Anxiety, depression, and end-of-life care utilization in adults with metastatic cancer.

OBJECTIVE: End-of-life care for patients with cancer is often overly burdensome, and palliative and hospice care are underutilized. The objective of this study was to evaluate whether the mental health diagnoses of anxiety and depression were associated with variation in end-of-life care in metastatic cancer. METHODS: This study used electronic health data from 1,333 adults with metastatic cancer who received care at two academic health centers in Louisiana, USA, and died between 1/1/2011-12/31/2017. The study used descriptive statistics to characterize the sample and logistic regression to examine whether anxiety and depression diagnoses in the six months before death were associated with utilization outcomes (chemotherapy, intensive care unit [ICU] visits, emergency department visits, mechanical ventilation, inpatient hospitalization, palliative care encounters, and hospice utilization), while controlling for key demographic and health covariates. RESULTS: Patients (56.1% male; 65.6% White, 31.1% Black) commonly experienced depression (23.9%) and anxiety (27.2%) disorders within six months of death. Anxiety was associated with an increased likelihood of chemotherapy (odds ratio [OR] = 1.42, p = 0.016), ICU visits (OR = 1.40, p = 0.013), and inpatient hospitalizations (OR = 1.85, p < 0.001) in the 30 days before death. Anxiety (OR = 1.95, p < 0.001) and depression (OR = 1.34, p = 0.038) were associated with a greater likelihood of a palliative encounter. CONCLUSIONS: Patients with metastatic cancer who had an anxiety disorder were more likely to have burdensome end-of-life care, including chemotherapy, ICU visits, and inpatient hospitalizations in the 30 days before death. Depression and anxiety both increased the odds of palliative encounters. These results emphasize the importance of mental health considerations in end-of-life care.

Clinical Effectiveness of Decision Support for Prescribing Opioids for Chronic Noncancer Pain: A Prospective Cohort Study.

OBJECTIVES: This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing. METHODS: Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use. RESULTS: Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change. CONCLUSIONS: EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed.

Proportions of resting memory T cells and monocytes in blood have prognostic significance in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline of lung function. Here, we tested the importance of differential proportions of blood immune cells to IPF clinical outcomes. We used Cibersort to deconvolute immune cell components based on PBMCs or whole blood IPF genomics datasets. We found that a higher proportion of resting memory (RM) T cells was associated with a better survival and a higher DLco (diffusing capacity for carbon monoxide) in IPF patients. The association was also found in opposite direction for monocytes. Additionally, in IPF patients as compared to healthy controls, proportions of monocytes were observed to be higher, yet RM T cells were observed to be lower. Taken together, our result suggests a beneficial effect of RM T cells and a detrimental effect of monocytes for IPF. Future genomics studies of IPF should be more focused on these two types of cells.

Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome.

BACKGROUND: More effective treatments are needed for patients with postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D). Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week-long trial to assess the efficacy and safety of oral glutamine therapy in patients who developed IBS-D with increased intestinal permeability following an enteric infection. METHODS: Eligible adults were randomised to glutamine (5 g/t.i.d.) or placebo for 8 weeks. The primary end point was a reduction of ≥50 points on the Irritable Bowel Syndrome Severity Scoring System (IBS-SS). Secondary endpoints included: raw IBS-SS scores, changes in daily bowel movement frequency, stool form (Bristol Stool Scale) and intestinal permeability. RESULTS: Fifty-four glutamine and 52 placebo subjects completed the 8-week study. The primary endpoint occurred in 43 (79.6%) in the glutamine group and 3 (5.8%) in the placebo group (a 14-fold difference). Glutamine also reduced all secondary endpoint means: IBS-SS score at 8 weeks (301 vs 181, p<0.0001), daily bowel movement frequency (5.4 vs 2.9±1.0, p<0.0001), Bristol Stool Scale (6.5 vs 3.9, p<0.0001) and intestinal permeability (0.11 vs 0.05; p<0.0001). 'Intestinal hyperpermeability' (elevated urinary lactulose/mannitol ratios) was normalised in the glutamine but not the control group. Adverse events and rates of study-drug discontinuation were low and similar in the two groups. No serious adverse events were observed. CONCLUSIONS: In patients with IBS-D with intestinal hyperpermeability following an enteric infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related endpoints. Large randomised clinical trials (RCTs) should now be done to validate these findings, assess quality of life benefits and explore pharmacological mechanisms. TRIAL REGISTRATION NUMBER: NCT01414244; Results.

Asthma severity, not asthma control, is worse in atopic compared with nonatopic adolescents with asthma.

BACKGROUND: The effects of atopic and nonatopic asthma phenotypes on asthma morbidity are unclear. Moreover, asthma morbidity in patients without atopy might be mediated by immunoglobulin E (IgE). OBJECTIVE: To determine differences in morbidity in patients with asthma with and without atopy in a population of inner-city adolescents with asthma and to assess the impact of total IgE (tIgE) in this population. METHODS: Data were obtained from 546 inner-city adolescents in the Asthma Control Evaluation study. A positive skin prick test reaction to 14 aeroallergens and specific IgE to 5 aeroallergens determined atopic status. High (≥75th percentile) and low (≤25th percentile) tIgE levels were categorized. Asthma control (Asthma Control Test) and asthma severity (Composite Asthma Severity Index [CASI]) were measured at multiple time points over 1 year. Fractional exhaled nitric oxide (FeNO) and measurements of morbidity also were collected. Multivariable and repeated measures analyses modeled the relation between atopic status and morbidity. RESULTS: Baseline CASI scores increased 0.90 point (P < .05) and FeNO increased 0.85 natural logarithmic unit (P < .001) in participants with vs without atopy. Repeated measures analyses showed consistent results. Participants without atopy and increased tIgE had FeNO 0.73 natural log unit higher (P < .01) than low tIgE and a nonsignificant increase in CASI. The CASI score and FeNO levels were higher for high than for low tIgE in participants with atopy. CONCLUSION: In this population, participants with atopic asthma had worse asthma severity and higher FeNO compared with those with nonatopic asthma, but no difference in control. In all participants, higher tIgE indicated worse severity and higher FeNO. In this population, asthma severity and FeNO might be mediated by IgE in the 2 asthma phenotypes.

Using modified approaches on marginal regression analysis of longitudinal data with time-dependent covariates.

Quadratic inference functions (QIFs) and estimating equations using the conjugate gradient method (CGM) for fitting marginal models to longitudinal data show appealing features in improving the efficiency without making assumptions on the correlation structure. However, our simulation study shows that both methods produce biased and inefficient estimates of regression parameters when time-dependent covariates are present. In this paper, we extend both the QIF and CGM methods for fitting marginal models to longitudinal data with time-dependent covariates. The idea is to restrict the moment conditions to the ones that are only valid to certain types of time-dependent covariates. Our simulations show that efficiency on estimating regression parameters is achieved using modified approaches. Furthermore, we apply the modified approach to anthropometric screening data to evaluate the association between body mass index and morbidity in children in the Philippines.

Exposures to thoracic particulate matter, endotoxin, and glucan during post-Hurricane Katrina restoration work, New Orleans 2005-2012.

In the aftermath of Hurricane Katrina, which devastated the city of New Orleans in August 2005, restoration workers were at risk for respiratory illness from exposure to airborne particles and microbial agents. In support of an epidemiologic investigation of this risk, an exposure assessment for restoration work activities (demolition, trash & debris management, landscape restoration, sewer/waterline repair, and mold remediation) was performed from 2005 to 2012. For 2005 and 2006, Occupational Safety and Health Administration (OSHA) data (n = 730) for personal and area monitoring of total and respirable dust exposures of restoration workers were accessed and analyzed. The most significant exposures were for demolition work, with average respirable dust exposures in 2005 above the action level of 2.5 mg/m(3) and 17.6% of exposures exceeding the permissible exposure limit (PEL) (5 mg/m(3)). Additional personal and area monitoring for thoracic particulate matter was performed from 2007 to 2012 (n = 774) and samples were assayed for endotoxin and (1→3, 1→6)-ß-D-glucan (n = 202). In order to integrate the OSHA data with the later monitoring data, three independent predictive models were developed to convert total and respirable dust measures into the equivalent thoracic dust. The three models were not statistically different and the modeling results were in good agreement with an overall coefficient of variation of 16% for the thoracic dust means across work activities estimated by each of the three models. Overall, thoracic dust exposure levels decreased by about an order of magnitude within the first year after Katrina and then more gradually declined and stabilized through 2012. Estimated average exposures to endotoxin and microbial glucan in 2005 were as high as 256 EU/m(3) and 118 µg/m(3), respectively, and likewise were seen to decrease dramatically and stabilize after 2005. The results of this exposure assessment support previously published reports of respiratory illness including sinusitis, toxic pneumonitis, and Katrina Cough among restoration workers in the years immediately after the hurricane.

Biochemical and molecular characteristics among infants with abnormal newborn screen for very-long-chain acyl-CoA dehydrogenase deficiency: A single center experience.

Objective: To define the biochemical and molecular characteristics and diagnostic outcomes of a large US cohort of VLCAD deficiency positive cases as detected by newborn screening (NBS) with MS:MS. This relatively common disorder of fatty acid oxidation is screened for in every state in America and often results in extensive testing of multiple samples to arrive at a diagnostic conclusion. Materials and methods: We compared NBS dried blood spot (DBS) acylcarnitine profile (ACP) C14, C14:1, C14:2, C14:1/C12:1 ratio and plasma C14, C14:1, C14:2, C14:1/C12:1, C14:1/C16 and C14:1/C2 ratios among true positive and false positive cases. Results of VLCAD enzyme analysis, molecular testing and fibroblast fatty acid oxidation probe assay were analyzed. Results: The presence of compound heterozygous or homozygous pathogenic variants, along with elevations of C14, C14:1 and C14:1/C12:1 ratio, identified 19 VLCAD deficiency cases. All were asymptomatic at most recent follow-up visits. The C14:1/C12:1 ratio in NBS-DBS ACP and plasma acylcarnitine profiles at follow-up (follow-up plasma ACP), is the most useful marker to differentiate between true and false positive cases. Among all cases with molecular analysis data available, approximately 56.7% had a single pathogenic mutation. Lymphocyte enzyme analysis (n = 61) was uninformative in 23% of cases studied. Conclusion: VLCAD deficiency NBS by MS:MS is highly effective at identifying asymptomatic affected infants. Our cohort showed that elevation of C14:1/C12:1, in both NBS DBS and plasma ACP, was informative in discriminating affected from unaffected individuals and contributes to improve the accuracy of confirmatory testing of infants with presumptive positive for VLCAD deficiency.

Return to Play After Shoulder Arthroscopy in Major League Baseball Pitchers vs Position Players.

Background: Recovery from shoulder arthroscopy may vary between professional pitchers and position players in Major League Baseball (MLB). The time that it takes to return to play (RTP) and the level of skills to be regained after surgery are important factors for an athlete to consider when making career decisions. Purpose: To identify MLB players who had arthroscopic shoulder surgery and observe their rates of RTP to MLB and the minor league, as well as to compare pre- and postinjury performance statistics and career metrics. Study Design: Descriptive epidemiology study. Methods: Public records (press releases, http://www.prosportstransactions.com, http://www.baseball-reference.com) were searched and analyzed to determine the number of days from shoulder arthroscopy to RTP and pre- and postinjury statistics for pitchers and position players in the MLB and minor league from 1998 to 2018. To meet inclusion criteria, a player must have undergone shoulder arthroscopy after having played at least 1 game in the MLB and had no identifiable concomitant injuries. Results: Of 134 players, 89 (66.4%) returned to MLB. Fifty-four of 89 pitchers (60.7%) and 35 of 45 position players (77.8%) returned to MLB (P = .048). Forty-nine of 54 pitchers (90.7%) and 23 of 35 position players (65.7%) who returned to MLB returned to the minor league first. The mean time to RTP was 469.6 days (range, 100-1079 days) for pitchers and 301.6 days (range, 94-1488) for position players (P = .002). The WAR statistic (wins above replacement) for the pitchers decreased significantly (P = .004) after shoulder arthroscopy. Conclusion: MLB position players returned to play at higher rates and more quickly than did pitchers. The WAR statistic declined in pitchers during the first season of RTP. Players undergoing arthroscopic shoulder surgery should be aware of these possible outcomes in time to RTP and postoperative performance.

TEXT MY BP MEDS NOLA: A pilot study of text-messaging and social support to increase hypertension medication adherence.

Study objective: Non-Hispanic Black (NHB) adults have high hypertension (HTN) and cardiovascular disease (CVD) burden. Medication nonadherence limits control and self-measured blood pressure (SMBP) improves diagnosis and adherence. This predominantly NHB cohort pilot, via community-clinical linkages, with uncontrolled HTN and low adherence, utilized bidirectional electronic messaging (BEM) with team-care, to assess medication adherence, quality of life, and BP. Setting: Academic clinic and community sources. Design: Recruitment included: uncontrolled HTN (BP ≥130/80 mm Hg), low adherence (Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4) ≥1 score), and smartphone access. Participants and interventions: Participants (N = 36) received validated Bluetooth-enabled BP devices, synced to smartphones, via a secured cloud-based application. Main outcome measures: Demographics, adherence scores, Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQOL-14), BP, body mass index (BMI), 8 weeks daily BEM, SMBP and text responses were obtained. Results: Age was 58.7 ± 12.8 years; BMI 34.8 ± 7.9; 63.9 % female; 88.9 % self-identified NHB adults; 72.2 % with obesity; 74.3 % with diabetes. K-Wood-MAS-4 adherence composite score improved: 2.19 to 1.58 (median -0.5, p = 0.0001). Systolic BP decreased by 10.5 ± 20.0 mm Hg (median -11.0, p = 0.0027). QOL did not significantly change. Mean 7-day average SBP/DBP differences were -4.94 ± 16.82 (median -3.5, p = 0.0285) and -0.17 ± 7.42 (median 0, p = 0.7001), respectively. Social support with taking BP medication was: "yes" (n = 19); 143.8 mm Hg to 131.5 mm Hg (median -12.5, p = 0.0198) and "no" (n = 14); 142.32 mm Hg to 130.25 mm Hg (median -4.0, p = 0.0771). Conclusions: Community-clinical linkages and SMBP with BEM significantly improved medication adherence and SBP without modifying pharmacotherapy.

Short-term outdoor temperature change and emergency department visits for asthma among children: a case-crossover study.

Although weather changes are known to cause asthma symptoms, their impact on asthma-related health-care utilization is poorly understood. The objective of the present study was to determine the association between short-term outdoor temperature change and asthma-related emergency department (ED) visits among children 3-18 years of age in Detroit, Michigan, in 2000-2001. Descriptive analyses of patient and ED visit characteristics were performed. A case-crossover study utilizing time-stratified controls was conducted to determine the impact of maximum temperature change and change rate measured during 4-, 8-, 12-, and 24-hour periods. Multivariable conditional logistic regression demonstrated the relation between ED visits and temperature change after controlling for other weather and pollutant measures. There were 4,804 asthma-related ED visits during the study period, and they occurred most frequently in the fall and during morning hours. The case-crossover study showed a statistically significant inverse relation between ED visits and maximum 24-hour temperature change after adjustment for climatic factors (for temperature change, odds ratio = 0.992, P = 0.04; for temperature change rate, odds ratio 0.972, P = 0.01). The association persisted after air pollutant measures were added to the model, although the association was not significant. Despite the finding that a greater 24-hour temperature change decreased the risk of asthma-related ED visits, the overall results suggested a negligible association with short-term temperature change.

CD5-negative mantle cell lymphoma: clinicopathologic features of an indolent variant that confers a survival advantage.

Conventionally, mantle cell lymphoma (MCL) is an aggressive CD5-positive B-cell malignancy with poor prognosis and limited survival. However, a small subset of patients presents with indolent disease and can be managed on a 'watch and wait' approach. CD5-negative MCL has recently been recognized as a more favorable variant of MCL, but its clinical and biological implications remain ill-defined. We performed the most extensive review to-date of all reported cases of CD5-negative MCL and included unpublished cases diagnosed at our institutions to further characterize this disease subset. Based on our analysis of 356 cases of CD5-negative MCL, we conclude that median overall survival exceeds 14 years and is independent of favorable prognostic markers such as leukemic non-nodal disease, absence of SOX11, and low Ki-67.

Socioeconomic Status and Survival in Nasopharyngeal Carcinoma: A Population-Based Study.

OBJECTIVES/HYPOTHESIS: To evaluate survival for nasopharyngeal carcinoma in relation to socioeconomic status. STUDY DESIGN: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) Census Tract-level Socioeconomic Status Database (2000-2016). METHODS: Patients with nasopharyngeal carcinoma diagnosed between 2000 and 2016 were identified. Data were stratified based on socioeconomic status, divided into three groups: group 1 being the poorest and group 3 the wealthiest. Univariate analysis as well as multivariate Cox regression analysis adjusted for individual variables was performed. RESULTS: A total of 5,527 patients were included in the study, with 33% in group 1, 34% in group 2, and 33% in group 3. There was a significant difference between groups in regard to age at diagnosis, race, histologic subtype, overall stage, tumor stage, nodal stage, and whether or not they received radiation. Patients in group 1, the poorest socioeconomic status, were more likely to be young (P = .003), black (P < .0001), present with higher overall stage (P = .009), tumor stage (P = .01), and nodal stage (P = .02), and less likely to receive radiation (P = .005). In multivariate analysis, there was a significant difference in survival between the groups, with group 1 patients less likely to survive compared to group 3 (hazard ratio = 1.28; 95% CI 1.07-1.57). CONCLUSIONS: Patients in the poorest socioeconomic status presented with more advanced nasopharyngeal cancer and were less likely to receive radiation when compared with individuals of higher socioeconomic status. The poorest socioeconomic status groups were less likely to survive from their disease when controlling for other variables. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2719-2723, 2021.

Acute estradiol and progesterone therapy in hospitalised adults to reduce COVID-19 severity: a randomised control trial.

INTRODUCTION: As of November 2021, COVID-19 has killed more than 5 million people globally, including over 750 000 in the USA. Apart from corticosteroids, most available therapeutic options are at best marginally efficient in reducing disease severity and are extremely expensive. The systematic investigation of clinically approved drugs is a priority to determine what does mitigate disease severity. Oestradiol (E2) and progesterone (P4) produce a state of anti-inflammatory immune responses and immune tolerance, and enhanced antibody production. The goal of this trial is to evaluate the efficacy of a short E2 and P4 therapy, in addition to standard of care (SOC), in mitigating disease severity in COVID-19 hospitalised patients. METHODS AND ANALYSIS: Phase 2, randomised, double blind, placebo-controlled, single-centre trial. Patients hospitalised for confirmed COVID-19, with scores 3-5 on the 9-point WHO ordinal scale are randomised between two arms: (1) Oestradiol cypionate intramuscular (IM) and micronised progesterone oral (PO), in addition to SOC, and (2) placebo, in addition to SOC. The primary outcome is the proportion of patients improving to scores 1 or 2 on the WHO scale through day 28. Secondary outcomes include length of hospital stay, duration of mechanical ventilation, cause of death, readmission rates, change in inflammatory biomarkers between admission and occurrence of primary endpoint, and adverse events. Study sample size will be up to 120 participants. The trial is currently recruiting subjects. ETHICS AND DISSEMINATION: The sponsor of this study is the Center of Excellence in Sex-Based Biology & Medicine at Tulane University, New Orleans, Louisiana, USA. Ethical approval was obtained from the Tulane institutional review board on 14 May 2021. The study was reviewed by the US Food and Drug Administration and granted Investigational New Drug #152 499. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04865029; Pre-results.

Depression, anxiety, pain and chronic opioid management in primary care: Type II effectiveness-implementation hybrid stepped wedge cluster randomized trial.

Even though current prescribing trends reveal that high-dose opioid prescribing and opioid prescribing in general has decreased, sustained efforts are needed to help providers adopt and maintain safe prescribing behaviors. The purpose of this four-year type 2 effectiveness-implementation hybrid stepped wedge cluster randomized trial is to: (1) compare the clinical and cost effectiveness of electronic medical record-based clinical decision support [EMR-CDS] versus additional integrated, collaborative behavioral health [EMR-CDS + BHI-CCM] for opioid management of patients with co-morbid chronic non-cancer pain with depression or anxiety; and (2) examine facilitators and barriers to implementing these interventions within 35 primary care clinics in a integrated delivery health system. The EMR-CDS alerts providers to employ opioid risk mitigation and safe prescribing practices at the point of care. The BHI-CCM consists of primary care embedded community health workers for case management; licensed clinical social workers for cognitive behavioral therapy, and a clinical pharmacist for medication management who provide care management via telemedicine (virtual video or audio only visits) under the guidance of a consulting psychiatrist. The primary outcome is reduction in the percentage of patients with average daily opioid dose ≥50 mg morphine equivalent. Secondary outcomes include changes in service utilization, patient reported outcomes and processes of care. The investigators anticipate that study results will elucidate the role of technology versus care team optimization in changing opioid prescribing behaviors. The investigators further anticipate that integrated mental/behavioral health care will increase value-based care and the efficiency with which guideline concordant care is delivered.

Racial Disparities in End-of-Life Care Between Black and White Adults With Metastatic Cancer.

CONTEXT: The comfort of patients with cancer near the end of life (EOL) is often undermined by unnecessary and burdensome treatments. There is a need for more research examining racial disparities in EOL care, especially in regions with a history of racial discrimination. OBJECTIVES: To examine whether black adults received more burdensome EOL care than white adults in a population-based data set of cancer decedents in Louisiana, a state with a history of slavery and long-standing racial disparities. METHODS: This was a retrospective analysis of EOL care from the Research Action for Health Network (REACHnet), a regional Patient-Centered Outcomes Research Institute-funded database. The sample consisted of 875 white and 415 black patients with metastatic cancer who died in Louisiana from 2011 to 2017. We used logistic regression to examine whether race was associated with five indicators of burdensome care in the last 30 days of life: chemotherapy use, inpatient hospitalization, intensive care unit admission, emergency department (ED) admission, and mechanical ventilation. RESULTS: Most patients (85.0%) received at least one indicator of burdensome care: hospitalization (76.5%), intensive care unit admission (44.1%), chemotherapy (29.1%), mechanical ventilation (23.0%), and ED admission (18.3%). Odds ratios (ORs) indicated that black individuals were more likely than white individuals to be hospitalized (OR = 1.66; 95% CI = 1.21-2.28; P = 0.002) or admitted to the ED (OR = 1.57; 95% CI = 1.16-2.13; P = 0.004) during their last month of life. CONCLUSION: Findings have implications for informing health care decision making near the EOL for patients, families, and clinicians, especially in regions with a history of racial discrimination and disparities.

Sex differences in soluble prorenin receptor in patients with type 2 diabetes.

BACKGROUND: The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. METHODS: Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. RESULTS: Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. CONCLUSIONS: In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19.

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, Setting, and Participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001). Conclusions and Relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.

Factors associated with HIV and syphilis screenings among pregnant women at first antenatal visit in Lusaka, Zambia.

OBJECTIVES: To identify characteristics associated with obtaining HIV and syphilis screenings of pregnant women attending a first antenatal visit in Lusaka, Zambia. RESULTS: Among 18,231 participants from April 2015 to January 2016, 95% obtained HIV screening, 29% obtained syphilis screening, and 4% did not obtain antenatal HIV or syphilis screenings. Divorced/separated women were associated with a moderate decrease in prevalence of obtaining HIV (adjusted prevalence ratio (aPR) 0.88, 95% confidence interval (95% CI) 0.82, 0.95) and syphilis (aPR 0.51, 95% CI 0.27, 0.96) screenings compared to married women. Women with previous pregnancies were associated with a slight decrease in prevalence of obtaining HIV screening (aPR 0.97, 95% CI 0.95, 0.99) compared to women without previous pregnancy. Older women ≥ 35 years were associated with a slight decrease in prevalence of obtaining HIV screening (aPR 0.96, 95% CI 0.92, 0.99) compared to younger women. The statistically significant differences were not of clinical relevance as defined by a proportional difference of 10 percent. Findings of this study show that a vast majority of pregnant women are obtaining HIV screenings but not syphilis screenings during first antenatal visit. Provision of antenatal HIV and syphilis screening at first visit is only weakly related to patient level factors.