries

The six countries with significant crossover from male to female dominance were Canada, Denmark, Germany, New Zealand, the Netherlands, and the United States.

Further analysis showed that, in general, age-specific lung cancer incidence rates decreased in successive male birth cohorts in these six countries. There was more variation across female birth cohorts.

Calculating female-to-male incidence rate ratios, the team found, for example, the IRR increased in New Zealand from 1.0 in the 1953 birth cohort to 1.6 in the 1968 birth cohort for people aged 40-44 years.

In addition, among adults aged 45-49 years in the Netherlands, the IRR rose from 0.7 in those born in the circa 1948 cohort to 1.4 in those from the circa 1958 cohort.

Overall, female-to-male IRRs increased notably among the following groups:

• Individuals aged 30-34 years in Canada, Denmark, and Germany.
• Those aged 40-44 years in Germany, the Netherlands, and the United States.
• Those aged 44-50 years in the Netherlands and the United States.
• Those aged 50-54 years in Canada, Denmark, and New Zealand.

Countries with an insignificant crossover from male to female dominance of lung cancer were located across Africa, the Americas, Asia, Europe, and Oceania.

Again, incidence rates were typically characterized by falling rates of lung cancer among men in more recent birth cohorts, and lung cancer incidence trends were more variable in women.

The team writes: “Of note, the six countries demonstrating a significant crossover are among those considered to be more advanced in the tobacco epidemic.

“Many of the countries where the crossover was insignificant or when there was no crossover are considered to be late adopters of the tobacco epidemic, with the effects of the epidemic on the burden of lung cancer and other smoking-related diseases beginning to manifest more recently, or perhaps yet to come.”

They suggest that low- and middle-resource countries may not follow the tobacco epidemic pattern of high-income countries, and so “we may not see higher lung cancer incidence rates in women than men for the foreseeable future in these countries.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most of us did our postgraduate training in tertiary medical centers, ivory towers of medicine often attached to or closely affiliated with medical schools. These are the places where the buck stops. Occasionally, a very complex patient might be sent to another tertiary center that claims to have a supersubspecialist, a one-of-a-kind physician with nationally recognized expertise. But for most patients, the tertiary medical center is the end of the line, and his or her physicians must manage with the resources at hand. They may confer with one another but there is no place for them to pass the buck.

Yuri_Arcurs/DigitalVision/Getty Images

But most of us who chose primary care left the comforting cocoon of the teaching hospital complex when we finished our training. Those first few months and years in the hinterland can be angst producing. Until we have established our own personal networks of consultants and mentors, patients with more than run-of-the-mill complaints may prompt us to reach for the phone or fire off an email call for help to our recently departed mother ship.

It can take awhile to establish the self-confidence – or at least the appearance of self-confidence – that physicians are expected to exude. But even after years of experience, none of us wants to watch a patient die or suffer preventable complications under our care when we know there is another facility that can provide a higher lever of care just an ambulance ride or short helicopter trip away.

Our primary concern is of course assuring that our patient is receiving the best care. How quickly we reach for the phone to refer out the most fragile patients depends on several factors. Do we practice in a community that has a historic reputation of having a low threshold for malpractice suits? How well do we know the patient and her family? Have we had time to establish bidirectional trust?

Is the patient’s diagnosis one that we feel comfortable with or is the diagnosis one that we believe could quickly deteriorate without warning? For example, a recently published study revealed that 20% of pediatric trauma patients were overtriaged and that the mechanism of injury – firearms or motor vehicle accidents – appeared to have an outsized influence in the triage decision (Trauma Surg Acute Care Open. 2019 Dec 29. doi: 10.1136/tsaco-2019-000300).

Courtesy Dr. William G. Wilkoff

Because I have no experience with firearm injuries and minimal experience with motor vehicle injuries I can understand why the emergency medical technicians might be quick to ship these patients to the trauma center. However, I hope that, were I offered better training and more opportunities to gain experience with these types of injuries, I would have a lower overtriage percentage.

Which begs the question of what is an acceptable rate of overtriage or overreferral? It’s the same old question of how many normal appendixes should one remove to avoid a fatal outcome. Each of us arrives at a given clinical crossroads with our own level of experience and comfort level. Our level of confidence in our local peer and specialty support network helps us decide when it is time to transfer a patient to a higher-level facility.

But in the final analysis it boils down to a personal decision and our own basic level of anxiety. Let’s face it, some of us worry more than others. Physicians come in all shades of anxiety. A hot potato in your hands may feel only room temperature to me.

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

Most of us did our postgraduate training in tertiary medical centers, ivory towers of medicine often attached to or closely affiliated with medical schools. These are the places where the buck stops. Occasionally, a very complex patient might be sent to another tertiary center that claims to have a supersubspecialist, a one-of-a-kind physician with nationally recognized expertise. But for most patients, the tertiary medical center is the end of the line, and his or her physicians must manage with the resources at hand. They may confer with one another but there is no place for them to pass the buck.

Yuri_Arcurs/DigitalVision/Getty Images

But most of us who chose primary care left the comforting cocoon of the teaching hospital complex when we finished our training. Those first few months and years in the hinterland can be angst producing. Until we have established our own personal networks of consultants and mentors, patients with more than run-of-the-mill complaints may prompt us to reach for the phone or fire off an email call for help to our recently departed mother ship.

It can take awhile to establish the self-confidence – or at least the appearance of self-confidence – that physicians are expected to exude. But even after years of experience, none of us wants to watch a patient die or suffer preventable complications under our care when we know there is another facility that can provide a higher lever of care just an ambulance ride or short helicopter trip away.

Our primary concern is of course assuring that our patient is receiving the best care. How quickly we reach for the phone to refer out the most fragile patients depends on several factors. Do we practice in a community that has a historic reputation of having a low threshold for malpractice suits? How well do we know the patient and her family? Have we had time to establish bidirectional trust?

Is the patient’s diagnosis one that we feel comfortable with or is the diagnosis one that we believe could quickly deteriorate without warning? For example, a recently published study revealed that 20% of pediatric trauma patients were overtriaged and that the mechanism of injury – firearms or motor vehicle accidents – appeared to have an outsized influence in the triage decision (Trauma Surg Acute Care Open. 2019 Dec 29. doi: 10.1136/tsaco-2019-000300).

Courtesy Dr. William G. Wilkoff

Because I have no experience with firearm injuries and minimal experience with motor vehicle injuries I can understand why the emergency medical technicians might be quick to ship these patients to the trauma center. However, I hope that, were I offered better training and more opportunities to gain experience with these types of injuries, I would have a lower overtriage percentage.

Which begs the question of what is an acceptable rate of overtriage or overreferral? It’s the same old question of how many normal appendixes should one remove to avoid a fatal outcome. Each of us arrives at a given clinical crossroads with our own level of experience and comfort level. Our level of confidence in our local peer and specialty support network helps us decide when it is time to transfer a patient to a higher-level facility.

But in the final analysis it boils down to a personal decision and our own basic level of anxiety. Let’s face it, some of us worry more than others. Physicians come in all shades of anxiety. A hot potato in your hands may feel only room temperature to me.

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

Most of us did our postgraduate training in tertiary medical centers, ivory towers of medicine often attached to or closely affiliated with medical schools. These are the places where the buck stops. Occasionally, a very complex patient might be sent to another tertiary center that claims to have a supersubspecialist, a one-of-a-kind physician with nationally recognized expertise. But for most patients, the tertiary medical center is the end of the line, and his or her physicians must manage with the resources at hand. They may confer with one another but there is no place for them to pass the buck.

Yuri_Arcurs/DigitalVision/Getty Images

But most of us who chose primary care left the comforting cocoon of the teaching hospital complex when we finished our training. Those first few months and years in the hinterland can be angst producing. Until we have established our own personal networks of consultants and mentors, patients with more than run-of-the-mill complaints may prompt us to reach for the phone or fire off an email call for help to our recently departed mother ship.

It can take awhile to establish the self-confidence – or at least the appearance of self-confidence – that physicians are expected to exude. But even after years of experience, none of us wants to watch a patient die or suffer preventable complications under our care when we know there is another facility that can provide a higher lever of care just an ambulance ride or short helicopter trip away.

Our primary concern is of course assuring that our patient is receiving the best care. How quickly we reach for the phone to refer out the most fragile patients depends on several factors. Do we practice in a community that has a historic reputation of having a low threshold for malpractice suits? How well do we know the patient and her family? Have we had time to establish bidirectional trust?

Is the patient’s diagnosis one that we feel comfortable with or is the diagnosis one that we believe could quickly deteriorate without warning? For example, a recently published study revealed that 20% of pediatric trauma patients were overtriaged and that the mechanism of injury – firearms or motor vehicle accidents – appeared to have an outsized influence in the triage decision (Trauma Surg Acute Care Open. 2019 Dec 29. doi: 10.1136/tsaco-2019-000300).

Courtesy Dr. William G. Wilkoff

Because I have no experience with firearm injuries and minimal experience with motor vehicle injuries I can understand why the emergency medical technicians might be quick to ship these patients to the trauma center. However, I hope that, were I offered better training and more opportunities to gain experience with these types of injuries, I would have a lower overtriage percentage.

Which begs the question of what is an acceptable rate of overtriage or overreferral? It’s the same old question of how many normal appendixes should one remove to avoid a fatal outcome. Each of us arrives at a given clinical crossroads with our own level of experience and comfort level. Our level of confidence in our local peer and specialty support network helps us decide when it is time to transfer a patient to a higher-level facility.

But in the final analysis it boils down to a personal decision and our own basic level of anxiety. Let’s face it, some of us worry more than others. Physicians come in all shades of anxiety. A hot potato in your hands may feel only room temperature to me.

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

I agree wholeheartedly with Dr. William G. Wilkoff’s doubts that an increase in medical schools/students and/or foreign medical graduates is the answer to the physician shortage felt by many areas of the country (Letters From Maine, “Help Wanted,” Nov. 2019, page 19). All you have to do is look at the glut of physicians – and just about any other profession – in metropolitan areas versus rural America, and ask basic questions regarding why those doctors practice where they do. You will quickly discover that most are willing to trade the possibility of a higher salary in areas where their presence is more needed to achieve more school choices, jobs for a spouse, and likely a more favorable call schedule. Something more attractive than salary or the prospect of more “elbow room” is desired.

Here in Mississippi we may have found an answer to the problem. A few years ago our state legislature started the Mississippi Rural Health Scholarship Program that pays for recipients to attend a state-run medical school on scholarship in exchange for agreeing to practice at least 4 years in a rural area of the state (less than 20k population) following their primary care residency (family medicine, pediatrics, ob.gyn., med-peds, internal medicine, and, recently added, psychiatry). Although a recent increase in the number of pediatric residency slots at our state’s sole program will no doubt also have a positive effect to this end, such a scholarship program as the one implemented by Mississippi is the best way to compete with the various intangibles that lead people to choose bigger cities over rural areas of the state to practice their trade. Once there, many – like myself – will find that such a practice is not only a good business decision but often is a wonderful place to raise a family. Meanwhile, our own practice just added a fourth physician as a result of said Rural Health Scholarship Program, and we could not be more satisfied with the result.
 

I agree wholeheartedly with Dr. William G. Wilkoff’s doubts that an increase in medical schools/students and/or foreign medical graduates is the answer to the physician shortage felt by many areas of the country (Letters From Maine, “Help Wanted,” Nov. 2019, page 19). All you have to do is look at the glut of physicians – and just about any other profession – in metropolitan areas versus rural America, and ask basic questions regarding why those doctors practice where they do. You will quickly discover that most are willing to trade the possibility of a higher salary in areas where their presence is more needed to achieve more school choices, jobs for a spouse, and likely a more favorable call schedule. Something more attractive than salary or the prospect of more “elbow room” is desired.

Here in Mississippi we may have found an answer to the problem. A few years ago our state legislature started the Mississippi Rural Health Scholarship Program that pays for recipients to attend a state-run medical school on scholarship in exchange for agreeing to practice at least 4 years in a rural area of the state (less than 20k population) following their primary care residency (family medicine, pediatrics, ob.gyn., med-peds, internal medicine, and, recently added, psychiatry). Although a recent increase in the number of pediatric residency slots at our state’s sole program will no doubt also have a positive effect to this end, such a scholarship program as the one implemented by Mississippi is the best way to compete with the various intangibles that lead people to choose bigger cities over rural areas of the state to practice their trade. Once there, many – like myself – will find that such a practice is not only a good business decision but often is a wonderful place to raise a family. Meanwhile, our own practice just added a fourth physician as a result of said Rural Health Scholarship Program, and we could not be more satisfied with the result.
 

I agree wholeheartedly with Dr. William G. Wilkoff’s doubts that an increase in medical schools/students and/or foreign medical graduates is the answer to the physician shortage felt by many areas of the country (Letters From Maine, “Help Wanted,” Nov. 2019, page 19). All you have to do is look at the glut of physicians – and just about any other profession – in metropolitan areas versus rural America, and ask basic questions regarding why those doctors practice where they do. You will quickly discover that most are willing to trade the possibility of a higher salary in areas where their presence is more needed to achieve more school choices, jobs for a spouse, and likely a more favorable call schedule. Something more attractive than salary or the prospect of more “elbow room” is desired.

Here in Mississippi we may have found an answer to the problem. A few years ago our state legislature started the Mississippi Rural Health Scholarship Program that pays for recipients to attend a state-run medical school on scholarship in exchange for agreeing to practice at least 4 years in a rural area of the state (less than 20k population) following their primary care residency (family medicine, pediatrics, ob.gyn., med-peds, internal medicine, and, recently added, psychiatry). Although a recent increase in the number of pediatric residency slots at our state’s sole program will no doubt also have a positive effect to this end, such a scholarship program as the one implemented by Mississippi is the best way to compete with the various intangibles that lead people to choose bigger cities over rural areas of the state to practice their trade. Once there, many – like myself – will find that such a practice is not only a good business decision but often is a wonderful place to raise a family. Meanwhile, our own practice just added a fourth physician as a result of said Rural Health Scholarship Program, and we could not be more satisfied with the result.
 

Cervical cancer is the second most common cancer among women in lower- and middle-income countries, but universal human papillomavirus vaccination for girls would reduce new cervical cancer cases by about 90% over the next century, according to researchers.

Adding twice-lifetime cervical screening with human papillomavirus (HPV) testing would further reduce the incidence of cervical cancer, including in countries with the highest burden, the researchers reported in The Lancet.

Marc Brisson, PhD, of Laval University, Quebec City, and colleagues conducted this study using three models identified by the World Health Organization. The models were used to project reductions in cervical cancer incidence for women in 78 low- and middle-income countries based on the following HPV vaccination and screening scenarios:

• Universal girls-only vaccination at age 9 years, assuming 90% of girls vaccinated and a vaccine that is perfectly effective
• Girls-only vaccination plus cervical screening with HPV testing at age 35 years
• Girls-only vaccination plus screening at ages 35 and 45.

All three scenarios modeled would result in the elimination of cervical cancer, Dr. Brisson and colleagues found. Elimination was defined as four or fewer new cases per 100,000 women-years.

The simplest scenario, universal girls-only vaccination, was predicted to reduce age-standardized cervical cancer incidence from 19.8 cases per 100,000 women-years to 2.1 cases per 100,000 women-years (89.4% reduction) by 2120. That amounts to about 61 million potential cases avoided, with elimination targets reached in 60% of the countries studied.

HPV vaccination plus one-time screening was predicted to reduce the incidence of cervical cancer to 1.0 case per 100,000 women-years (95.0% reduction), and HPV vaccination plus twice-lifetime screening was predicted to reduce the incidence to 0.7 cases per 100,000 women-years (96.7% reduction).

Dr. Brisson and colleagues reported that, for the countries with the highest burden of cervical cancer (more than 25 cases per 100,000 women-years), adding screening would be necessary to achieve elimination.

To meet the same targets across all 78 countries, “our models predict that scale-up of both girls-only HPV vaccination and twice-lifetime screening is necessary, with 90% HPV vaccination coverage, 90% screening uptake, and long-term protection against HPV types 16, 18, 31, 33, 45, 52, and 58,” the researchers wrote.

Dr. Brisson and colleagues claimed that a strength of this study is the modeling approach, which compared three models “that have been extensively peer reviewed and validated with postvaccination surveillance data.”

The researchers acknowledged, however, that their modeling could not account for variations in sexual behavior from country to country, and the study was not designed to anticipate behavioral or technological changes that could affect cervical cancer incidence in the decades to come.

The study was funded by the WHO, the United Nations, and the Canadian and Australian governments. The WHO contributed to the study design, data analysis and interpretation, and writing of the manuscript. Two study authors reported receiving indirect industry funding for a cervical screening trial in Australia.

SOURCE: Brisson M et al. Lancet. 2020 Jan 30. doi: 10.1016/S0140-6736(20)30068-4.

Cervical cancer is the second most common cancer among women in lower- and middle-income countries, but universal human papillomavirus vaccination for girls would reduce new cervical cancer cases by about 90% over the next century, according to researchers.

Adding twice-lifetime cervical screening with human papillomavirus (HPV) testing would further reduce the incidence of cervical cancer, including in countries with the highest burden, the researchers reported in The Lancet.

Marc Brisson, PhD, of Laval University, Quebec City, and colleagues conducted this study using three models identified by the World Health Organization. The models were used to project reductions in cervical cancer incidence for women in 78 low- and middle-income countries based on the following HPV vaccination and screening scenarios:

• Universal girls-only vaccination at age 9 years, assuming 90% of girls vaccinated and a vaccine that is perfectly effective
• Girls-only vaccination plus cervical screening with HPV testing at age 35 years
• Girls-only vaccination plus screening at ages 35 and 45.

All three scenarios modeled would result in the elimination of cervical cancer, Dr. Brisson and colleagues found. Elimination was defined as four or fewer new cases per 100,000 women-years.

The simplest scenario, universal girls-only vaccination, was predicted to reduce age-standardized cervical cancer incidence from 19.8 cases per 100,000 women-years to 2.1 cases per 100,000 women-years (89.4% reduction) by 2120. That amounts to about 61 million potential cases avoided, with elimination targets reached in 60% of the countries studied.

HPV vaccination plus one-time screening was predicted to reduce the incidence of cervical cancer to 1.0 case per 100,000 women-years (95.0% reduction), and HPV vaccination plus twice-lifetime screening was predicted to reduce the incidence to 0.7 cases per 100,000 women-years (96.7% reduction).

Dr. Brisson and colleagues reported that, for the countries with the highest burden of cervical cancer (more than 25 cases per 100,000 women-years), adding screening would be necessary to achieve elimination.

To meet the same targets across all 78 countries, “our models predict that scale-up of both girls-only HPV vaccination and twice-lifetime screening is necessary, with 90% HPV vaccination coverage, 90% screening uptake, and long-term protection against HPV types 16, 18, 31, 33, 45, 52, and 58,” the researchers wrote.

Dr. Brisson and colleagues claimed that a strength of this study is the modeling approach, which compared three models “that have been extensively peer reviewed and validated with postvaccination surveillance data.”

The researchers acknowledged, however, that their modeling could not account for variations in sexual behavior from country to country, and the study was not designed to anticipate behavioral or technological changes that could affect cervical cancer incidence in the decades to come.

The study was funded by the WHO, the United Nations, and the Canadian and Australian governments. The WHO contributed to the study design, data analysis and interpretation, and writing of the manuscript. Two study authors reported receiving indirect industry funding for a cervical screening trial in Australia.

SOURCE: Brisson M et al. Lancet. 2020 Jan 30. doi: 10.1016/S0140-6736(20)30068-4.

Cervical cancer is the second most common cancer among women in lower- and middle-income countries, but universal human papillomavirus vaccination for girls would reduce new cervical cancer cases by about 90% over the next century, according to researchers.

Adding twice-lifetime cervical screening with human papillomavirus (HPV) testing would further reduce the incidence of cervical cancer, including in countries with the highest burden, the researchers reported in The Lancet.

Marc Brisson, PhD, of Laval University, Quebec City, and colleagues conducted this study using three models identified by the World Health Organization. The models were used to project reductions in cervical cancer incidence for women in 78 low- and middle-income countries based on the following HPV vaccination and screening scenarios:

• Universal girls-only vaccination at age 9 years, assuming 90% of girls vaccinated and a vaccine that is perfectly effective
• Girls-only vaccination plus cervical screening with HPV testing at age 35 years
• Girls-only vaccination plus screening at ages 35 and 45.

All three scenarios modeled would result in the elimination of cervical cancer, Dr. Brisson and colleagues found. Elimination was defined as four or fewer new cases per 100,000 women-years.

The simplest scenario, universal girls-only vaccination, was predicted to reduce age-standardized cervical cancer incidence from 19.8 cases per 100,000 women-years to 2.1 cases per 100,000 women-years (89.4% reduction) by 2120. That amounts to about 61 million potential cases avoided, with elimination targets reached in 60% of the countries studied.

HPV vaccination plus one-time screening was predicted to reduce the incidence of cervical cancer to 1.0 case per 100,000 women-years (95.0% reduction), and HPV vaccination plus twice-lifetime screening was predicted to reduce the incidence to 0.7 cases per 100,000 women-years (96.7% reduction).

Dr. Brisson and colleagues reported that, for the countries with the highest burden of cervical cancer (more than 25 cases per 100,000 women-years), adding screening would be necessary to achieve elimination.

To meet the same targets across all 78 countries, “our models predict that scale-up of both girls-only HPV vaccination and twice-lifetime screening is necessary, with 90% HPV vaccination coverage, 90% screening uptake, and long-term protection against HPV types 16, 18, 31, 33, 45, 52, and 58,” the researchers wrote.

Dr. Brisson and colleagues claimed that a strength of this study is the modeling approach, which compared three models “that have been extensively peer reviewed and validated with postvaccination surveillance data.”

The researchers acknowledged, however, that their modeling could not account for variations in sexual behavior from country to country, and the study was not designed to anticipate behavioral or technological changes that could affect cervical cancer incidence in the decades to come.

The study was funded by the WHO, the United Nations, and the Canadian and Australian governments. The WHO contributed to the study design, data analysis and interpretation, and writing of the manuscript. Two study authors reported receiving indirect industry funding for a cervical screening trial in Australia.

SOURCE: Brisson M et al. Lancet. 2020 Jan 30. doi: 10.1016/S0140-6736(20)30068-4.

In this edition of “How I Will Treat My Next Patient,” I highlight the potential role of new models for predicting risks of common, clinically important situations in general oncology practice: severe neutropenia in lung cancer patients and locoregional recurrence of breast cancer.

Predicting neutropenia

Accurate, lung cancer–specific prediction models would be useful to estimate risk of chemotherapy-induced neutropenia (CIN), especially febrile neutropenia (FN), since that particular toxicity is linked to infection, dose delays and dose reductions that can compromise treatment efficacy, and poor health-related quality of life. Lung cancer patients are often older adults, with advanced disease and comorbid conditions, so they are a particularly vulnerable population for CIN.

Xiaowen Cao of Duke University, Durham, N.C., and coinvestigators published a model for predicting risk of severe CIN in advanced lung cancer patients, based on 10 pretreatment variables (Lung Cancer. 2020 Jan 5. doi: 10.1016/j.lungcan.2020.01.004). They developed their model to overcome limitations of the previously published work of Gary H. Lyman, MD, and colleagues that is not specific to lung cancer and incorporated relative dose intensity as a predictor (Cancer. 2011;117:1917-27). Relative dose intensity is not determined until after a treatment course is completed.

The new prediction model was based on a lung cancer data set encompassing 11,352 patients from 67 phase 2-3 cooperative group studies conducted between 1991 and 2010. In this data set, the Lyman model had an area under the curve of 0.8772 in patients with small cell lung cancer, but an area under the curve of just 0.6787 in non–small cell lung cancer.

The derivation model was derived from about two-thirds of the patients, randomly selected. The validation set was conducted using the remaining third. The variables included were readily clinically available: age, gender, weight, body mass index, insurance status, disease stage, number of metastatic sites, chemotherapy agents used, number of chemotherapy agents, planned growth factor use, duration of planned therapy, pleural effusion, presence of symptoms, and performance status. Their model had an area under the curve of 0.8348 in the training set and 0.8234 in the testing set.
 

How these results influence practice

The risk of an initial episode of FN is highest during a patient’s initial cycle of chemotherapy, when most patients are receiving full-dose treatment, often without prophylactic measures. Guidelines from the National Comprehensive Cancer Network suggest the use of prophylactic growth factors in patients with more than a 20% risk of FN, and considering using prophylaxis in patients with 10%-20% risk of FN. Underestimating those risks and failure to take adequate precautions may be particularly important for patients with lung cancer who are generally older adults, with comorbid conditions.

The comprehensive risk model for neutropenic complications that was developed by Dr. Lyman and colleagues was based on a large, prospective cohort including nearly 3,800 patients. The model had a 90% sensitivity and 96% predictive value, but was not lung cancer specific and, in this latest study, did not perform as well in the 85% of lung cancer patients with non–small cell lung cancer. The Lyman data, however, was obtained in cancer patients treated with investigator-choice chemotherapy in community practices. It remains the National Comprehensive Cancer Network standard for evaluating FN risk in patients embarking on chemotherapy for advanced malignancies. That should remain the case, pending the additional validation testing of the new lung cancer–specific model at independent institutions, treating heterogeneous patients in real-world settings.
 

Locoregional recurrence

A retrospective cohort analysis of SWOG 8814, a phase 3 study of tamoxifen alone versus chemotherapy plus by tamoxifen in postmenopausal, node-positive, hormone receptor–positive breast cancer patients suggests that the 21-gene assay recurrence score (RS) can aid decisions about radiotherapy (RT).

Wendy A. Woodward, MD, PhD, and colleagues, analyzed patients who underwent mastectomy or breast-conserving surgery as their local therapy (JAMA Oncol. 2020 Jan 9. doi: 10.1001/jamaoncol.2019.5559). They found that patients with an intermediate or high RS – according to the 21-gene assay OncotypeDX – had more locoregional recurrences (LRR; breast, chest wall, axilla, internal mammary, supraclavicular or infraclavicular nodes).

There were 367 patients in SWOG 8814 who received tamoxifen alone or cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen. LRR was observed in 5.8% of patients with a low RS (less than 18) and in 13.8% of patients with an intermediate or high RS (more than 18). The estimated 10-year cumulative LRR incidence rates were 9.7% and 16.5%, respectively (P = .02).

In the subset of patients with one to three positive nodes who had mastectomy without radiotherapy, the LRR was 1.5% for those with low RS and 11.1% for those with intermediate or high RS (P = .051). No difference by RS was found in the 10-year rates of LRR among patients with four or more involved nodes who received a mastectomy without RT (25.9% vs. 27.0%; P = .27).

In multivariate analysis, incorporating RS, type of surgery, and number of involved nodes, intermediate or high RS was a significant predictor of LRR, with a hazard ratio of 2.36 (P = .04). The investigators suggested that RS, when available, should be one of the factors considered in selecting patients for postmastectomy RT.
 

How these results influence practice

Selecting the node-positive, hormone receptor–positive, breast cancer patients who should receive postmastectomy RT is difficult and controversial. This is particularly true for those postmenopausal patients with fewer than four involved nodes, no lymphatic or vascular invasion, and no extracapsular spread of disease into the axillary fat. Limited information exists on the ability of genomic assays to identify LRR risk.

Eleftherios P. Mamounas, MD, and colleagues examined the results of NSABP B-28, a trial of chemotherapy plus tamoxifen (J Natl Cancer Inst. 2017;109[4]. doi:10.1093/jnci/djw259). Postmastectomy RT was not permitted. They found high RS correlated with greater LRR and low RS with decreased LRR among patients with one to three positive nodes. At first blush, the prospectively treated cohort of SWOG 8814 represents a uniformly treated cohort with long-term follow-up (median, 8.5 years) and extends in an independent analysis the findings of NSABP B-28.

However, as Dr. Woodward and colleagues point out, the current study has limitations. The use of RT was extracted retrospectively and may be underreported. More modern chemotherapy and RT may lower LRR from the risks observed in SWOG 8814. Finally, the modest numbers of LRR events precluded secondary analysis of RS as a continuous variable. This is important because the risk group cutoffs suggested by the authors are not aligned with those in the recently published TailorRx study or the ongoing RxPonder trial.

The TailorRT (Regional Radiotherapy in Biomarker Low Risk Node Positive Breast Cancer) study examines the safety of omitting RT among patients with low RS and one to three positive nodes. Until the TailorRT results are reported, the controversy regarding the role of postmastectomy RT in this group will continue for patients with low nodal tumor burden and less aggressive tumor features, including low RS.

An observed LRR risk of 11.1% in SWOG 8814 among patients with N1 disease and an RS above 18 suggest that genomic risk could be one of the factors that may justify postmastectomy RT in postmenopausal patients with node-positive, hormone receptor–positive breast cancer until additional data emerge from the contemporary trials.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I highlight the potential role of new models for predicting risks of common, clinically important situations in general oncology practice: severe neutropenia in lung cancer patients and locoregional recurrence of breast cancer.

Predicting neutropenia

Accurate, lung cancer–specific prediction models would be useful to estimate risk of chemotherapy-induced neutropenia (CIN), especially febrile neutropenia (FN), since that particular toxicity is linked to infection, dose delays and dose reductions that can compromise treatment efficacy, and poor health-related quality of life. Lung cancer patients are often older adults, with advanced disease and comorbid conditions, so they are a particularly vulnerable population for CIN.

Xiaowen Cao of Duke University, Durham, N.C., and coinvestigators published a model for predicting risk of severe CIN in advanced lung cancer patients, based on 10 pretreatment variables (Lung Cancer. 2020 Jan 5. doi: 10.1016/j.lungcan.2020.01.004). They developed their model to overcome limitations of the previously published work of Gary H. Lyman, MD, and colleagues that is not specific to lung cancer and incorporated relative dose intensity as a predictor (Cancer. 2011;117:1917-27). Relative dose intensity is not determined until after a treatment course is completed.

The new prediction model was based on a lung cancer data set encompassing 11,352 patients from 67 phase 2-3 cooperative group studies conducted between 1991 and 2010. In this data set, the Lyman model had an area under the curve of 0.8772 in patients with small cell lung cancer, but an area under the curve of just 0.6787 in non–small cell lung cancer.

The derivation model was derived from about two-thirds of the patients, randomly selected. The validation set was conducted using the remaining third. The variables included were readily clinically available: age, gender, weight, body mass index, insurance status, disease stage, number of metastatic sites, chemotherapy agents used, number of chemotherapy agents, planned growth factor use, duration of planned therapy, pleural effusion, presence of symptoms, and performance status. Their model had an area under the curve of 0.8348 in the training set and 0.8234 in the testing set.
 

How these results influence practice

The risk of an initial episode of FN is highest during a patient’s initial cycle of chemotherapy, when most patients are receiving full-dose treatment, often without prophylactic measures. Guidelines from the National Comprehensive Cancer Network suggest the use of prophylactic growth factors in patients with more than a 20% risk of FN, and considering using prophylaxis in patients with 10%-20% risk of FN. Underestimating those risks and failure to take adequate precautions may be particularly important for patients with lung cancer who are generally older adults, with comorbid conditions.

The comprehensive risk model for neutropenic complications that was developed by Dr. Lyman and colleagues was based on a large, prospective cohort including nearly 3,800 patients. The model had a 90% sensitivity and 96% predictive value, but was not lung cancer specific and, in this latest study, did not perform as well in the 85% of lung cancer patients with non–small cell lung cancer. The Lyman data, however, was obtained in cancer patients treated with investigator-choice chemotherapy in community practices. It remains the National Comprehensive Cancer Network standard for evaluating FN risk in patients embarking on chemotherapy for advanced malignancies. That should remain the case, pending the additional validation testing of the new lung cancer–specific model at independent institutions, treating heterogeneous patients in real-world settings.
 

Locoregional recurrence

A retrospective cohort analysis of SWOG 8814, a phase 3 study of tamoxifen alone versus chemotherapy plus by tamoxifen in postmenopausal, node-positive, hormone receptor–positive breast cancer patients suggests that the 21-gene assay recurrence score (RS) can aid decisions about radiotherapy (RT).

Wendy A. Woodward, MD, PhD, and colleagues, analyzed patients who underwent mastectomy or breast-conserving surgery as their local therapy (JAMA Oncol. 2020 Jan 9. doi: 10.1001/jamaoncol.2019.5559). They found that patients with an intermediate or high RS – according to the 21-gene assay OncotypeDX – had more locoregional recurrences (LRR; breast, chest wall, axilla, internal mammary, supraclavicular or infraclavicular nodes).

There were 367 patients in SWOG 8814 who received tamoxifen alone or cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen. LRR was observed in 5.8% of patients with a low RS (less than 18) and in 13.8% of patients with an intermediate or high RS (more than 18). The estimated 10-year cumulative LRR incidence rates were 9.7% and 16.5%, respectively (P = .02).

In the subset of patients with one to three positive nodes who had mastectomy without radiotherapy, the LRR was 1.5% for those with low RS and 11.1% for those with intermediate or high RS (P = .051). No difference by RS was found in the 10-year rates of LRR among patients with four or more involved nodes who received a mastectomy without RT (25.9% vs. 27.0%; P = .27).

In multivariate analysis, incorporating RS, type of surgery, and number of involved nodes, intermediate or high RS was a significant predictor of LRR, with a hazard ratio of 2.36 (P = .04). The investigators suggested that RS, when available, should be one of the factors considered in selecting patients for postmastectomy RT.
 

How these results influence practice

Selecting the node-positive, hormone receptor–positive, breast cancer patients who should receive postmastectomy RT is difficult and controversial. This is particularly true for those postmenopausal patients with fewer than four involved nodes, no lymphatic or vascular invasion, and no extracapsular spread of disease into the axillary fat. Limited information exists on the ability of genomic assays to identify LRR risk.

Eleftherios P. Mamounas, MD, and colleagues examined the results of NSABP B-28, a trial of chemotherapy plus tamoxifen (J Natl Cancer Inst. 2017;109[4]. doi:10.1093/jnci/djw259). Postmastectomy RT was not permitted. They found high RS correlated with greater LRR and low RS with decreased LRR among patients with one to three positive nodes. At first blush, the prospectively treated cohort of SWOG 8814 represents a uniformly treated cohort with long-term follow-up (median, 8.5 years) and extends in an independent analysis the findings of NSABP B-28.

However, as Dr. Woodward and colleagues point out, the current study has limitations. The use of RT was extracted retrospectively and may be underreported. More modern chemotherapy and RT may lower LRR from the risks observed in SWOG 8814. Finally, the modest numbers of LRR events precluded secondary analysis of RS as a continuous variable. This is important because the risk group cutoffs suggested by the authors are not aligned with those in the recently published TailorRx study or the ongoing RxPonder trial.

The TailorRT (Regional Radiotherapy in Biomarker Low Risk Node Positive Breast Cancer) study examines the safety of omitting RT among patients with low RS and one to three positive nodes. Until the TailorRT results are reported, the controversy regarding the role of postmastectomy RT in this group will continue for patients with low nodal tumor burden and less aggressive tumor features, including low RS.

An observed LRR risk of 11.1% in SWOG 8814 among patients with N1 disease and an RS above 18 suggest that genomic risk could be one of the factors that may justify postmastectomy RT in postmenopausal patients with node-positive, hormone receptor–positive breast cancer until additional data emerge from the contemporary trials.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I highlight the potential role of new models for predicting risks of common, clinically important situations in general oncology practice: severe neutropenia in lung cancer patients and locoregional recurrence of breast cancer.

Predicting neutropenia

Accurate, lung cancer–specific prediction models would be useful to estimate risk of chemotherapy-induced neutropenia (CIN), especially febrile neutropenia (FN), since that particular toxicity is linked to infection, dose delays and dose reductions that can compromise treatment efficacy, and poor health-related quality of life. Lung cancer patients are often older adults, with advanced disease and comorbid conditions, so they are a particularly vulnerable population for CIN.

Xiaowen Cao of Duke University, Durham, N.C., and coinvestigators published a model for predicting risk of severe CIN in advanced lung cancer patients, based on 10 pretreatment variables (Lung Cancer. 2020 Jan 5. doi: 10.1016/j.lungcan.2020.01.004). They developed their model to overcome limitations of the previously published work of Gary H. Lyman, MD, and colleagues that is not specific to lung cancer and incorporated relative dose intensity as a predictor (Cancer. 2011;117:1917-27). Relative dose intensity is not determined until after a treatment course is completed.

The new prediction model was based on a lung cancer data set encompassing 11,352 patients from 67 phase 2-3 cooperative group studies conducted between 1991 and 2010. In this data set, the Lyman model had an area under the curve of 0.8772 in patients with small cell lung cancer, but an area under the curve of just 0.6787 in non–small cell lung cancer.

The derivation model was derived from about two-thirds of the patients, randomly selected. The validation set was conducted using the remaining third. The variables included were readily clinically available: age, gender, weight, body mass index, insurance status, disease stage, number of metastatic sites, chemotherapy agents used, number of chemotherapy agents, planned growth factor use, duration of planned therapy, pleural effusion, presence of symptoms, and performance status. Their model had an area under the curve of 0.8348 in the training set and 0.8234 in the testing set.
 

How these results influence practice

The risk of an initial episode of FN is highest during a patient’s initial cycle of chemotherapy, when most patients are receiving full-dose treatment, often without prophylactic measures. Guidelines from the National Comprehensive Cancer Network suggest the use of prophylactic growth factors in patients with more than a 20% risk of FN, and considering using prophylaxis in patients with 10%-20% risk of FN. Underestimating those risks and failure to take adequate precautions may be particularly important for patients with lung cancer who are generally older adults, with comorbid conditions.

The comprehensive risk model for neutropenic complications that was developed by Dr. Lyman and colleagues was based on a large, prospective cohort including nearly 3,800 patients. The model had a 90% sensitivity and 96% predictive value, but was not lung cancer specific and, in this latest study, did not perform as well in the 85% of lung cancer patients with non–small cell lung cancer. The Lyman data, however, was obtained in cancer patients treated with investigator-choice chemotherapy in community practices. It remains the National Comprehensive Cancer Network standard for evaluating FN risk in patients embarking on chemotherapy for advanced malignancies. That should remain the case, pending the additional validation testing of the new lung cancer–specific model at independent institutions, treating heterogeneous patients in real-world settings.
 

Locoregional recurrence

A retrospective cohort analysis of SWOG 8814, a phase 3 study of tamoxifen alone versus chemotherapy plus by tamoxifen in postmenopausal, node-positive, hormone receptor–positive breast cancer patients suggests that the 21-gene assay recurrence score (RS) can aid decisions about radiotherapy (RT).

Wendy A. Woodward, MD, PhD, and colleagues, analyzed patients who underwent mastectomy or breast-conserving surgery as their local therapy (JAMA Oncol. 2020 Jan 9. doi: 10.1001/jamaoncol.2019.5559). They found that patients with an intermediate or high RS – according to the 21-gene assay OncotypeDX – had more locoregional recurrences (LRR; breast, chest wall, axilla, internal mammary, supraclavicular or infraclavicular nodes).

There were 367 patients in SWOG 8814 who received tamoxifen alone or cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen. LRR was observed in 5.8% of patients with a low RS (less than 18) and in 13.8% of patients with an intermediate or high RS (more than 18). The estimated 10-year cumulative LRR incidence rates were 9.7% and 16.5%, respectively (P = .02).

In the subset of patients with one to three positive nodes who had mastectomy without radiotherapy, the LRR was 1.5% for those with low RS and 11.1% for those with intermediate or high RS (P = .051). No difference by RS was found in the 10-year rates of LRR among patients with four or more involved nodes who received a mastectomy without RT (25.9% vs. 27.0%; P = .27).

In multivariate analysis, incorporating RS, type of surgery, and number of involved nodes, intermediate or high RS was a significant predictor of LRR, with a hazard ratio of 2.36 (P = .04). The investigators suggested that RS, when available, should be one of the factors considered in selecting patients for postmastectomy RT.
 

How these results influence practice

Selecting the node-positive, hormone receptor–positive, breast cancer patients who should receive postmastectomy RT is difficult and controversial. This is particularly true for those postmenopausal patients with fewer than four involved nodes, no lymphatic or vascular invasion, and no extracapsular spread of disease into the axillary fat. Limited information exists on the ability of genomic assays to identify LRR risk.

Eleftherios P. Mamounas, MD, and colleagues examined the results of NSABP B-28, a trial of chemotherapy plus tamoxifen (J Natl Cancer Inst. 2017;109[4]. doi:10.1093/jnci/djw259). Postmastectomy RT was not permitted. They found high RS correlated with greater LRR and low RS with decreased LRR among patients with one to three positive nodes. At first blush, the prospectively treated cohort of SWOG 8814 represents a uniformly treated cohort with long-term follow-up (median, 8.5 years) and extends in an independent analysis the findings of NSABP B-28.

However, as Dr. Woodward and colleagues point out, the current study has limitations. The use of RT was extracted retrospectively and may be underreported. More modern chemotherapy and RT may lower LRR from the risks observed in SWOG 8814. Finally, the modest numbers of LRR events precluded secondary analysis of RS as a continuous variable. This is important because the risk group cutoffs suggested by the authors are not aligned with those in the recently published TailorRx study or the ongoing RxPonder trial.

The TailorRT (Regional Radiotherapy in Biomarker Low Risk Node Positive Breast Cancer) study examines the safety of omitting RT among patients with low RS and one to three positive nodes. Until the TailorRT results are reported, the controversy regarding the role of postmastectomy RT in this group will continue for patients with low nodal tumor burden and less aggressive tumor features, including low RS.

An observed LRR risk of 11.1% in SWOG 8814 among patients with N1 disease and an RS above 18 suggest that genomic risk could be one of the factors that may justify postmastectomy RT in postmenopausal patients with node-positive, hormone receptor–positive breast cancer until additional data emerge from the contemporary trials.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.