BACKGROUND:Clinical screening for basic social needs—such as food and housing insecurity—is becoming more common as health systems develop programs to address social determinants of health. Clinician ...attitudes toward such programs are largely unexplored.
OBJECTIVE:To describe the attitudes and experiences of social needs screening among a variety of clinicians and other health care professionals.
RESEARCH DESIGN:Multicenter electronic and paper-based survey.
SUBJECTS:Two hundred fifty-eight clinicians including primarily physicians, social workers, nurses, and pharmacists from a large integrated health system in Southern California.
MEASURES:Level of agreement with prompts exploring attitudes toward and barriers to screening and addressing social needs in different clinical settings.
RESULTS:Overall, most health professionals supported social needs screening in clinical settings (84%). Only a minority (41%) of clinicians expressed confidence in their ability to address social needs, and less than a quarter (23%) routinely screen for social needs currently. Clinicians perceived lack of time to ask (60%) and resources (50%) to address social needs as their most significant barriers. We found differences by health profession in attitudes toward and barriers to screening for social needs, with physicians more likely to cite time constraints as a barrier.
CONCLUSIONS:Clinicians largely support social needs programs, but they also recognize key barriers to their implementation. Health systems interested in implementing social needs programs should consider the clinician perspective around the time and resources required for such programs and address these perceived barriers.
Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not ...adequately disentangled their effects.
To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19.
Retrospective cohort study.
Kaiser Permanente Southern California, a large integrated health care organization.
Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020.
Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex.
Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m
, those with BMIs of 40 to 44 kg/m
and greater than 45 kg/m
had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected.
Deaths occurring outside a health care setting and not captured in membership files may have been missed.
Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention.
Roche-Genentech.
Background
As more health care organizations integrate social needs screening and navigation programs into clinical care delivery, the patient perspective is necessary to guide implementation and ...achieve patient-centered care.
Objectives
To examine patients’ perceptions of whether social needs affect health and attitudes toward healthcare system efforts to screen for and address social needs.
Research Design
Multi-site, self-administered survey to assess (1) patient perceptions of the health impact of commonly identified social needs; (2) experience of social needs; (3) degree of support for a health system addressing social needs, including which social needs should be screened for and intervened upon; and (4) attitudes toward a health system utilizing resources to address social needs. Analyses were conducted using multivariable logistic regression models with clinic site cluster adjustment.
Subjects
Adult patients at seven primary care clinics within a large, integrated health system in Southern California.
Main Measures
Survey measures of experience with, acceptability of, and attitudes toward clinical social determinants of health screening and navigation.
Key Results
A total of 1161 patients participated, representing a 79% response rate. Most respondents (69%) agreed that social needs impact health and agreed their health system should ask about social needs (85%) and help address social needs (88%). Patients with social needs in the last year were more likely to (1) agree social needs impact health (OR 10.2,
p
< 0.001), (2) support their health system asking patients about social needs (OR 3.7,
p
< 0.001), and (3) support addressing patient social needs (OR 3.5,
p
< 0.001). Differences by social need history, gender, age, race, ethnicity, and education were found.
Conclusions
Most patients at a large integrated health system supported clinical social needs screening and intervention. Differences in attitudes by social need history, gender, age, race, ethnicity, and education may indicate opportunities to develop more equitable, patient-centered approaches to addressing social needs.
Prostate-specific membrane antigen (PSMA; folate hydrolase) prostate cancer (PC) expression has theranostic utility.
To elucidate PC PSMA expression and associate this with defective DNA damage ...repair (DDR).
Membranous PSMA (mPSMA) expression was scored immunohistochemically from metastatic castration-resistant PC (mCRPC) and matching, same-patient, diagnostic biopsies, and correlated with next-generation sequencing (NGS) and clinical outcome data.
Expression of mPSMA was quantitated by modified H-score. Patient DNA was tested by NGS. Gene expression and activity scores were determined from mCRPC transcriptomes. Statistical correlations utilised Wilcoxon signed rank tests, survival was estimated by Kaplan-Meier test, and sample heterogeneity was quantified by Shannon's diversity index.
Expression of mPSMA at diagnosis was associated with higher Gleason grade (p=0.04) and worse overall survival (p=0.006). Overall, mPSMA expression levels increased at mCRPC (median H-score interquartile range: castration-sensitive prostate cancer CSPC 17.5 0.0–60.0 vs mCRPC 55.0 2.8–117.5). Surprisingly, 42% (n=16) of CSPC and 27% (n=16) of mCRPC tissues sampled had no detectable mPSMA (H-score <10). Marked intratumour heterogeneity of mPSMA expression, with foci containing no detectable PSMA, was observed in all mPSMA expressing CSPC (100%) and 37 (84%) mCRPC biopsies. Heterogeneous intrapatient mPSMA expression between metastases was also observed, with the lowest expression in liver metastases. Tumours with DDR had higher mPSMA expression (p=0.016; 87.5 25.0–247.5 vs 20 0.3–98.8; difference in medians 60 5.0–95.0); validation cohort studies confirmed higher mPSMA expression in patients with deleterious aberrations in BRCA2 (p<0.001; median H-score: 300 165–300; difference in medians 195.0 100.0–270.0) and ATM (p=0.005; 212.5 136.3–300; difference in medians 140.0 55.0–200) than in molecularly unselected mCRPC biopsies (55.0 2.75–117.5). Validation studies using mCRPC transcriptomes corroborated these findings, also indicating that SOX2 high tumours have low PSMA expression.
Membranous PSMA expression is upregulated in some but not all PCs, with mPSMA expression demonstrating marked inter- and intrapatient heterogeneity. DDR aberrations are associated with higher mPSMA expression and merit further evaluation as predictive biomarkers of response for PSMA-targeted therapies in larger, prospective cohorts.
Through analysis of prostate cancer samples, we report that the presence of prostate-specific membrane antigen (PSMA) is extremely variable both within one patient and between different patients. This may limit the usefulness of PSMA scans and PSMA-targeted therapies. We show for the first time that prostate cancers with defective DNA repair produce more PSMA and so may respond better to PSMA-targeting treatments.
Membranous prostate-specific membrane antigen (mPSMA) expression is upregulated in many, but not all, prostate cancers. Importantly, prostate-specific membrane antigen (PSMA) expression demonstrates marked intra- and interpatient heterogeneity, limiting the clinical utility of PSMA theranostics. Defective DNA repair gene aberrations are associated with significantly higher mPSMA expression levels in metastatic castration-resistant prostate cancer and may serve as predictive biomarkers for PSMA-targeted therapies.
There is limited data regarding the rates and severity of child maltreatment in medical settings during the COVID-19 pandemic, and the reports are somewhat contradictory.
To examine the rates of ...emergency department (ED) child maltreatment (CM) diagnosis before and after the California statewide stay-at-home order, as well as potential disparities by age, gender, race/ethnicity, and Medicaid status.
A retrospective pre-post interrupted time series was conducted using data from the electronic health records of children (<18 years) with at least one emergency department visit between January 1, 2019 and September 30, 2021. Enactment of the stay-at-home order in California, March 2020 was used to determine a change in trend of rates of diagnosis of CM in the ED.
Overall the study included 407,228 pediatric ED visits. There was a significant change in the percentage of CM visits immediately after the stay-at-home order, followed by small month to month decreases returning to near pre-stay-at-home order levels. This significant increase was driven by higher risk for children <4 years old. The increased rate of CM in the first month after the stay-at-home order was also elevated for female, Black, and Hispanic children.
Our results indicated the rates of CM diagnoses in the ED doubled after the March 2020 stay-at-home order in California. Additionally, our findings suggest that some children may be at higher risk than others, which supports the importance of social safety nets for children in times of national emergency.
ABSTRACT
Background
The demands for healthcare resources following a COVID-19 diagnosis are substantial, but not currently quantified.
Objective
To describe trends in healthcare utilization within ...180 days for patients diagnosed with COVID-19 and identify patient factors associated with increased healthcare use.
Design
Observational cohort study.
Patients
A total of 64,011 patients with a test-confirmed COVID-19 diagnosis from March to September 2020 in a large integrated healthcare system in Southern California.
Main Measures
Overall healthcare utilization during the 180 days following COVID-19 diagnosis, as well as encounter types and reasons for visits during the first 30 days. Poisson regression was used to identify patient factors associated with higher utilization. Analyses were performed separately for patients who were and were not hospitalized for COVID-19.
Key Results
Healthcare utilization was about twice as high for hospitalized patients compared to non-hospitalized patients in all time periods. The average number of visits was highest in the first 30 days (hospitalized: 12.3 visits/30 person-days; non-hospitalized: 6.6) and gradually decreased over time. In the first 30 days, the majority of healthcare visits were telehealth encounters (hospitalized: 9.0 visits; non-hospitalized: 5.6 visits), and the most prevalent reasons for visits were COVID-related diagnoses, COVID-related symptoms, and respiratory-related conditions. For hospitalized patients, older age (≥65: RR 1.27, 95% CI 1.15–1.41), female gender (RR 1.07, 95% CI 1.05–1.09), and higher BMI (≥40: RR 1.07, 95% CI 1.03–1.10) were associated with higher total utilization. For non-hospitalized patients, older age, female gender, higher BMI, non-white race/ethnicity, former smoking, and greater number of pre-existing comorbidities were all associated with increased utilization.
Conclusions
Patients with COVID-19 seek healthcare frequently within 30 days of diagnosis, placing high demands on health systems. Identifying ways to support patients diagnosed with COVID-19 while adequately providing the usual recommended care to our communities will be important as we recover from the pandemic.
Abstract Background The androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and ...enzalutamide. Objective To develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone-sensitive prostate cancer (HSPC) to CRPC. Design, setting, and participants Following monoclonal antibody generation and validation, we retrospectively identified patients who had HSPC and CRPC tissue available for AR-V7 immunohistochemical (IHC) analysis. Outcome measurements and statistical analysis Nuclear AR-V7 expression was determined using IHC H score (HS) data. The change in nuclear AR-V7 expression from HSPC to CRPC and the association between nuclear AR-V7 expression and overall survival (OS) was determined. Results and limitations Nuclear AR-V7 expression was significantly lower in HSPC (median HS 50, interquartile range IQR 17.5–90) compared to CRPC (HS 135, IQR 80–157.5; p < 0.0001), and in biopsy tissue taken before (HS 80, IQR 30–136.3) compared to after (HS 140, IQR 105–167.5; p = 0.007) abiraterone or enzalutamide treatment. Lower nuclear AR-V7 expression at CRPC biopsy was associated with longer OS (hazard ratio 1.012, 95% confidence interval 1.004–1.020; p = 0.003). While this monoclonal antibody primarily binds to AR-V7 in PC biopsy tissue, it may also bind to other proteins. Conclusions We provide the first evidence that nuclear AR-V7 expression increases with emerging CRPC and is prognostic for OS, unlike antibody staining for the AR N-terminal domain. These data indicate that AR-V7 is important in CRPC disease biology; agents targeting AR splice variants are needed to test this hypothesis and further improve patient outcome from CRPC. Patient summary In this study we found that levels of the protein AR-V7 were higher in patients with advanced prostate cancer. A higher level of AR-V7 identifies a group of patients who respond less well to certain prostate cancer treatments and live for a shorter period of time.
Resistance to androgen receptor (AR) blockade in castration-resistant prostate cancer (CRPC) is associated with sustained AR signaling, including through alternative splicing of AR (AR-SV). ...Inhibitors of transcriptional coactivators that regulate AR activity, including the paralog histone acetyltransferase proteins p300 and CBP, are attractive therapeutic targets for lethal prostate cancer. Herein, we validate targeting p300/CBP as a therapeutic strategy for lethal prostate cancer and describe CCS1477, a novel small-molecule inhibitor of the p300/CBP conserved bromodomain. We show that CCS1477 inhibits cell proliferation in prostate cancer cell lines and decreases AR- and C-MYC-regulated gene expression. In AR-SV-driven models, CCS1477 has antitumor activity, regulating AR and C-MYC signaling. Early clinical studies suggest that CCS1477 modulates KLK3 blood levels and regulates CRPC biopsy biomarker expression. Overall, CCS1477 shows promise for the treatment of patients with advanced prostate cancer. SIGNIFICANCE: Treating CRPC remains challenging due to persistent AR signaling. Inhibiting transcriptional AR coactivators is an attractive therapeutic strategy. CCS1477, an inhibitor of p300/CBP, inhibits growth and AR activity in CRPC models, and can affect metastatic CRPC target expression in serial clinical biopsies.
.
.
Castration-resistant prostate cancer (CRPC) that has developed resistance to the new-generation androgen receptor (AR) antagonist enzalutamide is a lethal disease. Transcriptome analysis of multiple ...prostate cancer models identified CXCR7, an atypical chemokine receptor, as one of the most upregulated genes in enzalutamide-resistant cells. AR directly repressed
by binding to an enhancer 110 kb downstream of the gene and expression was restored upon androgen deprivation. We demonstrate that CXCR7 is a critical regulator of prostate cancer sensitivity to enzalutamide and is required for CRPC growth
and
. Elevated CXCR7 activated MAPK/ERK signaling through ligand-independent, but β-arrestin 2-dependent mechanisms. Examination of patient specimens showed that CXCR7 and pERK levels increased significantly from localized prostate cancer to CRPC and further upon enzalutamide resistance. Preclinical studies revealed remarkable efficacies of MAPK/ERK inhibitors in suppressing enzalutamide-resistant prostate cancer. Overall, these results indicate that CXCR7 may serve as a biomarker of resistant disease in patients with prostate cancer and that disruption of CXCR7 signaling may be an effective strategy to overcome resistance. SIGNIFICANCE: These findings identify CXCR7-mediated MAPK activation as a mechanism of resistance to second-generation antiandrogen therapy, highlighting the therapeutic potential of MAPK/ERK inhibitors in CRPC.
Invertebrates are dominant species in primary tropical rainforests, where their abundance and diversity contributes to the functioning and resilience of these globally important ecosystems. However, ...more than one-third of tropical forests have been logged, with dramatic impacts on rainforest biodiversity that may disrupt key ecosystem processes. We find that the contribution of invertebrates to three ecosystem processes operating at three trophic levels (litter decomposition, seed predation and removal, and invertebrate predation) is reduced by up to one-half following logging. These changes are associated with decreased abundance of key functional groups of termites, ants, beetles and earthworms, and an increase in the abundance of small mammals, amphibians and insectivorous birds in logged relative to primary forest. Our results suggest that ecosystem processes themselves have considerable resilience to logging, but the consistent decline of invertebrate functional importance is indicative of a human-induced shift in how these ecological processes operate in tropical rainforests.
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