Recent publications
Historically, thalidomide-induced congenital malformations have served as an important example of the enhanced susceptibility of developing embryos to chemical perturbation. The compound produced a wide variety of congenital malformations in humans, which were initially detected by an association with a relatively rare limb defect labeled phocomelia. Although true phocomelia in the most severe form is a transverse defect with intercalary absence of limb regions, it is proposed that thalidomide produces a longitudinal limb phenotype in humans under usual circumstances that can become transverse in severe cases with a preferential sensitivity of forelimb over hindlimb, preaxial over postaxial, and left more impacted than the corresponding non-autopod limb bones on the right. The thalidomide-induced limb phenotype in humans is described and followed by a hierarchical comparison with various laboratory animal species. Mechanistic studies have been hampered by the fact that only non-human primates and rabbits have malformations that are anatomically similar to humans. Included in this review are unpublished data on limb malformations produced by thalidomide in rhesus monkeys from experiments performed more than 50 years ago. The critical period in gestation for the induction of phocomelia may initiate prior to the development of the embryonic limb bud, which contrasts with other chemical and physical agents that are known to produce this phenotype. The importance of toxicokinetic parameters is reviewed including dose, enantiomers, absorption, distribution, and both non-enzymatic and enzymatic biotransformations. The limb embryopathy mechanism that provides a partial explanation of the limb phenotype is that cereblon binds to thalidomide creating a protein complex that ubiquitinates protein substrates (CRL4CRBN) that are not targets for the complex in the absence of the thalidomide. One of these neosubstrates is SALL4 which when mutated causes a syndrome that phenocopies aspects of thalidomide embryopathy. Other candidate neosubstrates for the complex that have been found in non-human species may contribute to an understanding of the limb defect including PLZF, p63, and various zinc finger transcription factors. It is proposed that it is important to consider the species-specificity of the compound when considering potential mechanistic pathways and that some of the more traditional mechanisms for explaining the embryopathy, such as anti-angiogenesis and redox perturbation, may contribute to a full understanding of this teratogen.
VA strives to improve women Veterans’ access to comprehensive care. We assessed if availability of specialized clinic arrangements for women or specialized providers (women’s health primary care providers) was associated with women Veterans’ ratings of primary care experiences.
Cross sectional.
We linked patient-level survey data (Survey of Healthcare Experiences of Patients, FY 2017, n=4264) with primary care clinic-level data (Clinical Practice Organizational Survey, primary care module, 2017–2018, n=126) from clinics with ≥300 women Veterans.
Our dependent variables were derived from top ratings for items rating access, care coordination, comprehensiveness (behavioral health assessed), provider communication, and primary care provider. Our variables of interest were the availability of specialized clinic arrangements such as women’s health clinics and specialized providers such as women’s health primary care providers.
We conducted multi-level, multivariate logistic regression predicting women Veterans’ optimal ratings of care, controlling for patient-, clinic-, and area-level characteristics.
Women Veterans receiving care at general primary care clinics with no women’s health primary care providers had a lower likelihood of rating provider communication as optimal (Adjusted Odds Ratio .60, 95%CI .45–.78) or rating the primary care provider as 9 or 10/10 (Adjusted Odds Ratio .61, 95%CI .42–.86). Women Veterans receiving care at VA sites with a gynecology clinic had a higher likelihood of rating access as optimal (Adjusted Odds Ratio 1.40, 95%CI 1.01–1.94).
Our study found that availability of women’s health primary care providers in general primary care and availability of gynecology clinics were associated with higher likelihood of women Veterans rating care experiences as optimal. Almost all VA sites have women’s health primary care providers available, increasing availability at every site remains an important goal. Relatively few VA community-based outpatient clinics offer gynecology clinics, offering opportunities for improved care experiences among women Veterans.
Since 1980 in the United States (US), more than 10 million arrests have occurred each year. With a majority of those incarcerated being parents, millions of children and remaining household members are adversely affected. Despite the volume of US arrests, few studies provide family context and child considerations about the time period of arrest. This study sought to describe family experiences and considerations to best support youth during parental arrest. Qualitative data were gathered using semi-structured, in-depth phone interviews from March to August 2020 with adolescents (12–18 years) who have had a parent incarcerated, caregivers of children of incarcerated parents, and parents upon one year of release of incarceration. Participants were recruited using flyers and emails to community-based organizations and schools. General themes emerged through qualitative content analysis and inductive open coding procedures. Data from 26 participants were summarized (10 adolescents, 10 caregivers, and six parents upon one year of release from jail/prison). Upon arrest, family experiences were described as traumatizing and stigmatizing regardless of whether the child was present to observe the arrest. The effects of witnessing the arrest were influenced by officer treatment. Families shared how limited household- and community-based resources were available to help the family cope with the consequences of the arrest. Results underscore the need for family-centered approaches and improved interventions upon arrest that may better support children and family members during this time. Recommendations for better transparency, connection, and transition supports are discussed.
South Africa continues to document high HIV prevalence, particularly among pregnant women, highlighting significant prevention gaps. This viewpoint triangulates findings from the Sixth South African HIV Prevalence Survey, the 2022 Antenatal HIV Sentinel Survey, and our ongoing “Philani Ndiphile” trial, which is evaluating STI screening algorithms to improve pregnancy outcomes. Despite a recent national decline in antenatal HIV prevalence, the Philani trial recorded an HIV prevalence of 28.6% among pregnant women, mirroring high rates across the Eastern Cape Province. The trial cohort also revealed a significant increasing trend in HIV prevalence with age, from 6% at 18 years to 63% at 43 years, highlighting the need for age-targeted interventions in young women of childbearing age.
National progress toward UNAIDS’ targets for HIV status knowledge and ART initiation is evident; however, viral suppression remains a challenge, reflected in the 20% of Philani participants newly initiated or reinitiated on ART at their first antenatal visit. Efforts to reduce new HIV infections require strengthening, as high incidence rates persist among young women and during pregnancy and postpartum.
Expanding access to oral and long-acting PrEP for pregnant and postpartum women is critical. Current coverage is low, and while new options show promise, implementation guidance remains limited. Socioeconomic factors, such as poverty and intimate partner violence, exacerbate HIV risk. Comprehensive interventions, including educational and vocational support, engaging male partners, and addressing STIs are essential. Continued support from global health partnerships and innovation in prevention strategies are vital to ending the epidemic and ensuring equitable outcomes.
Introduction:
Artificial intelligence (AI) has many applications in health care. Popular AI chatbots, such as ChatGPT, have the potential to make complex health topics more accessible to the general public. The study aims to assess the accuracy of current long-acting reversible contraception information provided by ChatGPT.
Methods:
We presented a set of 8 frequently-asked questions about long-acting reversible contraception (LARC) to ChatGPT, repeated over three distinct days. Each question was repeated with the LARC name changed (e.g., 'hormonal implant' vs 'Nexplanon') to account for variable terminology. Two coders independently assessed the AI-generated answers for accuracy, language inclusivity, and readability. Scores from the three duplicated sets were averaged.
Results:
A total of 264 responses were generated. 69.3% of responses were accurate. 16.3% of responses contained inaccurate information. The most common inaccuracy was outdated information regarding the duration of use of LARCs. 14.4% of responses included misleading statements based on conflicting evidence, such as claiming intrauterine devices increase one's risk for pelvic inflammatory disease. 45.1% of responses used gender-exclusive language and referred only to women. The average Flesch readability ease score was 42.8 (SD 7.1), correlating to a college reading level.
Conclusion:
ChatGPT offers important information about LARCs, though a minority of responses are found to be inaccurate or misleading. A significant limitation is AI's reliance on data from before October 2021. While AI tools can be a valuable resource for simple medical queries, users should be cautious of the potential for inaccurate information.
Short condensation:
ChatGPT generally provides accurate and adequate information about long-acting contraception. However, it occasionally makes false or misleading claims.
Background
Women’s reproductive experiences may enact reorganization of physiological systems with lifelong health consequences. We test the hypothesis that women’s history of breastfeeding will be positively associated with neurocognitive benefits in post‐menopausal women. This hypothesis is justified by breastfeeding’s well‐established benefits for mothers’ glucose homeostasis, beta‐cell function, adipose tissue mobilization, and lipid metabolism, which would plausibly be beneficial for later‐life brain health.
Method
The Women’s Health Initiative (WHI) was a long‐term, large, US health study in the 1990s‐early 2000s. The WHI Memory Study (WHIMS) was an ancillary study in which cognitively healthy women at baseline were annually assessed. A subset of WHIMS participants were recruited into the WHI Study of Cognitive Aging (WHISCA), which included more comprehensive annual assessments of cognitive function and mood. We use WHIMS participant scores on the Modified Mini Mental State Exam “3MS,” which measures global cognitive functioning, and WHISCA participant scores on the California Verbal Learning Test‐Long Delay (CVLT‐LD), which measures long‐term memory. We employed linear mixed‐effects models to examine the association of 3MS and CVLT‐LD scores with women’s breastfeeding history, controlling for the effects of parity, age, reproductive span, hormone therapies (HT) and duration, and time since HT cessation.
Result
In the WHIMS (N = 6,069) and WHISCA (N = 1,932) cohorts (Table 1 demographics), we found that the number of children a woman breastfed was positively associated with better global cognition (b = 0.059, p = 0.047) and long‐term memory (b = 0.176, p = 0.016). The cumulative number of months a woman breastfed was positively associated with better global cognition (b = 0.064, p = 0.024) and long‐term memory (b = 0.198, p = 0.005). Women who had breastfed ever for at least one month, compared to those who did not, exhibited better long‐term memory (b = 0.671, p = 0.005), and no significant effect for global cognition. Women with a higher breastfeeding‐to‐pregnancy duration ratio exhibited better long‐term memory (b = 0.962, p = 0.000), with no significant effect for global cognition (Table 2, Fig. 1).
Conclusion
Our findings indicate long‐term cognitive benefits of breastfeeding for women, above and beyond any effects of parity. It is possible that breastfeeding could be beneficial for women by endowing resilience against neurodegenerative disorders, consistent with our previous observations from two small cohort pilot studies.
Background
Matrescence, like adolescence, is a critical period for neurodevelopment characterized by hormonal changes that reshape the brain in preparation for new experiences and subsequent learning. Women exhibit greater age‐matched Alzheimer’s disease (AD) risk than men, yet little is known about long‐term neurological health consequences of reproduction (Buckley, 2019), the defining biological difference between the sexes. We tested the hypothesis that greater number of months pregnant would be positively associated with cortical thickness (CT), particularly in regions within the default mode network (DMN). DMN disruption is well‐established in AD pathology (Dennis, 2014). Research also indicates that synaptic pruning within the DMN during pregnancy is related to improved maternal attachment and reduced hostility toward the infant, with these changes persisting post‐partum (Hoekzema, 2017; Garcia, 2021). Moreover, in late life, beneficial changes due to motherhood have been shown in the DMN (Orchard, 2021).
Method
We used data from 1004 older women from the Women’s Health Initiative Magnetic Resonance Imaging (MRI) study (Coker, 2009) (Table 1). CT was estimated from T1‐weighted MRI using FreeSurfer. The effect of cumulative pregnancy duration on mean CT was assessed using a linear mixed model, controlling for parity (number of complete pregnancies), breastfeeding duration, age, reproductive span, estrogen, and progestogen hormone therapies (HT) and duration, and time since HT cessation. Cortical surface analyses used linear regression, accounting for the same confounders, and were corrected for multiple comparisons using cluster‐wise probability.
Results
The number of months a woman was pregnant was positively associated with global cortical thickness (b = 0.002, p = 0.002). Cortical surface analysis revealed only positive regional associations with CT, including most regions of the DMN (Figure 1; Table 2), as well as several clusters outside the DMN. Notably, the anterior cingulate (ACG) did not show a significant association.
Conclusions
This work supports the hypothesis that pregnancy may be beneficial for late‐life brain health, particularly in regions important to AD‐pathology such as the DMN, with benefits extending beyond the effect of parity and breastfeeding. Future directions of this work include subcortical analysis and examining whether genetic risk for AD (such as APOE) modifies the relationship between pregnancy and cortical atrophy.
Background
Patients with cholera have been shown to be protected against subsequent cholera for 3 years after their initial episode. We aimed to assess protection at 10 years of follow-up.
Methods
In this retrospective cohort study, cohorts of patients treated for cholera (index patients) and contemporaneously selected age-matched individuals without cholera (controls), randomly selected from the population of Matlab, Bangladesh, were assembled between 1990 and 2009 and followed for up to 10 years. Selection of participants who had no history of cholera in the 5 years before selection proceeded in secular sequence, and selection was done without replacement. Protection against subsequent treated cholera was assessed in proportional hazards models and waning of protection was assessed non-parametrically with use of smoothing of protection curves.
Findings
We included 3925 index patients and 23 550 matched controls. Patients with El Tor cholera (26 subsequent episodes among 3619 index patients) had a 48·6% (95% CI 23·1 to 65·7; p=0·0012) lower risk of El Tor cholera than controls, with no evidence of waning during up to 10 years of follow-up (p=0·87). Index patients aged 5 years and older with El Tor cholera (nine subsequent episodes among 2279 index patients) were at a 61·7% (23·6 to 80·8; p=0·0065) lower risk of El Tor cholera, whereas index patients younger than 5 years with El Tor cholera (17 subsequent episodes among 1340 index patients) had a 36·2% (–5·0 to 61·3; p=0·077) lower risk (p=0·26 for the difference by age).
Interpretation
Protection against El Tor cholera associated with previous El Tor cholera was moderate in magnitude and sustained over 10 years of follow-up. These findings suggest the potential for sustained, long-term protection by oral cholera vaccines in populations with endemic cholera and help inform models of cholera in endemic settings.
Funding
Bill & Melinda Gates Foundation.
The Public Health Extreme Events Research (PHEER) Network is a researcher-led network that aims to advance the public health disaster science field by coordinating a community of practice that can rapidly mobilize to conduct time-sensitive research in the aftermath of disasters. This presentation will introduce PHEER to the public health emergency preparedness and response community and allow for input into the evolving public health research framework.
Learning Objectives
Participants will understand the goals and objectives of the PHEER Network.
Participants will learn about how they can be involved in the PHEER Network.
Background
Gastric cancer disproportionately impacts populations in resource‐limited settings. Within a safety‐net network, we assessed the utility of computed tomography (CT) as a single staging modality.
Methods
We utilized a clinical database of gastric cancer patients treated within the Los Angeles County safety‐net hospital system from 2016 to 2023 in conjunction with retrospective imaging review by certified radiologists. We assessed agreement between clinical and pathological staging for patients who underwent curative gastrectomy using the Kappa coefficient.
Results
Of 107 patients with available CT imaging, 43.9% ( n = 47) were staged with CT as a single modality. Most tumors displayed infiltrating (75%) or diffuse (28%) morphology, 41% displayed adequate gastric distention and regional lymphadenopathy was common (68%). Twenty‐nine patients underwent curative gastrectomy. Overall agreement was minimal ( κ = 0.29, 95% CI [0.071−0.51], p = 0.022), weak for T3/T4 tumors ( κ = 0.50, 95% CI [0.17−0.82], p < 0.01), and weak for Hispanic/Latino patients ( κ = 0.47, 95% CI [0.19−0.76], p < 0.01).
Conclusions
There was minimal agreement between clinical and pathologic staging when assessing clinical stage by CT imaging alone, suggesting that CT is not adequate as a single modality staging tool. While every effort should be made to obtain multimodal staging, larger studies are warranted to improve CT imaging protocols for staging in resource‐limited settings.
Background
Before SARS-CoV-2 vaccination availability, medical center employees were at high risk of COVID-19. However, risk factors for SARS-CoV-2 infection in medical center employees, both healthcare and non-healthcare workers, are poorly understood.
Methods
From September-December 2020, free IgG antibody testing was offered to all employees at a large urban medical center. Participants were asked to complete a questionnaire on work and non-work related risk factors for COVID-19 infection.
Results
SARS-CoV-2 seropositivity was found in 4.7%. Seropositivity was associated with close contact with COVID-19 cases with or without the use of adequate personal protective equipment (PPE), (OR 3.1 [95% CI 1.4–6.9] and OR 4.7 [95% CI 2.0–11.0] respectively), never wearing a mask outside of work (OR 10.1 [95% CI 1.9–57]), and Native Hawaiian/Pacific Islander race (OR 6.3 95% CI (1.6–25)].
Conclusions
Among workers in a large urban medical center, SARS-CoV-2 seropositivity was associated with work-related COVID-19 close contacts and low mask use outside of work, suggesting that non-workplace close contacts are also relevant routes of COVID-19 spread among healthcare workers.
U.S. state electronic prescription drug monitoring programs (PDMPs) are associated with reduced opioid dispensing among people with chronic pain and may impact use of other chronic pain treatments. In states with medical cannabis laws (MCLs), patients can use cannabis for chronic pain management, reducing their need for chronic-pain related treatment visits and moderating effects of PDMP laws.
Given high rates of chronic pain among Medicaid enrollees, we examined associations between PDMP enactment in the presence or absence of MCL on chronic pain-related outpatient and emergency department (ED) visits.
We created annual cohorts of Medicaid enrollees with chronic pain diagnoses using national Medicaid claims data from 2002–2013 and 2016. Negative binomial hurdle models produced adjusted odds ratios (aOR) for the likelihood of any chronic pain-related outpatient or ED visit and incident rate ratios (IRR) for the rate of visits among patients with ≥ 1 visit.
Medicaid enrollees aged 18–64 years with chronic pain (N = 4,878,462).
A 3-level state-year variable with the following categories: 1) no PDMP, 2) PDMP enactment in the absence of MCL, or 3) PDMP enactment in the presence of MCL. Healthcare codes for chronic pain-related outpatient and ED visits each year.
The sample was primarily female (67.2%), non-Hispanic White (51.2%), and ages 40–55 years (37.2%). Compared to no-PDMP states, PDMP enactment in the absence of MCL was not associated with chronic pain-related outpatient visits but PDMP enactment in the presence of MCL was associated with lower odds of chronic pain-related outpatient visits (aOR = 0.81, 95% CI:0.71–0.92). PDMP enactment was not associated with ED visits, irrespective of MCL.
During a period of PDMP and MCL expansion, our findings suggest treatment shifts for persons with chronic pain away from outpatient settings, potentially related to increased use of cannabis for chronic pain management.
The COVID-19 pandemic exacerbated challenges in the child care industry, leading to closures and financial strain. Early care and education (ECE) providers faced reduced income, increased debt, and material hardships such as food insecurity. Using survey data collected through the Child Care Resource Center (CCRC), this study examines the association between food insecurity risk, sociodemographic factors, and pandemic-related service changes among ECE providers in California. The results showed that income, race, and increased food costs were significantly associated with a higher risk of food insecurity among ECE providers. Compared to incomes greater than USD 60,000, those earning USD 40,000–USD 49,999 and USD 50,000–USD 59,999 had higher odds of food insecurity (OR: 1.94, 95% CI: 0.683–1.86; OR: 2.12, 95% CI: 0.623–1.81, respectively). Black (OR: 1.89, 95% CI: 1.21–2.94) and multi-racial respondents (OR: 1.71, 95% CI: 1.1–2.65) had higher odds of food insecurity than white respondents. Lastly, respondents experiencing increased food costs had greater odds of food insecurity (OR: 4.52, 95% CI: 2.74–7.45). These findings suggest the need for policies and interventions aimed at increasing food access among vulnerable ECE providers. Such interventions will better protect them from financial shocks and the risk of food insecurity, and will support their crucial role in healthy child growth and development.
Background
Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients.
Methods
We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016, and December 31, 2020, within Los Angeles County’s safety-net hospital system. Gastric cancer–specific survival was compared between the two cohorts using the Kaplan–Meier estimate and Cox proportional-hazards regression model.
Results
In total, 448 patients who received care from five medical centers were included; 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34–2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs. 60.7 years, P < 0.01), demonstrate higher state area deprivation index (6.4 vs. 5.0, P < 0.01), and present with metastatic disease (59.8% vs. 45%, P = 0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival [HR 1.56, (95% CI, 1.06–2.28); P = 0.02].
Conclusions
Hispanic patients treated within a large, multicenter safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors.
Impact
Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.
Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates (must-query PDMPs), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrIs) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI, 0.5-1.0) additional opioid-involved overdose deaths per 100 000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI, 0.4-0.9) more opioid-involved deaths relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by nonprescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.
This article is part of a Special Collection on Mental Health.
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