Search

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

BackgroundCorneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.MethodsA cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.FindingsWe assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.InterpretationWe did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.FundingNational Eye Institute.

OBJECTIVE: To assess the association between Genomic Classifier (GC)-risk group and post-radical prostatectomy treatment in clinical practice. METHODS: Two prospective observational cohorts of men with prostate cancer (PCa) who underwent RP in two referral centers and had GC testing post-prostatectomy between 2013 and 2018 were included. The primary endpoint of the study was to assess the association between GC-risk group and time to secondary therapy. Univariable (UVA) and multivariable (MVA) Cox proportional hazards models were constructed to assess the association between GC-risk group and time to receipt of secondary therapy after RP, where secondary therapy is defined as receiving either RT or ADT after RP. RESULTS: A total of 398 patients are included in the analysis. Patients with high-GC risk were more likely to receive any secondary therapy (OR: 6.84) compared to patients with low/intermediate-GC risk. The proportion of high-GC risk patients receiving RT at 2 years post-RP was 31.5%, compared to only 6.3% among the low/intermediate-GC risk patients. CONCLUSION: This study demonstrates that physicians in routine practice used GC to identify high risk patients who might benefit the most from secondary treatment. As such, GC score was independent predictor of receipt of secondary treatment.

BackgroundThe presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement.ObjectiveTo investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups.Design, setting, and participantsA machine learning approach was developed for ICC segmentation using 70 RP patients and validated in a cohort of 749 patients from four sites whose median year of surgery was 2007 and with median follow-up of 28 mo. ICC was segmented on one representative hematoxylin and eosin RP slide per patient and the fraction of tumor area composed of ICC, the cribriform area index (CAI), was measured.Outcome measurements and statistical analysisThe association between CAI and BCR was measured in terms of the concordance index (c index) and hazard ratio (HR).Results and limitationsCAI was correlated with BCR (c index 0.62) in the validation set of 411 patients with ICC morphology, especially those with Gleason grade group 2 cancer (n = 192; c index 0.66), and was less prognostic when patients without ICC were included (c index 0.54). A doubling of CAI in the group with ICC morphology was prognostic after controlling for Gleason grade, surgical margin positivity, preoperative prostate-specific antigen level, pathological T stage, and age (HR 1.19, 95% confidence interval 1.03-1.38; p = 0.018).ConclusionsAutomated image analysis and machine learning could provide an objective, quantitative, reproducible, and high-throughput method of quantifying ICC area. The performance of CAI for grade group 2 cancer suggests that for patients with little Gleason 4 pattern, the ICC fraction has a strong prognostic role.Patient summaryMachine-based measurement of a specific cell pattern (cribriform; sieve-like, with lots of spaces) in images of prostate specimens could improve risk stratification for patients with prostate cancer. In the future, this could help in expanding the criteria for active surveillance.

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p

ObjectiveTo explore the incidence of and potential risk factors for acute urine retention (AUR) after robot-assisted radical prostatectomy (RARP) and its effect on early urine continence.MethodsA retrospective analysis of patients who underwent RARP by a single surgeon between July 2016 and June 2017 was performed to assess the incidence of AUR and its effect on early continence. Continence was assessed through self-reported questionnaires completed approximately three months after surgery. Early urine continence was defined as using zero pads per day at the time of the three-month follow-up. Descriptive statistics and logistic regression analysis were used to assess independent predictor of AUR.ResultsOf 379 patients, 19 (5%) developed AUR after RARP. No significant difference in baseline characteristics between those who developed AUR post-RARP and those who did not. There was no statistically significant difference in the reported early continence and number of pads used per day between patients with AUR and patients without AUR (31.6% vs. 23.1%, P = 0.39), (1.6 vs. 1.4, P = 0.913), respectively.ConclusionAUR post-RARP is an infrequent postoperative complication with no impact on early continence rate. No patient-related factors were associated with the development of AUR.

Social media posts regarding measles vaccination were classified as pro-vaccination, expressing vaccine hesitancy, uncertain, or irrelevant. Spearman correlations with Centers for Disease Control and Prevention-reported measles cases and differenced smoothed cumulative case counts over this period were reported (using time series bootstrap confidence intervals). A total of 58,078 Facebook posts and 82,993 tweets were identified from 4 January 2009 to 27 August 2016. Pro-vaccination posts were correlated with the US weekly reported cases (Facebook: Spearman correlation 0.22 (95% confidence interval: 0.09 to 0.34), Twitter: 0.21 (95% confidence interval: 0.06 to 0.34)). Vaccine-hesitant posts, however, were uncorrelated with measles cases in the United States (Facebook: 0.01 (95% confidence interval: -0.13 to 0.14), Twitter: 0.0011 (95% confidence interval: -0.12 to 0.12)). These findings may result from more consistent social media engagement by individuals expressing vaccine hesitancy, contrasted with media- or event-driven episodic interest on the part of individuals favoring current policy.

BACKGROUND:Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met. METHODS:A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1-5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation-follicular [TF] and trachomatous inflammation-intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level. RESULTS:Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children. CONCLUSION:Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger. TRIAL REGISTRATION:ClinicalTrials.gov NCT00792922.

Background & aimsActivating mutation of the KRAS gene is common in some cancers, such as pancreatic cancer, but rare in other cancers. Chronic pancreatitis is a predisposing condition for pancreatic ductal adenocarcinoma (PDAC), but how it synergizes with KRAS mutation is not known.MethodsWe used a mouse model to express an activating mutation of Kras in conjunction with obstruction of the main pancreatic duct to recapitulate a common etiology of human chronic pancreatitis. Because the cell of origin of PDAC is not clear, Kras mutation was introduced into either duct cells or acinar cells.ResultsAlthough KrasG12D expression in both cell types was protective against damage-associated cell death, chronic pancreatitis induced p53, p21, and growth arrest only in acinar-derived cells. Mutant duct cells did not elevate p53 or p21 expression and exhibited increased proliferation driving the appearance of PDAC over time.ConclusionsOne mechanism by which tissues may be susceptible or resistant to KRASG12D-initiated tumorigenesis is whether they undergo a p53-mediated damage response. In summary, we have uncovered a mechanism by which inflammation and intrinsic cellular programming synergize for the development of PDAC.

ObjectiveThe present study compared sleep sufficiency in youth with current Tourette's disorder (TD), history of TD and matched case controls, and examined predictors of sufficient sleep using a large US population-based survey.MethodParticipants were 673 caregivers of youth aged 6 to 17 years (298 with current TD, 122 with a history of TD with no endorsement of current diagnosis, and 254 matched case controls) from the 2007 and 2011-2012 versions of the National Survey of Children's Health. History and current TD status, current comorbidity (attention deficit/hyperactivity disorder, anxiety, and depression) and psychiatric medication status were assessed by yes/no items. Current TD severity was dichotomized into mild or moderate/severe symptoms. Sleep was assessed by parent-reported number of sufficient nights their child slept in the past week.ResultsUnivariate analysis of variance yielded significant group differences in nights of sufficient sleep (F[2,369.70] = 71.53, p < .001), with controls having 1.5 more nights per week relative to both TD groups (p < .001). With respect to predictors of sufficient sleep, the analysis of covariance yielded a significant age × sex × TD severity interaction (F[1,15.84] = 4.28, p = .04) such that older adolescent males with mild TD had significantly fewer nights of sufficient sleep than children (p = .004) and early adolescents (p = .002; F[2,54.93] = 7.45, p = .001). Early adolescent females with moderate/severe TD had fewer nights of sufficient sleep relative to males (p = .008). Comorbidity type and psychiatric medication status did not significantly predict sleep.ConclusionFindings suggest that insufficient sleep in youth with TD persists independently of comorbidity or psychiatric medication status. Findings highlight the importance of clinical sleep monitoring in this population.

Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs. Moreover, we identify four transcription factors, JUN, activating transcription factor 2 (ATF2), myocyte-specific enhancer factor 2A (MEF2A), and SRY-Box 11 (SOX11), as being the major downstream mediators through which DLK/LZK activation leads to RGC cell death. Increased understanding of the DLK pathway has implications for understanding and treating neurodegenerative diseases.

BackgroundAntibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger.MethodsA population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The prespecified outcome was α-diversity (inverse Simpson's α-diversity index), with secondary outcomes of β and γ Simpson's and Shannon's diversities.ResultsAt 5 days after treatment, 40 children aged 1-60 months were analyzed in the azithromycin-treated group and 40 children in the placebo-treated group. Diversity of the gut microbiome was significantly lower in the treated group (inverse Simpson's α-diversity, 5.03; 95% confidence interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P = .03). Similarly, the Shannon's α-diversity was lower in the treated group (10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P = .004). Simpson's community-level (γ) diversity decreased with azithromycin exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P = .00008), although β-diversity was not significantly reduced (2.56, 95% CI, 1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26).ConclusionsOral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community.Clinical trials registrationNCT02048007.

Depression is a prominent cause of global morbidity, and one of the most common medical conditions during pregnancy. Prenatal depression can lead to detrimental outcomes including preterm birth, low birth weight, and postpartum depression. Screening for depression is recommended at least once during the perinatal period. However, even after a diagnosis of depression, several barriers to treatment exist, including cost and patient opposition to treatment. This literature review examines the effectiveness of yoga practice in pregnant women who are depressed or have depressive symptoms. Five research articles published within the last five years were selected that support a yoga practice innovation for prenatal depression management. The utility of yoga is demonstrated in these articles in clinically depressed pregnant women and pregnant women with symptoms of depression or anxiety. A yoga practice protocol shown to be effective in prenatal depression was replicated, and based on that protocol, this paper proposes that clinics that care for depressed pregnant women employ an evidence-based yoga intervention spanning twelve weeks with a minimum of twice weekly yoga practice. Research has shown that yoga practice is safe, efficacious, practical, and decreases prenatal depressive symptoms. Future research should include the diverse demographics of socioeconomic status, prenatal care access, and ethnicity of depressed pregnant women to strengthen the data supporting yoga practice for prenatal depression management.Faculty advisor: Lorraine Evangelista, Ph.D.  l.evangelista@uci.edu - Program in Nursing Science

Objectives To determine if different formats for conveying machine learning (ML)-derived postpartum depression risks impact patient classification of recommended actions (primary outcome) and intention to seek care, perceived risk, trust, and preferences (secondary outcomes). Materials and methods We recruited English-speaking females of childbearing age (18-45 years) using an online survey platform. We created 2 exposure variables (presentation format and risk severity), each with 4 levels, manipulated within-subject. Presentation formats consisted of text only, numeric only, gradient number line, and segmented number line. For each format viewed, participants answered questions regarding each outcome. Results Five hundred four participants (mean age 31 years) completed the survey. For the risk classification question, performance was high (93%) with no significant differences between presentation formats. There were main effects of risk level (all P  < .001) such that participants perceived higher risk, were more likely to agree to treatment, and more trusting in their obstetrics team as the risk level increased, but we found inconsistencies in which presentation format corresponded to the highest perceived risk, trust, or behavioral intention. The gradient number line was the most preferred format (43%). Discussion and conclusion All formats resulted high accuracy related to the classification outcome (primary), but there were nuanced differences in risk perceptions, behavioral intentions, and trust. Investigators should choose health data visualizations based on the primary goal they want lay audiences to accomplish with the ML risk score. [ABSTRACT FROM AUTHOR]

Background: The application of artificial intelligence (AI) to health and health care is rapidly increasing. Several studies have assessed the attitudes of health professionals, but far fewer studies have explored the perspectives of patients or the general public. Studies investigating patient perspectives have focused on somatic issues, including those related to radiology, perinatal health, and general applications. Patient feedback has been elicited in the development of specific mental health care solutions, but broader perspectives toward AI for mental health care have been underexplored. Objective: This study aims to understand public perceptions regarding potential benefits of AI, concerns about AI, comfort with AI accomplishing various tasks, and values related to AI, all pertaining to mental health care. Methods: We conducted a 1-time cross-sectional survey with a nationally representative sample of 500 US-based adults. Participants provided structured responses on their perceived benefits, concerns, comfort, and values regarding AI for mental health care. They could also add free-text responses to elaborate on their concerns and values. Results: A plurality of participants (245/497, 49.3%) believed AI may be beneficial for mental health care, but this perspective differed based on sociodemographic variables (all P<.05). Specifically, Black participants (odds ratio [OR] 1.76, 95% CI 1.03-3.05) and those with lower health literacy (OR 2.16, 95% CI 1.29-3.78) perceived AI to be more beneficial, and women (OR 0.68, 95% CI 0.46-0.99) perceived AI to be less beneficial. Participants endorsed concerns about accuracy, possible unintended consequences such as misdiagnosis, the confidentiality of their information, and the loss of connection with their health professional when AI is used for mental health care. A majority of participants (80.4%, 402/500) valued being able to understand individual factors driving their risk, confidentiality, and autonomy as it pertained to the use of AI for their mental health. When asked who was responsible for the misdiagnosis of mental health conditions using AI, 81.6% (408/500) of participants found the health professional to be responsible. Qualitative results revealed similar concerns related to the accuracy of AI and how its use may impact the confidentiality of patients' information. Conclusions: Future work involving the use of AI for mental health care should investigate strategies for conveying the level of AI's accuracy, factors that drive patients'mental health risks, and how data are used confidentially so that patients can determine with their health professionals when AI may be beneficial. It will also be important in a mental health care context to ensure the patient--health professional relationship is preserved when AI is used. [ABSTRACT FROM AUTHOR]