Key clinical point: Loncastuximab tesirine (Lonca) shows long-term efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 7.8 months, 48.3% of patients achieved an overall response, with a complete response being achieved by 24.8% of patients, 44% and 31% of whom remained event-free for ≥ 1 year and ≥ 2 years, respectively. The median overall and progression-free survival durations were 9.5 and 4.9 months, respectively. No new safety concerns were detected.

Study details: This long-term follow-up analysis of the phase 2 LOTIS-2 study included 145 heavily pretreated adult patients with relapsed or refractory DLBCL who received Lonca once every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles).

Disclosures: This study was funded by ADC Therapeutics SA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or honoraria from various sources, including ADC Therapeutics. Four authors declared being employees of and holding equity and stock options in ADC Therapeutics.

Source: Caimi PF et al. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase 2 LOTIS-2 study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283459

Key clinical point: Loncastuximab tesirine (Lonca) shows long-term efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 7.8 months, 48.3% of patients achieved an overall response, with a complete response being achieved by 24.8% of patients, 44% and 31% of whom remained event-free for ≥ 1 year and ≥ 2 years, respectively. The median overall and progression-free survival durations were 9.5 and 4.9 months, respectively. No new safety concerns were detected.

Study details: This long-term follow-up analysis of the phase 2 LOTIS-2 study included 145 heavily pretreated adult patients with relapsed or refractory DLBCL who received Lonca once every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles).

Disclosures: This study was funded by ADC Therapeutics SA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or honoraria from various sources, including ADC Therapeutics. Four authors declared being employees of and holding equity and stock options in ADC Therapeutics.

Source: Caimi PF et al. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase 2 LOTIS-2 study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283459

Key clinical point: Loncastuximab tesirine (Lonca) shows long-term efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 7.8 months, 48.3% of patients achieved an overall response, with a complete response being achieved by 24.8% of patients, 44% and 31% of whom remained event-free for ≥ 1 year and ≥ 2 years, respectively. The median overall and progression-free survival durations were 9.5 and 4.9 months, respectively. No new safety concerns were detected.

Study details: This long-term follow-up analysis of the phase 2 LOTIS-2 study included 145 heavily pretreated adult patients with relapsed or refractory DLBCL who received Lonca once every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles).

Disclosures: This study was funded by ADC Therapeutics SA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or honoraria from various sources, including ADC Therapeutics. Four authors declared being employees of and holding equity and stock options in ADC Therapeutics.

Source: Caimi PF et al. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase 2 LOTIS-2 study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283459

Key clinical point: Parsaclisib led to clinically meaningful improvements and a manageable safety profile in Bruton tyrosine kinase inhibitor (BTKi)-naive patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: Among BTKi-naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) of patients achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 (95% CI 9.0-not evaluable) months. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions.

Study details: This phase 2 CITADEL-205 study included adult patients with relapsed or refractory MCL previously treated with 1-3 systemic therapies, with (n = 53) or without (n = 108) prior BTKi treatment, who received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily.

Disclosures: This study was funded by Incyte Corporation. Some authors declared serving as consultants, advisors, or board members for or receiving research funding, honoraria, or travel and accommodation expenses from Incyte and others. Four authors declared being employees of and owning stocks in Incyte.

Source: Zinzani PL et al. Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory mantle cell lymphoma (CITADEL-205): A phase 2 study. EClinicalMedicine. 2023;62:102131 (Aug 10). doi: 10.1016/j.eclinm.2023.102131

Key clinical point: Parsaclisib led to clinically meaningful improvements and a manageable safety profile in Bruton tyrosine kinase inhibitor (BTKi)-naive patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: Among BTKi-naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) of patients achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 (95% CI 9.0-not evaluable) months. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions.

Study details: This phase 2 CITADEL-205 study included adult patients with relapsed or refractory MCL previously treated with 1-3 systemic therapies, with (n = 53) or without (n = 108) prior BTKi treatment, who received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily.

Disclosures: This study was funded by Incyte Corporation. Some authors declared serving as consultants, advisors, or board members for or receiving research funding, honoraria, or travel and accommodation expenses from Incyte and others. Four authors declared being employees of and owning stocks in Incyte.

Source: Zinzani PL et al. Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory mantle cell lymphoma (CITADEL-205): A phase 2 study. EClinicalMedicine. 2023;62:102131 (Aug 10). doi: 10.1016/j.eclinm.2023.102131

Key clinical point: Parsaclisib led to clinically meaningful improvements and a manageable safety profile in Bruton tyrosine kinase inhibitor (BTKi)-naive patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: Among BTKi-naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) of patients achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 (95% CI 9.0-not evaluable) months. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions.

Study details: This phase 2 CITADEL-205 study included adult patients with relapsed or refractory MCL previously treated with 1-3 systemic therapies, with (n = 53) or without (n = 108) prior BTKi treatment, who received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily.

Disclosures: This study was funded by Incyte Corporation. Some authors declared serving as consultants, advisors, or board members for or receiving research funding, honoraria, or travel and accommodation expenses from Incyte and others. Four authors declared being employees of and owning stocks in Incyte.

Source: Zinzani PL et al. Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory mantle cell lymphoma (CITADEL-205): A phase 2 study. EClinicalMedicine. 2023;62:102131 (Aug 10). doi: 10.1016/j.eclinm.2023.102131

Poor adherence to medication is a real challenge in health care. Despite evidence indicating therapeutic benefit from adhering to a prescribed regimen, it is estimated that around 50% of patients around the world don’t take their medication as it is prescribed – and some simply don’t take them at all.

Nonadherence to medication can be primary or secondary. Primary medication nonadherence occurs when a new medication is prescribed for a patient, but the patient does not obtain the medication or an appropriate alternative within an acceptable period after it was prescribed. Secondary nonadherence measures prescription refills among patients who previously filled their first prescriptions. With most medication adherence research to date focused on secondary nonadherence, PMN has been identified as a major research gap.

Growth in electronic prescribing has partially resolved this issue, and new measures have emerged linking electronic prescribing databases with pharmacy dispensing databases. A study conducted in a network of primary care services in Canada has sought to identify the predictive factors of primary nonadherence and which drugs could be at greatest risk of primary nonadherence when prescribed by a primary care physician
 

Adherence measures

Measuring medication adherence is challenging but can be done using various approaches. It comprises the following approaches:

• Subjective measurements obtained by asking patients, family members, caregivers, and physicians about the patient’s medication use
• Objective measurements obtained by counting pills, examining pharmacy refill records, or using electronic medication event monitoring systems
• Biochemical measurements obtained by adding a nontoxic marker to the medication and detecting its presence in blood or urine or measurement of serum drug levels.

Determining factors

A myriad of factors contributes to poor medication adherence. Some are related to patients (e.g., suboptimal health literacy and lack of involvement in the treatment decision-making process), others are related to physicians (e.g., prescription of complex drug regimens, communication barriers, ineffective communication of information about adverse effects, and provision of care by multiple physicians), and still others are related to health care systems (e.g., office visit time limitations, limited access to care, and lack of health information technology).

Primary nonadherence

The literature has reported substantial variation in primary nonadherence, with estimates ranging from as little as 1.9% of incident prescriptions never filled to as much as 75%.

Investigators for the Canadian study estimated the rate of primary nonadherence, defined as failure to dispense a new medication or its equivalent within 6 months of the prescription date, using data from 150,565 new prescriptions issued to 34,243 patients.
 

Rate of nonadherence

The following patterns of primary nonadherence were observed:

• Primary nonadherence was lowest for prescriptions issued by prescribers aged 35 years or younger (17.1%) and male prescribers (15.1%).
• It was similar among patients of both sexes.
• It was lowest in the oldest subjects, decreasing with age (odds ratio, 0.91 for each additional 10 years).
• It was highest for drugs prescribed mostly on an as-needed basis, including topical corticosteroids (35.1%) and antihistamines (23.4%).

Predictors of nonadherence

The odds of primary nonadherence exhibited the following patterns:

• Lower for prescriptions issued by male clinicians (OR, 0.66)
• Significantly greater, compared with anti-infectives, for dermatological agents (OR, 1.36) and lowest for cardiovascular agents (OR, 0.46).
• Lower across therapeutic drug categories (except for respiratory agents) for those aged 65 years and older than for those younger than age 65.

In conclusion, in a general medicine setting, the odds of primary nonadherence were higher for younger patients, those who received primary care services from female prescribers, and older patients who were prescribed more medications. Across therapeutic categories, the odds of primary nonadherence were lowest for cardiovascular system agents and highest for dermatological agents.

To date, the lack of a standardized terminology, operational definition, and measurement methods of primary nonadherence has limited our understanding of the extent to which patients do not avail themselves of prescriber-ordered pharmaceutical treatment. These results reaffirm the need to compare the prevalence of such nonadherence in different health care settings.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Poor adherence to medication is a real challenge in health care. Despite evidence indicating therapeutic benefit from adhering to a prescribed regimen, it is estimated that around 50% of patients around the world don’t take their medication as it is prescribed – and some simply don’t take them at all.

Nonadherence to medication can be primary or secondary. Primary medication nonadherence occurs when a new medication is prescribed for a patient, but the patient does not obtain the medication or an appropriate alternative within an acceptable period after it was prescribed. Secondary nonadherence measures prescription refills among patients who previously filled their first prescriptions. With most medication adherence research to date focused on secondary nonadherence, PMN has been identified as a major research gap.

Growth in electronic prescribing has partially resolved this issue, and new measures have emerged linking electronic prescribing databases with pharmacy dispensing databases. A study conducted in a network of primary care services in Canada has sought to identify the predictive factors of primary nonadherence and which drugs could be at greatest risk of primary nonadherence when prescribed by a primary care physician
 

Adherence measures

Measuring medication adherence is challenging but can be done using various approaches. It comprises the following approaches:

• Subjective measurements obtained by asking patients, family members, caregivers, and physicians about the patient’s medication use
• Objective measurements obtained by counting pills, examining pharmacy refill records, or using electronic medication event monitoring systems
• Biochemical measurements obtained by adding a nontoxic marker to the medication and detecting its presence in blood or urine or measurement of serum drug levels.

Determining factors

A myriad of factors contributes to poor medication adherence. Some are related to patients (e.g., suboptimal health literacy and lack of involvement in the treatment decision-making process), others are related to physicians (e.g., prescription of complex drug regimens, communication barriers, ineffective communication of information about adverse effects, and provision of care by multiple physicians), and still others are related to health care systems (e.g., office visit time limitations, limited access to care, and lack of health information technology).

Primary nonadherence

The literature has reported substantial variation in primary nonadherence, with estimates ranging from as little as 1.9% of incident prescriptions never filled to as much as 75%.

Investigators for the Canadian study estimated the rate of primary nonadherence, defined as failure to dispense a new medication or its equivalent within 6 months of the prescription date, using data from 150,565 new prescriptions issued to 34,243 patients.
 

Rate of nonadherence

The following patterns of primary nonadherence were observed:

• Primary nonadherence was lowest for prescriptions issued by prescribers aged 35 years or younger (17.1%) and male prescribers (15.1%).
• It was similar among patients of both sexes.
• It was lowest in the oldest subjects, decreasing with age (odds ratio, 0.91 for each additional 10 years).
• It was highest for drugs prescribed mostly on an as-needed basis, including topical corticosteroids (35.1%) and antihistamines (23.4%).

Predictors of nonadherence

The odds of primary nonadherence exhibited the following patterns:

• Lower for prescriptions issued by male clinicians (OR, 0.66)
• Significantly greater, compared with anti-infectives, for dermatological agents (OR, 1.36) and lowest for cardiovascular agents (OR, 0.46).
• Lower across therapeutic drug categories (except for respiratory agents) for those aged 65 years and older than for those younger than age 65.

In conclusion, in a general medicine setting, the odds of primary nonadherence were higher for younger patients, those who received primary care services from female prescribers, and older patients who were prescribed more medications. Across therapeutic categories, the odds of primary nonadherence were lowest for cardiovascular system agents and highest for dermatological agents.

To date, the lack of a standardized terminology, operational definition, and measurement methods of primary nonadherence has limited our understanding of the extent to which patients do not avail themselves of prescriber-ordered pharmaceutical treatment. These results reaffirm the need to compare the prevalence of such nonadherence in different health care settings.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Poor adherence to medication is a real challenge in health care. Despite evidence indicating therapeutic benefit from adhering to a prescribed regimen, it is estimated that around 50% of patients around the world don’t take their medication as it is prescribed – and some simply don’t take them at all.

Nonadherence to medication can be primary or secondary. Primary medication nonadherence occurs when a new medication is prescribed for a patient, but the patient does not obtain the medication or an appropriate alternative within an acceptable period after it was prescribed. Secondary nonadherence measures prescription refills among patients who previously filled their first prescriptions. With most medication adherence research to date focused on secondary nonadherence, PMN has been identified as a major research gap.

Growth in electronic prescribing has partially resolved this issue, and new measures have emerged linking electronic prescribing databases with pharmacy dispensing databases. A study conducted in a network of primary care services in Canada has sought to identify the predictive factors of primary nonadherence and which drugs could be at greatest risk of primary nonadherence when prescribed by a primary care physician
 

Adherence measures

Measuring medication adherence is challenging but can be done using various approaches. It comprises the following approaches:

• Subjective measurements obtained by asking patients, family members, caregivers, and physicians about the patient’s medication use
• Objective measurements obtained by counting pills, examining pharmacy refill records, or using electronic medication event monitoring systems
• Biochemical measurements obtained by adding a nontoxic marker to the medication and detecting its presence in blood or urine or measurement of serum drug levels.

Determining factors

A myriad of factors contributes to poor medication adherence. Some are related to patients (e.g., suboptimal health literacy and lack of involvement in the treatment decision-making process), others are related to physicians (e.g., prescription of complex drug regimens, communication barriers, ineffective communication of information about adverse effects, and provision of care by multiple physicians), and still others are related to health care systems (e.g., office visit time limitations, limited access to care, and lack of health information technology).

Primary nonadherence

The literature has reported substantial variation in primary nonadherence, with estimates ranging from as little as 1.9% of incident prescriptions never filled to as much as 75%.

Investigators for the Canadian study estimated the rate of primary nonadherence, defined as failure to dispense a new medication or its equivalent within 6 months of the prescription date, using data from 150,565 new prescriptions issued to 34,243 patients.
 

Rate of nonadherence

The following patterns of primary nonadherence were observed:

• Primary nonadherence was lowest for prescriptions issued by prescribers aged 35 years or younger (17.1%) and male prescribers (15.1%).
• It was similar among patients of both sexes.
• It was lowest in the oldest subjects, decreasing with age (odds ratio, 0.91 for each additional 10 years).
• It was highest for drugs prescribed mostly on an as-needed basis, including topical corticosteroids (35.1%) and antihistamines (23.4%).

Predictors of nonadherence

The odds of primary nonadherence exhibited the following patterns:

• Lower for prescriptions issued by male clinicians (OR, 0.66)
• Significantly greater, compared with anti-infectives, for dermatological agents (OR, 1.36) and lowest for cardiovascular agents (OR, 0.46).
• Lower across therapeutic drug categories (except for respiratory agents) for those aged 65 years and older than for those younger than age 65.

In conclusion, in a general medicine setting, the odds of primary nonadherence were higher for younger patients, those who received primary care services from female prescribers, and older patients who were prescribed more medications. Across therapeutic categories, the odds of primary nonadherence were lowest for cardiovascular system agents and highest for dermatological agents.

To date, the lack of a standardized terminology, operational definition, and measurement methods of primary nonadherence has limited our understanding of the extent to which patients do not avail themselves of prescriber-ordered pharmaceutical treatment. These results reaffirm the need to compare the prevalence of such nonadherence in different health care settings.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

TOPLINE:

Drug use disorder increased the likelihood of in-hospital mortality more than 10-fold in patients with ankylosing spondylitis (AS), compared with patients who did not die while hospitalized.

METHODOLOGY:

• Researchers reviewed data from 2,125 adults with AS who were hospitalized between 2015 and 2017, using the Cerner Health Facts Database.
• The final analysis included 41 patients with AS who died while hospitalized and 260 random control patients with AS who did not die.
• The mean age of the deceased patients with AS was 70 years, 85% were male, and 81% were White; 71% had hypertension, 32% had kidney disease, and 22% had congestive heart failure.

TAKEAWAY:

• Among the patients with AS, cardiovascular disease was the most frequent cause of death, followed by infection, respiratory failure, and fracture/trauma in 15, 14, 8, and 7 patients, respectively. (Some patients had more than one cause of death recorded in the discharge summary.)
• The most common cardiac causes of death were myocardial infarction and cardiac arrest, while the top causes of acute respiratory failure were pneumonia and pulmonary embolism.
• Drug abuse, including opioid dependence, was significantly associated with death among hospitalized patients with AS (adjusted odds ratio, 10.9; P = .001).
• Heart failure and kidney disease were the comorbidities most strongly associated with mortality; the odds of death in the presence of heart failure rose 2.76-fold, and it increased 2.46-fold in the presence of kidney disease.

IN PRACTICE:

Underlying comorbidities, especially cardiac and renal, are associated with mortality in AS, and patients should be screened early on for these comorbidities to help reduce the odds of death.

SOURCE:

First author Mohamad Bittar, MD, of the University of Tennessee Health Science Center, Memphis, and colleagues reported their findings in Clinical Rheumatology).

LIMITATIONS:

The study lacked AS-specific data such as disease activity scores, which were not in the database. Also missing were variables linked to disease activity and mortality, including smoking, BMI levels, and C-reactive protein levels.

DISCLOSURES:

The study received no outside funding. Several coauthors disclosed financial relationships with UCB, Amgen, Pfizer, AbbVie, Novartis, and Eli Lilly.

A version of this article first appeared on Medscape.com.

TOPLINE:

Drug use disorder increased the likelihood of in-hospital mortality more than 10-fold in patients with ankylosing spondylitis (AS), compared with patients who did not die while hospitalized.

METHODOLOGY:

• Researchers reviewed data from 2,125 adults with AS who were hospitalized between 2015 and 2017, using the Cerner Health Facts Database.
• The final analysis included 41 patients with AS who died while hospitalized and 260 random control patients with AS who did not die.
• The mean age of the deceased patients with AS was 70 years, 85% were male, and 81% were White; 71% had hypertension, 32% had kidney disease, and 22% had congestive heart failure.

TAKEAWAY:

• Among the patients with AS, cardiovascular disease was the most frequent cause of death, followed by infection, respiratory failure, and fracture/trauma in 15, 14, 8, and 7 patients, respectively. (Some patients had more than one cause of death recorded in the discharge summary.)
• The most common cardiac causes of death were myocardial infarction and cardiac arrest, while the top causes of acute respiratory failure were pneumonia and pulmonary embolism.
• Drug abuse, including opioid dependence, was significantly associated with death among hospitalized patients with AS (adjusted odds ratio, 10.9; P = .001).
• Heart failure and kidney disease were the comorbidities most strongly associated with mortality; the odds of death in the presence of heart failure rose 2.76-fold, and it increased 2.46-fold in the presence of kidney disease.

IN PRACTICE:

Underlying comorbidities, especially cardiac and renal, are associated with mortality in AS, and patients should be screened early on for these comorbidities to help reduce the odds of death.

SOURCE:

First author Mohamad Bittar, MD, of the University of Tennessee Health Science Center, Memphis, and colleagues reported their findings in Clinical Rheumatology).

LIMITATIONS:

The study lacked AS-specific data such as disease activity scores, which were not in the database. Also missing were variables linked to disease activity and mortality, including smoking, BMI levels, and C-reactive protein levels.

DISCLOSURES:

The study received no outside funding. Several coauthors disclosed financial relationships with UCB, Amgen, Pfizer, AbbVie, Novartis, and Eli Lilly.

A version of this article first appeared on Medscape.com.

TOPLINE:

Drug use disorder increased the likelihood of in-hospital mortality more than 10-fold in patients with ankylosing spondylitis (AS), compared with patients who did not die while hospitalized.

METHODOLOGY:

• Researchers reviewed data from 2,125 adults with AS who were hospitalized between 2015 and 2017, using the Cerner Health Facts Database.
• The final analysis included 41 patients with AS who died while hospitalized and 260 random control patients with AS who did not die.
• The mean age of the deceased patients with AS was 70 years, 85% were male, and 81% were White; 71% had hypertension, 32% had kidney disease, and 22% had congestive heart failure.

TAKEAWAY:

• Among the patients with AS, cardiovascular disease was the most frequent cause of death, followed by infection, respiratory failure, and fracture/trauma in 15, 14, 8, and 7 patients, respectively. (Some patients had more than one cause of death recorded in the discharge summary.)
• The most common cardiac causes of death were myocardial infarction and cardiac arrest, while the top causes of acute respiratory failure were pneumonia and pulmonary embolism.
• Drug abuse, including opioid dependence, was significantly associated with death among hospitalized patients with AS (adjusted odds ratio, 10.9; P = .001).
• Heart failure and kidney disease were the comorbidities most strongly associated with mortality; the odds of death in the presence of heart failure rose 2.76-fold, and it increased 2.46-fold in the presence of kidney disease.

IN PRACTICE:

Underlying comorbidities, especially cardiac and renal, are associated with mortality in AS, and patients should be screened early on for these comorbidities to help reduce the odds of death.

SOURCE:

First author Mohamad Bittar, MD, of the University of Tennessee Health Science Center, Memphis, and colleagues reported their findings in Clinical Rheumatology).

LIMITATIONS:

The study lacked AS-specific data such as disease activity scores, which were not in the database. Also missing were variables linked to disease activity and mortality, including smoking, BMI levels, and C-reactive protein levels.

DISCLOSURES:

The study received no outside funding. Several coauthors disclosed financial relationships with UCB, Amgen, Pfizer, AbbVie, Novartis, and Eli Lilly.

A version of this article first appeared on Medscape.com.

Adults with nonsevere community-acquired pneumonia (CAP) responded nearly equally to three first-line and alternative antibiotic regimens, based on data from more than 23,000 individuals.

Current recommendations for the treatment of CAP vary across guidelines, wrote Anthony D. Bai, MD, of Queen’s University, Kingston, Ont., and colleagues. However, most guidelines were based on studies that were not powered to examine the effect of treatments on mortality, they said.

“Large observational studies could fill this gap by comparing multiple treatment arms, including patients not well represented in trials, and having a large sample size powered to detect a difference in mortality,” they noted.

In a study published in Chest, the researchers reviewed data from 23,512 consecutive patients admitted to 19 hospitals in Canada for CAP between 2015 and 2021. Patients were treated with one of four initial antibiotic regimens: beta-lactam plus macrolide (BL+M), beta-lactam alone (BL), respiratory fluoroquinolone (FQ), or beta-lactam plus doxycycline (BL+D). Of these, BL+M is generally considered the first-line regimen, the researchers noted.

Patients were divided into four groups according to their initial antibiotic treatment within 48 hours of admission; 9,340 patients received BL+M, 9,146 received BL, 4,510 received FQ, and 516 received BL+D. The duration of any antibiotic that was active against CAP was at least 4 days, or until hospital discharge or death.

The primary outcome was all-cause in-hospital mortality, which was 7.5%, 9.7%, 6.7%, and 6.0% for patients in each of the four treatment groups, respectively. Relative to the first-line therapy of BL+M, the adjusted risk differences for BL, FQ, and BL+D were 1.5%, –0.9%, and –1.9%, respectively.

The adjusted in-hospital mortality was not significantly different between BL+M and either FQ or BL+D, but the difference of 1.5% seen with BL alone suggested a “small but clinically important difference,” the researchers noted.

Key secondary outcomes were the length of hospital stay and being discharged alive. The median length of stay was 4.6 days for BL+M, 5.2 days for BL, 4.6 days for FQ, and 6.0 days for BL+D. Patients treated with BL also had a longer time to hospital discharge, which suggests that BL may not be as effective as the other regimens, the researchers said. In addition, patients in the BL group had a subdistribution hazard ratio of 0.90 for being discharged alive, compared with the BL+M group after adjustment with propensity scores and overlap weighting.

Overall, the results support dropping BL as a first-line regimen in the current ATS/IDSA guidelines, and support the recommendation of BL+M, FQ, and BL+D as similarly effective options as listed in other guidelines, applied according to other patient characteristics. For example, “Doxycycline may be preferred over a macrolide in many cases such as macrolide allergy, prolonged QT, or high [Clostridioides] difficile risk,” the researchers said.

The findings were limited by several factors including the lack of follow-up data after hospital discharge.

However, the results were strengthened by the large sample size and use of a comprehensive database that allowed adjustment for many variables, as well as the availability of complete follow-up data for the time spent in the hospital. Based on this study, clinicians may choose a respiratory fluoroquinolone, a beta-lactam plus macrolide, or a beta-lactam plus doxycycline for equally effective antibiotic treatment of CAP, based on the best fit for each individual patient, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Adults with nonsevere community-acquired pneumonia (CAP) responded nearly equally to three first-line and alternative antibiotic regimens, based on data from more than 23,000 individuals.

Current recommendations for the treatment of CAP vary across guidelines, wrote Anthony D. Bai, MD, of Queen’s University, Kingston, Ont., and colleagues. However, most guidelines were based on studies that were not powered to examine the effect of treatments on mortality, they said.

“Large observational studies could fill this gap by comparing multiple treatment arms, including patients not well represented in trials, and having a large sample size powered to detect a difference in mortality,” they noted.

In a study published in Chest, the researchers reviewed data from 23,512 consecutive patients admitted to 19 hospitals in Canada for CAP between 2015 and 2021. Patients were treated with one of four initial antibiotic regimens: beta-lactam plus macrolide (BL+M), beta-lactam alone (BL), respiratory fluoroquinolone (FQ), or beta-lactam plus doxycycline (BL+D). Of these, BL+M is generally considered the first-line regimen, the researchers noted.

Patients were divided into four groups according to their initial antibiotic treatment within 48 hours of admission; 9,340 patients received BL+M, 9,146 received BL, 4,510 received FQ, and 516 received BL+D. The duration of any antibiotic that was active against CAP was at least 4 days, or until hospital discharge or death.

The primary outcome was all-cause in-hospital mortality, which was 7.5%, 9.7%, 6.7%, and 6.0% for patients in each of the four treatment groups, respectively. Relative to the first-line therapy of BL+M, the adjusted risk differences for BL, FQ, and BL+D were 1.5%, –0.9%, and –1.9%, respectively.

The adjusted in-hospital mortality was not significantly different between BL+M and either FQ or BL+D, but the difference of 1.5% seen with BL alone suggested a “small but clinically important difference,” the researchers noted.

Key secondary outcomes were the length of hospital stay and being discharged alive. The median length of stay was 4.6 days for BL+M, 5.2 days for BL, 4.6 days for FQ, and 6.0 days for BL+D. Patients treated with BL also had a longer time to hospital discharge, which suggests that BL may not be as effective as the other regimens, the researchers said. In addition, patients in the BL group had a subdistribution hazard ratio of 0.90 for being discharged alive, compared with the BL+M group after adjustment with propensity scores and overlap weighting.

Overall, the results support dropping BL as a first-line regimen in the current ATS/IDSA guidelines, and support the recommendation of BL+M, FQ, and BL+D as similarly effective options as listed in other guidelines, applied according to other patient characteristics. For example, “Doxycycline may be preferred over a macrolide in many cases such as macrolide allergy, prolonged QT, or high [Clostridioides] difficile risk,” the researchers said.

The findings were limited by several factors including the lack of follow-up data after hospital discharge.

However, the results were strengthened by the large sample size and use of a comprehensive database that allowed adjustment for many variables, as well as the availability of complete follow-up data for the time spent in the hospital. Based on this study, clinicians may choose a respiratory fluoroquinolone, a beta-lactam plus macrolide, or a beta-lactam plus doxycycline for equally effective antibiotic treatment of CAP, based on the best fit for each individual patient, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Adults with nonsevere community-acquired pneumonia (CAP) responded nearly equally to three first-line and alternative antibiotic regimens, based on data from more than 23,000 individuals.

Current recommendations for the treatment of CAP vary across guidelines, wrote Anthony D. Bai, MD, of Queen’s University, Kingston, Ont., and colleagues. However, most guidelines were based on studies that were not powered to examine the effect of treatments on mortality, they said.

“Large observational studies could fill this gap by comparing multiple treatment arms, including patients not well represented in trials, and having a large sample size powered to detect a difference in mortality,” they noted.

In a study published in Chest, the researchers reviewed data from 23,512 consecutive patients admitted to 19 hospitals in Canada for CAP between 2015 and 2021. Patients were treated with one of four initial antibiotic regimens: beta-lactam plus macrolide (BL+M), beta-lactam alone (BL), respiratory fluoroquinolone (FQ), or beta-lactam plus doxycycline (BL+D). Of these, BL+M is generally considered the first-line regimen, the researchers noted.

Patients were divided into four groups according to their initial antibiotic treatment within 48 hours of admission; 9,340 patients received BL+M, 9,146 received BL, 4,510 received FQ, and 516 received BL+D. The duration of any antibiotic that was active against CAP was at least 4 days, or until hospital discharge or death.

The primary outcome was all-cause in-hospital mortality, which was 7.5%, 9.7%, 6.7%, and 6.0% for patients in each of the four treatment groups, respectively. Relative to the first-line therapy of BL+M, the adjusted risk differences for BL, FQ, and BL+D were 1.5%, –0.9%, and –1.9%, respectively.

The adjusted in-hospital mortality was not significantly different between BL+M and either FQ or BL+D, but the difference of 1.5% seen with BL alone suggested a “small but clinically important difference,” the researchers noted.

Key secondary outcomes were the length of hospital stay and being discharged alive. The median length of stay was 4.6 days for BL+M, 5.2 days for BL, 4.6 days for FQ, and 6.0 days for BL+D. Patients treated with BL also had a longer time to hospital discharge, which suggests that BL may not be as effective as the other regimens, the researchers said. In addition, patients in the BL group had a subdistribution hazard ratio of 0.90 for being discharged alive, compared with the BL+M group after adjustment with propensity scores and overlap weighting.

Overall, the results support dropping BL as a first-line regimen in the current ATS/IDSA guidelines, and support the recommendation of BL+M, FQ, and BL+D as similarly effective options as listed in other guidelines, applied according to other patient characteristics. For example, “Doxycycline may be preferred over a macrolide in many cases such as macrolide allergy, prolonged QT, or high [Clostridioides] difficile risk,” the researchers said.

The findings were limited by several factors including the lack of follow-up data after hospital discharge.

However, the results were strengthened by the large sample size and use of a comprehensive database that allowed adjustment for many variables, as well as the availability of complete follow-up data for the time spent in the hospital. Based on this study, clinicians may choose a respiratory fluoroquinolone, a beta-lactam plus macrolide, or a beta-lactam plus doxycycline for equally effective antibiotic treatment of CAP, based on the best fit for each individual patient, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A silent disorder is rising among older people worldwide, as millions unknowingly grapple with glaucoma, ophthalmologists warn.

It’s predicted that by 2050, the number of people with glaucoma will surge by more than 200%, highlighting an urgent need for heightened awareness, early detection, and advanced treatment strategies.

“That’s a lot of people with a blinding disease who don’t know they have it,” said Joel S. Schuman, MD, professor of ophthalmology and codirector of the Glaucoma Service at Wills Eye Hospital in Philadelphia. “Late in the disease, people may notice they’re tripping over the curb, or walking into things they didn’t see. It really is only in very advanced disease that people notice there’s anything wrong.”

Glaucoma is the second leading cause of blindness worldwide, affecting 3 million people in the United States, and yet half of those affected are unaware, according to the Centers for Disease Control and Prevention. 

Recent research at the University of Gothenburg in Sweden underscores glaucoma’s stealthy nature: Five percent of 560 70-year-olds had the disease, and half of those did not know they had it before they took part in the study. 

“Living with glaucoma, especially without realizing it, can be very isolating,” said Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital, who did the study. “It may lead people to stay at home to avoid the trouble.”

Once symptoms arise, some may notice patchy blind spots in their peripheral vision, and in their central vision in late stages.

While many people assume they are getting clumsier with age, Dr. Schuman said, they often have a condition that can be slowed with the right treatment. 

Though there are various types of the disease, about 9 in 10 people in the United States have primary open-angle glaucoma (POAG).  

It is most common among people over the age of 60, those with a family history of glaucoma, and people who have diabetes. It disproportionately affects Black people, who are six times more likely than are White people to have advanced vision loss from the disease. 

More than 120,000 people in the United States are blind from glaucoma, accounting for 9%-12% of all cases of blindness. Glaucoma treatments range from eye drops to laser treatments to surgery, all of which aim to reduce eye pressure. Some doctors will recommend oral medication along with eye drops.

“We have a lot of treatment options, and they work pretty well,” Dr. Schuman said. “But the first step is the person knowing they have glaucoma, and the second step is that person seeking care.

Rarer types of glaucoma include normal-tension glaucoma, which is more common among people of Japanese ancestry, and congenital glaucoma, which affects about 1 in 10,000 babies born in the United States.

The best way to ensure early detection and treatment is to get regular eye exams – every 2-4 years for adults under the age of 55, and annually thereafter, said Annie Wu, MD, clinical assistant professor of ophthalmology at the Kellogg Eye Center at the University of Michigan. 

The fact that glaucoma’s symptoms are slow to develop, coupled with a lack of access to eye specialists many Americans face, makes the disease even more dangerous. 

The University of Pennsylvania is among those trying to change that. The Philadelphia school has hosted free glaucoma screening programs for Black residents.  

There are a number of organizations that offer access to free glaucoma screening. 
 

A version of this article first appeared on WebMD.com.

A silent disorder is rising among older people worldwide, as millions unknowingly grapple with glaucoma, ophthalmologists warn.

It’s predicted that by 2050, the number of people with glaucoma will surge by more than 200%, highlighting an urgent need for heightened awareness, early detection, and advanced treatment strategies.

“That’s a lot of people with a blinding disease who don’t know they have it,” said Joel S. Schuman, MD, professor of ophthalmology and codirector of the Glaucoma Service at Wills Eye Hospital in Philadelphia. “Late in the disease, people may notice they’re tripping over the curb, or walking into things they didn’t see. It really is only in very advanced disease that people notice there’s anything wrong.”

Glaucoma is the second leading cause of blindness worldwide, affecting 3 million people in the United States, and yet half of those affected are unaware, according to the Centers for Disease Control and Prevention. 

Recent research at the University of Gothenburg in Sweden underscores glaucoma’s stealthy nature: Five percent of 560 70-year-olds had the disease, and half of those did not know they had it before they took part in the study. 

“Living with glaucoma, especially without realizing it, can be very isolating,” said Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital, who did the study. “It may lead people to stay at home to avoid the trouble.”

Once symptoms arise, some may notice patchy blind spots in their peripheral vision, and in their central vision in late stages.

While many people assume they are getting clumsier with age, Dr. Schuman said, they often have a condition that can be slowed with the right treatment. 

Though there are various types of the disease, about 9 in 10 people in the United States have primary open-angle glaucoma (POAG).  

It is most common among people over the age of 60, those with a family history of glaucoma, and people who have diabetes. It disproportionately affects Black people, who are six times more likely than are White people to have advanced vision loss from the disease. 

More than 120,000 people in the United States are blind from glaucoma, accounting for 9%-12% of all cases of blindness. Glaucoma treatments range from eye drops to laser treatments to surgery, all of which aim to reduce eye pressure. Some doctors will recommend oral medication along with eye drops.

“We have a lot of treatment options, and they work pretty well,” Dr. Schuman said. “But the first step is the person knowing they have glaucoma, and the second step is that person seeking care.

Rarer types of glaucoma include normal-tension glaucoma, which is more common among people of Japanese ancestry, and congenital glaucoma, which affects about 1 in 10,000 babies born in the United States.

The best way to ensure early detection and treatment is to get regular eye exams – every 2-4 years for adults under the age of 55, and annually thereafter, said Annie Wu, MD, clinical assistant professor of ophthalmology at the Kellogg Eye Center at the University of Michigan. 

The fact that glaucoma’s symptoms are slow to develop, coupled with a lack of access to eye specialists many Americans face, makes the disease even more dangerous. 

The University of Pennsylvania is among those trying to change that. The Philadelphia school has hosted free glaucoma screening programs for Black residents.  

There are a number of organizations that offer access to free glaucoma screening. 
 

A version of this article first appeared on WebMD.com.

A silent disorder is rising among older people worldwide, as millions unknowingly grapple with glaucoma, ophthalmologists warn.

It’s predicted that by 2050, the number of people with glaucoma will surge by more than 200%, highlighting an urgent need for heightened awareness, early detection, and advanced treatment strategies.

“That’s a lot of people with a blinding disease who don’t know they have it,” said Joel S. Schuman, MD, professor of ophthalmology and codirector of the Glaucoma Service at Wills Eye Hospital in Philadelphia. “Late in the disease, people may notice they’re tripping over the curb, or walking into things they didn’t see. It really is only in very advanced disease that people notice there’s anything wrong.”

Glaucoma is the second leading cause of blindness worldwide, affecting 3 million people in the United States, and yet half of those affected are unaware, according to the Centers for Disease Control and Prevention. 

Recent research at the University of Gothenburg in Sweden underscores glaucoma’s stealthy nature: Five percent of 560 70-year-olds had the disease, and half of those did not know they had it before they took part in the study. 

“Living with glaucoma, especially without realizing it, can be very isolating,” said Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital, who did the study. “It may lead people to stay at home to avoid the trouble.”

Once symptoms arise, some may notice patchy blind spots in their peripheral vision, and in their central vision in late stages.

While many people assume they are getting clumsier with age, Dr. Schuman said, they often have a condition that can be slowed with the right treatment. 

Though there are various types of the disease, about 9 in 10 people in the United States have primary open-angle glaucoma (POAG).  

It is most common among people over the age of 60, those with a family history of glaucoma, and people who have diabetes. It disproportionately affects Black people, who are six times more likely than are White people to have advanced vision loss from the disease. 

More than 120,000 people in the United States are blind from glaucoma, accounting for 9%-12% of all cases of blindness. Glaucoma treatments range from eye drops to laser treatments to surgery, all of which aim to reduce eye pressure. Some doctors will recommend oral medication along with eye drops.

“We have a lot of treatment options, and they work pretty well,” Dr. Schuman said. “But the first step is the person knowing they have glaucoma, and the second step is that person seeking care.

Rarer types of glaucoma include normal-tension glaucoma, which is more common among people of Japanese ancestry, and congenital glaucoma, which affects about 1 in 10,000 babies born in the United States.

The best way to ensure early detection and treatment is to get regular eye exams – every 2-4 years for adults under the age of 55, and annually thereafter, said Annie Wu, MD, clinical assistant professor of ophthalmology at the Kellogg Eye Center at the University of Michigan. 

The fact that glaucoma’s symptoms are slow to develop, coupled with a lack of access to eye specialists many Americans face, makes the disease even more dangerous. 

The University of Pennsylvania is among those trying to change that. The Philadelphia school has hosted free glaucoma screening programs for Black residents.  

There are a number of organizations that offer access to free glaucoma screening. 
 

A version of this article first appeared on WebMD.com.

A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.
 

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
 

Association, not causation

Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.

“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.

What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.

“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.

“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.

Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”

Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.

“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.

Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.

“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.

The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.

A version of this article first appeared on Medscape.com.

A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.
 

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
 

Association, not causation

Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.

“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.

What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.

“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.

“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.

Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”

Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.

“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.

Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.

“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.

The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.

A version of this article first appeared on Medscape.com.

A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.
 

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
 

Association, not causation

Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.

“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.

What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.

“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.

“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.

Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”

Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.

“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.

Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.

“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.

The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.

A version of this article first appeared on Medscape.com.

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Women with premenstrual disorders may be more likely go through menopause before they are 45 years old, a new study suggests. 

Women with premenstrual disorders, or PMDs, were also more likely to have moderate or severe night sweats or hot flashes during menopause, the researchers found.

Published in JAMA Network Open, the new findings stem from data from more than 3,600 nurses who contributed their health information to a database between 1991 and 2017. Women with PMDs were more than twice as likely as women without PMDs to have early menopause.

Most women have menopause between the ages of 45 and 55 years old, according to the World Health Organization. 

There are numerous PMDs, including the well-known premenstrual syndrome, which is considered a mild disorder affecting up to 30% of women that causes symptoms like crankiness and bloating. A less common PMD is premenstrual dysphoric disorder, which can severely impact a woman’s life through psychological, gastrointestinal, skin, and neurological problems.

Previous research has linked PMDs during the reproductive years and postmenopausal issues like hot flashes and night sweats to increased risks of health problems like high blood pressure, heart conditions, and diabetes.

“It is important to identify women at risk for early menopause because of its link with poorer heart, brain, and bone health,” Stephanie Faubion, MD, MBA, a doctor at the Mayo Clinic and medical director of the North American Menopause Society, told CNN. Dr. Faubion was not involved in the study.

That said, it’s important to note that the study was observational – meaning researchers can’t say for certain that PMDs will cause early menopause. Rather, the study shows there may be a correlation between the two, Donghao Lu, MD, an associate professor in the department of medical epidemiology and biostatistics at the Karolinska Institute, told CNN.

A version of this article first appeared on Medscape.com.

Women with premenstrual disorders may be more likely go through menopause before they are 45 years old, a new study suggests. 

Women with premenstrual disorders, or PMDs, were also more likely to have moderate or severe night sweats or hot flashes during menopause, the researchers found.

Published in JAMA Network Open, the new findings stem from data from more than 3,600 nurses who contributed their health information to a database between 1991 and 2017. Women with PMDs were more than twice as likely as women without PMDs to have early menopause.

Most women have menopause between the ages of 45 and 55 years old, according to the World Health Organization. 

There are numerous PMDs, including the well-known premenstrual syndrome, which is considered a mild disorder affecting up to 30% of women that causes symptoms like crankiness and bloating. A less common PMD is premenstrual dysphoric disorder, which can severely impact a woman’s life through psychological, gastrointestinal, skin, and neurological problems.

Previous research has linked PMDs during the reproductive years and postmenopausal issues like hot flashes and night sweats to increased risks of health problems like high blood pressure, heart conditions, and diabetes.

“It is important to identify women at risk for early menopause because of its link with poorer heart, brain, and bone health,” Stephanie Faubion, MD, MBA, a doctor at the Mayo Clinic and medical director of the North American Menopause Society, told CNN. Dr. Faubion was not involved in the study.

That said, it’s important to note that the study was observational – meaning researchers can’t say for certain that PMDs will cause early menopause. Rather, the study shows there may be a correlation between the two, Donghao Lu, MD, an associate professor in the department of medical epidemiology and biostatistics at the Karolinska Institute, told CNN.

A version of this article first appeared on Medscape.com.

Women with premenstrual disorders may be more likely go through menopause before they are 45 years old, a new study suggests. 

Women with premenstrual disorders, or PMDs, were also more likely to have moderate or severe night sweats or hot flashes during menopause, the researchers found.

Published in JAMA Network Open, the new findings stem from data from more than 3,600 nurses who contributed their health information to a database between 1991 and 2017. Women with PMDs were more than twice as likely as women without PMDs to have early menopause.

Most women have menopause between the ages of 45 and 55 years old, according to the World Health Organization. 

There are numerous PMDs, including the well-known premenstrual syndrome, which is considered a mild disorder affecting up to 30% of women that causes symptoms like crankiness and bloating. A less common PMD is premenstrual dysphoric disorder, which can severely impact a woman’s life through psychological, gastrointestinal, skin, and neurological problems.

Previous research has linked PMDs during the reproductive years and postmenopausal issues like hot flashes and night sweats to increased risks of health problems like high blood pressure, heart conditions, and diabetes.

“It is important to identify women at risk for early menopause because of its link with poorer heart, brain, and bone health,” Stephanie Faubion, MD, MBA, a doctor at the Mayo Clinic and medical director of the North American Menopause Society, told CNN. Dr. Faubion was not involved in the study.

That said, it’s important to note that the study was observational – meaning researchers can’t say for certain that PMDs will cause early menopause. Rather, the study shows there may be a correlation between the two, Donghao Lu, MD, an associate professor in the department of medical epidemiology and biostatistics at the Karolinska Institute, told CNN.

A version of this article first appeared on Medscape.com.

A small, nonmechanical, implanted device that continuously releases the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) and designed for improving glucose control in people with type 2 diabetes received a resounding, unanimous rejection Sept. 21 from an advisory committee of the Food and Drug Administration.

The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.

“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
 

“No evidence of improved adherence”

Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.

However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
 

Seven years of FDA review

This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.

Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week. 

But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”

All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A small, nonmechanical, implanted device that continuously releases the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) and designed for improving glucose control in people with type 2 diabetes received a resounding, unanimous rejection Sept. 21 from an advisory committee of the Food and Drug Administration.

The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.

“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
 

“No evidence of improved adherence”

Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.

However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
 

Seven years of FDA review

This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.

Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week. 

But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”

All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A small, nonmechanical, implanted device that continuously releases the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) and designed for improving glucose control in people with type 2 diabetes received a resounding, unanimous rejection Sept. 21 from an advisory committee of the Food and Drug Administration.

The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.

“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
 

“No evidence of improved adherence”

Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.

However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
 

Seven years of FDA review

This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.

Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week. 

But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”

All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
 

A version of this article appeared on Medscape.com.