Does the Recombinant Herpes Zoster Vaccine Protect Against Herpes Zoster Ophthalmicus?
BACKGROUND AND PURPOSE:
- In clinical trials, the recombinant herpes zoster vaccine (RZV) has demonstrated efficacy in preventing postherpetic neuralgia (PHN) but data on protection against herpes zoster ophthalmicus (HZO) is limited
- Zerbo et al. (JAMA Network Open, 2025) investigated whether RZV is associated with a reduction in the risk of PHN and HZO
METHODS:
- Cohort study
- 4 health plans in the Vaccine Safety Datalink
- Between January 1, 2018, to December 31, 2022
- Population
- Adults aged ≥50
- Exposures
- Vaccination status
- Partially vaccinated: ≥30 days from first dose but no second dose
- Fully vaccinated: ≥30 days from second dose
- Unvaccinated
- Vaccination status
- Study design
- Cox regression was used to estimate hazard ratios
- Vaccine effectiveness (VE) was estimated as 1 minus the HR, scaled as a percentage
- Primary outcome
- VE against PHN and HZO
RESULTS:
- 1,999,885 individuals
- Aged 50 to 69: 74.5% | Aged >70: 25.5%
- Male: 46.6%
- Fully vaccinated: 28.8% | Partially vaccinated: 9.3%
- Had herpes zoster: 2.3%
- VE against PHN
- Fully vaccinated: 87% (95% CI, 83 to 90)
- Partially vaccinated: 69% (95% CI, 59 to 76)
- VE against HZO
- Fully vaccinated: 78% (95% CI, 73 to 82)
- Partially vaccinated: 68% (95% CI, 58 to 76)
- VE waned slightly after 2 years, but still remained above 74% for both outcomes
CONCLUSION:
- Two doses of RZV was effective at reducing the risk of both postherpetic neuralgia and herpes zoster ophthalmicus
- The authors state
This study was limited by its case finding, which missed persons with PHN or HZO who did not seek care
Nonetheless, in this large cohort, we found RZV to be associated with reducing the risk PHN and HZO
Learn More – Primary Sources:
Recombinant Zoster Vaccination and Risk of Postherpetic Neuralgia or Zoster Ophthalmicus
Does ChatGPT Give Responses to Breast Cancer Patient Questions Comparable to Medical Experts?
BACKGROUND AND PURPOSE:
- Liao et al. (JCO Clinical Cancer Informatics, 2025) compared the accuracy and reproducibility of ChatGPT’s recommendations in response to breast cancer patient questions vs consensus expert opinion
METHODS:
- Comparative study
- Participants
- Breast cancer patients participating in a weekly international breast cancer webinar series
- Comparisons
- Responses given by a tumor board of renowned experts
- Responses given to the same question by ChatGPT-4.0
- Study design
- Questions were supplied to ChatGPT 3 separate times to assess reproducibility
RESULTS:
- 362 breast cancer patients
- ChatGPT-generated content that was entirely concordant with the recommendations of breast cancer experts: 46%
- ChatGPT’s responses were not necessarily incorrect but often omitted specific details about clinical management
- ChatGPT’s responses demonstrated higher concordance with experts on topics related to earlier stages of breast cancer (0, I, II, III), compared to questions asked by advanced (IV) patients
- P=0.019
- ChatGPT’s responses were less accurate when responding to patients about
- Molecular markers and genetic testing: P=0.025
- Antibody drug conjugates: P=0.006
- ChatGPT’s responses that were entirely consistent across different patients with the same question: 32%
CONCLUSION:
- Questions directed at ChatGPT by breast cancer patients entirely matched the responses written by experts less than half of the time
- Additionally, ChatGPT’s responses were inconsistent between users, even when patients asked the exact same question
- The authors state
As currently constructed, ChatGPT is not engineered to generate identical outputs to the same input and was less likely to correctly interpret and recommend treatments for complex breast cancer patients
Learn More – Primary Sources:
Accuracy and Reproducibility of ChatGPT Responses to Breast Cancer Tumor Board Patients
Do Physicians Correctly Identify Errors in AI Generated Responses to Patient Portal Messages?
BACKGROUND AND PURPOSE:
- Biro et al. (npj Digital Medicine, 2025) assessed whether primary care physicians could identify and correct errors in AI-generated draft responses to patient portal messages
METHODS:
- Cross-sectional simulation study
- Hospital system in Baltimore-Washington area
- 20 primary care physicians from 13 clinical sites
- Participants
- Primary care physicians
- Study design
- Primary care physicians were presented with 18 patient portal messages and AI-generated draft responses
- 4 of the responses contained errors
- Physician edits to the AI responses were evaluated to see whether these errors were eliminated prior to the messages being “sent”
- Primary care physicians were presented with 18 patient portal messages and AI-generated draft responses
- Primary outcome
- Likelihood of physicians addressing errors in AI generated responses
- Secondary outcomes
- Physician’s perspectives on AI generated responses
RESULTS:
- 20 primary care physicians
- Each of the AI drafts containing errors was “missed” by at least 13 participants
- Mean number of erroneous AI drafts that each participant missed: 66.6%
- Only 1 participant successfully addressed all erroneous drafts
- Survey results found that the participants viewed the drafts favorably
- Agreed drafts were helpful: 95%
- Agreed drafts reduced cognitive workload: 80%
- Agreed that the drafts were trustworthy: 90%
- Agreed the drafts were empathetic: 75%
- Agreed drafts were accurate: 70%
- Agreed drafts were safe to use: 75%
CONCLUSION:
- AI generated drafts of responses to patient portal messages contained factual errors or harmful omissions
- Of the drafts that contained errors, most physicians did not revise the drafts to address these errors
- Physicians missed, on average, two thirds of erroneous messages
- The authors state
To better support the use of AI enabled technologies for practice efficiency, additional research is needed to identify the specific types of errors LLMs are likely to make, and the context under which these errors are most prevalent
Learn More – Primary Sources:
Opportunities and risks of artificial intelligence in patient portal messaging in primary care
Hospital Staffing Shortages and Physician Burnout
BACKGROUND AND PURPOSE:
- Work overload among health care providers during and following the COVID-19 pandemic resulted in burnout and further staffing shortages
- Rotenstein et al. (JAMA Internal Medicine, 2025) assessed the prevalence of incompletely staffed teams and its association with burnout and work intentions of US physicians
METHODS:
- Cross-sectional study
- December 13, 2022 to March 31, 2025
- Data derived from AMA Organizational Biopsy tool
- Population
- Physicians who responded to questions related to team staffing
- Exposures
- Self-reported incomplete staffing
- Study design
- Multivariable logistic regression models were used to assess the association of incomplete team staffing >25% of the time with primary outcomes
- Adjustments: Years in practice | Gender | Race and ethnicity | Part-time vs full-time | Specialty grouping | Practice setting
- Primary outcome
- Burnout: Assessed with the Mini Z’s single-item burnout measure (rate level of burnout from 1 to 5)
- Career intentions
- Self-reported intent to reduce clinical working hours (ITR)
- Self-reported intent to leave workforce (ITL)
RESULTS:
- 970 physicians | 15 organizations
- Women: 43.4% | Full-time: 67.2% | Outpatient setting only: 64.4%
- Nearly half of respondents reported working with an incompletely staffed team >25% of the time
- Overall: 47.9%
- Primary care: 44.8%
- Medical: 38.5%
- Surgical: 49.3%
- Other: 62.4%
- Respondents who met criteria for burnout: 47.9%
- Respondents who indicated likely or definite ITR in next 12 months: 26.4%
- Respondents who indicated likely or definite ITL in next 24 months: 15.4%
- Working with an incompletely staffed team more than 25% of the time was associated with greater prevalence of
- Burnout
- Incomplete: 61.1% | Not incomplete: 35.8% | P<0.001
- Adjusted odds ratio (aOR) 2.21 (95% CI, 1.59 to 3.06)
- ITR
- Incomplete: 31.2% | Not incomplete: 22.0% | P<0.001
- aOR 1.43 (95% CI, 1.01 to 2.03)
- ITL
- Incomplete: 18.1% | Not incomplete: 12.9% | P<0.02
- aOR 1.49 (95% CI, 1.07 to 2.34)
- Burnout
CONCLUSION:
- US Physicians commonly report incomplete staffing following the pandemic
- Working with an incompletely staffed team was associated with higher rates of burnout, intention to reduce hours, and intention to leave the health care workforce
- The authors state
The cross-sectional nature of the study does not allow us to infer causation
Future studies should test policies and interventions that facilitate sustainable and robust staffing of health care teams
Learn More – Primary Sources:
Incomplete Team Staffing, Burnout, and Work Intentions Among US Physicians
COVID-19 Diagnosis and Management
SUMMARY:
Long Covid (LC) is an infection-associated (IACC) that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. LC is known by other terms e.g., Post-Acute Sequelae of COVID (PASC), long-haul COVID, chronic COVID, post-acute COVID-19. The estimated incidence of cases worldwide is 400 million and remains a major public health concern. LC is a systemic disease that can affect any organ system. Anyone is at risk, however women, Hispanic and Latino people, unvaccinated individuals, those with underlying health conditions, adults age 65 and older or those with more severe COVID-19 illness are more at risk for developing LC.
Clinical Presentation
- Can present in multiple ways and be comprised of multiple or single symptoms or diagnoses
- Most common symptoms include: Shortness of breath | Cough | Persistent Fatigue | Post-Exertional Malaise | Difficulty concentrating | Memory Changes | Headaches | Lightheadedness | Tachycardia | Insomnia | Dysgeusia | Anosmia | GI changes
- Common diagnoses: ILD and hypoxemia | CV disease and arrythmias | cognitive impairment mood disorders | anxiety | migraines | stroke | VTE | POTS | Dysautonomia | Myalgic Encephalitis/Chronic Fatigue Syndrome(ME/CFS) | Mast Cell Activation Syndrome (MCAS) | Fibromyalgia | Connective Tissue Disease | Autoimmune conditions i.e., SLE, RA, Sjogren’s | Diabetes
- LC can follow asymptomatic, mild or severe SARS-CoV2 infection
- Anyone at risk however these groups are more at risk:
- Women
- Hispanic and Latino People
- Unvaccinated individuals
- Those with underlying health conditions
- Adults age 65 and older
- Severe acute COVID-19 illness e.g., hospitalized or in ICU
- Can be continuous from time of acute SARS-CoV-2 infection or delayed in onset for weeks or months following completely recovery from acute illness and persist for months to years
- Prior health conditions may be exacerbated by LC
Diagnosis
- There is no biomarker or imaging currently available to conclusively diagnosis LC
- LC is a clinical diagnosis with ICD 10 Code: U09.9 (Post Covid-19 Condition, unspecified)
- LC is considered a disability per the Americans with Disability Act
Pathophysiology
- Different mechanisms likely account for various symptoms
- Suspected mechanisms: persistent reservoirs of SARS-CoV-2 in tissues|Immune dysregulation with or without reactivation of underlying pathogens (e.g., herpesviruses)|microbiome perturbations|autoimmunity|microvascular blood clotting with endothelial dysfunction|dysfunctional brain signaling in the brainstem|serotonin deficiency|reduction of skeletal muscle mitochondria enzyme activity| accumulation of amyloid-containing deposits in skeletal muscle
Prevention
- Decreasing risk of severe acute COVID-19 illness via vaccination (at least one dose)
- Avoiding infection via masking or physical distancing in high-risk environments
- Research studies that suggest treatment with anti-virals during the acute-COVID 19 phase can reduce risk of developing LC
Treatment
- Treatment is directed at specific symptoms and can be pharmacologic and non-pharmacologic e.g., cognitive behavioral therapy, energy conservation strategies, physical therapy
- Physical activity recommendations must be tailored to patients’ activity tolerance to prevent post exertional malaise or post exertional symptom exacerbation
- Validation of patient’s experience and reassurance of symptoms being taken seriously
- Addressing comorbidities and modifiable risk factors e.g., uncontrolled diabetes,
- Documentation for personalized work accommodations
- Consider referring to clinical trials
KEY POINTS:
- Long Covid is an infection associated chronic condition that occurs after a SARS-CoV-infection and is present for at least months as a continuous, relapsing and remitting or progressive disease state that affects one or more organ system
- There is no biomarker, and the diagnosis is based on clinical presentation
- LC can result in significant disability and decreased quality of life and treatment is mainly supportive and symptom based at this time
Learn More – Primary Sources
National Academies of Science, Engineering and Medicine Long Covid Definition
An Overview of Long Covid
Background:
COVID-19 (coronavirus disease 2019) is a respiratory disease caused by the SARS-CoV-2 virus. As of June 1, 2024 nearly 1.2 million people have died of COVID-19 in the U.S. The Infectious Diseases Society of America (IDSA) has developed evidence-based, frequently updated guidelines for the treatment and management of COVID-19. Recommendations are categorized as strong or conditional based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
- Diagnosis
- Outpatient Treatment
- Pre-Exposure Prophylaxis
- Post-Exposure Prophylaxis
- Antiviral Therapies
- Other Therapies
- Primary Sources
Diagnosis:
- Symptoms are wide ranging from mild to severe illness and generally appear 2-14 days after exposure to the virus and may include: Fever or chills | Cough | Dyspnea or Tachypnea | Odynophagia | Congestion or rhinorrhea | Anosmia or Dysguesia | Fatigue | Myalgias | Headache | Nausea or Vomiting | Diarrhea
- Testing is helpful for guiding management and to distinguish from other respiratory viruses with overlapping symptoms. There are two main types of test:
- Nucleic Acid Amplifications Test (NAAT) or Polymerase Chain Reaction (PCR)
- Considered gold standard with high sensitivity and specificity
- Takes several hours to result
- Antigen tests:
- Takes 15-30 minutes to result and can be done at home or in office
- Less sensitive than NAAT and may result in false negative
- Repeat testing indicated in 24-48 hours if clinical suspicion high
- Nucleic Acid Amplifications Test (NAAT) or Polymerase Chain Reaction (PCR)
- Definitions of COVID-19 Severity
- Mild to moderate COVID-19 (SpO2 ³ 94% on RA and no need for supplemental O2)
- Severe COVID-19 (Sp < 94% on RA or needing low-flow supplemental oxygen)
- Critical COVID-19 needing high-flow oxygen | non-invasive ventilation | ECMO
Outpatient Treatment
Clinical evaluation should consider patient and pathogen specific factors that can influence choice of COVID-19 treatments.
The evaluation should at least include assessment of the following: Severity of acute COVID-19 | Date of onset of symptoms| Risk factors for progression to severe disease or death | Degree of chronic and acute end-organ dysfunction| age | pregnancy status | variant susceptibility
Risk factors for progression to severe disease: age > 60 | BMI > 25 | Diabetes | HTN | CV disease | Cancer | Immunosuppression | Chronic Lung Disease | Under immunization
Pre-Exposure Prophylaxis
- Pemivibart: Suggested for moderately or severely immunocompromised individuals aged 12+ when regional variants are susceptible (Conditional; Low certainty)
- Benefits are higher in severely immunocompromised adults but lower in adolescents.
- Risks include a 0.6% chance of anaphylaxis.
- Evusheld (Tixagevimab/Cilgavimab): No longer authorized in the U.S. due to inactivity against circulating variants.
Post-Exposure Prophylaxis
- Neutralizing antibody combinations (e.g., Bamlanivimab/Etesevimab, Casirivimab/Imdevimab) are no longer authorized due to inactivity against Omicron variants.
- Remdesivir:
- Suggested for mild-to-moderate cases at high risk of severe disease if initiated within seven days of symptom onset (Conditional; Low certainty).
- Reduced risk of hospitalization and death by 87% in unvaccinated outpatients at high risk of severe disease
- Administered via IV for 3 days
- Caution when CrCl< 30 mL/min
- Nirmatrelvir/Ritonavir
- Suggested for mild-to -moderate cases at high risk of severe disease if initiated within five days of symptom onset (Conditional recommendation, Low certainty of evidence)
- Reduced risk of hospitalization and death by 87% in unvaccinated outpatients with COVID-19 at higher risk of severe disease
- 5-day oral course
- Reduced dosage for eGFR £60 mL/min and ³30mL/min
- Not recommended for eGFR £30 mL/min
- Viral Rebound i.e., Recurrence of symptoms after improvement and negative test results has been estimated to occur in 0.8% to 6.6% treated with Nirmatrelvir/Ritonavir. Repeated course of anti-viral is not recommended and no known negative outcome from viral rebound.
- Several drug interactions due to the ritonavir component and clinicians evaluate these e.g., Liverpool COVID-19 Interaction (see more “Learn More)
- Molnupiravir
- In ambulatory patients (≥18 years) with mild-to-moderate COVID-19 at high risk for progression to severe disease who have no other treatment options, the IDSA guideline panel suggests molnupiravir initiated within five days of symptom onset rather than no molnupiravir. (Conditional recommendation†, Low certainty of evidence)
- Molnupiravir was shown to have low efficacy against severe outcomes in clinical trials and has little evidence of effectiveness particularly among vaccinated individuals.
- 5-day oral course
- Avoid in pregnant women and advise contraception during treatment and for four days after treatment for women
- Men of reproductive potential who are sexually active with females of childbearing potential should use a reliable method of contraception during treatment and for at least three months after the last dose of molnupiravir
- Viral Rebound has also been described with molnupiravir and a repeated anti-viral course is not recommended nor are there any known negative outcomes from viral rebound
Other Therapies
- Hydroxychloroquine/Chloroquine: Strongly discouraged for treatment or prophylaxis at all severity levels.
- Convalescent Plasma:
- Conditional use suggested for immunocompromised patients or ambulatory high-risk individuals with no other options.
- Inhaled Corticosteroids: Advised against in ambulatory mild-to-moderate cases unless prescribed for other conditions.
- Famotidine: Suggested against its use in both ambulatory and hospitalized severe cases.
Learn More – Primary Sources
IDSA COVID-19 Treatment and Management Guidelines
CDC COVID-19 Treatment for Outpatients
Accuracy of Home Rapid Antigen Test
Management of Drug Interactions Nirmatrelvir/Ritonavir
RCT Results: Bedtime vs Morning Use of Antihypertensive Medications to Reduce Cardiovascular Risk
BACKGROUND AND PURPOSE:
- Some studies support bedtime vs morning administration of BP medications to reduce cardiovascular risk, but evidence is inconsistent
- Garrison et al. (JAMA, 2025) sought to determine the effect of bedtime vs morning administration of antihypertensive medications on major cardiovascular events and death
METHODS:
- Multicenter, open-label, pragmatic randomized clinical trial with blinded end-point assessment
- BedMed Randomized Clinical Trial
- Recruited through 436 primary care clinicians in 5 Canadian provinces
- Participants
- Community-dwelling adult patients with hypertension
- Taking ≥1 once-daily antihypertensive medication
- Interventions
- Using all once-daily antihypertensive medications at bedtime
- Using all in the morning
- Primary outcome
- Composite of time to first occurrence of
- All-cause death or hospitalization/ED visit for stroke | Acute coronary syndrome | Heart failure
- Composite of time to first occurrence of
- Secondary outcomes
- All-cause unplanned hospitalizations/ED visits
- Safety outcomes
- Visual | Cognitive | Fall- and/or fracture-related
RESULTS:
- Bedtime: 1677 participants | Morning: 1680 participants
- Female: 56.4% | Median age: 67 years
- Monotherapy: 53.7%
- Median follow-up: 4.6 years
- There was no difference in the rate of the primary outcome between the bedtime and morning groups
- Bedtime: 2.3 per 100 patient-years | Morning: 2.4 per 100 patient-years
- Adjusted hazard ratio (aHR) 0.96 (95% CI, 0.77 to 1.19) | P=0.70
- Additionally, there was also no difference in
- Individual components of the primary outcome
- All-cause hospitalizations/ED visits
- Safety outcomes
- Falls/fractures | Glaucoma diagnoses | 18-month cognitive decline
CONCLUSION:
- For adults receiving antihypertensive medications in primary care, taking once-daily medications at bedtime was safe but did not reduce cardiovascular risk compared to taking medication in the morning
- The authors state
Antihypertensive medication administration time did not affect the risks and benefits of BP-lowering medication and instead should be guided by patient preferences
Learn More – Primary Sources:
BedMed – Pragmatic Trials Collaborative
Is Semaglutide or Tirzepatide Superior for Body Weight Reduction in Patients with Obesity?
BACKGROUND AND PURPOSE:
- The efficacy of both tirzepatide (dual GIP and GLP-1 receptor agonist) and semaglutide (selective GLP-1 receptor agonist) for the treatment of obesity is well established
- It is not clear whether one is more efficacious or safer than the other
- Aronne et al. (NEJM, 2025) assessed whether tirzepatide or semaglutide was superior to the other for the treatment of obesity without type 2 diabetes
METHODS:
- Phase 3b, open-label, controlled trial
- 32 sites in the US and Puerto Rico
- Participants
- Adult participants with obesity
- No type 2 diabetes
- Interventions
- Maximum tolerated dose of tirzepatide (10 mg or 15 mg)
- Maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg)
- Study design
- Medications administered subcutaneously once weekly for 72 weeks
- 1:1 randomization
- If patients stopped due to side effects were encouraged to remain in the trial for follow-up
- Nutritional and physical activity counseling provided to all participants
- Primary outcome
- Least-squares mean percent change in weight from baseline to week 72
- Secondary outcomes
- Weight reductions of at least 10% | 15% | 20% | 25%
- Change in waist circumference from baseline to week 72
RESULTS:
- 751 participants
- The percent change in weight at week 72 was greater in the tirzepatide group (P<0.001)
- Tirzepatide: −20.2% (95% CI, −21.4 to −19.1)
- Semaglutide: −13.7% (95% CI, −14.9 to −12.6)
- Mean change in waist circumference was also greater with tirzepatide (P<0.001)
- Tirzepatide: −18.4 cm (95% CI, −19.6 to −17.2)
- Semaglutide: −13.0 cm (95% CI, −14.3 to −11.7)
- Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%
- Most common adverse events in both treatment groups were gastrointestinal
- Most were mild to moderate
- Most occurred during dose escalation
CONCLUSION:
- In the setting of obesity but no diabetes, a 20.2% weight reduction was seen with tirzepatide vs a 13.7% reduction with semaglutide
- Adverse events were similar for tirzepatide and semaglutide
- The authors state
In this trial, treatment with tirzepatide, a dual GIP and GLP-1 receptor agonist, was superior to treatment with semaglutide, a selective GLP-1 receptor agonist, with respect to reduction in body weight and waist circumference
Learn More – Primary Sources:
Tirzepatide as Compared with Semaglutide for the Treatment of Obesity
RCT: Yoga vs Strength Exercise for Knee Osteoarthritis Pain
BACKGROUND AND PURPOSE:
- Exercise therapy is recommended as a first-line treatment for knee osteoarthritis (OA), but it’s not clear whether different types of exercise have a greater benefit
- Abafita et al. (JAMA Network Open, 2025) compared the effectiveness of yoga vs strengthening exercise for reducing knee pain in patients with knee OA
METHODS:
- Single-center, assessor-blinded, parallel-arm, active-controlled, superiority randomized clinical trial
- Participants
- Adults ≥40 years
- Knee OA
- Knee pain levels of ≥40 on a 100-mm VAS
- Interventions
- Yoga exercise
- Strengthening exercise
- Both groups received
- Weeks 1 to 12: 2 supervised and 1 home-based session per week
- Weeks 13 to 24: 3 unsupervised home-based sessions per week
- Study design
- There was a prespecified noninferiority margin of 10 mm
- Analysis was by intention to treat
- Primary outcome
- Difference in VAS score over 12 weeks
- Secondary outcomes
- Knee pain over 24 weeks using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
- Quality of life scores
- 25 other outcomes
RESULTS:
- Yoga: 58 participants | Strengthening: 59 participants
- The between group mean difference in VAS knee pain change over 12 weeks was not statistically different, and remained within the noninferiority margin
- –1.1 mm (95% CI, –7.8 to 5.7)
- Of the 27 secondary outcomes assessed over 12 and 24 weeks, 7 were statistically significant in favor of yoga
- WOMAC pain: −44.5 mm (95% CI, −70.7 to −18.3)
- WOMAC function: −139 mm (95% CI, −228.3 to −49.7)
- WOMAC stiffness: −17.6 mm (95% CI, −30.9 to −4.3)
- Patient global assessment: −7.6 mm (95% CI, −15.1 to −0.2)
- 40-m fast-paced walk test: 1.8 (95% CI, 0.4 to 3.2)
- Depression at 12 weeks: −1.1 (95% CI, −1.9 to −0.2)
- Quality of life at 24 weeks: 0.04 (95% CI, 0.0 to 0.07)
- Adverse events were similar in both groups and mild
CONCLUSION:
- Both yoga and strength-based training reduced knee pain for patients with knee OA
- Yoga did significantly improve several other outcomes, compared to strength-based training, including depression, quality of life and knee function
- The authors state
Overall, these findings suggest that integrating yoga as an alternative or complementary exercise option in clinical practice may help in managing knee OA
Learn More – Primary Sources:
Yoga or Strengthening Exercise for Knee Osteoarthritis: A Randomized Clinical Trial
Does Exposure to Smoking Cessation Drugs During Pregnancy Increase the Risk of Major Malformations?
BACKGROUND AND PURPOSE:
- Smoking cessation pharmacotherapies may be used by pregnant people who wish to quit smoking during pregnancy, but evidence on fetal safety is limited
- Tran et al. (JAMA Intern Med, 2025) assessed whether prenatal use of smoking cessation pharmacotherapies like nicotine replacement therapy (NRT), varenicline, and bupropion was associated with increased risks of major congenital malformations (MCMs)
METHODS:
- Retrospective cohort study
- Common protocol in New South Wales (NSW, Australia), New Zealand (NZ), Norway, and Sweden
- Data derived from national registers
- Births between 2001 and 2020
- Population
- All births to women who
- Smoked during the first trimester or
- Received smoking cessation pharmacotherapy
- All births to women who
- Exposures
- Receipt of smoking cessation pharmacotherapy 90 days before conception or during the first trimester
- NRT | Varenicline | Bupropion
- Unexposed: smoking during the first trimester, but no pharmacotherapy
- Receipt of smoking cessation pharmacotherapy 90 days before conception or during the first trimester
- Study design
- Propensity score matching used to match exposed infants to unexposed infants
- Primary outcome
- Major congenital malformations
RESULTS:
- 267,522 women | 391,474 infants
- Exposed to NRT: 9325 infants | Varenicline: 3031 | Bupropion: 1042
- Compared with unexposed infants, there were no differences in prevalence of MCMs overall following exposure to any of the pharmacotherapies
- NRT
- Exposed: 37.6 per 1000 live births | Unexposed: 34.4
- Adjusted relative risk (aRR) 1.10 (95% CI, 0.98 to 1.22)
- Varenicline
- Exposed: 32.7 per 1000 live births | Unexposed: 36.6
- aRR 0.90 (95% CI, 0.73 to 1.10)
- Bupropion
- Exposed: 35.5 per 1000 live births | Unexposed: 38.8
- aRR 0.93 (95% CI, 0.67 to 1.29)
- NRT
- For NRT, there was no difference in the risk of MCMs by most subtypes
- Heart | Limbs | Genital organs | Kidney/urinary tract | Respiratory system | Orofacial clefts
- There was a higher risk of digestive organ MCMs with NRT but not statistically significant after multiple comparisons
- Exposed: 3.8 per 1000 live births | Unexposed: 2.5
- aRR 1.53 (95% CI, 1.05 to 2.23) | P=0.41
- For varenicline, there was also no difference in the risk of MCMs by most subtypes with enough data
- Heart | Limbs | Genital organs
- There was a higher risk of kidney/urinary tract MCMs but not statistically significant after multiple comparisons (small sample set)
- Exposed: 11.5 | Unexposed: 4.2 per 1000 live births
- aRR 2.75 (95% CI, 1.42 to 5.34) | P=0.09
- For bupropion, data were too sparse to estimate the risk of MCM by subtype
CONCLUSION:
- Use of nicotine replacement therapy, varenicline, and bupropion was not associated with an increased risk of congenital malformations vs smoking
- The authors state
Overall, our findings are reassuring given the extensive detrimental effects of smoking on maternal and child health
Larger studies providing more robust estimates of risk for the remaining malformation subgroups are needed
Learn More – Primary Sources:
Risk of Major Congenital Malformations Following Prenatal Exposure to Smoking Cessation Medicines
US Poll Results: Public Utilization and Confidence in AI for Healthcare Information
BACKGROUND AND PURPOSE:
- Orrall and Rekito (JAMA, 2025) report results of a poll conducted to investigate adults’ trust in AI to inform their health decisions
METHODS:
- Poll administered by KFF
- KFF is an endowed national nonprofit organization that integrates policy research, polling, and journalism to serve as a reliable and independent source of healthcare information
- Population
- Nationally representative sample of Black, Hispanic and White adults in the US
- Study design
- Questions asked about
- Frequency of AI use
- Trust in AI sources
- Whether participants thought AI was doing more to help or hurt people trying to find accurate health information online
- Questions asked about
RESULTS:
- 2428 participants
- Reported ever using AI: 63%
- Reported using several times per day: 11%
- Younger adults were more likely to use AI than older adults
- Adults that report using AI chatbots (e.g. ChatGPT) to receive health information at least once per month: 17%
- Adults <30 years old: 25%
- Adults ≥65 years old: 10%
- Most adults who used AI were not that confident it provided accurate health information
- Reported being “not too confident” or “not at all confident” in the accuracy of AI-generated health information: 63%
- Reported being “very confident” in it: 5%
- Respondents did say they were more confident that AI provided accurate information about practical tasks such as cooking or home maintenance
- Most adults weren’t sure whether AI was helping or hurting people seeking accurate health information
- “Not sure” among users of AI: 49%
- “AI is doing more to hurt” among users: 21%
- “AI is doing more to help” among users: 30%
CONCLUSION:
- In this poll of US adults, nearly one in five reported using AI to find health information at least once per month
- Users tended to be younger
- However, most (63%) were not confident that AI provided accurate information
- The authors state
Although only about 1 in 3 respondents reported trusting AI-derived health information, a larger percentage said they trusted chatbots to provide accurate information about other topics
More than half of total adults said they had a “great deal” or “fair amount” of trust in AI for practical tasks, like cooking and home maintenance
Learn More – Primary Sources:
Poll: Trust in AI for Accurate Health Information Is Low
Is The Incidence of Cervical Cancer Higher in Rural Counties vs Urban Ones?
BACKGROUND AND PURPOSE:
- Amboree et al. (JAMA Network Open, 2025) assessed rural-urban disparities in cervical cancer incidence and mortality
METHODS:
- Cross-sectional study
- Population
- Cervical cancer cases in National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (NPCR-SEER) database
- Between 2001 and 2019
- Exposures
- Rurality
- Study design
- Cervical cancer rates were corrected to account for hysterectomy prevalence
- Joinpoint regression was used to calculate trends in incidence and derive annual percentage change (APC)
- Primary outcome
- Annual incidence
- Age-adjusted 5-year mortality rates per 100,000 women
RESULTS:
- Cervical cancer cases: 222,425
- From urban counties: 84.3% | Non-Hispanic White: 59.9%
- Hysterectomy-corrected incidence rates
- Rural counties: 11.9 per 100,000 women
- Urban counties: 10.0 per 100,000 women
- After decreasing from 2001 to 2012, incidence increased in rural counties between 2012 to 2019
- 2012 to 2019: APC 0.85% (95% CI, 0.08 to 2.05)
- Incidence also decreased in urban counties between 2001 and 2013, but plateaued from 2013 to 2019
- 2013 to 2019: APC –0.03% (95% CI, –0.89 to 2.00)
- The gap between rural and urban incidence rates widened from 2013 to 2019
- 2013: rate ratio 1.16 (95% CI, 1.10 to 1.22)
- 2019: rate ratio 1.25 (95% CI, 1.19 to 1.31)
- During 2012 to 2019, among rural White women, cervical cancer incidence increased
- 1.05% per year (95% CI, 0.24 to 2.33)
- Incidence also increased among non-Hispanic Black women, but this was not statistically significant
- 9.07 (95% CI, –2.84 to 17.84)
- Incidence declined among rural Hispanic women
- Incidence declined or plateaued for all women in urban counties
- Mortality was higher in rural vs urban counties during 2015 to 2019
- 1.42 (95% CI, 1.33 to 1.51)
- Compared with their urban counterparts, mortality among rural women was higher
- Hispanic women: rate ratio 1.33 (59% CI, 1.12 to 1.58)
- Black women: rate ratio 1.58 (95% CI, 1.32 to 1.90)
- White women: rate ratio 1.54 (95% CI, 1.43 to 1.67)
CONCLUSION:
- The incidence of cervical cancer cases has recently risen by 0.85% per year among rural women, especially rural White women
- Both incidence and mortality were higher among rural vs urban counties
- The authors state
The increase in incidence and mortality in rural US counties may reflect lower screening coverage and lower utilization of diagnostic and therapeutic care, likely resulting from heightened access barriers experienced in rural areas
Additionally, if unaddressed, lower human papillomavirus (HPV) vaccine uptake in rural areas may contribute to further widening disparities in the future
Learn More – Primary Sources:
Rural-Urban Disparities in Cervical Cancer Incidence and Mortality Among US Women
Meta-Analysis: Which Migraine Treatment Methods Are Most Effective?
BACKGROUND AND PURPOSE:
- Gartlehner et al. (Annals of Internal Medicine, 2025) compared benefits and harms of pharmacologic treatments for acute attacks of episodic migraine in adults
METHODS:
- Systematic review and meta-analysis
- Inclusion criteria
- Head-to-head and placebo-controlled trials
- Studies that included adult patients who received initial treatment or second-step treatment for acute attacks of episodic migraine, comparing pharmacologic interventions to other interventions or placebo
- Study design
- Risk of bias was assessed
- Certainty of evidence was assessed with GRADE criteria
- Primary outcomes
- Pain freedom at 2 hours and 48 hours
- Need for rescue medication
- Nausea or vomiting
RESULTS:
- 21 head-to-head studies | 164 placebo-controlled trials
- Triptans were more effective than acetaminophen and NSAIDS for pain outcomes at 2 hours and pain freedom at 48 hours
- Pain freedom at 2 hours, compared to acetaminophen
- Absolute risk difference (ARD) 0.16 (95% CI, 0.02 to 0.38)
- Risk ratio (RR) 1.64 (95% CI, 1.08 to 2.49)
- Low certainty
- Pain freedom at 2 hours, compared to NSAIDs
- ARD 0.10 (95% CI, 0.06 to 0.16)
- RR 1.42 (95% CI, 1.23 to 1.65)
- High certainty
- Pain freedom at 2 hours, compared to acetaminophen
- Triptan and acetaminophen combinations were more effective than acetaminophen alone
- ARD 0.30 (95% CI, 0.04 to 0.74)
- RR 2.17 (95% CI, 1.17 to 4.03)
- Moderate certainty
- Triptan and acetaminophen combinations were not more effective than a triptan alone
- ARD 0.13 (95% CI, –0.10 to 0.53)
- RR 1.33 (95% CI, 0.75 to 2.34)
- Low certainty
- Triptan and NSAID combinations were more effective for pain outcomes at 2 hours and pain freedom up to 48 hours compared with
- Acetaminophen (low COE)
- RR 1.91 (95% CI, 1.21 to 3.00)
- Low certainty
- Gepants
- RR 1.96 (95% CI, 1.50 to 2.56)
- Low certainty
- NSAIDs
- ARD 0.11 (95% CI, 0.06 to 0.17)
- RR 1.66 (95% CI, 1.35 to 2.05)
- High certainty
- Triptan monotherapy
- ARD 0.04 (95% CI, –0.01 to 0.09)
- RR 1.17 (95% CI, 0.97 to 1.40)
- Moderate certainty
- Acetaminophen (low COE)
- Triptans had a higher risk of adverse events
- One study found triptans more cost-effective than ditan and gepant
CONCLUSION:
- When treating episodic migraine, triptans or a combination or triptan and NSAID was most effective at achieving pain relief at 2 hours and sustained pain freedom at 48 hours
- These findings are reflected in the new ACP migraine guidelines (see ‘Learn More – Primary Sources’ below)
Learn More – Primary Sources:
RCT Results: Which Hereditary Cancer Risk Assessment Strategies are Most Likely to be Successful in a Primary Care Setting?
BACKGROUND AND PURPOSE:
- Many cancers are caused by heritable factors that can be readily identified with multigene test
- Swisher et al. (JAMA Network Open, 2025) compared two population-based engagement strategies for identifying primary care patients with a family or personal history of cancer and offering eligible individuals genetic testing for cancer susceptibility
METHODS:
- Clinical cluster-randomized trial
- EDGE (Early Detection of Genetic Risk) trial
- Participants
- English-speaking patients ≥25 years old
- Primary care visit between April 2021 and March 2022
- Interventions
- Point of care (POC) engagement: Cancer history assessment conducted by staff immediately preceding clinical appointments
- Direct patient engagement (DPE): Letter and email outreach facilitated at-home completion of cancer history assessment
- Study design
- Patients who completed risk assessment and met prespecified criteria were offered at home genetic testing at no cost
- Logistic regression models were used to compare approaches
- Analysis was by intention-to-treat
- Primary outcomes
- Proportion of patients who completed risk assessment
- Proportion of patients who completed genetic testing
RESULTS:
- 95,623 patients had a primary care visit
- Completed risk assessment: 13,705
- Patients who completed the risk assessment were
- Predominantly female: 64.7%
- Predominantly 65 to 84 years: 39.6%
- The POC approach resulted in a higher proportion of patients completing risk assessment
- POC: 19.1% | DPE: 8.7%
- Adjusted odds ratio (aOR) 2.68 (95% CI, 1.72 to 4.17) | P<0.001
- Neither approach was better at getting patients to complete testing
- POC: 1.5% | DPE: 1.6%
- aOR 0.96 (95% CI, 0.64 to 1.46) | P=0.86
- Among those eligible for testing, POC test completion was approximately half of that for the DPE approach
- POC: 24.7% | DPE: 44.7%
- aOR 0.49 (95% CI, 0.37 to 0.64) | P<0.001
- The proportion of tested patients identified with an actionable pathogenic variant was significantly lower for the POC approach than the DPE approach
- POC: 3.8% | DPE: 6.6%
- aOR 0.61 (95% CI, 0.44 to 0.85) | P=0.003
CONCLUSION:
- Patients who received point of care cancer history assessment during primary care visits were more likely to complete the risk assessment than patients who received a letter or email asking them to complete the assessment
- Both approaches led to similar rates of genetic testing completion but the email group had a higher rate of pathogenic mutations
- The authors state
Relative to patients in the POC arm, those in the DPE arm who completed screening were more likely to have a personal history of cancer and 2 or more first-degree relatives with cancer, resulting in a higher proportion who were eligible for testing
Using a combination of engagement strategies may be the optimal approach for greater reach and impact
Learn More – Primary Sources:
Pneumococcal Vaccination Guidelines
Background:
Streptococcus pneumonia (pneumococcus) can cause pneumonia, meningitis, bacteremia, otitis media and sinusitis, with older adults being most at risk for serious illness and death. Pneumococcal bacteria are spread via direct contact with respiratory secretions e.g., saliva or mucus. Vaccination is the best way to prevent infection. After the introduction of pneumococcal vaccinations for adults and children in the US in the early and mid 2000s, the rates of invasive pneumococcal disease decreased substantially.
Types of Vaccine:
- Pneumococcal conjugate vaccines (PCVs): PCV15 | PCV20 | PCV21
- Pneumococcal polysaccharide vaccine: PPSV23
- Each vaccine protects against different serotypes of pneumococcal bacteria
NOTE: New formulations and changes in guidelines have occurred over the past few years which has led to confusion regarding timing and selection of vaccine types, especially in adults who have already received a single dose of PPSV23 or PCV13. The CDC has created an application (‘PneumoRecs VaxAdvisor’) specifically for individualized guidance tailored for your patient (see under “Learn More” below)
Vaccine Recommendations:
- All adults age ≥ 50 years
- If PCV 20 or 21 used vaccination is considered complete, and no further doses are necessary
- If PCV 15 used, administer a dose of PPSV23 one year later OR at least 8 weeks in adults with immunocompromising conditions | cochlear implant | CSF leak
- Adults aged 19-49 with certain underlying health conditions e.g, Chronic Lung, Liver or Heart Disease | Diabetes Mellitus| Asplenia | Sickle Cell Disease | Immunosuppression | Cochlear Implant | Malignancy | Alcoholism
- Depending on age and type(s) of vaccine received, patients may be recommended to receive additional pneumococcal vaccines
- Adults 65 years or older have the option to get PCV20 or PCV21 to increase the number of pneumococcal serotypes covered, or they may elect not get additional pneumococcal vaccines. They can get PCV20 or PCV21 if they have received both:
- PCV13 (but not PCV15, PCV20, or PCV21) at any age and
- PPSV23 at or after the age of 65 years old
Special Considerations:
- Native Americans and Alaskan Indians populations should receive PCV20 alone or PCV15 and PPSV23 in series given the high prevalence of Serotype 4 Pneumococcal disease that is not covered by PCV 21
Learn More – Primary Resources:
CDC Pneumococcal Vaccine Recommendations
CDC MMWR Expanded Recommendations for Use of Pneumoccoccal Vaccination Jan 2025
Serotype 4 Pneumoccocal Disease increase in Native American/Alaskan Indian Populations
Have 2023 Cancer Screening Rates Rebounded After the COVID-19 Pandemic-Related Screening Declines?
BACKGROUND AND PURPOSE:
- Cancer screening rates declined during COVID and in the immediate aftermath, leading to increased cancer diagnoses at later stages
- Star et al. (JAMA, 2025) estimated post-pandemic cancer screening rates in 2023 relative to previously documented declines through 2021
METHODS:
- Analysis of screening trends
- Data from National Health Interview Survey
- Population
- Nationally representative cross-sectional cohort of noninstitutionalized US adults
- Exposures
- Before the COVID-19 pandemic: 2019
- During: 2021
- After: 2023
- Study design
- Adjustments were made for nonresponse bias
- Screening eligibility and strategies were defined according to the USPSTF recommendations
- Logistic regression models estimated adjusted prevalence ratios (aPRs)
- Adjustments: was Age | Race and ethnicity | Education | Insurance | Region
- Primary outcomes
- Self-reported breast | Cervical | Colorectal cancer screening
RESULTS:
- 2023 eligibility for screening
- Breast cancer: 6829 | Cervical cancer: 8888 | Colorectal cancer: 13,144
- Between 2019 and 2023, reported past-year breast and colorectal cancer screening increased
- Breast: 7% increase
- Prevalence estimate 59.7 to 64.9%
- aPR 1.07 (95% CI, 1.04 to 1.10)
- Colorectal: 12%
- Prevalence estimate: 21.2 to 24.3%
- aPR 1.12 (95% CI, 1.06 to 1.18)
- Breast: 7% increase
- Underlying these increases were
- Rebounds between 2021 and 2023 in breast cancer screening
- 56.9 to 64.9%
- aPR 1.14 (95% CI, 1.11 to 1.18)
- Rebounds between 2021 and 2023 in colonoscopy screening
- 13.8 to 15.7%
- aPR 1.13 (95% CI, 1.06 to 1.22)
- Sustained increases in stool testing
- 2019: 6.6%
- 2021: 10.1%
- 2023: 10.1%
- Rebounds between 2021 and 2023 in breast cancer screening
- Reported cervical cancer screening in 2023 remained below 2019 estimates
- 14% decrease
- Prevalence estimate 46.8 to 40.9%
- aPR 0.86 (95% CI, 0.82 to 0.90)
- Colorectal cancer screening increased between 2019 and 2023 for college graduates, but did not change in individuals with a high school degree or less
- Breast cancer screening met or exceeded 2019 levels across screening groups as screening rebounded between 2021 and 2023
- Cervical cancer screening rebounded between 2021 and 2023 among college graduates, but remained below 2019 levels for most education groups
CONCLUSION:
- Reported breast and colorectal cancer screening rates rebounded after pandemic-related decreases
- In 2023 screening rates were higher than pre-pandemic levels
- Cervical cancer screening remained below pre-pandemic levels
- The authors state
Cervical cancer screening rates remained below prepandemic levels, a troubling trend as early-stage diagnoses continued to decrease in 2021
The persistent decline may in part reflect longer-term declines in patient knowledge and clinician recommendation of cervical cancer screening
Learn More – Primary Sources:
Cancer Screening 3 Years After the Onset of the COVID-19 Pandemic
Is There an Increased Risk of Stroke and Heart Attack Associated with Modern Hormonal Contraceptive Use?
BACKGROUND AND PURPOSE:
- Some studies have found a link between hormonal contraception and stroke and myocardial infarction
- However, there is also contradictory evidence, and research has mostly focused on the combined oral contraceptive pill
- Yonis et al. (BMJ, 2025) evaluated the association between contemporary hormonal contraceptive use and the risk of incident ischemic stroke and myocardial infarction
METHODS:
- Nationwide, prospective cohort study
- Nationwide prospective cohort study of all Danish women
- Participants
- All women aged 15 to 49 living in Denmark between 1996 and 2021
- No history of
- Arterial or venous thrombosis | Cancer (except non-melanoma skin cancer) | Thrombophilia | Liver disease | Kidney disease | Use of antipsychotics | Infertility treatment | Hormone therapy use | Oophorectomy | Hysterectomy | PCOS | Endometriosis
- Exposures
- Hormonal contraceptive use and type
- Study design
- Poisson regression used to estimate adjusted incidence rate ratios
- Primary outcome
- First time diagnosis of ischemic stroke or myocardial infarction
RESULTS:
- 2,025,691 women | 22,209,697 person years of follow-up
- Ischemic stroke: 4730 | Myocardial infarction: 2072
- Standardized ischemic stroke rate
- No hormonal contraceptive use: 18 (95% CI, 18 to 19) per 100,000 person years
- Combined pill: 39 (95% CI, 36 to 42) per 100,000 person years
- Progestin-only pill: 33 (95% CI, 25 to 44) per 100,000 person years
- IUD: 23 (95% CI, 17 to 29) per 100,000 person years
- Standardized myocardial infarction rate
- No hormonal contraceptive use: 8 (95% CI, 8 to 9) per 100,000 person years
- Combined pill: 18 (95% CI, 16 to 20) per 100,000 person years
- Progestin-only pill: 13 (95% CI, 8 to 19) per 100,000 person years
- IUD: 11 (95% CI, 7 to 16) per 100,000 person years
- Compared with no use, current use of combined oral contraception was associated with a higher rate of stroke and myocardial infarction
- Stroke: adjusted rate ratio (aRR) 2.0 (95% CI, 1.9 to 2.2)
- Extra strokes per 100,000 person years: 21 (95% CI, 18 to 24)
- Myocardial infarction: aRR 2.0 (95% CI, 1.7 to 2.2)
- Extra myocardial infarctions per 100,000 person years: 10 (95% CI, 7 to 12)
- Stroke: adjusted rate ratio (aRR) 2.0 (95% CI, 1.9 to 2.2)
- Compared with no use, current use of combined oral contraception was also associated with a higher rate of stroke and myocardial infarction
- Stroke: aRR 1.6 (95% CI, 1.3 to 2.0)
- Extra strokes per 100,000 person years: 15 (95% CI, 6 to 24)
- Myocardial infarction: aRR 1.5 (95% CI, 1.1 to 2.1)
- Extra myocardial infarctions per 100,000 person years: 4 (95% CI, –1 to 9)
- Stroke: aRR 1.6 (95% CI, 1.3 to 2.0)
- Increased arterial thrombotic risk was also observed with use of the
- Combined vaginal ring
- Stroke: aRR 2.4 (95% CI, 1.5 to 3.7)
- Myocardial infarction: aRR 3.8 (95% CI, 2.0 to 7.3)
- Patch
- Stroke: aRR 3.4 (95% CI, 1.3 to 9.1)
- No myocardial infarctions
- Progestin-only implant
- Stroke: aRR 2.1 (95% CI, 1.2 to 3.8)
- ≤3 myocardial infarctions
- Combined vaginal ring
- There was no increased risk of arterial thrombosis with the progestin-only IUD
- Stroke: aRR 1.1 (95% CI, 1.0 to 1.3)
- Myocardial infarction: aRR 1.1 (95% CI, 0.9 to 1.3)
CONCLUSION:
- Use of most modern contraceptive methods was associated with an increased rate of ischemic stroke and, in some cases, myocardial infarction
- Absolute risk remained small
- The progestin-only IUD was not associated with increased rates of either stroke or myocardial infarction
- Limitation of this study include observational design vs RCT and therefore possible residual confounding
- The authors state in an opinion paper
Our findings underscore the critical need for continued research into the cardiovascular effects of hormonal contraception
Future studies should focus on identifying potential biological mechanisms underlying these risks, exploring how individual factors such as genetic predisposition, lifestyle, and comorbidities interact with contraceptive use
Learn More – Primary Sources:
Editorial: Arterial thrombosis in users of contemporary hormonal contraception
Opinion: Research on hormonal contraceptives is needed to monitor their evolving safety profile
