How does use of hospice and hospital services at the end of life differ by race and ethnicity among patients with dementia?This cohort study found that non-Hispanic Black and Hispanic decedents with dementia used less hospice but more emergency department and inpatient services, and incurred roughly 60% higher Medicare inpatient expenditures at the end of life, compared with non-Hispanic White decedents. The proportion of dementia beneficiaries completing advance care planning was significantly lower among non-Hispanic Black and Hispanic decedents compared with non-Hispanic White decedents.These results highlight the importance of understanding how end-of-life care utilization and treatment preferences among patients with dementia differ across racial and ethnic groups. This cohort study examines Medicare and Medicaid claims data alongside sociodemographic data from national surveys to differences in the utilization of end-of-life care services by race and ethnicity. The pool of studies examining ethnic and racial differences in hospice use and end-of-life hospitalizations among patients with dementia is limited and results are conflicting, making it difficult to assess health care needs of underresourced racial and ethnic groups.To explore differences in end-of-life utilization of hospice and hospital services among patients with dementia by race and ethnicity.This cohort study used national survey data from the Health and Retirement Study linked with Medicare and Medicaid claims that reflected a range of socioeconomic, health, and psychosocial characteristics. Eligible participants were Medicare fee-for-service beneficiaries aged 65 years or older diagnosed with dementia who died between 2000 and 2016. Analyses were performed from June to December 2021.Race and ethnicity.We examined the frequency and costs of hospice care, emergency department (ED) visits, and hospitalizations during the last 180 days of life among Medicare decedents with dementia. We analyzed the proportion of dementia decedents with advance care planning and their end-of-life care preferences.P < .001) and inpatient services  and incurred roughly 60% higher inpatient expenditures at the end of life compared with White decedents . A higher proportion of Black and Hispanic than White beneficiaries with dementia who were enrolled in hospice were subsequently admitted to the ED  or hospital  before death. The proportion of dementia beneficiaries completing advance care planning was lower among Black (146 of 704 [20.7%]) and Hispanic (66 of 308 [21.4%]) beneficiaries compared with White beneficiaries (1871 of 3274 [57.1%]). A higher proportion of Black and Hispanic decedents with dementia had written instructions choosing all care possible to prolong life (30 of 144 [20.8%] and 12 of 65 [18.4%] vs 72 of 1852 [3.9%]), whereas a higher proportion of White decedents preferred to limit care in certain situations (1708 of 1840 [92.8%] vs 114 of 141 [80.9%] and 51 of 64 [79.7%]), withhold treatments (1448 of 1799 [80.5%] vs 87 of 140 [62.1%] and 41 of 62 [66.1%]), and forgo extensive life-prolonging measures (1712 of 1838 [93.1%] vs 120 of 138 [87.0%] and 54 of 65 [83.1%]).The cohort sample included 5058 beneficiaries with dementia . In adjusted analysis, non-Hispanic Black decedents , nursing home residents , and survey respondents represented by a proxy  were less likely to use hospice, whereas older decedents , women , and decedents with higher education , more severe cognitive impairment , and more instrumental activities of daily living limitations  were associated with higher hospice enrollment. A higher proportion of Black and Hispanic decedents with dementia used ED (645 of 809 [79.7%] and 274 of 357 [76.8%] vs 2753 of 3892 [70.7%]; The results of this cohort study highlight unique end-of-life care utilization and treatment preferences across racial and ethnic groups among patients with dementia. Medicare should consider alternative payment models to promote culturally competent end-of-life care and reduce low-value interventions and costs among the population with dementia. Hospice, for example, provides comfort care and support for terminal patients and their families. Older adults with dementia are among those who are most likely to benefit from end-of-life hospice care because these individuals often experience multiple distressing symptoms  and poor quality of life.2 To qualify for the Medicare hospice benefit, a patient must be certified by 2 physicians as terminally ill, defined as having a medical prognosis of 6 months or less.3 However, prognostic challenges in dementia, such as its long disease duration and unpredictable trajectories, make certifying eligibility for the Medicare hospice benefit difficult. Although hospice utilization in the Medicare population has increased in recent decades, the service remains underused, with only half of Medicare decedents enrolling in the hospice benefit.5 Individuals with noncancer illness, including those with dementia, and from underserved communities have lower hospice utilization rates.8Despite advances in dementia prevention and treatment,11 However, the pool of studies examining racial and ethnic differences in hospice use and end-of-life hospitalizations among patients with dementia is limited and the results conflicting.9 For example, one analysis of nursing home residents with advanced dementia in Boston found that Black individuals were more likely than White to receive hospice referrals,12 whereas a US national study suggested that hospice use was lower among Black residents.13 The type and intensity of care individuals receive at the end of life may differ for those with more advanced dementia,10 but claims-based analyses lack sufficient clinical detail to characterize cognitive function. Furthermore, while studies have examined dementia end-of-life care, the analyses often are restricted to nursing home residents.16 These estimates are limited because they omit a substantial proportion of dementia patients living at home or other settings prior to death.6 The samples typically lack racial and ethnic diversity, and thus robust data on non-White decedents with dementia are sparse.9 For example, prior examinations of hospice use have compared differences between Black and White patients with dementia but lacked data on other racial or ethnic groups.18 The limitations of previous analyses, such as a lack of dementia severity measures and use of unrepresentative samples, make it difficult to assess unique end-of-life care needs for underresourced racial and ethnic groups.Some evidence suggests that, among individuals with dementia, non-Hispanic Black individuals experience more aggressive end-of-life care  compared with non-Hispanic White individuals.This study examined the frequency and costs of end-of-life hospice care, emergency department (ED) visits, and hospitalizations among Medicare decedents with dementia. Our study extends existing research by analyzing how dementia end-of-life care utilization patterns differ by race and ethnicity. We supplemented claims data with national survey data that included measures of cognitive function and socioeconomic factors known to affect end-of-life care. We also analyzed ethnic and racial differences in patient instructions regarding end-of-life treatment based on survey data. Our sample included community-dwelling patients and nursing home residents, thus making our findings more representative of the general dementia population. We hypothesized that non-Hispanic Black and Hispanic patients with dementia had lower hospice use but more ED and hospital admissions at the end of life compared with non-Hispanic White patients.STROBE) reporting guideline.The Tufts Medical Center/Tufts University Health Sciences institutional review board approved this cohort study via expedited review procedures per 45 CFR 46.110(b)(4); informed consent was not required because the study analyzed existing, secondary data. We followed the Strengthening the Reporting of Observational Studies in Epidemiology , part B , and part D  claims, as well as Medicaid analytic extracts and summary files for dually eligible beneficiaries. These health insurance claims included diagnosis codes, medical and prescription drug utilization, date of service, and reimbursement for all services rendered.We used data from the 2000-2016 Health and Retirement Study (HRS) linked with Medicare and Medicaid claims. The HRS is a nationally representative biennial survey of US adults aged 50 or older, collecting a range of respondent socioeconomic, health, and psychosocial characteristics.International Classification of Diseases, Ninth or Tenth Revisions diagnosis codes.22 We required all patients to have continuous enrollment in Medicare fee-for-service for at least 6 months prior to death.Our sample included HRS respondents aged 65 years and older diagnosed with dementia who died between 2000 and 2016  as an indicator of poor end-of-life care quality.We examined the average number of outpatient ED visits, inpatient ED visits, and hospital stays during the last 180 days of life, as well as Medicare expenditures for these visits. We calculated total expenditures for inpatient ED and hospital admissions combined because those payments cannot be separately identified in Medicare claims.23 Additionally, we examined the proportion of potentially avoidable hospitalizations for ambulatory care sensitive chronic conditions  and acute infections , as defined by the AHRQ Prevention Quality Indicators, version 2021.24We identified major causes of hospitalizations based on principal discharge diagnoses, using the Agency for Healthcare Research and Quality (AHRQ) Clinical Classifications Software (CCS) and Clinical Classifications Software Refined (CCSR) tools.25 The interview asked whether the participant had advance care planning, ie, written instructions specifying the treatment or care they wanted to receive during the final days of life. Of those study participants with advance care planning, the interview asked whether these instructions expressed any desire to: (1) receive all care possible to prolong life; (2) limit care in certain situations; (3) have any treatment withheld; or (4) keep them comfortable and pain free but forego extensive measures to prolong life .We examined patient end-of-life care preferences using the HRS exit interview data reported by a proxy within 2 years after the study participant’s death.We developed 2-part models to assess whether Medicare expenditures for hospice, outpatient ED, and inpatient services differed by race and ethnicity, categorized as non-Hispanic White, non-Hispanic Black, and Hispanic. The first part used a logistic regression to estimate the probability of any use; the second part used a generalized linear model (GLM) with log link and γ distribution to estimate mean expenditures among users. Combining results from these 2 model components yielded population expenditure estimates. We standardized all Medicare expenditures to 2016 US$.Covariates in both logistic regression and GLM included age, sex, education, cognition, functional limitations, comorbidities, Medicare-Medicaid dual eligibility, nursing home status, and proxy respondent. We measured cognition using HRS-imputed Telephone Interview for Cognitive Status (TICS) scores for self-respondents and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) scores for those study participants represented by a proxy. We quantified functional status in terms of the number of limitations in activities of daily living  and instrumental ADL . For end-of-life care preferences, we analyzed the proportion of beneficiaries with advance care planning and their specific instructions (as detailed in “Outcome measures”) by race and ethnicity. All analyses were performed from June to December 2021.P < .001), had higher education levels , better cognitive scores , and fewer functional limitations , were more likely to live in a nursing home  and less likely to be dually eligible for Medicare and Medicaid .Our study sample included 5058 beneficiaries with dementia; 3892 beneficiaries (76.9%) were non-Hispanic White, 809 (16.0%) were non-Hispanic Black, and 357 (7.1%) were Hispanic. Overall, the mean (SD) age of beneficiaries was 85.5 (8.0) years and 3038 participants were women (60.1%) . CompareP < .001). In adjusted analysis, Black decedents , nursing home residents , and respondents represented by a proxy were less likely to use hospice , whereas older age , women , higher education , more severe cognitive impairment , and more IADL limitations  were associated with higher hospice enrollment  used hospice care in their last 180 days of life . The proP = .41)  length of stay was 1.6 (2.0) months, and Hispanic decedents with dementia had the shortest stays  . Late hoP = .41) .P < .001) (P < .001). Admissions to the hospital after hospice enrollment were also more common among Black and Hispanic decedents than among White decedents . Overall, Black and Hispanic decedents with dementia had more ED visits , more hospitalizations , and longer hospital length of stay  compared with White decedents. End-of-life outpatient ED expenditures were similar across ethnic and racial groups, whereas estimated mean inpatient expenditures were substantially higher among Black and Hispanic than among White decedents   . Even amecedent) .Dementia beneficiaries were most frequently hospitalized for circulatory system diseases at the end of life , followed by respiratory  and infectious and parasitic diseases  . Injury Treatment preferences for end-of-life care among dementia decedents differed substantially by race and ethnicity . The proOur findings showed substantial ethnic and racial differences in dementia end-of-life care utilization patterns and patient treatment preferences. Black and Hispanic decedents with dementia used less hospice but more ED and inpatient services, and incurred roughly 60% higher Medicare inpatient expenditures at the end of life compared with White decedents. Among hospice users, more Black and Hispanic than White decedents with dementia were subsequently admitted to the ED or hospital before death.27 Nonetheless, to our knowledge, this is the first study to quantify such differences among racially and ethnically diverse Medicare decedents with dementia in both community and nursing home settings. Understanding how and when individuals with dementia use hospice and other end-of-life care across populations is one of the highest research priorities identified by the National Academies of Sciences, Engineering, and Medicine.28 Our study provides new evidence highlighting unique end-of-life care utilization and treatment preferences across racial and ethnic groups among patients with dementia.The trends in racial and ethnic differences in end-of-life care observed in our sample of dementia beneficiaries are not entirely surprising given the health care utilization patterns in the overall Medicare population.31 Studies have suggested several possible reasons, in addition to cultural and religious or spiritual values. For instance, mistrust of the health care system due to medical racism and health inequalities in the US may lead more non-White patients to perceive hospice care as “giving up” and motivate them to request more aggressive, life-sustaining interventions.33 Our data showed that although most dementia beneficiaries desire less invasive care at the end of life, preferences to limit care, withhold treatment, or forgo life-prolonging measures were much less common among Black and Hispanic patients.Race and ethnicity are known to be associated with end-of-life care type and intensity independent of other social determinants of health.34 In our data, it is unclear which beneficiaries with dementia and family caregivers had physician counseling about end-of-life care, but we found that only 1 in 5 Black and Hispanic decedents with dementia completed advance care planning—a much lower proportion than their White peers.30 These written instructions give persons with dementia a voice in making end-of-life medical decisions when they become unable to understand or speak for themselves. Dementia education programs should foster community outreach and help patients with dementia and their caregivers understand end-of-life care issues, including the benefits of advance care planning.30Additionally, such mistrust may compromise patient-physician communication, reducing access to high-quality end-of-life care. Researchers have documented racial and ethnic inequity in the provision of, and access to, hospice care.39 In our sample, fewer than half of Medicare decedents with dementia used hospice services during the last 6 months of life. Although hospice is not always the right choice for terminal patients, more beneficiaries with dementia could appropriately benefit from the service. In particular, our results highlighted 2 concerning trends that may limit the full benefits of hospice received by dementia beneficiaries and caregivers. First, the timing of hospice enrollment was suboptimal. We found that almost 1 in 3 beneficiaries with dementia entered hospice very close to the end of life  and for a short time period. This proportion was higher compared with the general Medicare population.3 Second, some dementia beneficiaries in hospice, especially Black and Hispanic beneficiaries, were subsequently admitted to the ED or hospital before death, suggesting a live discharge. Overall, we found that beneficiaries with dementia had similarly frequent ED visits and hospitalizations at the end of life compared with the general Medicare population.6 Health care professionals make decisions prospectively about whether to admit patients with dementia to the hospital. Some hospitalizations are necessary and expected as part of the natural course of treatment, whereas others may be considered low-value at the end of life. These transitions not only impose burdens on older adults with dementia and their caregivers but also increase mortality and costs.40 Medicare should consider alternative payment models, such as bundling services into an episode of care,41 as one way to address suboptimal hospice use and burdensome end-of-life transitions among dementia beneficiaries. These strategies would help incentivize high-quality services, reduce low-value, unnecessary ED visits and hospitalizations,41 and promote end-of-life discussions. Such discussions may reduce aggressive medical interventions near death and facilitate earlier hospice referrals.39 Medicare could provide more comprehensive reimbursement to hospital-based palliative care teams6 and reward hospitals for improved access to and delivery of effective hospice care for dementia patients.Hospice care may improve quality of life of terminally ill patients and their caregivers and reduce Medicare costs.18 We did not use diagnoses reported on death certificates because those records likely underreport dementia as an underlying cause of death.42 Future investigations would benefit from additional efforts, such as expert reviews of death certificates, proxy interviews, and medical record reviews, to determine how our findings differ by cause of death. Second, we relied on diagnosis codes in claims data to identify patients with dementia because HRS lacks a direct measure of dementia status and because there is no uniformly accepted case definition for dementia in observational studies. Our sample may have omitted individuals with undiagnosed dementia, of which a higher proportion are non-White individuals.22 Third, our sample had too few Asian Americans or patients from other racial or ethnic groups to allow further analyses. Fourth, our analyses were limited to fee-for-service beneficiaries aged 65 years or older, and thus the results might not fully generalize to Medicare Advantage enrollees or younger patients. Fifth, our data spanned from 2000 to 2016; we did not evaluate changes over time in hospital or doctor behavior or Medicare enrollment. For example, enrollment in Medicare Advantage has increased substantially over the last decade, especially among non-White beneficiaries.43 Finally, preferences for end-of-life care were based on proxy reports after the study participant’s death 25 and therefore recall bias was possible.This study had several limitations. First, we could not ascertain cause of death, a factor that may affect end-of-life care.3 our results suggest that end-of-life care for beneficiaries with dementia remains suboptimal, especially for Black and Hispanic patients. The type and intensity of care individuals receive at the end of life is a complex issue, even more so among older adults with dementia because of their impaired ability to plan and communicate care preferences. Doctors and staff should address these communication barriers, especially in underresourced racial and ethnic communities. Medicare should consider alternative payment models to promote culturally competent end-of-life care and reduce low-value interventions and costs among the dementia population.Although use of Medicare hospice benefits has increased,


Paragonimus is often accompanied by chronic respiratory symptoms such as cough, the accumulation of sputum, hemoptysis, and chest pain. Prolonged symptoms, including respiratory symptoms, after coronavirus disease 2019 infection (COVID-19) are collectively called post-COVID-19 conditions. Paragonimiasis and COVID-19 may cause similar respiratory symptoms. We encountered five cases of paragonimiasis in patients in Japan for whom diagnoses were delayed due to the initial characterization of the respiratory symptoms as a post-COVID-19 condition. The patients had consumed homemade drunken freshwater crabs together. One to three weeks after consuming the crabs, four of the five patients were diagnosed with probable COVID-19. The major symptoms reported included cough, dyspnea, and chest pain. The major imaging findings were pleural effusion, pneumothorax, and nodular lesions of the lung. All the patients were diagnosed with paragonimiasis based on a serum antibody test and peripheral blood eosinophilia  and were treated successfully with 75 mg/kg/day praziquantel for 3 days. Before diagnosing a post-COVID-19 condition, it is necessary to consider whether other diseases, including paragonimiasis, may explain the symptoms. Further, chest radiographic or blood tests should be performed in patients with persistent respiratory symptoms after being infected with COVID-19 to avoid overlooking the possibility of infection.Paragonimiasis caused by trematodes belonging to the genus  Paragonimus, for which the majority are found in Asia. Humans can become infected by consuming raw or uncooked freshwater crabs, crayfish, or the meat of wild boars or deer. Although some cases are asymptomatic, the presenting symptoms typically include cough, the accumulation of sputum, and chest pain [Paragonimiasis is a food-borne parasitic disease caused by trematodes belonging to the genus est pain . Delayedest pain .The coronavirus disease 2019 (COVID-19) pandemic has led to the delayed diagnosis of various diseases, including lung cancer , gynecolHerein, we report a cluster of five Japanese cases of paragonimiasis in which a diagnosis was delayed due to the mischaracterization of the symptoms as a post-COVID-19 condition.The clinical characteristics of the patients considered are summarized in All five patients consumed raw freshwater crabs (self-prepared drunken crabs) at a dinner party that they had attended together. One to three weeks after the party, four of the five patients presented to our hospital with complaints regarding a cough and were diagnosed with confirmed or likely COVID-19 . The mean time from the symptoms’ onset to the initial visit to our hospital was 5.4 months.2 agonist (LABA) and 15 mg of oral prednisolone (PSL) for 3 weeks. The inhalation of ICS/LABA led to a temporary improvement in his symptoms.Three patients presented to their primary care physicians complaining of respiratory symptoms before visiting our hospital. All three patients were considered to be affected by post-COVID-19 symptoms. Of the three patients, two were placed under observation and one (Case 1), who had asthma-like symptoms including a fluctuating cough and dyspnea, was treated with inhaled corticosteroids (ICS)/long-acting βAt our hospital, the reported symptoms included cough , dyspnea (three patients), chest pain (two patients), fatigue (one patient), epigastric pain (one patient), and abdominal discomfort (one patient). Physical examination revealed a slight fever in Case 1 and bilateral decreases in breath sounds of the lower lung in Cases 1 and 4. Blood tests showed increased levels of eosinophils ranging from 560 to 15,610/μL (9.8–71.5%) in all five patients and increased levels of immunoglobulin E (IgE) ranging from 1857 to 3487 IU/L in three of the five patients. In contrast, C-reactive protein levels were near normal. Chest radiography and computed tomography (CT) showed pleural effusion , pneumothorax (three patients), nodular lesions with a cavity (one patient) and without cavity (one patient), infiltration of the lung (one patient), ascites (one patient), and a linear low attenuation area of the liver (one patient) A–E.Paragonimus IgG antibody, which was measured using a microplate enzyme-linked immunosorbent assay (ELISA). Cross-competition ELISA between P. westermani and P. s. miyazakii antigens suggested P. westermani infection.Pleural effusion fluid was examined in two patients. Both patients had exudative effusions, with a predominance of eosinophils and lymphocytes in Case 4 and lymphocytes in Case 5, examined by manual cell counting. A bronchoscopy was performed only in Case 1. To distinguish lung cancer and tuberculosis, a transbronchial lung biopsy of a right-sided nodule was performed. The biopsy specimen showed inflammatory changes, mainly eosinophils, without parasite eggs. Based on the finding of eosinophilia and the dietary history of raw freshwater crab consumption, we suggested that the symptoms were probably caused by a parasitic infection. We searched for parasite eggs in the pleural effusion and bronchial lavage fluid as well; however, we could not find any eggs. All five patients had high titers of serum All patients were treated with 75 mg/kg/day of praziquantel (PZQ) for 3 days, which led to an improvement in their symptoms and signs, including cough and dyspnea, eosinophilia, and pleural effusion. In Case 2, pleural fluid drainage was performed prior to PZQ administration.The incidence of paragonimiasis has decreased in Japan, and the number of cases diagnosed annually ranges from 17 to 49 . ClusterA certain proportion of patients with COVID-19 experience sequelae after infection, which is known as long COVID  or post-In the cases considered in this study, the patients obtained freshwater crabs (the Japanese mitten crab) from a market. A meal of homemade drunken crabs was consumed by seven people. Six of the seven visited our hospital, with five suffering from paragonimiasis. Among the five patients with paragonimiasis, four had been previously diagnosed with or had been considered likely to be affected by COVID-19. Clearly, it was challenging for both patients and physicians to look past a diagnosis of a “post-COVID-19 condition”. Atypical findings of eosinophilia, pleural effusion, and pneumothorax helped to exclude the possibility that the patients were afflicted by a post-COVID-19 condition, leading to the correct diagnosis of paragonimiasis. These cases highlight the importance of educating citizens regarding the safe preparation of freshwater crab. In addition, health centers should alert markets that sell infected freshwater crabs to any potential danger. Moreover, physicians should be aware they may encounter patients with paragonimiasis due to the globalization of dietary cultures.In Case 1, the asthma-like symptoms of cough and dyspnea improved immediately after the inhalation of ICS/LABA and oral PSL, although the patient had no history of bronchial asthma or allergy. The effectiveness of ICS/LABA and PSL may contribute to the delayed diagnosis of paragonimiasis. Harada et al.  reportedIn conclusion, physicians should consider whether diagnoses other than post-COVID-19 conditions such as paragonimiasis may explain respiratory symptoms in patients suspected to have recently been infected with COVID-19. Physicians should examine chest radiographs and blood tests in patients with persistent respiratory symptoms after COVID-19 to aid correct diagnoses.


Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer. Over the past 5 years, the 5-year survival rate for people with PDAC has increased incrementally, from 6% to 10%, largely owing to improved therapeutics. Surgery remains the only curative therapy. However, PDAC can quickly advance to the metastatic stage. For up to 85% of patients with PDAC, their tumours are not surgically resectable at the point of diagnosis, making therapeutic options for these patients limited. Non-invasive biomarkers have been widely studied for PDAC diagnosis in blood and urine samples, but only carbohydrate antigen 19-9 (CA19-9) has received approval from the US Food and Drug Administration. Unfortunately, the sensitivity and specificity of CA19-9 are inadequate for PDAC diagnosis, and its clinical use is restricted to monitoring treatment response and recurrence in patients who are already diagnosed with PDAC. There is an urgent clinical need for better biomarkers and tools for the early diagnosis of PDAC.eBioMedicine in Januarya study published in , 2022, researchers from Hospital del Mar Medical Research Institute (Spain) reported soluble AXL (sAXL) in plasma samples as a novel non-invasive biomarker for PDAC diagnosis at the initial stages of the disease. The authors of the study showed that plasma sAXL levels could discriminate PDAC from chronic pancreatitis, with better performance than the CA19-9 biomarker (Area under the ROC Curve (AUC) 0·827 vs 0·673), and blood detection of both sAXL and CA19-9 panel by ELISA improved accuracy of diagnosis of PDAC (89·9% sensitivity and 100% specificity). In addition to protein biomarkers, RNAs in extracellular vesicles from plasma samples could be a putative diagnostic biomarker for PDAC. In their Gut in 2020study published in , Shenglin Huang and colleagues from Fudan University (China) conducted long RNA (exLR) profiling on extracellular vesicles in patients with PDAC, patients with chronic pancreatitis, as well as healthy participants and developed a diagnostic signature that comprised eight exLRs for early detection of PDAC. This diagnostic signature showed a higher ability to distinguish PDAC from chronic pancreatitis (AUC 0·931) than CA19-9 (0·873).In volatile organic compounds in urine specimens, detected by ion mobility spectrometry-based methods, have the ability to distinguish healthy individuals from patients with PDAC. In their study published in British Journal of Cancer in 2020, researchers from Queen Mary University of London (UK) reported a urinary biomarker panel  and constructed a biomarker-based risk score, termed as the PancRISK for early detection of PDAC, which is currently being validated in a multicentre, prospective, observational study UroPanc (NCT04449406).As with blood, urine is another convenient biofluid for the detection of pancreatic cancer at the resectable stage. Both protein and RNA biomarkers in urine samples have been widely reported. Patterns of Guta recent study published in  in December, 2021, researchers from Spain and Germany explored the potential of faecal and salivary microbiota as diagnostic biomarkers for PDAC. They showed that faecal metagenomic classifiers had much better performance than saliva-based classifiers and could identify patients with PDAC with an AUC score of up to 0·84 based on a set of 27 microbial species, with consistent accuracy across early and late disease stages. When combined with serum levels of CA19-9, the diagnostic performance further improved up to an AUC score of 0·94, indicating the potential for non-invasive, robust, and specific faecal microbiota-based early diagnosis for PDAC.Studies have shown that microbiota might affect the malignant phenotype and prognosis of pancreatic cancer, and the association of microbiome with pancreatic cancer has been widely reported. In 3-step approach  has been agreed upon in the field: (1) define what constitutes a high-risk group, (2) enrich the high-risk group further to define a very high-risk group and, (3) find the lesion in the very high-risk group.Early diagnosis is essential and challenging for patients with PDAC. Despite its high mortality rate, the prevalence of PDAC is very low, with an incidence of 8–12 cases per 100 000 people per year, and a 1·3% lifetime risk for the disease. This low prevalence means that there could be unacceptably high rates of false-positive results in population-based screening, which could lead to unnecessary biopsies for a definitive diagnosis. However, screening individuals in high-risk groups can increase accuracy and reduce false-positive results. Therefore, a eBioMedicine papervery recent  published in January, 2022, a collaborative team led by Eithne Costello from University of Liverpool (UK) reported a method that can enrich the very high-risk subpopulation in patients with new-onset type 2 diabetes, which represents the largest high-risk group for PDAC. A subgroup of individuals with new-onset type 2 diabetes have diabetes secondary to pancreatic disease, which is frequently termed type 3c diabetes (including both PDAC-related diabetes and chronic pancreatitis-related diabetes). In their study, researchers showed that the combination of adiponectin and interleukin-1 receptor antagonist could stratify patients with new-onset type 2 diabetes into those with type 2 diabetes and those with the less prevalent PDAC-related diabetes, who are commonly misdiagnosed as having type 2 diabetes. Machine learning technologies could also help to identify high-risk subgroups and potentially make a population-based screening of PDAC feasible. In PLOS ONE in 2021a study published in , Ananya Malhotra and colleagues from London School of Hygiene & Tropical Medicine (UK) conducted a case-control study using prospectively-collected electronic health records from primary care data, which included all symptoms, status variables . Based on these factors, researchers developed a machine learning approach that was able to identify patients who were at high-risk of developing pancreatic cancer up to 20 months before diagnosis. The algorithm could also be used alongside other non-invasive biomarkers and potentially increase the success rate of early diagnosis of PDAC.Following the DEF approach, in their eBioMedicine, as part of The Lancet Discovery Science, will continue to serve as a publishing platform for validated biomarker studies for human diseases, including pancreatic cancer.Although only a few non-invasive biomarkers for early diagnosis of PDAC are near clinical application, researchers continue to search for new candidate biomarkers with better performance and applicability. A combination of different biomarkers could help to improve early diagnosis. Before implementation in clinical practice, these emerging biomarkers should be independently validated in larger cohorts, and their real-world diagnostic ability needs to be evaluated in prospective studies.


Background: Allergic rhinitis and asthma exacerbation are strongly linked to respiratory viral and bacterial infections. COVID-19 pandemic has raised concerns about the risk of infection and the severity of COVID-19 infection in patients with asthma and allergic rhinitis. However, increasing evidence suggests that atopic disease protects against severe COVID-19 illness owing to the underlying type 2 inflammatory process. Many studies have reported the impact of asthma on COVID-19 disease; however, data on allergic rhinitis are scarce. In this study, we aimed to investigate the severity and outcome of COVID-19 disease in adult patients with allergic rhinitis in Qatar during the first pandemic wave.Methods: We conducted a retrospective chart review of adult patients with a confirmed diagnosis of asthma and/or allergic rhinitis who had a positive COVID-19 RT-PCR between February 01, 2020, and December 01, 2020. Parameters evaluated included the WHO classification of COVID-19 disease severity as mild, moderate, severe, and critical; COVID-19 disease outcome; and mortality. Patients with allergic rhinitis were defined as those with typical allergic rhinitis symptoms and positive skin prick test or specific IgE to perennial or seasonal inhaled allergens. Only data about patients with allergic rhinitis has been presented in this report.Results: We screened 97 EMR Cerner records of patients who had the diagnosis code for allergic rhinitis. Nine patients met the inclusion criteria of allergic rhinitis diagnosis; the remaining either had no allergy testing or had negative allergy tests. Seven (77.7%) patients had mild COVID-19, whereas only one (11.1%) patient each had moderate and severe disease. The length of hospital stays for 6 patients ranged from 5–13 days, and the remaining 3 patients were quarantined at home. No reports of critical cases or death were identified. All the patients recovered from COVID-19 with a favorable outcome.Conclusion: This preliminary data showed that most patients with allergic rhinitis had mild COVID-19 disease. Furthermore, all of them recovered well, similar to the available data from previous studies. A limitation of this study is the small population size.


Endometriosis affects reproductive-aged females and varies considerably in terms of symptom presentation, morphologic features, and treatment response. Most studies investigating symptom recurrence after an endometriosis-related surgery have been conducted among adults. The Endometriosis pain QUality aftEr Surgical Treatment (EndoQUEST) Study was established to assess characteristics and biomarkers that are associated with pain remediation and improved quality of life after an endometriosis-related surgery among adolescents and young adults. This paper describes the EndoQUEST methodology, summarizes baseline descriptive factors, and compares characteristics by participant retention status. We enrolled 100 surgically-confirmed endometriosis participants aged 12–23 years who provided questionnaire data on reproductive and behavioral factors, pain characteristics and quality of life at three time points; before surgery, 6 weeks to 26 weeks after surgery, and 1 year after surgery. Among these 100 participants, 88 provided blood and/or saliva at all three time points, while 12 provided blood and/or saliva samples only before surgery and 6 to 26 weeks after surgery. There was little evidence of lost to follow-up at 1 year after surgery due to pain symptoms, as pain and quality of life characteristics were similar between participants who completed the questionnaire 1 year after surgery and those who did not. Analyses utilizing these longitudinal data will advance personalized treatment decision making for adolescents and young adults with endometriosis. Endometriosis, characterized by endometrial-like tissue thriving outside the uterus, affects ~10% of reproductive-aged females, and can lead to debilitating pelvic pain and diminished quality of life (QoL) , endometAlthough AYA are more likely to present with revised American Society of Reproductive Medicine (rASRM) endometriosis stage I/II disease compared with adult women , 4, mostTo address this knowledge gap, we conducted a longitudinal cohort study of AYA undergoing an endometriosis-related surgery, including the assessment of pain symptoms, QoL, and biomarkers before surgery and at two time points post-surgery. Results of the EndoQUEST study will enable the identification of participant-related factors that distinguish endometriosis patients who will experience pain and QoL improvement after surgery from those who will not to advance personalized medical decision making. This paper provides a profile of the EndoQUEST cohort study design, including pre- and post-surgery factors related to retention through end of follow-up.EndoQUEST is a longitudinal, prospective cohort study. Questionnaire data on pain symptoms, QoL, demographics, reproductive, and medical history as well as blood and saliva samples, were collected: (i) prior to an endometriosis-related surgery (pre-surgery), (ii) between 6 and 26 weeks after surgery (post-surgery), and (iii) one year after surgery (Y1 post-surgery) . The stuParticipants were enrolled between February 2013 and January 2017 from the Women’s Health Study: from Adolescence to Adulthood (A2A) cohort, an ongoing longitudinal cohort oversampled for adolescents and women with endometriosis and described previously . A2A parAll participants underwent an endometriosis-related laparoscopic surgery with the same surgeon (MRL). Operative data on recent hormone use, surgical indication, rASRM score, lesion locations and colors, and presence of adhesions was collected on a surgical form compliant with the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect) recommended forms , 14. EndParticipants completed questionnaires at all three time points utilizing REDCap electronic data capture tools . To incrin utero and early childhood exposures and polycystic ovarian syndrome symptoms. In January 2014, we implemented an expanded version of the WERF EPHect clinical questionnaire at the pre-surgery time point [Early in EndoQUEST enrollment, while actively harmonizing with the WERF EPHect clinical questionnaire, we modified the pre-surgery questionnaire twice (Versions 1 and 2). Seven participants completed version 1 and 11 participants completed version 2. Versions 1 and 2 were very similar but did not include all of the WERF EPHect compliant questions. Missing items included me point  and 79 pAbout 20% of participants (n = 19) completed their pre-surgery questionnaire following their surgery, with time since surgery ranging from 1 to 102 days (median = 28 days). To ensure the integrity of these data, we compared demographics, QoL, and pain symptoms from these 19 participants to the 81 participants who completed their pre-surgery questionnaire prior to surgical intervention . We did The post-surgery questionnaire included the SF-12, 0–10 numeric rating scales for pain, and information on use of analgesics, opioids, hormone medications, and alternative and complementary therapies .The Y1 post-surgery questionnaire was an expanded version of the WERF EPHect standard clinical questionnaire and was virtually identical to Version 3 of the pre-surgery questionnaire.We collected blood and saliva samples pre-surgery, post-surgery, and Y1 post-surgery. Participants completed a questionnaire at sample collection to report date of last menstrual period, timing of last foods/beverages consumed, and recent hormone and other medication use. Blood samples were processed into plasma, serum and buffy coats, and stored at ≤-80°C per WERF EPHect fluids standard operating protocols .Of the 100 participants included in EndoQUEST, 74 had blood and saliva collected at all three time points  and 14 had blood and saliva collected only at the pre-surgery and post-surgery visits. One participant had only pre-surgery and post-surgery blood collected . Ten participants had only saliva collected .The mean age of participants was 16.8 years . To investigate the influence of this broad time period, we plan to conduct subgroup analyses restricting to those within smaller portions of the window, e.g., 6 to 13 weeks and >13 to 26 weeks. Further, three versions of the pre-surgery questionnaire were utilized as the questionnaire was refined over the early years of the study. We have harmonized the data across the three versions to validly capture data that can be interpreted consistently. Finally, most EndoQUEST participants are non-Hispanic White females; therefore, the results may not be generalizable to the broader endometriosis population. While the EndoQUEST participants were enrolled from a larger cohort that successfully enrolled 85% of eligible endometriosis patients, there is a need for future research on endometriosis among a more diverse population.Endometriosis diagnosed in AYA has been significantly understudied and analyses within the EndoQUEST study will assess patient characteristics and biologic markers in relation to pain symptoms at all three time points and to improvement by year 1. The long-term goals of the study are to discover pre-surgery markers of post-surgical pain response and QoL to advance discovery of personalized treatment algorithms.S1 TableThese questions are not included in the standard WERF EPHect clinical questionnaire.(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S1 Methods(DOCX)Click here for additional data file.


In dogs with non-resectable hepatic neoplasia, treatment options are limited. The objectives of this study were to describe the use of a novel drug-eluting embolic microsphere containing paclitaxel for use during transarterial chemoembolization (TACE), to compare results of liver-specific owner questionnaires and tumor volume pre- and post-TACE, and to measure systemic paclitaxel concentration post-TACE. Client-owned dogs with non-resectable hepatic neoplasia were prospectively enrolled. All owners completed questionnaires validated for the assessment of subjective outcomes in dogs with cancer before the TACE procedure and approximately 4 weeks after the TACE procedure. A CT scan was performed before TACE and 1 month after TACE; results were compared. Blood samples were obtained at specified time points post-TACE to determine systemic paclitaxel concentrations. Seven dogs  were enrolled. TACE was successfully performed in all dogs, and no intra-procedural complications were encountered. Questionnaire scores improved significantly post-TACE. Among the 6 dogs for which full data were available, median pre-TACE tumor volume was 390 cc  and median post-TACE tumor volume was 203 cc , which was significantly (P = .028) lower. All 6 dogs had a reduction in volume at the post-TACE measurement. Mean percent change in tumor volume was -45.6% (95%CI -58.6 to -32.6%). The mean plasma paclitaxel concentration in canine blood peaked at 4 days post-TACE procedure and was 25.7 ng/mL (range = 3.09–110 ng/mL) Median survival time was 629 days (95%CI 18 to upper limit not reached). The use of a novel paclitaxel-eluting microsphere in this cohort of dogs successfully decreased tumor volume significantly after TACE and improved clinical signs. Future investigation into the use of TACE and other similar therapies is warranted due to the promising outcomes noted in this cohort. Canine hepatic neoplasia can result in significant morbidity. Hepatocellular carcinoma (HCC) is the most common form of primary hepatic neoplasia and occurs in 3 major morphologic forms: diffuse, nodular and massive . The masHCC is one of the most commonly diagnosed solid cancers in humans and is a common cause of death from malignancy . SimilarOne such alternative is the transarterial administration of embolic agents solely  or combined with chemotherapy . These procedures involve the use of interventional radiologic techniques to deliver embolic agents directly to tumors to diminish or eliminate tumor blood supply –6. TumorAs the treatment options for dogs with hepatocellular neoplasia that is determined to be surgically challenging are limited, it is imperative that alternative therapies be evaluated. Therefore, the aims of this investigative group are three-fold: 1) to describe the procedure and technical outcome of transarterial chemoembolization (TACE) with a novel chemoembolic agent (paclitaxel-eluting microspheres), 2) to evaluate the effect that TACE has on clinical signs (as determined by an owner questionnaire) and tumor volume (as measured by computed tomographic imaging), and 3) to evaluate the systemic concentration of paclitaxel at varying time points and record toxicity associated with chemotherapy administration in a group of dogs with naturally-occurring hepatocellular neoplasia. The results of this study demonstrated that TACE was technically feasible in dogs with hepatocellular neoplasia utilizing a novel microsphere, dogs undergoing TACE demonstrated an improvement in clinical signs and a decrease in tumor volume, and paclitaxel delivered in this manner was well tolerated and able to be measured.Client-owned dogs with naturally-occurring hepatocellular neoplasia that was determined to be non-resectable  or in a location with great surgical risk were prospectively enrolled in the clinical trial from May 2017 until March 2019. The study protocol was explained to the owner, and informed consent was obtained prior to initiation of treatment; as part of this consent, owners consented to enrolling their dog in this study, allowing their dog to undergo the diagnostics and treatments described below and providing information in previously validated questionnaires. A cytologic or histopathologic diagnosis of hepatocellular neoplasia (either carcinoma or adenoma) was required. This study was approved by the Institutional Animal Care and Use Committee (Protocol #: 19518). Animals were excluded if any of the following criteria were identified: determination of potential surgical resectability after CT scan, receiving chemotherapy within 2 weeks prior to TACE or receiving corticosteroids or NSAIDs within 1 week prior to TACE. All dogs undergoing TACE were monitored closely for any pain associated with the procedure, and appropriate analgesia was administered as necessary.rd order arterial branch from the aorta) providing arterial blood supply only to the tumor tissue, and 2. the administration of the chemoembolic agent to the tumoral blood supply. Following TACE, all dogs were administered amoxicillin with clavulanic acid (14–20 mg/kg) orally two times daily for 30 days. Additionally, gastrointestinal protectants such as proton pump inhibitors, serotonin receptor antagonists, and selective neurokinin 1 receptor antagonists were administered as needed.Procedural-related adverse events were recorded as reported by Follette et al.  Procedur®, Ethicon US, LLC, Bridgewater, NJ) were placed around the femoral artery. An 18-gauge over-the-needle catheter  was introduced into the femoral artery and the needle was removed. An 0.035” hydrophilic guidewire  was introduced into the over-the-needle catheter and subsequently into the femoral artery. The over-the-needle catheter was removed over the guidewire. A vascular access sheath and dilator  were introduced into the femoral artery over the guidewire. The dilator was then removed over the guidewire. The fluoroscopy unit was then positioned over the abdomen of the patient. A 4 French hook catheter  was placed over the guidewire, and the guidewire/hook catheter combination was passed from the femoral artery through the external iliac artery to the abdominal aorta, and the celiac artery was subsequently selected. Once in the celiac artery, the main hepatic artery was selected. The guidewire was then removed from the vascular access sheath. A 50% saline/50% contrast medium  mixture was drawn into a syringe and attached to the hook catheter and injected under fluoroscopic guidance to perform an angiogram and identify the tumoral blood supply. During this angiogram, injected contrast medium was monitored closely to be sure that hepatopulmonary shunting was not occurring; lack of shunting was confirmed in all cases. Superselection of the hepatic arterial blood supply to the tumor was then performed with a combination of a microwire  and microcatheter .The procedure was performed as follows: All dogs were placed under general anesthesia utilizing an individualized protocol as determined by the clinical anesthesiology service and then transported to the fluoroscopy  suite. Each dog was placed in dorsal recumbency, and the groin region clipped, prepared with aseptic technique and draped. All TACE procedures were performed by a single author (WTNC). A 1–2 cm incision was made over the femoral artery, and the subcutaneous tissues were bluntly and sharply dissected until the artery was visualized. Two 3–0 polydioxanone sutures (PDSDrug-eluting bead TACE was performed (without ethiodized oil). The chemoembolic agent used was a bioabsorable polymer microsphere (75–100 μm diameter) loaded with paclitaxel (10% paclitaxel) . The syringe containing the paclitaxel-loaded microspheres was prepared. The microspheres were hydrated in saline; all but 1 ml of saline was then removed. Then, 8 ml of contrast medium was transferred to the syringe with the microspheres and transferred back and forth several times until appropriate suspension was noted. The created slurry of microspheres was transferred into 1 ml syringes and administered to the tumoral blood supply, being injected under fluoroscopic guidance. The slurry was injected in short bursts, and the flow of the slurry through the vessel being embolized was monitored closely to prevent retrograde flow. When cessation of the flow was documented fluoroscopically, the injection was discontinued. Selective and non-selective arteriography were then performed to assess the efficacy of the procedure. Additionally, arteriography was performed to ensure patency of the main hepatic artery and celiac artery. Upon completion of the arteriograms, the hook catheter was removed over the guidewire. The vascular access sheath was then removed from the femoral artery and the previously placed ligatures were tightened around the vessel. The subcutaneous tissue and skin were closed routinely.All owners completed questionnaires validated for the assessment of subjective outcomes in dogs with cancer before the TACE procedure and approximately 4 weeks after the TACE procedure. The questionnaires consisted of: the Canine Symptom Assessment Scale with a novel 4-item liver subscale (CSAS-Liver) and the Canine Owner-Reported Quality of Life Scale (CORQ). The CSAS is multi-dimensional symptom assessment tool that measures frequency, severity, dog distress and owner distress associated with 12 general and 4 liver-specific signs an owner might have observed during the preceding 10-day period; higher CSAS scores indicate greater symptom burden. The CORQ is a 17-item questionnaire that measures general quality of life as observed by the owner during the preceding week; higher scores indicate better quality of life.A pre-TACE complete blood count (CBC) and biochemical panel were performed in all dogs. Additionally, a biochemical panel was obtained 1 day after TACE and a CBC was obtained approximately 1 week after TACE. A CBC and biochemical panel were obtained approximately 4 weeks after TACE.A dual phase  contrast-enhanced CT scan  of the liver was performed prior to TACE and approximately 4 weeks after TACE. The CT scan was performed using a clinical protocol of overlapping (0.5:1) 2.0mm thick helical images prior to and after a systemic dose of iodinated contrast media. The images were reconstructed in soft tissue and bone algorithms. Tumor volumes were calculated by a single author who was blinded to study data using a commercially available imaging analysis software package . Briefly, contrast-enhanced CT images were imported into the software package and a freeform tool was used to draw a line around the tumor in a single image to create a region of interest (ROI). When needed, a repulsor tool was used to specifically align the ROI to only include the tumor tissue. This same procedure was performed on sequential images until the entire tumor was outlined. All ROIs were then selected, and a software tool for computing the tumor volume was utilized. The pre-TACE tumor volumes were compared to the 4-week post-TACE tumor volumes.Blood samples were obtained pre-treatment and at the following time points to allow for determination of intravascular paclitaxel concentration: 15 minutes, 1 hour, 4 hours, 8 hours, 24 hours, 4 days, 7 days, and 14 days after administration. Whole blood was obtained and placed in an EDTA tube. Blood samples were then flash frozen and stored at -80°C. Blood analysis was performed with liquid chromatography–mass spectrometry (LC-MS) to quantify the concentration of paclitaxel in canine blood.An adverse event (AE) post-TACE was categorized as either “chemotherapy-related” or “procedure-related”. Adverse events considered to be chemotherapy-related were reported and graded according to VCOG guidelines . AdverseThe endpoint used for power analysis was the proportional difference between pre-procedure and post-procedure tumor volume (cc) as obtained with CT scans, according to the formula: (post-TACE—pre-TACE)/pre-TACE. A sample size of 10 dogs was estimated to have 80% power to detect a 50% change in post-TACE volume as significantly different from zero change, assuming a SD of 50% and alpha = .05.The primary numerical endpoints to be analyzed were the volume measurements obtained during the CT scans. Secondary outcomes included describing and comparing clinical signs, AEs and quality of life before and after TACE, as measured via questionnaires. The relationship between CORQ and CSAS-Liver scores before and after TACE was estimated using Spearman rank correlation coefficients. CORQ scores , CSAS-Liver scores , and tumor volume measurements were compared before and after TACE using Wilcoxon signed rank tests. Mean score differences and percent change in tumor volume between time points were estimated with surrounding 95% confidence intervals (CI) using the Clopper-Pearson exact binomial method. Median survival time following TACE was estimated using the Kaplan-Meier method; dogs alive or lost to follow up were censored in the analysis. All tests were two-sided and P < .05 was statistically significant. Statistical analysis was performed using a commercially-available program .Prospectively, 7 dogs were enrolled in this trial. Study enrollment was closed early due to poor enrollment. Multiple other dogs were screened for the trial, but after CT evaluation, these dogs were considered to have liver tumors that were surgically resectable. The median age and weight of enrolled dogs were 12 years  and 8.9 kg . The gender distribution was 4 male castrated and 3 female spayed dogs, and the breeds included mixed breed (n = 4) and 1 each of dachshund, golden retriever, and Jack Russell terrier.The diagnosis of the liver masses included hepatocellular carcinoma (n = 6) and adenoma (n = 1). Tumor location and characteristics were as follows: right lateral and medial liver lobes and caudate lobe (n = 2), quadrate lobe (2), right lateral liver lobe and caudate lobe  (1), caudate lobe but involving common bile duct and portal vein (1), entire mid-liver affected, but could not characterize further (1). Tumors were considered either non-resectable or presenting too great of a surgical risk after surgical explore in 4/7 dogs and after CT in 3/7 dogs.No intra-procedural complications were encountered, and technical success was considered 100% as all tumoral blood supplies could be accessed and microspheres were successfully administered. Median procedural time was 165 minutes . Median days of hospitalization post-TACE was 3 , and all dogs were discharged.The most common pre-TACE owner-reported clinical signs were lack of energy , large or swollen abdomen , difficulty sleeping , panting , increased drinking , and yelping or crying out . Moaning, groaning or whining was reported in 2/7 (28.6%) dogs, and pain, cough, lack of appetite, sleepiness, vomiting, and increased frequency of urination were each reported in 1/7 (14.3%) dogs. Seizures, diarrhea, and pacing were not reported in any dog. Median preoperative CSAS-Liver score was 9.4 (range 0.0–19.2). Median pre-TACE CORQ score was 6.06 (range 4.82–6.88). There was a modest negative correlation  between preoperative CORQ and CSAS-Liver scores. One dog had no owner-reported clinical signs, one had 2 different clinical signs, one had 4 clinical signs, two had 5 clinical signs, and two had 7 clinical signs.Four-week-post-TACE questionnaire results were available for 6 dogs. Pain, lack of energy, panting, and pacing were each reported in 2/6 (33.3%) dogs. Cough, lack of appetite, sleepiness, vomiting, diarrhea, and large or swollen abdomen were each reported in 1/6 (16.7%) dogs. Difficulty sleeping, moaning, groaning, or whining, yelping or crying out, seizures, increased drinking, and increased frequency of urination were not reported in any dog. Median 4-week post-TACE CSAS-Liver score was 0.0 (range 0.0–12.2). Median 4-week post-TACE CORQ score was 6.91 (range 5.82–7.00). There was a strong negative correlation  between 4-week post-TACE CSAS-Liver and CORQ scores. Four dogs had no symptoms, one dog had 5 different symptoms, and one dog had 9 symptoms.All 6 dogs’ individual CSAS-Liver scores improved between pre- and post-TACE measurements, except the dog with a zero pre-TACE score also had a zero post-TACE score. Dogs’ postoperative CSAS-Liver scores were significantly (P = .035) lower than their preoperative scores, indicating lower postoperative clinical signs burden; the mean score difference was -5.8 (95%CI -11.0 to -0.2). Five of 6 dogs’ CORQ scores improved between preoperative and postoperative measurements, and one dog’s CORQ score worsened. The dog with the worsened score was the dog experiencing 9 different clinical signs. Dogs’ postoperative CORQ scores were not significantly different from their preoperative scores (p = .11); the mean score difference was +0.66 (95%CI -0.27 to 1.57).Pre-TACE values are available for all 7 dogs Tables  and 2; aAt least one of the hepatocellular leakage enzymes was increased in every dog pre-TACE with elevations in ALT in 6/7 and AST in 3/7 dogs. The ALT increased 1-day post-TACE by a median of 1,496% , and the AST increased 1-day post-TACE by a median of 5,160% . ALT was decreased from pre-TACE values in 5/6 dogs and AST was decreased from pre-TACE in 3/6 dogs at approximately 4 weeks post-TACE. In the dogs with decreased ALT and AST post-TACE, the ALT decreased 4 weeks post-TACE (as compared to pre-TACE) by a median of 42% , and the AST decreased 4 weeks post-TACE (as compared to pre-TACE) by a median of 31% . Bilirubin, which was normal in all dogs pre-TACE, increased above normal  in 2/7 dogs 1-day post-TACE and was normal in all dogs 4 weeks post-TACE.All dogs underwent a CT scan within 1-day prior to TACE, and 6 of 7 dogs underwent a 4-week post-TACE CT scan . Among t2 . The mean plasma paclitaxel concentration peaked at 4 days post-TACE procedure and was 25.7 ng/mL . After 14 days, the mean plasma paclitaxel concentration had decreased to 2.39 ng/mL .The median dose of paclitaxel administered during TACE was 87 mg/mFollowing TACE, 2/7 dogs exhibited no chemotherapy- or procedure-related AEs. One dog experienced a grade 4 neutropenia (104/uL) 1-week post-TACE. The dog was continued on the amoxicillin and clavulanic acid that had been previously prescribed and monitored for any other complications. At 2 weeks post-TACE (1-week later), the neutrophil count in that dog was 17,716/uL.For procedure-related AEs, 1 dog demonstrated a level 2 AE, and 1 dog demonstrated a level 5 AE. Abdominal ultrasonography of the dog with the level 2 AE demonstrated that the pancreas was hypoechoic and enlarged with surrounding hyperechoic peripancreatic fat indicating pancreatitis and regional peritonitis. The dog was hospitalized for fluid administration and monitoring for 7 days; at 10 days post-TACE, the dog was free from clinical signs. In the dog with a level 5 AE, clinical signs resolved 7 days after TACE, and the dog was discharged. However, at 12 days post-TACE, the dog was evaluated after the owner noted the abdomen to be distended. During abdominal ultrasonography, the pancreas was noted to be hypoechoic and enlarged with surrounding hyperechoic peripancreatic fat indicating pancreatitis and regional peritonitis. Additionally, space-occupying material was identified in the aorta and left external iliac arteries indicating vascular thrombosis. The hepatic mass was hypoechoic, devoid of power Doppler signal and surrounded by echogenic fat suggesting necrosis and secondary regional inflammation. The dog was hospitalized for 1 day and discharged as he improved clinically. However, he was reevaluated 6 days later (18 days post-TACE) for worsening signs of abdominal distension and ataxia in the hind limbs. Hospitalization and anti-thrombotic treatment were recommended; however, the owner declined and instead elected humane euthanasia. On necropsy, extensive necrosis of the tumor and capsular rupture were noted  as was sThis necropsy image is of the liver of a dog with a hepatocellular adenoma who underwent transarterial embolization and was euthanized 18 days after the procedure. The liver mass is very necrotic and has ruptured contributing to the constellation of clinical signs noted in this dog.Suspected PES signs were demonstrated in 5/7 dogs. Lethargy and hyporexia were noted post-embolization in 4/7 dogs, and 1 dog appeared nauseous; additionally, soft stool and fever were noted in 1 dog each. All signs were noted within the first 1–1.5 days post-TACE. Dogs were no longer exhibiting PES signs at a median time of 7 days  after TACE, although some clinical signs (as noted on the CSAS-Liver score) were noted at approximately 4-weeks post-TACE.At the time of data analysis, 4 dogs had died at 18, 248, 349, and 629 days post-TACE, and 3 dogs were alive at 514, 745, and 878 days post-TACE. Median survival time was 629 days (95%CI 18 to upper limit not reached).Dogs undergoing treatment of hepatocellular neoplasia via a novel drug-eluting microsphere experienced a significant improvement in clinical signs based on assessment via questionnaire and significant decrease in tumor volume. The treatment was well-tolerated with minimal adverse events, high hospital discharge rate and prolonged survival times. Additionally, the technical success was high with low procedure-related complications, although one dog experienced a Grade 5 toxicity.The use of TAE and TACE is particularly attractive for the treatment of hepatocellular neoplasia due to the dual blood supply of the liver. More specifically, normal liver parenchyma is supplied primarily by the portal vein whereas liver tumors receive blood supply almost exclusively from the hepatic artery , 11. TheThe use of hepatic embolization/chemoembolization in companion animals has been described retrospectively in a few reports; these studies have included a small number of dogs and both bland embolization and chemoembolization were described –14. In oThe decision-making regarding the addition of chemotherapy to embolization and the means by which chemotherapy is administered  remains controversial in human medicine; there is a paucity of information in veterinary patients and the best means of performing hepatic embolization has not yet been elucidated. The use of DEB-TACE in the treatment of liver neoplasia is commonplace in humans. DEB-TACE has been shown to be at least as equally effective as conventional TACE, but has been promoted as an alternative due to the potential for being a safer means of chemotherapy delivery . When de2) to dogs. Additionally, it is important to note that the drug administered in this study was paclitaxel without the addition of Cremophor®, which has been shown to cause hypersensitivity reactions in dogs regularly [The most common drug utilized in humans for DEB-TACE is doxorubicin. While several studies document the use of paclitaxel in the treatment of different canine tumors, this drug is still rarely utilized clinically . Paclitaegularly . The meaWhile it can be challenging to separate adverse events experienced secondary to chemotherapy from PES, the PES clinical signs encountered in this cohort of dogs was similar to what has historically been encountered in the authors’ clinic associated with bland embolization. The signs of PES in this cohort were common with 5 of 7 dogs demonstrating either lethargy, changes in appetite or gastrointestinal signs. Very little is understood about how PES manifests in companion animals, but based on the results of this small cohort, signs appear to be similar to what is expected in human patients undergoing liver TACE.One of the 7 dogs treated in this study died in the short-term at 18 days post-TACE. The signs demonstrated by this dog are likely secondary to the significant response experienced by the tumor and the subsequent inflammatory cascade induced by hepatic necrosis, pancreatitis or both. On necropsy, pancreatitis was likely influenced by the close proximity to the affected (and subsequently treated) region of liver. Pancreatitis is a major concern whenever performing TACE in dogs; part of the blood supply to the pancreas branches from the gastroduodenal artery which is a branch directly off the main hepatic artery, and this close association could lead to non-target embolization. Additionally, when large right-sided liver tumors are encountered, it is not unusual for the pancreas to be adjacent or adhered to these tumors, and inflammation induced in the liver from treatment could similarly occur in the pancreas.Clinical laboratory evaluation associated with treatment in this cohort of dogs produced some interesting results. Hepatocellular leakage enzymes (ALT and AST) were increased in most dogs pre-TACE; however, a dramatic increase in these enzymes was noted the day after TACE. This is an expected finding due to the nature of the treatment and the subsequent trauma caused to the hepatic tissue after TACE. Interestingly, the values at approximately 4-weeks post-TACE were improved from the pre-TACE values in most dogs.While the outcomes reported here are only for a small number of dogs, the median survival times encountered in this cohort are encouraging. Four of the 6 dogs that survived the short term, survived greater than a year and 2 survived greater than 2 years . Comparatively, dogs with massive hepatocellular carcinoma that did not undergo treatment in a separate study had a median survival time of 270 days [There are several limitations of this study that should be recognized. First, case numbers in this study were low; however, a benefit of the study design for this trial was that each treated dog could act as its own control due to evaluation of clinical signs and tumor volume pre- and post-TACE. Additionally, this procedure is technically challenging and requires fluoroscopy and exposure to chemotherapy, which increases the risk to both the dog and the clinicians involved in treatment. Lastly, this study did not perform comparisons with other available treatments. Other treatments have questionable efficacy when extensive liver neoplasia is encountered; however, further investigation is needed into how the outcomes associated with these different available options may compare.The use of a novel paclitaxel-eluting microsphere in this cohort of dogs successfully decreased tumor volume significantly approximately 4-weeks post-TACE and improved clinical signs. The technique described here was well-tolerated with minimal AEs and was able to be performed in a minimally invasive fashion. Future investigation into the use of DEB-TACE and other similar therapies is warranted due to the promising outcomes noted in this cohort, and the current lack of other effective treatment options in dogs with extensive hepatocellular neoplasia.S1 Data(XLSX)Click here for additional data file.


There was significant improvement in PCS score following hip replacement  but no change in controls . Following hip replacement, 46.7% of participants experienced clinically important improvement in PCS score, while 15.5% experienced worsened PCS score. Participants experiencing improved postoperative PCS score had significantly lower PCS and higher MCS scores preoperatively. The degree of preoperative physical function impairment was a significant indicator of older people most likely to benefit from hip replacement surgery.Uncertainty remains regarding the benefit of hip replacement in older adults in the context of age-related decline in physical function. This study aimed to examine the effect of hip replacement on functional outcomes and identify factors associated with clinically important improvement in physical function postoperatively in community-dwelling older adults. This cohort study was performed within the ASPREE trial, with 698 participants receiving hip replacement and 677 age- and sex-matched controls without knee or hip replacement during the trial drawn from 16,703 Australian participants aged ≥70 years. Health status  was assessed annually using the SF-12. Participants receiving hip replacement had significantly lower pre- and post-replacement PCS scores compared with controls ( Hip osteoarthritis (OA) causes significant pain and disability. There is no approved disease-modifying treatment that slows disease progression, with end-stage hip OA being managed with hip replacement. The median age for total hip replacement in Australia is 69 years, reflecting that a significant proportion of procedures are undertaken in older adults . Hip OA Total hip replacement is one of the most successful surgical procedures, providing excellent pain relief and function restoration for patients with severe hip OA . The incLarge-scale cohort studies provide an opportunity to assess functional outcomes following joint replacement compared to age- and sex-matched controls without joint replacement. This enables the effect of joint replacement in older adults to be examined in the context of age-related decline in physical function which is increased after the age of 70 years ,21. ThusThis cohort study was conducted within the ASPirin in Reducing Events in the Elderly (ASPREE) trial with study design, participant characteristics and primary results published previously ,23,24. IClinical documentation relating to hospitalizations for all knee and hip surgical procedures during the ASPREE trial was reviewed, and participants with any hip replacement procedure  were identified, with the first recorded in-trial hip replacement being used to confer hip replacement status. Participants with hip replacement were matched 1:1 by age (±1 year) at time of hip replacement and sex with controls (age at study entry) who did not have a joint replacement during the ASPREE trial, as shown in Health status was assessed annually using the Medical Outcomes Study Short Form 12 Health Survey Version 2 (SF-12v2) , a generGait speed, a simple, objective indicator of physical function and mobility ,28, was For cases, the pre-hip replacement measure was selected as the assessment undertaken at the study visit immediately prior to the hospitalization for hip replacement. The post-hip replacement measure was taken as the assessment undertaken at the first available study visit at least 6 months after the hospitalization for hip replacement. For controls, outcomes were examined at ASPREE study baseline, and then at 1 year for health status and 2 years for gait speed after randomization.2. Self-reported history of joint replacement before study enrolment was obtained from a sub-study, the ASPREE Longitudinal Study of Older Persons [Age, sex, weight, height, years of education, and morbidities or chronic conditions  were collected in the ASPREE study as previously described . Body ma Persons .t-tests were used for unadjusted analyses, and multiple linear regression models were fitted with change in functional outcomes as the dependent variable and hip replacement vs. control as the independent variable, adjusted for baseline BMI, education, morbidities or chronic conditions, and time between outcome measures. For aim 2, participants with hip replacement were categorized into three groups based on the minimal clinically important difference in PCS score, which was 4.6 points after total joint replacement [Characteristics of participants with hip replacement and age- and sex-matched controls were compared using independent samples t-tests or chi-square tests, when appropriate. For aim 1, i.e., comparisons of changes in functional outcomes between participants with hip replacement and controls, independent samples lacement : worseneStratified analyses by age category and sex were performed. Sensitivity analyses were undertaken, excluding participants who self-reported a history of joint replacement at baseline. To reduce the risk of type 1 error, adjustment for multiple comparisons was undertaken and alpha was set at 0.005 for this study. All analyses were undertaken using STATA 17 .This study analyzed 698 participants with hip replacement and 677 age- and sex-matched controls . The chap < 0.0001) (p < 0.0001)  . In the  0.0001) . Post-hi 0.0001) . p = 0.02) (p = 0.31)  . In the  = 0.02) . The pos = 0.31) . p < 0.0001), role physical , bodily pain , general health , vitality , social functioning , and role emotional  (p ≤ 0.005)  . Partici≤ 0.005) . In the ≤ 0.005) . p < 0.0001) (p = 0.0001)  . In the  0.0001) . Post-hi 0.0001) .Similar results were observed for males and females. Female participants with hip replacement experienced a greater improvement in PCS, physical function, role physical, and bodily pain than male participants with hip replacement, when compared with the controls . SimilarBaseline characteristics were compared among participants with hip replacement with worsened, stable, and improved PCS scores . FollowiIn this large cohort of healthy community-dwelling older adults, although participants experienced a significant improvement in PCS scores after hip replacement, their postoperative physical function remained significantly lower than age- and sex-matched controls. The greatest improvements were observed for the bodily pain and physical function domains of the SF-12. A higher level of preoperative physical function impairment was the strongest predictor of clinically important improvement in PCS score after hip replacement. Those who were already functioning well were less likely to benefit from this major surgery, suggesting that the level of physical function could be used to inform decision making as to which older adults will have functional improvement following hip replacement surgery.Functional improvement is an important patient-related outcome following hip replacement ,6,7,8,9.Age-related decline in physical function is commonly experienced in older people ,21, so tConsistent with results from previous studies ,35, our A strength of our study is that the study participants were drawn from a large, well- characterized, community-based clinical trial, which reduced the potential of bias in the selection of comparison group. With disability-free survival being the primary endpoint of the ASPREE trial, the participants were free of cardiovascular diseases and chronic disability at enrolment, reflecting the type of medically fit older individuals suitable for a hip replacement if clinically indicated. Thus, the ASPREE study offered us the ideal older population to examine the effect of hip replacement on functional outcomes. It was unbiased in terms of joint pain, but the ideal population to examine hip replacement. The approach of comparing participants with hip replacement with age- and sex-matched controls embedded in a large community-based clinical trial enables the functional outcomes of hip replacement to be investigated in the context of older adults with a similar likelihood of age-related functional decline. The health status profile in the current study sample was comparable to the wider ASPREE cohort where PCS scores declined with age and MCS scores tended to be stable with increasing age . With thn = 62, 8.9% of the 698 participants with hip replacement). The time between baseline and follow-up outcome measures was longer in participants with hip replacement than in controls and this was adjusted for in the analyses. Of the original age- and sex-matched sample, 78% of the participants had completed health status data at follow-up. Although the follow-up rate was lower in participants with hip replacement (64%) compared with age- and sex-matched controls (93%), which might introduce selection bias, there were no significant differences in age, sex, BMI, morbidities or chronic conditions, and baseline measures of PCS, MCS, and gait speed between participants with follow-up data and those without. It is less likely that the loss to follow-up would have affected the results of the study. The ASPREE trial did not collect detailed joint-specific data as the study focused on the overall assessment of wellbeing. We were unable to determine the type of joint replacement which could have been primary or revision hip replacement. The results of our study did not change in sensitivity analysis excluding participants with self-reported joint replacement at baseline. It is also acknowledged that being volunteers in a long-term clinical trial, the ASPREE participants may have had a greater interest in their health.There are limitations in our study. As the time points at which baseline data on function were collected were different for participants with hip replacement and age- and sex-matched controls, the participants with hip replacement may have a different experience during the ASPREE trial, such as longer time on study medication and possibility of a higher risk of developing major health events , compared with the matched controls. This might affect the functional measurements and thus introduce bias. However, only participants who were medically fit would undergo a hip replacement whereas those who developed severe morbidities could not have a hip replacement. It is less likely that the accumulation of major health events would have affected the results of our study, as the results did not change in an additional analysis excluding the small proportion of participants who developed major health events prior to hip replacement (In community-based older adults, although those receiving hip replacement experienced significant improvements in PCS score, their postoperative physical function remained significantly lower than age- and sex-matched controls. The greatest improvements were observed for bodily pain and physical function scores. Given that functional improvement is an important patient-related outcome after hip replacement, identifying those with poor preoperative physical function is most likely to identify older people most likely to benefit from hip replacement surgery. Further work is needed to optimize patient outcomes following hip replacement surgery. This will include identifying factors associated with better outcomes as well as ways to optimize selection of candidates for the surgery, including the timing of surgery and the risk–benefit ratio of hip replacement in community-dwelling older adults.


Smart Walk: a randomized pilot trial of an 8-month culturally tailored, smartphone-delivered physical activity (PA) intervention for African American women with obesity. Sixty participants  were randomized to the Smart Walk intervention (n = 30) or a wellness comparison intervention (n = 30). Results supported the acceptability and feasibility of the intervention, as demonstrated by participant retention (85% at 4 months and 78% at 8 months), Smart Walk app use, and intervention satisfaction . Smart Walk participants also reported greater increases in moderate-to-vigorous PA  and demonstrated clinically relevant, although not statistically significant , baseline to 4 months improvements in cardiorespiratory fitness , systolic blood pressure , diastolic blood pressure , and pulse wave velocity . Eight-month cardiometabolic outcomes followed similar trends, but had high rates of missing data (45–53%) due to COVID-19 restrictions. Collectively, findings demonstrated favorable outcomes for acceptability and feasibility, while also highlighting key areas for refinement in future research.This article reports the results of  Regular aerobic physical activity (PA) improves numerous cardiometabolic risk factors, including high blood pressure ,2,3, pooDespite the established cardiometabolic health benefits of aerobic PA, only 27% to 40% of African American (AA) women meet national PA guidelines   have coSmart Walk, a culturally tailored, Social Cognitive Theory (SCT)-based smartphone-delivered intervention designed to increase PA and reduce cardiometabolic disease risk among insufficiently active AA women with obesity. The primary study aim was to examine the feasibility and acceptability of the intervention. Feasibility was assessed by examining recruitment and retention rates and the research team’s ability to deliver the intervention as intended. Acceptability was assessed by examining participant utilization of the smartphone app and self-reported intervention satisfaction. The secondary aim was to examine patterns of change in PA, cardiometabolic disease risk factors, and theory-based psychosocial constructs targeted by the intervention. We hypothesized that results would demonstrate favorably for acceptability and feasibility of the smartphone-delivered PA intervention and expected participants receiving the PA intervention to demonstrate greater improvements in PA and cardiometabolic disease risk factors as compared to the comparison group.This paper reports the results of a randomized pilot trial evaluating Smart Walk smartphone-delivered PA intervention or the Smart Health smartphone-delivered attention-matched wellness comparison condition. Months 1–4 consisted of the active intervention phase and months 5–8 included a no-contact follow-up period. The 4-month active intervention period was selected because it provides sufficient time for participants to increase their PA  = 43.3 ± 17.7 min/week, omes see ; howevermall see .OR] = 2.62, 95% CI = , p = 0.276). At 8 months, 6 of 22 (27%) intervention group participants and 2 of 25 (8%) of comparison group participants met the 150 min/week recommendation . Among participants providing accelerometer data at 4 months, 5 of 23 (22%) in the intervention group and 8 of 22 (36%) in the comparison group averaged > 21.4 min/day of MVPA according to 1 min bouts . Based on a 10 min bout length, no intervention participants and only 1 control group participant met threshold . At 8 months, 3 of 12 intervention participants (25%) and 3 of 15 comparison participants (20%) met this threshold according to 1 min bouts . No participants met this threshold at 8 months based on a 10 min bout length.With respect to meeting national PA guidelines, at the 4-month follow-up, 6 of 24 (25%) intervention group participants, and 3 of 27 (11%) comparison group participants self-reported engaging in ≥150 min/week of MVPA , systolic blood pressure , diastolic blood pressure , and pulse wave velocity  and 8 months . Differences in change from baseline to 4 months in PA self-efficacy , social support from family  and PA self-regulation , were small to moderate in magnitude, with the intervention group demonstrating greater  improvements on these constructs relative to controls. Baseline to 8-month changes in social support from family  were similar to those observed at 4 months. Self-efficacy declined in both groups from baseline to 8 months, with only a negligible between-group difference in change . From baseline to 8 months, both groups showed increased self-regulation scores, with only small between-group difference in change . Outcome expectations and social support from friends showed negligible change in both groups at 4 and 8 months.As illustrated in The current study examined the acceptability and feasibility of a smartphone-delivered PA intervention for AA women and explored between-group differences for patterns of change in cardiometabolic disease risk outcomes and hypothesized theoretical mediators. Overall, results for the feasibility and acceptability of the intervention were favorable, while also affording insight into how the intervention could be refined prior to implementation of a fully powered RCT. Observed patterns of change in self-reported MVPA and several cardiometabolic disease outcomes, including cardiorespiratory fitness and blood pressure, further demonstrate the promise of our smartphone-delivered PA intervention. These encouraging findings make an important contribution to the limited body of research examining the utility of mHealth approaches in increasing PA and improving cardiometabolic health among AA women.Smart Walk intervention. The high retention rates at the end of the active 4-month intervention (85%) and at the 8-month follow-up (78%) are comparable to median rates of studies included in previous reviews of PA interventions for AA women  [Feasibility and acceptability of the intervention were supported by numerous indices, including participant recruitment and retention, results of the post-intervention satisfaction survey, and app use. Recruitment efforts yielded an enrollment rate of 7.5 women/month. Although comparison of this enrollment rate to other studies has limited utility due to the heterogeneity that exists across studies in regards to study populations, implementation settings, recruitment methods, and inclusion/exclusion criteria, this rate will be used to develop recruitment timelines for future intervention trials of the e., 83%) , includie., 83%) . To our Smart Walk intervention among AA women aged 50–65 years [Participants expressed a high level of satisfaction for the multi-media modules, text message, and Fitbit components of the mHealth intervention, as well as for the intervention as a whole, with all participants who completed the intervention indicating they would recommend the smartphone-delivered PA intervention to a friend. These satisfaction results mirror those of an earlier iteration of the structured PA intervention   and of a65 years , suggest65 years ,58,92. FSmart Walk app. We anticipate these strategies collectively will promote app engagement and foster a greater sense of social support for PA among study participants.App use and Fitbit wear data revealed that engagement was high during the initial weeks of the intervention, but declined gradually over the course of the intervention. Although decreased engagement over time is commonly reported in e- and mHealth interventions , it reprIntervention participants self-reported greater MVPA increases than comparison group participants at both post-intervention assessments. Changes in self-reported energy expenditure followed a similar pattern. Self-reported MVPA changes from baseline to 4 months are comparable to improvements observed in a previous e- and mHealth PA intervention with AA women  and thosSmart Walk participants  are comparable to those reported by meta-analyses examining the impact of aerobic exercise training on blood pressure outcomes [Meaningful, though not statistically significant, improvements in cardiorespiratory fitness and blood pressure were observed among intervention participants. The descriptive increase in fitness among PA intervention participants (increase of 1.1 mL/kg/min vs. a decrease of 0.8 mL/kg/min in comparison group) corresponds to a 7–13% decrease in risk for premature mortality . Likewisoutcomes ,99. Suchoutcomes ,101.Observed patterns of change for aortic pulse wave velocity, a measure of arterial stiffness and independent predictor of cardiovascular events and mortality ,103, werBMI was unchanged throughout the intervention. This outcome was not surprising, as weight loss from PA alone requires participants to engage in substantially more MVPA than levels promoted by the study  ,107. GluSubstantially greater improvement in behavioral capability for PA for intervention participants suggests that the intervention curriculum was successful in enhancing knowledge of national PA guidelines, the types of activities that constitute aerobic PA, and the health benefits of aerobic PA. We also observed small-to-moderate, albeit not statistically significant, baseline to 4-month increases in self-efficacy and self-regulation among intervention participants relative to comparison group participants. While promising, these finding highlight the need to further enhance the theoretical fidelity  of interThe study’s findings are encouraging, but it is important to recognize potential limitations. The primary focus for this stage of intervention development was on feasibility and acceptability of the smartphone-delivered intervention, rather than efficacy testing. Accordingly, when interpreting PA, cardiometabolic, and psychosocial outcomes, we focused on examining magnitudes of effect, rather than statistical significance. Results for these outcomes (and our subsequent discussion of them) should be interpreted as suggestive, rather than definitive. Additionally, the multi-component nature of the intervention limits our ability to determine if one component of the intervention may have been more strongly related to changes in PA behavior than another. To properly address this type of question, a design that can examine component-specific effects is needed . A third limitation was that although efforts were made to blind research technicians conducting cardiorespiratory fitness tests to participants’ study group allocation at 4- and 8-month follow-up assessments, this was not always possible. Standardized testing procedures were used to limit this potential bias. Other limitations include recruiting participants from single geographical area , using community-based recruitment methods, and providing compensation for participation . These considerations may limit generalizing results to AA women outside of the Phoenix metropolitan area and likely reflect a sample with increased motivation to adopt healthy lifestyle behaviors. Finally, restrictions on data collection related to the COVID-19 pandemic had serious impacts on conclusions that could be drawn from analyses of several 8-month outcomes. The lack of 8-month physiological study assessments for approximately 1/3 of our sample resulted in untrustworthy estimates from analyses of multiply imputed datasets, limiting us to complete-case analyses of cardiometabolic outcomes at 8 months. These restrictions also likely influenced PA behaviors and psychosocial outcomes among participants who were completing the study during the early stages of the pandemic.Despite limitations, numerous strengths of the study should also be noted. This is one of the first studies to examine the effects of a culturally tailored smartphone-delivered PA intervention among AA women, research necessary to advance e- and mHealth research on PA promotion. Second, we addressed several design limitations of previous studies , by inclSmart Walk intervention to enhance usability, engagement, and theoretical fidelity to Social Cognitive Theory constructs hypothesized to mediate intervention effects on PA outcomes prior to larger-scale efficacy testing. Specific refinements will include: (i) holding an in-person “kick-off” sessions at the beginning of the study for each cohort to further create a sense of community among participants prior to engaging virtually on the app; (ii) including additional app push notifications to prompt Fitbit wear (if needed) and for participants to view unviewed multi-media modules and discussion board posts, and (iii) incorporating lay community health coaches to actively facilitate participant engagement on the discussion boards and to provide virtual PA coaching sessions  to study participants.Future directions for this program of research include refining the This study demonstrated high acceptability and feasibility, and yielded promising findings regarding the intervention’s associations with increased PA and reduced cardiometabolic disease risk among insufficiently active AA women with obesity.