Flavopiridol – also known as alvocidib – showed minimal clinical response in patients with relapsed or refractory mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and other B-cell lymphomas, according to results from a single-center, phase 1/2 trial.

“Promising preclinical data in cell lines derived from MCL and activated DLBCL led to a series of clinical trials of flavopiridol in various hematological malignancies,” wrote Milos D. Miljković, MD, and colleagues in the lymphoid malignancies branch of the National Cancer Institute in Bethesda, Md. The findings were published in a letter to the editor in Leukemia & Lymphoma.

The study included 28 patients with relapsed/refractory MCL, DLBCL, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma who received a hybrid dosing regimen of the novel CDK inhibitor. Flavopiridol was administered as a 30-minute bolus, followed by a 4-hour infusion.

The researchers used an intrapatient dose escalation between the first and successive cycles, in addition to a three-plus-three interpatient escalation, to lessen the risk of tumor lysis syndrome (TLS).

The primary outcomes were the clinical response rate, maximum tolerated dose, dose-limiting toxicities, and toxicity profile of the hybrid dosing regimen.

Of 26 evaluable patients, one patient with DLBCL maintained a partial response for 84 days (overall response rate, 3.8%). One patient with MCL had a 50% decrease in the size of target lesions at 2 months, but this was not sustained at 4 months. In total, nine patients had stable disease for a disease control rate of 38.4%.

“[Flavopiridol] had minimal efficacy in patients with relapsed/refractory non-Hodgkin B-cell lymphoma, casting doubt on the utility of CDK inhibition in this disease,” the researchers wrote.

With respect to safety, there were eight dose-limiting toxicities reported in three patients. These included grade 3 TLS, elevated transaminase levels, hypoalbuminemia, hyperkalemia, non-neutropenic infection, and grade 4 metabolic acidosis and gastrointestinal perforation.

The most common treatment-related toxicities were hematologic, including neutropenia, anemia, thrombocytopenia, leukocytosis, and lymphopenia.

Dr. Miljković and colleagues noted that CDK inhibitor therapy may elicit better responses when used in combination with other agents.

“Ongoing trials of more specific CDK inhibitors in combination with other agents will help elucidate their role in lymphoma treatment,” they wrote.

The trial is sponsored by the National Cancer Institute and the study authors are employees of the National Cancer Institute.

SOURCE: Miljkovic MD et al. Leuk Lymphoma. 2019 Jun 17. doi: 10.1080/10428194.2019.1627540.

Flavopiridol – also known as alvocidib – showed minimal clinical response in patients with relapsed or refractory mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and other B-cell lymphomas, according to results from a single-center, phase 1/2 trial.

“Promising preclinical data in cell lines derived from MCL and activated DLBCL led to a series of clinical trials of flavopiridol in various hematological malignancies,” wrote Milos D. Miljković, MD, and colleagues in the lymphoid malignancies branch of the National Cancer Institute in Bethesda, Md. The findings were published in a letter to the editor in Leukemia & Lymphoma.

The study included 28 patients with relapsed/refractory MCL, DLBCL, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma who received a hybrid dosing regimen of the novel CDK inhibitor. Flavopiridol was administered as a 30-minute bolus, followed by a 4-hour infusion.

The researchers used an intrapatient dose escalation between the first and successive cycles, in addition to a three-plus-three interpatient escalation, to lessen the risk of tumor lysis syndrome (TLS).

The primary outcomes were the clinical response rate, maximum tolerated dose, dose-limiting toxicities, and toxicity profile of the hybrid dosing regimen.

Of 26 evaluable patients, one patient with DLBCL maintained a partial response for 84 days (overall response rate, 3.8%). One patient with MCL had a 50% decrease in the size of target lesions at 2 months, but this was not sustained at 4 months. In total, nine patients had stable disease for a disease control rate of 38.4%.

“[Flavopiridol] had minimal efficacy in patients with relapsed/refractory non-Hodgkin B-cell lymphoma, casting doubt on the utility of CDK inhibition in this disease,” the researchers wrote.

With respect to safety, there were eight dose-limiting toxicities reported in three patients. These included grade 3 TLS, elevated transaminase levels, hypoalbuminemia, hyperkalemia, non-neutropenic infection, and grade 4 metabolic acidosis and gastrointestinal perforation.

The most common treatment-related toxicities were hematologic, including neutropenia, anemia, thrombocytopenia, leukocytosis, and lymphopenia.

Dr. Miljković and colleagues noted that CDK inhibitor therapy may elicit better responses when used in combination with other agents.

“Ongoing trials of more specific CDK inhibitors in combination with other agents will help elucidate their role in lymphoma treatment,” they wrote.

The trial is sponsored by the National Cancer Institute and the study authors are employees of the National Cancer Institute.

SOURCE: Miljkovic MD et al. Leuk Lymphoma. 2019 Jun 17. doi: 10.1080/10428194.2019.1627540.

Flavopiridol – also known as alvocidib – showed minimal clinical response in patients with relapsed or refractory mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and other B-cell lymphomas, according to results from a single-center, phase 1/2 trial.

“Promising preclinical data in cell lines derived from MCL and activated DLBCL led to a series of clinical trials of flavopiridol in various hematological malignancies,” wrote Milos D. Miljković, MD, and colleagues in the lymphoid malignancies branch of the National Cancer Institute in Bethesda, Md. The findings were published in a letter to the editor in Leukemia & Lymphoma.

The study included 28 patients with relapsed/refractory MCL, DLBCL, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma who received a hybrid dosing regimen of the novel CDK inhibitor. Flavopiridol was administered as a 30-minute bolus, followed by a 4-hour infusion.

The researchers used an intrapatient dose escalation between the first and successive cycles, in addition to a three-plus-three interpatient escalation, to lessen the risk of tumor lysis syndrome (TLS).

The primary outcomes were the clinical response rate, maximum tolerated dose, dose-limiting toxicities, and toxicity profile of the hybrid dosing regimen.

Of 26 evaluable patients, one patient with DLBCL maintained a partial response for 84 days (overall response rate, 3.8%). One patient with MCL had a 50% decrease in the size of target lesions at 2 months, but this was not sustained at 4 months. In total, nine patients had stable disease for a disease control rate of 38.4%.

“[Flavopiridol] had minimal efficacy in patients with relapsed/refractory non-Hodgkin B-cell lymphoma, casting doubt on the utility of CDK inhibition in this disease,” the researchers wrote.

With respect to safety, there were eight dose-limiting toxicities reported in three patients. These included grade 3 TLS, elevated transaminase levels, hypoalbuminemia, hyperkalemia, non-neutropenic infection, and grade 4 metabolic acidosis and gastrointestinal perforation.

The most common treatment-related toxicities were hematologic, including neutropenia, anemia, thrombocytopenia, leukocytosis, and lymphopenia.

Dr. Miljković and colleagues noted that CDK inhibitor therapy may elicit better responses when used in combination with other agents.

“Ongoing trials of more specific CDK inhibitors in combination with other agents will help elucidate their role in lymphoma treatment,” they wrote.

The trial is sponsored by the National Cancer Institute and the study authors are employees of the National Cancer Institute.

SOURCE: Miljkovic MD et al. Leuk Lymphoma. 2019 Jun 17. doi: 10.1080/10428194.2019.1627540.

Nummular dermatitis, or nummular eczema, is an inflammatory skin condition that is considered to be a distinctive form of idiopathic eczema, while the term also is used to describe lesional morphology associated with other conditions.

The term nummular derives from the Latin word for “coin,” as lesions are commonly annular plaques. Lesions of nummular dermatitis can be single or multiple. The typical distribution involves the extremities and, although less common, it can affect the trunk as well. The morphology of lesions is consistent with a localized eczematous reaction, with induration, oozing, crusting, and/or scaling.

Nummular dermatitis may be associated with atopic dermatitis, or it can be an isolated condition.¹ While the pathogenesis is uncertain, instigating factors include xerotic skin, insect bites, or scratches or scrapes.¹Staphylococcus infection or colonization, contact allergies to metals such as nickel and less commonly mercury, sensitivity to formaldehyde or medicines such as neomycin, and sensitization to an environmental aeroallergen (such as Candida albicans, dust mites) are considered risk factors.²

The diagnosis of nummular dermatitis is clinical. Laboratory testing and/or biopsy generally are not necessary, although a bacterial culture can be considered in patients with exudative and/or crusted lesions to rule out impetigo as a primary process of secondary infection. In some cases, patch testing for allergic contact dermatitis may be useful.

The differential diagnosis of nummular dermatitis includes tinea corporis (ringworm), atopic dermatitis, allergic contact dermatitis, impetigo, and psoriasis. Tinea corporis usually presents as annular lesions with a distinct peripheral scaling, rather than the diffuse induration of nummular dermatitis. Potassium hydroxide preparation or fungal culture can identify tinea species. Nummular dermatitis may be seen in patients with atopic dermatitis, who should have typical history, morphology, and course consistent with standard diagnostic criteria. Allergic contact dermatitis can present with regional, localized eczematous plaques in areas exposed to contact allergens. Patterns of lesions in areas of contact and worsening with repeat exposures can be clues to this diagnosis. Impetigo can present with honey-colored crusted lesions and/or superficial erosions, or purulent pyoderma. Lesions can be single or multiple and generally appear less inflammatory than nummular dermatitis. Psoriasis lesions may be annular, are more common on extensor surfaces, and usually have more prominent overlying pinkish, silvery white or micaceous scale.

Management of nummular dermatitis requires strong anti-inflammatory medications, usually mid-potency or higher topical corticosteroids, along with moisturizers and limiting exposure to skin irritants. “Wet wraps,” with application of topical corticosteroids to wet skin with occlusive wet dressings can enhance response. Transition from higher strength topical corticosteroids to lower strength agents used intermittently can help achieve remission or cure. Management practices include less frequent bathing with lukewarm water, using hypoallergenic cleansers and detergents, and applying moisturizers frequently. If plaques do recur, they tend to do so in the same location and in some patients resolution may result in hyper or hypopigmentation. Refractory disease may be managed with intralesional steroid injections, or systemic medications such as methotrexate.³

Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital–San Diego and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Neither Dr. Tracy nor Dr. Eichenfield have any relevant financial disclosures. Email them at [email protected].

References

1. Pediatr Dermatol. 2012 Sep-Oct;29(5):580-3.

2. American Academy of Dermatology. Nummular Dermatitis Overview

3. Pediatr Dermatol. 2018 Sep;35(5):611-5.

Nummular dermatitis, or nummular eczema, is an inflammatory skin condition that is considered to be a distinctive form of idiopathic eczema, while the term also is used to describe lesional morphology associated with other conditions.

The term nummular derives from the Latin word for “coin,” as lesions are commonly annular plaques. Lesions of nummular dermatitis can be single or multiple. The typical distribution involves the extremities and, although less common, it can affect the trunk as well. The morphology of lesions is consistent with a localized eczematous reaction, with induration, oozing, crusting, and/or scaling.

Nummular dermatitis may be associated with atopic dermatitis, or it can be an isolated condition.¹ While the pathogenesis is uncertain, instigating factors include xerotic skin, insect bites, or scratches or scrapes.¹Staphylococcus infection or colonization, contact allergies to metals such as nickel and less commonly mercury, sensitivity to formaldehyde or medicines such as neomycin, and sensitization to an environmental aeroallergen (such as Candida albicans, dust mites) are considered risk factors.²

The diagnosis of nummular dermatitis is clinical. Laboratory testing and/or biopsy generally are not necessary, although a bacterial culture can be considered in patients with exudative and/or crusted lesions to rule out impetigo as a primary process of secondary infection. In some cases, patch testing for allergic contact dermatitis may be useful.

The differential diagnosis of nummular dermatitis includes tinea corporis (ringworm), atopic dermatitis, allergic contact dermatitis, impetigo, and psoriasis. Tinea corporis usually presents as annular lesions with a distinct peripheral scaling, rather than the diffuse induration of nummular dermatitis. Potassium hydroxide preparation or fungal culture can identify tinea species. Nummular dermatitis may be seen in patients with atopic dermatitis, who should have typical history, morphology, and course consistent with standard diagnostic criteria. Allergic contact dermatitis can present with regional, localized eczematous plaques in areas exposed to contact allergens. Patterns of lesions in areas of contact and worsening with repeat exposures can be clues to this diagnosis. Impetigo can present with honey-colored crusted lesions and/or superficial erosions, or purulent pyoderma. Lesions can be single or multiple and generally appear less inflammatory than nummular dermatitis. Psoriasis lesions may be annular, are more common on extensor surfaces, and usually have more prominent overlying pinkish, silvery white or micaceous scale.

Management of nummular dermatitis requires strong anti-inflammatory medications, usually mid-potency or higher topical corticosteroids, along with moisturizers and limiting exposure to skin irritants. “Wet wraps,” with application of topical corticosteroids to wet skin with occlusive wet dressings can enhance response. Transition from higher strength topical corticosteroids to lower strength agents used intermittently can help achieve remission or cure. Management practices include less frequent bathing with lukewarm water, using hypoallergenic cleansers and detergents, and applying moisturizers frequently. If plaques do recur, they tend to do so in the same location and in some patients resolution may result in hyper or hypopigmentation. Refractory disease may be managed with intralesional steroid injections, or systemic medications such as methotrexate.³

Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital–San Diego and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Neither Dr. Tracy nor Dr. Eichenfield have any relevant financial disclosures. Email them at [email protected].

References

1. Pediatr Dermatol. 2012 Sep-Oct;29(5):580-3.

2. American Academy of Dermatology. Nummular Dermatitis Overview

3. Pediatr Dermatol. 2018 Sep;35(5):611-5.

Nummular dermatitis, or nummular eczema, is an inflammatory skin condition that is considered to be a distinctive form of idiopathic eczema, while the term also is used to describe lesional morphology associated with other conditions.

The term nummular derives from the Latin word for “coin,” as lesions are commonly annular plaques. Lesions of nummular dermatitis can be single or multiple. The typical distribution involves the extremities and, although less common, it can affect the trunk as well. The morphology of lesions is consistent with a localized eczematous reaction, with induration, oozing, crusting, and/or scaling.

Nummular dermatitis may be associated with atopic dermatitis, or it can be an isolated condition.¹ While the pathogenesis is uncertain, instigating factors include xerotic skin, insect bites, or scratches or scrapes.¹Staphylococcus infection or colonization, contact allergies to metals such as nickel and less commonly mercury, sensitivity to formaldehyde or medicines such as neomycin, and sensitization to an environmental aeroallergen (such as Candida albicans, dust mites) are considered risk factors.²

The diagnosis of nummular dermatitis is clinical. Laboratory testing and/or biopsy generally are not necessary, although a bacterial culture can be considered in patients with exudative and/or crusted lesions to rule out impetigo as a primary process of secondary infection. In some cases, patch testing for allergic contact dermatitis may be useful.

The differential diagnosis of nummular dermatitis includes tinea corporis (ringworm), atopic dermatitis, allergic contact dermatitis, impetigo, and psoriasis. Tinea corporis usually presents as annular lesions with a distinct peripheral scaling, rather than the diffuse induration of nummular dermatitis. Potassium hydroxide preparation or fungal culture can identify tinea species. Nummular dermatitis may be seen in patients with atopic dermatitis, who should have typical history, morphology, and course consistent with standard diagnostic criteria. Allergic contact dermatitis can present with regional, localized eczematous plaques in areas exposed to contact allergens. Patterns of lesions in areas of contact and worsening with repeat exposures can be clues to this diagnosis. Impetigo can present with honey-colored crusted lesions and/or superficial erosions, or purulent pyoderma. Lesions can be single or multiple and generally appear less inflammatory than nummular dermatitis. Psoriasis lesions may be annular, are more common on extensor surfaces, and usually have more prominent overlying pinkish, silvery white or micaceous scale.

Management of nummular dermatitis requires strong anti-inflammatory medications, usually mid-potency or higher topical corticosteroids, along with moisturizers and limiting exposure to skin irritants. “Wet wraps,” with application of topical corticosteroids to wet skin with occlusive wet dressings can enhance response. Transition from higher strength topical corticosteroids to lower strength agents used intermittently can help achieve remission or cure. Management practices include less frequent bathing with lukewarm water, using hypoallergenic cleansers and detergents, and applying moisturizers frequently. If plaques do recur, they tend to do so in the same location and in some patients resolution may result in hyper or hypopigmentation. Refractory disease may be managed with intralesional steroid injections, or systemic medications such as methotrexate.³

Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital–San Diego and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Neither Dr. Tracy nor Dr. Eichenfield have any relevant financial disclosures. Email them at [email protected].

References

1. Pediatr Dermatol. 2012 Sep-Oct;29(5):580-3.

2. American Academy of Dermatology. Nummular Dermatitis Overview

3. Pediatr Dermatol. 2018 Sep;35(5):611-5.

The majority of adult cigarette smokers in the United States try to quit each year, but there was little change in the rate of quit attempts from 2011 to 2017, according to the Centers for Disease Control and Prevention.

The median percentage of adult smokers who tried to quit cigarettes over the past year went from 64.9% in 2011 to 65.4% in 2017, CDC investigators reported in the Morbidity and Mortality Weekly Report, but the rate has gone down since 2014, when it reached 66.9%.

“The limited progress in increasing quit attempts … together with the variation in quit attempt prevalence among states, underscores the importance of enhanced efforts to motivate and help smokers to quit,” wrote Kimp Walton, MS, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and associates.

State-specific trends in quit-attempt rates reflected the national situation. The prevalence of past-year cessation attempts went up significantly in four states (Kansas, Louisiana, Virginia, and West Virginia) from 2011 to 2017, went down significantly in two states (New York and Tennessee), and did not change significantly in the other 44 states and the District of Columbia, they wrote.

In 2017, cigarette smokers in Connecticut were the most likely to have tried to quit in the past year, with a rate of 71.6%. The only other places with rates greater than 70% were Delaware, D.C., New Jersey, and Texas. The lowest quit-attempt rate that year, 58.6%, belonged to Wisconsin, with Iowa and Missouri the only other states under 60%, the investigators reported based on data from annual Behavioral Risk Factor Surveillance System surveys.


“Because most smokers make multiple quit attempts before succeeding, as many as 30 on average, tobacco dependence is viewed as a chronic, relapsing condition that requires repeated intervention. Smokers should be encouraged to keep trying to quit until they succeed, and health care providers should be encouraged to keep supporting smokers until they quit,” investigators wrote.

[email protected]

SOURCE: Walton K et al. MMWR. 2019 Jul 19;68(28):621-6.

The majority of adult cigarette smokers in the United States try to quit each year, but there was little change in the rate of quit attempts from 2011 to 2017, according to the Centers for Disease Control and Prevention.

The median percentage of adult smokers who tried to quit cigarettes over the past year went from 64.9% in 2011 to 65.4% in 2017, CDC investigators reported in the Morbidity and Mortality Weekly Report, but the rate has gone down since 2014, when it reached 66.9%.

“The limited progress in increasing quit attempts … together with the variation in quit attempt prevalence among states, underscores the importance of enhanced efforts to motivate and help smokers to quit,” wrote Kimp Walton, MS, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and associates.

State-specific trends in quit-attempt rates reflected the national situation. The prevalence of past-year cessation attempts went up significantly in four states (Kansas, Louisiana, Virginia, and West Virginia) from 2011 to 2017, went down significantly in two states (New York and Tennessee), and did not change significantly in the other 44 states and the District of Columbia, they wrote.

In 2017, cigarette smokers in Connecticut were the most likely to have tried to quit in the past year, with a rate of 71.6%. The only other places with rates greater than 70% were Delaware, D.C., New Jersey, and Texas. The lowest quit-attempt rate that year, 58.6%, belonged to Wisconsin, with Iowa and Missouri the only other states under 60%, the investigators reported based on data from annual Behavioral Risk Factor Surveillance System surveys.


“Because most smokers make multiple quit attempts before succeeding, as many as 30 on average, tobacco dependence is viewed as a chronic, relapsing condition that requires repeated intervention. Smokers should be encouraged to keep trying to quit until they succeed, and health care providers should be encouraged to keep supporting smokers until they quit,” investigators wrote.

[email protected]

SOURCE: Walton K et al. MMWR. 2019 Jul 19;68(28):621-6.

The majority of adult cigarette smokers in the United States try to quit each year, but there was little change in the rate of quit attempts from 2011 to 2017, according to the Centers for Disease Control and Prevention.

The median percentage of adult smokers who tried to quit cigarettes over the past year went from 64.9% in 2011 to 65.4% in 2017, CDC investigators reported in the Morbidity and Mortality Weekly Report, but the rate has gone down since 2014, when it reached 66.9%.

“The limited progress in increasing quit attempts … together with the variation in quit attempt prevalence among states, underscores the importance of enhanced efforts to motivate and help smokers to quit,” wrote Kimp Walton, MS, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and associates.

State-specific trends in quit-attempt rates reflected the national situation. The prevalence of past-year cessation attempts went up significantly in four states (Kansas, Louisiana, Virginia, and West Virginia) from 2011 to 2017, went down significantly in two states (New York and Tennessee), and did not change significantly in the other 44 states and the District of Columbia, they wrote.

In 2017, cigarette smokers in Connecticut were the most likely to have tried to quit in the past year, with a rate of 71.6%. The only other places with rates greater than 70% were Delaware, D.C., New Jersey, and Texas. The lowest quit-attempt rate that year, 58.6%, belonged to Wisconsin, with Iowa and Missouri the only other states under 60%, the investigators reported based on data from annual Behavioral Risk Factor Surveillance System surveys.


“Because most smokers make multiple quit attempts before succeeding, as many as 30 on average, tobacco dependence is viewed as a chronic, relapsing condition that requires repeated intervention. Smokers should be encouraged to keep trying to quit until they succeed, and health care providers should be encouraged to keep supporting smokers until they quit,” investigators wrote.

[email protected]

SOURCE: Walton K et al. MMWR. 2019 Jul 19;68(28):621-6.

Background: Acute cystitis is a common condition in women and associated with morbidity. A commonly recommended preventative measure is increased oral hydration, but there is limited evidence to support this claim.

Though antibiotic prophylaxis is more effective at reducing cystitis, increased daily water intake is a safe and inexpensive method to prevent cystitis without increasing exposure to antimicrobial therapy. This study did rely on information obtained from phone calls with patients. It is also an open-label study design in which patients were not blinded to their assigned group. This would be less of an issue if episodes of cystitis were confirmed with culture. Another limitation of this study is that it included only ambulatory patients and excluded patients with pyelonephritis, so it may be less applicable to our hospitalized patients.

Bottom line: This study shows a benefit in recurrent cystitis by increased water intake in premenopausal women.

Citation: Hooton TM et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med. 2018 Nov;178(11):1509-15.

Dr. Astik is medical director, clinical documentation, at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Acute cystitis is a common condition in women and associated with morbidity. A commonly recommended preventative measure is increased oral hydration, but there is limited evidence to support this claim.

Though antibiotic prophylaxis is more effective at reducing cystitis, increased daily water intake is a safe and inexpensive method to prevent cystitis without increasing exposure to antimicrobial therapy. This study did rely on information obtained from phone calls with patients. It is also an open-label study design in which patients were not blinded to their assigned group. This would be less of an issue if episodes of cystitis were confirmed with culture. Another limitation of this study is that it included only ambulatory patients and excluded patients with pyelonephritis, so it may be less applicable to our hospitalized patients.

Bottom line: This study shows a benefit in recurrent cystitis by increased water intake in premenopausal women.

Citation: Hooton TM et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med. 2018 Nov;178(11):1509-15.

Dr. Astik is medical director, clinical documentation, at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Background: Acute cystitis is a common condition in women and associated with morbidity. A commonly recommended preventative measure is increased oral hydration, but there is limited evidence to support this claim.

Though antibiotic prophylaxis is more effective at reducing cystitis, increased daily water intake is a safe and inexpensive method to prevent cystitis without increasing exposure to antimicrobial therapy. This study did rely on information obtained from phone calls with patients. It is also an open-label study design in which patients were not blinded to their assigned group. This would be less of an issue if episodes of cystitis were confirmed with culture. Another limitation of this study is that it included only ambulatory patients and excluded patients with pyelonephritis, so it may be less applicable to our hospitalized patients.

Bottom line: This study shows a benefit in recurrent cystitis by increased water intake in premenopausal women.

Citation: Hooton TM et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections. JAMA Intern Med. 2018 Nov;178(11):1509-15.

Dr. Astik is medical director, clinical documentation, at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

The number of pregnancies among women taking isotretinoin has decreased since the introduction of the iPledge program, but pregnancy, abortions, and fetal defects associated with isotretinoin exposure are still occurring in women of reproductive age, according to a retrospective study published in JAMA Dermatology.

In 2006, the Food and Drug Administration implemented the iPledge program, with requirements that include women of childbearing age having a negative pregnancy test and evidence of using two forms of contraception monthly to use isotretinoin, a teratogen. “Although the number of pregnancy-related adverse events for patients taking isotretinoin has decreased since 2006, pregnancies, abortions, and fetal defects associated with isotretinoin exposure continue to be a problem,” Elizabeth Tkachenko, BS, from the University of Massachusetts Medical School, Worcester, and coauthors concluded. “Further research is required to determine the most efficacious system to reduce complications for patients and administrative requirements for physicians while at the same time maintaining access to this important drug.” (iPledge followed other Risk Evaluation and Mitigation Strategy systems for isotretinoin.)

She and her colleagues performed a retrospective evaluation of pregnancy-related adverse events related to isotretinoin that had occurred between January 1997 and December 2017 using the FDA Adverse Event Reporting System (FAERS), which receives reports from prescribers, consumers, and pharmaceutical manufacturers. While there could be many different classification terms for each individual, any number of adverse events reported by an individual was counted as one pregnancy. Ms. Tkachenko and colleagues classified abortions, pregnancies during contraception use, and pregnancy-related defects into separate subgroups for analysis.

From 1997 to 2017, there were 6,740 pregnancies among women (mean age, 24.6 years) during treatment with isotretinoin reported to FAERS, with 7 reports in 1997, and a peak of 768 pregnancies in 2006. Almost 70% (4,647) of the pregnancies were reported after iPledge was introduced. Between 2011 and 2017, there were 218-310 pregnancy reports each year.

Of the total number of pregnancy reports during the study period, 1,896 were abortions (28.1% of the total); 10.9% of the total number of pregnancy reports were spontaneous abortions (733). The number of abortions peaked in 2008, with 291 reports, of which 85% were therapeutic abortions. Also peaking in 2008 was the number of reports of pregnancies while taking a contraceptive (64). After 2008, pregnancies and abortions dropped.

Fetal defects peaked in 2000, with 34 cases reported, and dropped to four or fewer reports annually after 2008.

“Our findings demonstrate that reports of pregnancy among women taking isotretinoin are concentrated among those aged 20 to 29 years, peaked in 2006, and have been consistent since 2011,” the authors wrote.

Limitations of the study, they noted, include limitations of FAERS data and possible reporting fatigue among doctors and patients. The total number of isotretinoin courses prescribed to this patient population is also unknown, which affected their ability to determine the true rate of pregnancy-related adverse events, they noted.

The other authors for this study were from Harvard Medical School and the departments of dermatology at Brigham and Women’s Hospital, both in Boston, as well as the University of Pennsylvania, Philadelphia. One author reported support from an award by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and salary support from a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the trustees of the University of Pennsylvania. The other authors reported no relevant conflicts of interest.

SOURCE: Tkachenko E et al. JAMA Dermatol. 2019. doi: 10.1001/jamadermatol.2019.1388.

The number of pregnancies among women taking isotretinoin has decreased since the introduction of the iPledge program, but pregnancy, abortions, and fetal defects associated with isotretinoin exposure are still occurring in women of reproductive age, according to a retrospective study published in JAMA Dermatology.

In 2006, the Food and Drug Administration implemented the iPledge program, with requirements that include women of childbearing age having a negative pregnancy test and evidence of using two forms of contraception monthly to use isotretinoin, a teratogen. “Although the number of pregnancy-related adverse events for patients taking isotretinoin has decreased since 2006, pregnancies, abortions, and fetal defects associated with isotretinoin exposure continue to be a problem,” Elizabeth Tkachenko, BS, from the University of Massachusetts Medical School, Worcester, and coauthors concluded. “Further research is required to determine the most efficacious system to reduce complications for patients and administrative requirements for physicians while at the same time maintaining access to this important drug.” (iPledge followed other Risk Evaluation and Mitigation Strategy systems for isotretinoin.)

She and her colleagues performed a retrospective evaluation of pregnancy-related adverse events related to isotretinoin that had occurred between January 1997 and December 2017 using the FDA Adverse Event Reporting System (FAERS), which receives reports from prescribers, consumers, and pharmaceutical manufacturers. While there could be many different classification terms for each individual, any number of adverse events reported by an individual was counted as one pregnancy. Ms. Tkachenko and colleagues classified abortions, pregnancies during contraception use, and pregnancy-related defects into separate subgroups for analysis.

From 1997 to 2017, there were 6,740 pregnancies among women (mean age, 24.6 years) during treatment with isotretinoin reported to FAERS, with 7 reports in 1997, and a peak of 768 pregnancies in 2006. Almost 70% (4,647) of the pregnancies were reported after iPledge was introduced. Between 2011 and 2017, there were 218-310 pregnancy reports each year.

Of the total number of pregnancy reports during the study period, 1,896 were abortions (28.1% of the total); 10.9% of the total number of pregnancy reports were spontaneous abortions (733). The number of abortions peaked in 2008, with 291 reports, of which 85% were therapeutic abortions. Also peaking in 2008 was the number of reports of pregnancies while taking a contraceptive (64). After 2008, pregnancies and abortions dropped.

Fetal defects peaked in 2000, with 34 cases reported, and dropped to four or fewer reports annually after 2008.

“Our findings demonstrate that reports of pregnancy among women taking isotretinoin are concentrated among those aged 20 to 29 years, peaked in 2006, and have been consistent since 2011,” the authors wrote.

Limitations of the study, they noted, include limitations of FAERS data and possible reporting fatigue among doctors and patients. The total number of isotretinoin courses prescribed to this patient population is also unknown, which affected their ability to determine the true rate of pregnancy-related adverse events, they noted.

The other authors for this study were from Harvard Medical School and the departments of dermatology at Brigham and Women’s Hospital, both in Boston, as well as the University of Pennsylvania, Philadelphia. One author reported support from an award by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and salary support from a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the trustees of the University of Pennsylvania. The other authors reported no relevant conflicts of interest.

SOURCE: Tkachenko E et al. JAMA Dermatol. 2019. doi: 10.1001/jamadermatol.2019.1388.

The number of pregnancies among women taking isotretinoin has decreased since the introduction of the iPledge program, but pregnancy, abortions, and fetal defects associated with isotretinoin exposure are still occurring in women of reproductive age, according to a retrospective study published in JAMA Dermatology.

In 2006, the Food and Drug Administration implemented the iPledge program, with requirements that include women of childbearing age having a negative pregnancy test and evidence of using two forms of contraception monthly to use isotretinoin, a teratogen. “Although the number of pregnancy-related adverse events for patients taking isotretinoin has decreased since 2006, pregnancies, abortions, and fetal defects associated with isotretinoin exposure continue to be a problem,” Elizabeth Tkachenko, BS, from the University of Massachusetts Medical School, Worcester, and coauthors concluded. “Further research is required to determine the most efficacious system to reduce complications for patients and administrative requirements for physicians while at the same time maintaining access to this important drug.” (iPledge followed other Risk Evaluation and Mitigation Strategy systems for isotretinoin.)

She and her colleagues performed a retrospective evaluation of pregnancy-related adverse events related to isotretinoin that had occurred between January 1997 and December 2017 using the FDA Adverse Event Reporting System (FAERS), which receives reports from prescribers, consumers, and pharmaceutical manufacturers. While there could be many different classification terms for each individual, any number of adverse events reported by an individual was counted as one pregnancy. Ms. Tkachenko and colleagues classified abortions, pregnancies during contraception use, and pregnancy-related defects into separate subgroups for analysis.

From 1997 to 2017, there were 6,740 pregnancies among women (mean age, 24.6 years) during treatment with isotretinoin reported to FAERS, with 7 reports in 1997, and a peak of 768 pregnancies in 2006. Almost 70% (4,647) of the pregnancies were reported after iPledge was introduced. Between 2011 and 2017, there were 218-310 pregnancy reports each year.

Of the total number of pregnancy reports during the study period, 1,896 were abortions (28.1% of the total); 10.9% of the total number of pregnancy reports were spontaneous abortions (733). The number of abortions peaked in 2008, with 291 reports, of which 85% were therapeutic abortions. Also peaking in 2008 was the number of reports of pregnancies while taking a contraceptive (64). After 2008, pregnancies and abortions dropped.

Fetal defects peaked in 2000, with 34 cases reported, and dropped to four or fewer reports annually after 2008.

“Our findings demonstrate that reports of pregnancy among women taking isotretinoin are concentrated among those aged 20 to 29 years, peaked in 2006, and have been consistent since 2011,” the authors wrote.

Limitations of the study, they noted, include limitations of FAERS data and possible reporting fatigue among doctors and patients. The total number of isotretinoin courses prescribed to this patient population is also unknown, which affected their ability to determine the true rate of pregnancy-related adverse events, they noted.

The other authors for this study were from Harvard Medical School and the departments of dermatology at Brigham and Women’s Hospital, both in Boston, as well as the University of Pennsylvania, Philadelphia. One author reported support from an award by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and salary support from a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the trustees of the University of Pennsylvania. The other authors reported no relevant conflicts of interest.

SOURCE: Tkachenko E et al. JAMA Dermatol. 2019. doi: 10.1001/jamadermatol.2019.1388.

Researchers have characterized the clinical presentation, progression, and prognosis of leukemia cutis in a pediatric population, according to findings from a retrospective case series.

“To our knowledge, this is the largest reported case series of pediatric leukemia cutis,” wrote Elena Corina Andriescu of the University of Texas, Houston, and colleagues. The results were published in Pediatric Dermatology.

The study included 31 children with histologically confirmed leukemia cutis at one of two pediatric institutions. The researchers reviewed medical records to distinguish common features among patients.

Various clinical data, including disease subtype, related symptoms, management, and prognosis, were collected from January 1993 to March 2014. The children in the case series ranged in age up to 19 years with a median age at diagnosis of 26.8 months.

After analysis, the researchers reported that the magnitude and morphology of disease lesions differed among pediatric patients, with the most common sites being the lower extremities and head. The most common morphologies were nodules and papules. Additionally, the researchers found that lesions were often erythematous, violaceous, or both colors.

The majority of patients (65%) presented with concomitant systemic leukemia and leukemia cutis. The most common types of leukemia associated with the skin condition were acute myeloid leukemia (in 74% of cases) and acute lymphoblastic leukemia (in 16% of cases). The researchers saw no significant differences in leukemia cutis morphology or distribution based on the leukemia diagnosis.

“Most cases of leukemia cutis arose during initial leukemia episodes, rather than with relapsed leukemia,” they added.

Because of an insufficiency of specific genetic data, investigators were unable to make prognostic inferences in the majority of participants.

Two key limitations of the study were the small sample size and retrospective design. As a result, the investigators were unable to prospectively classify skin findings in a systematic manner. Despite these limitations, the authors noted that these findings add to the present knowledge of leukemia cutis in pediatric patients.

“Importantly, the presence of [leukemia cutis] changed the management of systemic leukemia in one‐third of patients,” the researchers wrote. “The potential for major changes in treatment plans such as adding radiation therapy and deferring hematopoietic stem cell transplantation underscores the importance of diagnosing [leukemia cutis].”

No funding sources were reported. The authors did not report conflicts of interest.

SOURCE: Andriescu EC et al. Pediatr Dermatol. 2019 Jul 5. doi: 10.1111/pde.13864.

Researchers have characterized the clinical presentation, progression, and prognosis of leukemia cutis in a pediatric population, according to findings from a retrospective case series.

“To our knowledge, this is the largest reported case series of pediatric leukemia cutis,” wrote Elena Corina Andriescu of the University of Texas, Houston, and colleagues. The results were published in Pediatric Dermatology.

The study included 31 children with histologically confirmed leukemia cutis at one of two pediatric institutions. The researchers reviewed medical records to distinguish common features among patients.

Various clinical data, including disease subtype, related symptoms, management, and prognosis, were collected from January 1993 to March 2014. The children in the case series ranged in age up to 19 years with a median age at diagnosis of 26.8 months.

After analysis, the researchers reported that the magnitude and morphology of disease lesions differed among pediatric patients, with the most common sites being the lower extremities and head. The most common morphologies were nodules and papules. Additionally, the researchers found that lesions were often erythematous, violaceous, or both colors.

The majority of patients (65%) presented with concomitant systemic leukemia and leukemia cutis. The most common types of leukemia associated with the skin condition were acute myeloid leukemia (in 74% of cases) and acute lymphoblastic leukemia (in 16% of cases). The researchers saw no significant differences in leukemia cutis morphology or distribution based on the leukemia diagnosis.

“Most cases of leukemia cutis arose during initial leukemia episodes, rather than with relapsed leukemia,” they added.

Because of an insufficiency of specific genetic data, investigators were unable to make prognostic inferences in the majority of participants.

Two key limitations of the study were the small sample size and retrospective design. As a result, the investigators were unable to prospectively classify skin findings in a systematic manner. Despite these limitations, the authors noted that these findings add to the present knowledge of leukemia cutis in pediatric patients.

“Importantly, the presence of [leukemia cutis] changed the management of systemic leukemia in one‐third of patients,” the researchers wrote. “The potential for major changes in treatment plans such as adding radiation therapy and deferring hematopoietic stem cell transplantation underscores the importance of diagnosing [leukemia cutis].”

No funding sources were reported. The authors did not report conflicts of interest.

SOURCE: Andriescu EC et al. Pediatr Dermatol. 2019 Jul 5. doi: 10.1111/pde.13864.

Researchers have characterized the clinical presentation, progression, and prognosis of leukemia cutis in a pediatric population, according to findings from a retrospective case series.

“To our knowledge, this is the largest reported case series of pediatric leukemia cutis,” wrote Elena Corina Andriescu of the University of Texas, Houston, and colleagues. The results were published in Pediatric Dermatology.

The study included 31 children with histologically confirmed leukemia cutis at one of two pediatric institutions. The researchers reviewed medical records to distinguish common features among patients.

Various clinical data, including disease subtype, related symptoms, management, and prognosis, were collected from January 1993 to March 2014. The children in the case series ranged in age up to 19 years with a median age at diagnosis of 26.8 months.

After analysis, the researchers reported that the magnitude and morphology of disease lesions differed among pediatric patients, with the most common sites being the lower extremities and head. The most common morphologies were nodules and papules. Additionally, the researchers found that lesions were often erythematous, violaceous, or both colors.

The majority of patients (65%) presented with concomitant systemic leukemia and leukemia cutis. The most common types of leukemia associated with the skin condition were acute myeloid leukemia (in 74% of cases) and acute lymphoblastic leukemia (in 16% of cases). The researchers saw no significant differences in leukemia cutis morphology or distribution based on the leukemia diagnosis.

“Most cases of leukemia cutis arose during initial leukemia episodes, rather than with relapsed leukemia,” they added.

Because of an insufficiency of specific genetic data, investigators were unable to make prognostic inferences in the majority of participants.

Two key limitations of the study were the small sample size and retrospective design. As a result, the investigators were unable to prospectively classify skin findings in a systematic manner. Despite these limitations, the authors noted that these findings add to the present knowledge of leukemia cutis in pediatric patients.

“Importantly, the presence of [leukemia cutis] changed the management of systemic leukemia in one‐third of patients,” the researchers wrote. “The potential for major changes in treatment plans such as adding radiation therapy and deferring hematopoietic stem cell transplantation underscores the importance of diagnosing [leukemia cutis].”

No funding sources were reported. The authors did not report conflicts of interest.

SOURCE: Andriescu EC et al. Pediatr Dermatol. 2019 Jul 5. doi: 10.1111/pde.13864.

CHICAGO – Ovarian cancer diagnoses – and treatment within 30 days of diagnosis – occur earlier under the Affordable Care Act, according to a comparison of National Cancer Database surveys from 2006-2009 and 2011-2014.

During the post-Affordable Care Act (ACA) years of 2011-2014, compared with the pre-ACA years of 2004-2009, a treatment group of women aged 21-64 years with ovarian cancer was more likely to be diagnosed at an early stage, compared with a control group of women aged 65 years and older (difference-in-differences [DD]=1.7%), Anna Jo Smith, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Also, the ACA was associated with more women aged 21-64 receiving treatment within 30 days of diagnosis (DD = 1.6%), said Dr. Smith, a 4th-year resident at Johns Hopkins University, Baltimore.

Among women with public insurance, the ACA was associated with even greater improvement in early-stage diagnosis and treatment within 30 days in the treatment group vs. the controls (DD = 2.5% for each), she said, noting that the improvements were seen across race, income, and education groups.

The findings are based on pre-ACA surveys from 35,842 women aged 21-64 years and 28,895 women aged 65 years, and from post-ACA surveys from 37,145 women and 30,604 women in those age groups, respectively, and were adjusted for patient race, living in a rural area, area-level household income and education level, Charlson comorbidity score, distance traveled for care, Census region, and care at an academic center.

The 2010 ACA expanded access to insurance and care for many Americans, and the objective of this study was to evaluate the impact of that access on women with ovarian cancer, Dr. Smith explained.

“Under the 2010 Affordable Care Act, women with ovarian cancer were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis,” she said. “As stage and treatment are the major determinants of survival advantage, these gains under the ACA may have long-term impacts on the survival, health, and well-being of women with ovarian cancer.”

Dr. Smith reported having no disclosures.

SOURCE: Smith A et al., ASCO 2019. Abstract LBA5563.

CHICAGO – Ovarian cancer diagnoses – and treatment within 30 days of diagnosis – occur earlier under the Affordable Care Act, according to a comparison of National Cancer Database surveys from 2006-2009 and 2011-2014.

During the post-Affordable Care Act (ACA) years of 2011-2014, compared with the pre-ACA years of 2004-2009, a treatment group of women aged 21-64 years with ovarian cancer was more likely to be diagnosed at an early stage, compared with a control group of women aged 65 years and older (difference-in-differences [DD]=1.7%), Anna Jo Smith, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Also, the ACA was associated with more women aged 21-64 receiving treatment within 30 days of diagnosis (DD = 1.6%), said Dr. Smith, a 4th-year resident at Johns Hopkins University, Baltimore.

Among women with public insurance, the ACA was associated with even greater improvement in early-stage diagnosis and treatment within 30 days in the treatment group vs. the controls (DD = 2.5% for each), she said, noting that the improvements were seen across race, income, and education groups.

The findings are based on pre-ACA surveys from 35,842 women aged 21-64 years and 28,895 women aged 65 years, and from post-ACA surveys from 37,145 women and 30,604 women in those age groups, respectively, and were adjusted for patient race, living in a rural area, area-level household income and education level, Charlson comorbidity score, distance traveled for care, Census region, and care at an academic center.

The 2010 ACA expanded access to insurance and care for many Americans, and the objective of this study was to evaluate the impact of that access on women with ovarian cancer, Dr. Smith explained.

“Under the 2010 Affordable Care Act, women with ovarian cancer were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis,” she said. “As stage and treatment are the major determinants of survival advantage, these gains under the ACA may have long-term impacts on the survival, health, and well-being of women with ovarian cancer.”

Dr. Smith reported having no disclosures.

SOURCE: Smith A et al., ASCO 2019. Abstract LBA5563.

CHICAGO – Ovarian cancer diagnoses – and treatment within 30 days of diagnosis – occur earlier under the Affordable Care Act, according to a comparison of National Cancer Database surveys from 2006-2009 and 2011-2014.

During the post-Affordable Care Act (ACA) years of 2011-2014, compared with the pre-ACA years of 2004-2009, a treatment group of women aged 21-64 years with ovarian cancer was more likely to be diagnosed at an early stage, compared with a control group of women aged 65 years and older (difference-in-differences [DD]=1.7%), Anna Jo Smith, MD, reported at the annual meeting of the American Society of Clinical Oncology.

Also, the ACA was associated with more women aged 21-64 receiving treatment within 30 days of diagnosis (DD = 1.6%), said Dr. Smith, a 4th-year resident at Johns Hopkins University, Baltimore.

Among women with public insurance, the ACA was associated with even greater improvement in early-stage diagnosis and treatment within 30 days in the treatment group vs. the controls (DD = 2.5% for each), she said, noting that the improvements were seen across race, income, and education groups.

The findings are based on pre-ACA surveys from 35,842 women aged 21-64 years and 28,895 women aged 65 years, and from post-ACA surveys from 37,145 women and 30,604 women in those age groups, respectively, and were adjusted for patient race, living in a rural area, area-level household income and education level, Charlson comorbidity score, distance traveled for care, Census region, and care at an academic center.

The 2010 ACA expanded access to insurance and care for many Americans, and the objective of this study was to evaluate the impact of that access on women with ovarian cancer, Dr. Smith explained.

“Under the 2010 Affordable Care Act, women with ovarian cancer were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis,” she said. “As stage and treatment are the major determinants of survival advantage, these gains under the ACA may have long-term impacts on the survival, health, and well-being of women with ovarian cancer.”

Dr. Smith reported having no disclosures.

SOURCE: Smith A et al., ASCO 2019. Abstract LBA5563.

In a recent article on this website, Jake Remaly reports on a study suggesting that maternal migraine is associated with infant colic. In a presentation at the annual meeting of the American Headache Society, Amy Gelfand, MD, a neurologist at the University of California, San Francisco, reported the results of a national survey of more than 1,400 parents (827 mothers, 592 fathers) collected via social media. She and her colleagues found that mothers with migraine were more likely to have an infant with colic, with an odds ratio of 1.7 that increased to 2.5 for mothers with more frequent migraine. Fathers with migraine were no more likely to have an infant with colic.

AntonioGuillem/Gety Images

In a video clip included in the article, Dr. Gelfand discusses the possibilities that she and her group considered as they attempted to explain the study’s findings. Are there such things as “migraine genes?” If so, the failure to discover a paternal association might suggest that these would be mitochondrial genes. The researchers wondered if a substance in breast milk was acting as trigger, but they found that the association between colic and migraine was unrelated to whether the baby was fed by breast or bottle.

In full disclosure, I was not one of the investigators. Neither my wife nor I have migraine, and although our children cried as infants, they wouldn’t have qualified as having colic. However, I spent more than 40 years immersed in more than 300,000 patient encounters and can claim membership in the International Brother/Sisterhood of Anecdotal Observers. And, as such will offer up my explanation for Dr. Gelfand’s findings.

It is clear to me that most, if not all, children with migraine have their headaches when they are sleep deprived. While my sample size is smaller, I believe the same association also is true for many of the adults I know who have migraine. At least in children, restorative sleep ends the migraine much as it does for an epileptic seizure.

Traditionally, colic has been thought to be somehow related to a gastrointestinal phenomenon by many extended family members and some physicians. However, in my experience, it is usually a symptom of sleep deprivation compounded by the failure of those around the children to realize the obvious and take appropriate action. Of course, some babies are reacting to sore tummies, but my guess is that most are having headaches. We may never know. Dr. Gelfand also shares my observation that colicky crying is more likely to occur “at the end of the day,” a time when we are tired and are less tolerant of overstimulation.

For decades, I have been convinced that migraine and colic are the same pathophysiologic process. However, the presentation varies depending on the age of the patients. Remember, infants can’t talk. It already has been shown that adults with migraine often were more likely to have been colicky infants. (Dr. Gelfand mentions this as well.) These unfortunate individuals probably have inherited a vulnerability to sleep deprivation that manifests itself as a headache. I hope to live long enough to be around when someone discovers the wrinkle in the genome that creates this vulnerability.

So, why did the researchers fail to find an association between fathers and colic? The answer is simple. We fathers are beginning to take on a larger role in parenting of infants and like to complain about how difficult it is. However, it is mothers who still have the lioness’ share of the work. They lose the most sleep and are starting off parenthood with 9 months of less than optimal sleep followed by who knows how many hours of energy-sapping labor. It’s surprising they all don’t have migraines.
 

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].

In a recent article on this website, Jake Remaly reports on a study suggesting that maternal migraine is associated with infant colic. In a presentation at the annual meeting of the American Headache Society, Amy Gelfand, MD, a neurologist at the University of California, San Francisco, reported the results of a national survey of more than 1,400 parents (827 mothers, 592 fathers) collected via social media. She and her colleagues found that mothers with migraine were more likely to have an infant with colic, with an odds ratio of 1.7 that increased to 2.5 for mothers with more frequent migraine. Fathers with migraine were no more likely to have an infant with colic.

AntonioGuillem/Gety Images

In a video clip included in the article, Dr. Gelfand discusses the possibilities that she and her group considered as they attempted to explain the study’s findings. Are there such things as “migraine genes?” If so, the failure to discover a paternal association might suggest that these would be mitochondrial genes. The researchers wondered if a substance in breast milk was acting as trigger, but they found that the association between colic and migraine was unrelated to whether the baby was fed by breast or bottle.

In full disclosure, I was not one of the investigators. Neither my wife nor I have migraine, and although our children cried as infants, they wouldn’t have qualified as having colic. However, I spent more than 40 years immersed in more than 300,000 patient encounters and can claim membership in the International Brother/Sisterhood of Anecdotal Observers. And, as such will offer up my explanation for Dr. Gelfand’s findings.

It is clear to me that most, if not all, children with migraine have their headaches when they are sleep deprived. While my sample size is smaller, I believe the same association also is true for many of the adults I know who have migraine. At least in children, restorative sleep ends the migraine much as it does for an epileptic seizure.

Traditionally, colic has been thought to be somehow related to a gastrointestinal phenomenon by many extended family members and some physicians. However, in my experience, it is usually a symptom of sleep deprivation compounded by the failure of those around the children to realize the obvious and take appropriate action. Of course, some babies are reacting to sore tummies, but my guess is that most are having headaches. We may never know. Dr. Gelfand also shares my observation that colicky crying is more likely to occur “at the end of the day,” a time when we are tired and are less tolerant of overstimulation.

For decades, I have been convinced that migraine and colic are the same pathophysiologic process. However, the presentation varies depending on the age of the patients. Remember, infants can’t talk. It already has been shown that adults with migraine often were more likely to have been colicky infants. (Dr. Gelfand mentions this as well.) These unfortunate individuals probably have inherited a vulnerability to sleep deprivation that manifests itself as a headache. I hope to live long enough to be around when someone discovers the wrinkle in the genome that creates this vulnerability.

So, why did the researchers fail to find an association between fathers and colic? The answer is simple. We fathers are beginning to take on a larger role in parenting of infants and like to complain about how difficult it is. However, it is mothers who still have the lioness’ share of the work. They lose the most sleep and are starting off parenthood with 9 months of less than optimal sleep followed by who knows how many hours of energy-sapping labor. It’s surprising they all don’t have migraines.
 

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].

In a recent article on this website, Jake Remaly reports on a study suggesting that maternal migraine is associated with infant colic. In a presentation at the annual meeting of the American Headache Society, Amy Gelfand, MD, a neurologist at the University of California, San Francisco, reported the results of a national survey of more than 1,400 parents (827 mothers, 592 fathers) collected via social media. She and her colleagues found that mothers with migraine were more likely to have an infant with colic, with an odds ratio of 1.7 that increased to 2.5 for mothers with more frequent migraine. Fathers with migraine were no more likely to have an infant with colic.

AntonioGuillem/Gety Images

In a video clip included in the article, Dr. Gelfand discusses the possibilities that she and her group considered as they attempted to explain the study’s findings. Are there such things as “migraine genes?” If so, the failure to discover a paternal association might suggest that these would be mitochondrial genes. The researchers wondered if a substance in breast milk was acting as trigger, but they found that the association between colic and migraine was unrelated to whether the baby was fed by breast or bottle.

In full disclosure, I was not one of the investigators. Neither my wife nor I have migraine, and although our children cried as infants, they wouldn’t have qualified as having colic. However, I spent more than 40 years immersed in more than 300,000 patient encounters and can claim membership in the International Brother/Sisterhood of Anecdotal Observers. And, as such will offer up my explanation for Dr. Gelfand’s findings.

It is clear to me that most, if not all, children with migraine have their headaches when they are sleep deprived. While my sample size is smaller, I believe the same association also is true for many of the adults I know who have migraine. At least in children, restorative sleep ends the migraine much as it does for an epileptic seizure.

Traditionally, colic has been thought to be somehow related to a gastrointestinal phenomenon by many extended family members and some physicians. However, in my experience, it is usually a symptom of sleep deprivation compounded by the failure of those around the children to realize the obvious and take appropriate action. Of course, some babies are reacting to sore tummies, but my guess is that most are having headaches. We may never know. Dr. Gelfand also shares my observation that colicky crying is more likely to occur “at the end of the day,” a time when we are tired and are less tolerant of overstimulation.

For decades, I have been convinced that migraine and colic are the same pathophysiologic process. However, the presentation varies depending on the age of the patients. Remember, infants can’t talk. It already has been shown that adults with migraine often were more likely to have been colicky infants. (Dr. Gelfand mentions this as well.) These unfortunate individuals probably have inherited a vulnerability to sleep deprivation that manifests itself as a headache. I hope to live long enough to be around when someone discovers the wrinkle in the genome that creates this vulnerability.

So, why did the researchers fail to find an association between fathers and colic? The answer is simple. We fathers are beginning to take on a larger role in parenting of infants and like to complain about how difficult it is. However, it is mothers who still have the lioness’ share of the work. They lose the most sleep and are starting off parenthood with 9 months of less than optimal sleep followed by who knows how many hours of energy-sapping labor. It’s surprising they all don’t have migraines.
 

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].

The Food and Drug Administration has rejected AstraZeneca’s supplemental New Drug Application for the sodium-glucose cotransporter 2 inhibitor dapagliflozin (Farxiga) as an adjunct treatment to insulin in adult patients with type 1 diabetes.

The company said in a press statement that the FDA had issued a complete response letter regarding the application. No reason was given for the decision, but the company said it would work with the agency to discuss the next steps.

The once-daily therapy has been approved as both a monotherapy and combination therapy, as an adjunct to diet and exercise, for improving glycemic control in adults with type 2 diabetes who cannot achieve control with insulin alone. It also has additional demonstrated benefits of weight loss and reduction in blood pressure.

On March 25, 2019, the drug received its first approval for treatment of patients with type 1 diabetes when the European Commission gave it the green light for use in patients with a body mass index of 27 kg/m² or more when insulin alone does not provide adequate glycemic control. Japan followed a few days later with its approval of the sodium-glucose cotransporter 2 inhibitor, also for type 1 disease in adults.

The approvals for type 1 diabetes in the European Union and Japan were based on data from the phase 3 DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) trial program (DEPICT-1 and DEPICT-2), which showed that 5 mg dapagliflozin, taken daily as an oral adjunct to insulin in patients with hard-to-control type 1 disease, reduced blood glucose levels from baseline (the primary endpoint). Secondary endpoints – reductions in weight and total daily insulin use – were also achieved.

Dapagliflozin’s safety profile in the trials in patients with type 1 diabetes was consistent with that established in patients with type 2 disease. However, there was a higher number of cases of diabetic ketoacidosis events in patients who received dapagliflozin. Diabetic ketoacidosis is a known complication for adults with type 1 diabetes and is more prevalent in patients with type 1 disease than in those with type 2.

The Food and Drug Administration has rejected AstraZeneca’s supplemental New Drug Application for the sodium-glucose cotransporter 2 inhibitor dapagliflozin (Farxiga) as an adjunct treatment to insulin in adult patients with type 1 diabetes.

The company said in a press statement that the FDA had issued a complete response letter regarding the application. No reason was given for the decision, but the company said it would work with the agency to discuss the next steps.

The once-daily therapy has been approved as both a monotherapy and combination therapy, as an adjunct to diet and exercise, for improving glycemic control in adults with type 2 diabetes who cannot achieve control with insulin alone. It also has additional demonstrated benefits of weight loss and reduction in blood pressure.

On March 25, 2019, the drug received its first approval for treatment of patients with type 1 diabetes when the European Commission gave it the green light for use in patients with a body mass index of 27 kg/m² or more when insulin alone does not provide adequate glycemic control. Japan followed a few days later with its approval of the sodium-glucose cotransporter 2 inhibitor, also for type 1 disease in adults.

The approvals for type 1 diabetes in the European Union and Japan were based on data from the phase 3 DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) trial program (DEPICT-1 and DEPICT-2), which showed that 5 mg dapagliflozin, taken daily as an oral adjunct to insulin in patients with hard-to-control type 1 disease, reduced blood glucose levels from baseline (the primary endpoint). Secondary endpoints – reductions in weight and total daily insulin use – were also achieved.

Dapagliflozin’s safety profile in the trials in patients with type 1 diabetes was consistent with that established in patients with type 2 disease. However, there was a higher number of cases of diabetic ketoacidosis events in patients who received dapagliflozin. Diabetic ketoacidosis is a known complication for adults with type 1 diabetes and is more prevalent in patients with type 1 disease than in those with type 2.

The Food and Drug Administration has rejected AstraZeneca’s supplemental New Drug Application for the sodium-glucose cotransporter 2 inhibitor dapagliflozin (Farxiga) as an adjunct treatment to insulin in adult patients with type 1 diabetes.

The company said in a press statement that the FDA had issued a complete response letter regarding the application. No reason was given for the decision, but the company said it would work with the agency to discuss the next steps.

The once-daily therapy has been approved as both a monotherapy and combination therapy, as an adjunct to diet and exercise, for improving glycemic control in adults with type 2 diabetes who cannot achieve control with insulin alone. It also has additional demonstrated benefits of weight loss and reduction in blood pressure.

On March 25, 2019, the drug received its first approval for treatment of patients with type 1 diabetes when the European Commission gave it the green light for use in patients with a body mass index of 27 kg/m² or more when insulin alone does not provide adequate glycemic control. Japan followed a few days later with its approval of the sodium-glucose cotransporter 2 inhibitor, also for type 1 disease in adults.

The approvals for type 1 diabetes in the European Union and Japan were based on data from the phase 3 DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) trial program (DEPICT-1 and DEPICT-2), which showed that 5 mg dapagliflozin, taken daily as an oral adjunct to insulin in patients with hard-to-control type 1 disease, reduced blood glucose levels from baseline (the primary endpoint). Secondary endpoints – reductions in weight and total daily insulin use – were also achieved.

Dapagliflozin’s safety profile in the trials in patients with type 1 diabetes was consistent with that established in patients with type 2 disease. However, there was a higher number of cases of diabetic ketoacidosis events in patients who received dapagliflozin. Diabetic ketoacidosis is a known complication for adults with type 1 diabetes and is more prevalent in patients with type 1 disease than in those with type 2.

LOS ANGELES – Scientists testing an unusual hypothesis about the pathogenesis of Alzheimer’s disease say that use of an experimental antimicrobial drug to target a common oral infection was associated with biomarker improvements in people with the disease.

At the Alzheimer’s Association International Conference, Michael Detke, MD, PhD, of Cortexyme in South San Francisco, Calif., presented findings from a small cohort (n = 9) of people with mild to moderate Alzheimer’s disease (AD).

Six patients, mean age 72, were randomized to 4 weeks’ treatment with an agent called COR388, which inhibits toxic proteases produced by Porphyromonas gingivalis, a bacterium that colonizes the mouth and gums and has been found in the brains and cerebrospinal fluid of people with AD more than in non-AD patients. Another three subjects were randomized to placebo.

At 28 days, the CSF levels of an Alzheimer’s-associated apolipoprotein E (ApoE) fragment and serum levels of RANTES, a chemokine associated with chronic inflammation, were reduced from baseline by about one-third in treated subjects, compared with placebo subjects (P less than .05).

“In AD, ApoE is known to be fragmented and the fragments are known to be neurotoxic,” Dr. Detke, the lead study author, said in an interview. “We hypothesized that these P. gingivalis proteases may be acting on ApoE cleavage – so if you bind the proteases you should reduce the fragments. We saw in this study that ApoE fragment was reduced by 30%, or back to about normal levels.”

It is difficult to eradicate P. gingivalis infection using conventional antibiotics. The experimental agent COR388 “does not kill the bacteria but rather neutralizes it by binding to the proteases it produces, making the bacteria benign,” Dr. Detke said.


While hypotheses involving infectious causes of Alzheimer’s remain on the periphery of dementia research, Dr. Detke and his colleagues will soon be able to test theirs in a more meaningful way. At the conference, Dr. Detke presented detailed plans for a phase 2/3, placebo-controlled, clinical trial of COR388 in 570 patients aged 55-80 with mild to moderate AD.

Patients in the study are currently being randomized to 48 weeks of treatment with one of two doses, or placebo, with cognitive and biomarker endpoints planned, including for amyloid-beta, tau, and serum, plasma, and CSF markers of neuroinflammation.

Dr. Detke is an employee of Cortexyme, as are another 8 of the study’s 11 authors.

LOS ANGELES – Scientists testing an unusual hypothesis about the pathogenesis of Alzheimer’s disease say that use of an experimental antimicrobial drug to target a common oral infection was associated with biomarker improvements in people with the disease.

At the Alzheimer’s Association International Conference, Michael Detke, MD, PhD, of Cortexyme in South San Francisco, Calif., presented findings from a small cohort (n = 9) of people with mild to moderate Alzheimer’s disease (AD).

Six patients, mean age 72, were randomized to 4 weeks’ treatment with an agent called COR388, which inhibits toxic proteases produced by Porphyromonas gingivalis, a bacterium that colonizes the mouth and gums and has been found in the brains and cerebrospinal fluid of people with AD more than in non-AD patients. Another three subjects were randomized to placebo.

At 28 days, the CSF levels of an Alzheimer’s-associated apolipoprotein E (ApoE) fragment and serum levels of RANTES, a chemokine associated with chronic inflammation, were reduced from baseline by about one-third in treated subjects, compared with placebo subjects (P less than .05).

“In AD, ApoE is known to be fragmented and the fragments are known to be neurotoxic,” Dr. Detke, the lead study author, said in an interview. “We hypothesized that these P. gingivalis proteases may be acting on ApoE cleavage – so if you bind the proteases you should reduce the fragments. We saw in this study that ApoE fragment was reduced by 30%, or back to about normal levels.”

It is difficult to eradicate P. gingivalis infection using conventional antibiotics. The experimental agent COR388 “does not kill the bacteria but rather neutralizes it by binding to the proteases it produces, making the bacteria benign,” Dr. Detke said.


While hypotheses involving infectious causes of Alzheimer’s remain on the periphery of dementia research, Dr. Detke and his colleagues will soon be able to test theirs in a more meaningful way. At the conference, Dr. Detke presented detailed plans for a phase 2/3, placebo-controlled, clinical trial of COR388 in 570 patients aged 55-80 with mild to moderate AD.

Patients in the study are currently being randomized to 48 weeks of treatment with one of two doses, or placebo, with cognitive and biomarker endpoints planned, including for amyloid-beta, tau, and serum, plasma, and CSF markers of neuroinflammation.

Dr. Detke is an employee of Cortexyme, as are another 8 of the study’s 11 authors.

LOS ANGELES – Scientists testing an unusual hypothesis about the pathogenesis of Alzheimer’s disease say that use of an experimental antimicrobial drug to target a common oral infection was associated with biomarker improvements in people with the disease.

At the Alzheimer’s Association International Conference, Michael Detke, MD, PhD, of Cortexyme in South San Francisco, Calif., presented findings from a small cohort (n = 9) of people with mild to moderate Alzheimer’s disease (AD).

Six patients, mean age 72, were randomized to 4 weeks’ treatment with an agent called COR388, which inhibits toxic proteases produced by Porphyromonas gingivalis, a bacterium that colonizes the mouth and gums and has been found in the brains and cerebrospinal fluid of people with AD more than in non-AD patients. Another three subjects were randomized to placebo.

At 28 days, the CSF levels of an Alzheimer’s-associated apolipoprotein E (ApoE) fragment and serum levels of RANTES, a chemokine associated with chronic inflammation, were reduced from baseline by about one-third in treated subjects, compared with placebo subjects (P less than .05).

“In AD, ApoE is known to be fragmented and the fragments are known to be neurotoxic,” Dr. Detke, the lead study author, said in an interview. “We hypothesized that these P. gingivalis proteases may be acting on ApoE cleavage – so if you bind the proteases you should reduce the fragments. We saw in this study that ApoE fragment was reduced by 30%, or back to about normal levels.”

It is difficult to eradicate P. gingivalis infection using conventional antibiotics. The experimental agent COR388 “does not kill the bacteria but rather neutralizes it by binding to the proteases it produces, making the bacteria benign,” Dr. Detke said.


While hypotheses involving infectious causes of Alzheimer’s remain on the periphery of dementia research, Dr. Detke and his colleagues will soon be able to test theirs in a more meaningful way. At the conference, Dr. Detke presented detailed plans for a phase 2/3, placebo-controlled, clinical trial of COR388 in 570 patients aged 55-80 with mild to moderate AD.

Patients in the study are currently being randomized to 48 weeks of treatment with one of two doses, or placebo, with cognitive and biomarker endpoints planned, including for amyloid-beta, tau, and serum, plasma, and CSF markers of neuroinflammation.

Dr. Detke is an employee of Cortexyme, as are another 8 of the study’s 11 authors.