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Peripheral artery disease (PAD) has high morbidity and mortality rates. A metabolomics approach was employed to determine whether consumption of bean-rich diets for 8 weeks would impact the metabolomic profile of individuals with PAD. Serum and urine, collected from 54 participants with clinical PAD at baseline and after 8 weeks on 0.3 cups beans/day (n = 19), 0.6 cups beans/day (n = 20), or control (n = 23) diet, and the beans were extracted and analyzed using LC-QTOF-MS. As a result, PGE2 p-acetamidophenyl ester, PGF2α diethyl amide and 5-l-glutamyl-l-alanine were significantly changed in the serum or urine of bean groups compared with control. Significant changes (P < 0.05) in the profile and/or levels of 22 flavonoids present in bean extracts showed the potential importance of the mixture of beans used in this study. In a subset of participants taking metoprolol, after 8 weeks the bean-rich diets significantly elevated metoprolol in the serum while reducing it in urine compared with baseline. In addition, the diets significantly enhanced the urinary excretion of metformin. In conclusion, several biochemical pathways including prostaglandins and glutathione were affected by bean consumption. Significant changes in the metabolism of metoprolol and metformin with bean consumption suggested the presence of diet-drug interactions that may require adjustment of the prescribed dose. ClinicalTrials.gov Identifier: NCT01382056. Novelty: Bean consumption by people with PAD alters the levels of certain metabolites in serum and urine. Different bean types (black, red kidney, pinto, navy) have unique flavonoid profiles. Metabolomics revealed potential diet–drug interactions as serum and/or urinary levels of metoprolol and metformin are modified by bean consumption.

Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs exhibited an approximately twofold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat circle, HIV-1 integration, and gag RNA expression. SCT PBMCs had higher HO-1 messenger RNA (mRNA) and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population-level effect of SCT on HIV-1 prevalence, we assessed SCT among women living with HIV (WLH) in the WIHS (Women Interagency HIV-1 Study). Among WIHS African-American participants, the prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; odds ratio, 0.57; 95% confidence interval, 0.36-0.92; P = .020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow-up (P = .003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors, including HO-1 and RNR2, might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.

We examined partner-seeking and sexual behaviors among a representative sample of U.S. adults (N = 1,161) during the first year of the COVID-19 pandemic. Approximately 10% of survey respondents sought a new partner, with age and sexual identity being associated with partner seeking behavior. Approximately 7% of respondents had sex with a new partner, which marks a decrease as compared to a pre-pandemic estimate from 2015 - 2016 in which 16% of U.S. adults reported having sex with a new partner during the past year. Among respondents who had in-person sex with a new partner during the first year of the pandemic, public health guidelines for in-person sexual activity were infrequently followed.

Modern polymer science suffers from the curse of multidimensionality. The large chemical space imposed by including combinations of monomers into a statistical copolymer overwhelms polymer synthesis and characterization technology and limits the ability to systematically study structure-property relationships. To tackle this challenge in the context of 19F magnetic resonance imaging (MRI) agents, we pursued a computer-guided materials discovery approach that combines synergistic innovations in automated flow synthesis and machine learning (ML) method development. A software-controlled, continuous polymer synthesis platform was developed to enable iterative experimental-computational cycles that resulted in the synthesis of 397 unique copolymer compositions within a six-variable compositional space. The nonintuitive design criteria identified by ML, which were accomplished by exploring 10 copolymer compositions that outperformed state-of-the-art materials.

Objectives Research on the impact of coronavirus disease 2019 (COVID-19) among older adults has primarily focused on relatively acute virus outcomes, but it is likely financial hardships during this time have eroded the adaptive capacity of older adults. It is also possible these impacts vary by race and ethnicity. We examine changes in psychological resilience (PR) among older adults before and during the pandemic to determine whether financial hardships and other stressors have altered this resource for White, Black, and Hispanic older adults. Method Using the COVID-19 module released by the Health and Retirement Study (n = 735), we examined changes in PR between 2016 and 2020 related to financial hardships during COVID-19. We tested interactions to determine whether the effects were patterned by race and ethnicity. Results Consistent with previous literature, resilience was relatively stable during this time on average. Financial hardship during COVID-19 diminished resilience, but this effect was concentrated primarily among White Americans. Discussion The results suggest that PR is a relatively stable resource in later life, even during the pandemic. However, this resource may be affected in the face of specific challenges in later life. Policies related to financial hardship during the pandemic should be seen as supporting the capacity for older adults to adapt to current as well as future challenges.

Dynamic treatment regimes (DTRs) include a sequence of treatment decision rules, in which treatment is adapted over time in response to the changes in an individual’s disease progression and health care history. In medical practice, nested test-and-treat strategies are common to improve cost-effectiveness. For example, for patients at risk of prostate cancer, only patients who have high prostate-specific antigen (PSA) need a biopsy, which is costly and invasive, to confirm the diagnosis and help determine the treatment if needed. A decision about treatment happens after the biopsy, and is thus nested within the decision of whether to do the test. However, current existing statistical methods are not able to accommodate such a naturally embedded property of the treatment decision within the test decision. Therefore, we developed a new statistical learning method, Step-adjusted Tree-based Reinforcement Learning, to evaluate DTRs within such a nested multi-stage dynamic decision framework using observational data. At each step within each stage, we combined the robust semi-parametric estimation via Augmented Inverse Probability Weighting with a tree-based reinforcement learning method to deal with the counterfactual optimization. The simulation studies demonstrated robust performance of the proposed methods under different scenarios. We further applied our method to evaluate the necessity of prostate biopsy and identify the optimal test-and-treat regimes for prostate cancer patients using data from the Johns Hopkins University prostate cancer active surveillance dataset.

Summary It is becoming increasingly common for researchers to consider incorporating external information from large studies to improve the accuracy of statistical inference instead of relying on a modestly sized data set collected internally. With some new predictors only available internally, we aim to build improved regression models based on individual-level data from an “internal” study while incorporating summary-level information from “external” models. We propose a meta-analysis framework along with two weighted estimators as the composite of empirical Bayes estimators, which combines the estimates from different external models. The proposed framework is flexible and robust in the ways that (i) it is capable of incorporating external models that use a slightly different set of covariates; (ii) it is able to identify the most relevant external information and diminish the influence of information that is less compatible with the internal data; and (iii) it nicely balances the bias-variance trade-off while preserving the most efficiency gain. The proposed estimators are more efficient than the naïve analysis of the internal data and other naïve combinations of external estimators.

Dynamic prediction methods incorporate longitudinal biomarker information to produce updated, more accurate predictions of conditional survival probability. There are two approaches for obtaining dynamic predictions: (1) a joint model of the longitudinal marker and survival process, and (2) an approximate approach that specifies a model for a specific component of the joint distribution. In the case of a binary marker, an illness-death model is an example of a joint modeling approach that is unified and produces consistent predictions. However, previous literature has shown that approximate approaches, such as landmarking, with additional flexibility can have good predictive performance. One such approach proposes using a Gaussian copula to model the joint distribution of conditional continuous marker and survival distributions. It has the advantage of specifying established, flexible models for the marginals for which goodness-of-fit can be assessed, and has easy estimation that can be implemented in standard software. In this article, we provide a Gaussian copula approach for dynamic prediction to accommodate a binary marker using a continuous latent variable formulation. We compare the predictive performance of this approach to joint modeling and landmarking using simulations and demonstrate its use for obtaining dynamic predictions in an application to a prostate cancer study.

With medical tests becoming increasingly available, concerns about over-testing, over-treatment and health care cost dramatically increase. Hence, it is important to understand the influence of testing on treatment selection in general practice. Most statistical methods focus on average effects of testing on treatment decisions. However, this may be ill-advised, particularly for patient subgroups that tend not to benefit from such tests. Furthermore, missing data are common, representing large and often unaddressed threats to the validity of most statistical methods. Finally, it is often desirable to conduct analyses that can be interpreted causally. Using the Rubin Causal Model framework, we propose to classify patients into four potential outcomes subgroups, defined by whether or not a patient’s treatment selection is changed by the test result and by the direction of how the test result changes treatment selection. This subgroup classification naturally captures the differential influence of medical testing on treatment selections for different patients, which can suggest targets to improve the utilization of medical tests. We can then examine patient characteristics associated with patient potential outcomes subgroup memberships. We used multiple imputation methods to simultaneously impute the missing potential outcomes as well as regular missing values. This approach can also provide estimates of many traditional causal quantities of interest. We find that explicitly incorporating causal inference assumptions into the multiple imputation process can improve the precision for some causal estimates of interest. We also find that bias can occur when the potential outcomes conditional independence assumption is violated; sensitivity analyses are proposed to assess the impact of this violation. We applied the proposed methods to examine the influence of 21-gene assay, the most commonly used genomic test in the United States, on chemotherapy selection among breast cancer patients.

Law enforcement officers’ health and wellness is important at the individual and community levels in terms of maintaining a fit workforce to uphold the mission of public safety. The current study was designed to assess officer wellness across the U.S. From a nationally representative random sample of 1,135 local and state agencies, a random, probability-based sample of officers was selected, oversampling for female officers. Latent class analyses were conducted to assess wellness profiles based on a set of eleven physical, psychological, and behavioral health indicators for 2,232 officers. Personal and professional characteristics were included as auxiliary variables in models of the resulting classes. Results from this sample indicated that over two-thirds of officers fit a healthy profile, whereas one in four officers presents with moderate health concerns and nearly 6% are classified in a profile of broad health concerns. In this sample, sexual assault in childhood, greater exposure to critical incidents, working a current rotation schedule, and being female were characteristics associated with broad health concerns. Emotional and/or physical assault in childhood, greater exposure to critical incidents, and being female were characteristics associated with moderate health concerns, whereas older age and being Hispanic were protective factors. In sum, full-time sworn law enforcement officers across the U.S. are reasonably healthy but their exposures to stressful situations put them at increased risk particularly in terms of post-traumatic stress, risky drinking, and suicidality. These results are important for agency administrators and policymakers to consider in terms of wellness programs, prevention efforts and budget allocations.

OBJECTIVE To assess comorbidity across five common health conditions. METHODS Surveys were collected from a probability-based sample of US law enforcement officers, and latent class models estimated for hypertension (HTN), high blood cholesterol (LDL), diabetes (DM), a gastrointestinal disorder (GI), and sleep apnea (SA). RESULTS The majority of officers (69.4%) were classified in a Healthy profile. One in four officers (23.7%) were classified in a LDL-HTN-DM profile. About 7% of officers were classified in a GI-SA-HTN profile. Age, sex, body mass index (BMI), exercise, and working a rotating shift assignment distinguished class membership. CONCLUSION Most officers reported good health. Law enforcement administrative or clinical assessments using readily accessible measures might be informative in identifying risk categories of need for more targeted prevention and treatment support.

BACKGROUND: Tumor infiltrating lymphocytes (TILs) aid in informing treatment for head and neck squamous cell carcinoma (HNSCC). Nevertheless, little is known about the role of diet on TILs. METHODS: Immunohistologic expression of CD4, CD8, CD68, CD103, CD104 and FOXP3 were assessed in tissue microarrays from 233 previously untreated HNSCC patients. Associations between these markers and pre-treatment dietary patterns were evaluated using linear regression. Associations between baseline serum carotenoids, tocopherols and TILs were assessed using logistic regression. Cox models evaluated the association between diet and TILs on overall and recurrence-free survival. RESULTS: Consumption of a Western dietary pattern was associated with lower CD8+ and FOXP3+ infiltrates (p-value:0.03 and 0.02, respectively). Multivariable logistic regression models demonstrated significantly higher CD8+ (OR:2.21;p-value:0.001) and FOXP3+ (OR:4.26;p-value

OBJECTIVE This was a retrospective, cohort study investigating the efficacy and safety of continuous low-dose postoperative tranexamic acid (PTXA) on drain output and transfusion requirements following adult spinal deformity surgery. METHODS One hundred forty-seven patients undergoing posterior instrumented thoracolumbar fusion of ≥ 3 vertebral levels at a single institution who received low-dose PTXA infusion (0.5-1 mg/kg/hr) for 24 hours were compared to 292 control patients who did not receive PTXA. The cohorts were propensity matched based on age, sex, American Society of Anesthesiologist physical status classification, body mass index, number of surgical levels, revision surgery, operative duration, and total intraoperative TXA dose (n = 106 in each group). Primary outcome was 72-hour postoperative drain output. Secondary outcomes were number of allogeneic blood transfusions. RESULTS There was no significant difference in postoperative drain output in the PTXA group compared to control (660 ± 420 mL vs. 710 ± 490 mL, p = 0.46). The PTXA group received significantly more crystalloid (6,100 ± 3,100 mL vs. 4,600 ± 2,400 mL, p < 0.001) and red blood cell transfusions postoperatively (median [interquartile range]: 1 [0-2] units vs. 0 [0-1] units; incidence rate ratio [95% confidence interval], 1.6 [1.2-2.2]; p = 0.001). Rates of adverse events were comparable between groups. CONCLUSION Continuous low-dose PTXA infusion was not associated with reduced drain output after spinal deformity surgery. No difference in thromboembolic incidence was observed. A prospective dose escalation study is warranted to investigate the efficacy of higher dose PTXA.

Author(s): Heidenreich, Paul A; Fonarow, Gregg C; Breathett, Khadijah; Jurgens, Corrine Y; Pisani, Barbara A; Pozehl, Bunny J; Spertus, John A; Taylor, Kenneth G; Thibodeau, Jennifer T; Yancy, Clyde W; Ziaeian, Boback

This paper provides guidance for researchers with some mathematical background on the conduct of time-to-event analysis in observational studies based on intensity (hazard) models. Discussions of basic concepts like time axis, event definition and censoring are given. Hazard models are introduced, with special emphasis on the Cox proportional hazards regression model. We provide check lists that may be useful both when fitting the model and assessing its goodness of fit and when interpreting the results. Special attention is paid to how to avoid problems with immortal time bias by introducing time-dependent covariates. We discuss prediction based on hazard models and difficulties when attempting to draw proper causal conclusions from such models. Finally, we present a series of examples where the methods and check lists are exemplified. Computational details and implementation using the freely available R software are documented in Supplementary Material. The paper was prepared as part of the STRATOS initiative.

In rapidly urbanising low-income towns and cities, there remains an absence of scientific evidence and regulatory structures to sustain the quality and quantity of groundwater used for low-cost water supplies and to reconcile this with continued use of the subsurface for low-cost sanitation. Here, we analyse the relationship between the density of on-site sanitation and shallow groundwater quality in the Thiaroye aquifer of Quaternary sands in Dakar, Senegal. On-site sanitation was mapped using object-oriented classification and visual interpretation of high-resolution, optical satellite images and ground-truthing surveys. Groundwater quality was assessed over a three-year period (2017–2019) from a network of 61 sources comprising boreholes, dug-wells, hand tubewells and piezometers. More than 253,000 on-site sanitation facilities are identified over an area of 520 km2 with densities ranging from 1 to 70 per hectare. A moderate, statistically significant linear relationship (r2 = 0.55, p « 0.01) is found between the density of on-site sanitation facilities and nitrate concentrations in sampled groundwater sources. Groundwater contamination beyond the WHO drinking-water guideline value (50 mg/L) occurs where densities of on-site sanitation facilities exceed 4 (±4) per hectare, a threshold commonly surpassed in peri-urban areas underlain by the Thiaroye aquifer of Dakar.

BACKGROUND Anatomical site is strongly associated with head and neck cancer etiology, and etiology and patient sociodemographic characteristics are prognostic factors for survival. It is not known whether the effects of these predictors persist over the postdiagnosis period or are strongest proximal to the time of diagnosis. METHODS Using survival times and causes of death for 180,434 patients with head and neck cancer in the Surveillance, Epidemiology, and End Results cancer registry (1973-2015), the empirical cumulative incidences of cancer-specific death and other-cause death were calculated with a competing risks framework, and the time-dependent effects (hazard ratios) of anatomical tumor site (oropharynx, oral cavity, or hypopharynx/larynx), age, sex, race, and year of diagnosis on cancer-specific death and other-cause death, stratified by tumor stage, were estimated. RESULTS All effects were significantly time-varying (P

Aim The involvement of pelvic sidewall (PSW) lymph nodes in rectal cancer is a marker of locally advanced disease and poor prognosis. Eastern countries generally advocate lateral lymph node dissection (LLND) over the Western approach of neoadjuvant chemoradiotherapy and more limited surgery. The aim of this study was to evaluate how these advanced cancers were treated in three UK Health Boards. Methodology This was a retrospective review of three colorectal multidisciplinary team meetings from 2008 to 2016. All patients with rectal cancer and suspicious PSW lymph nodes on pretreatment MRI were included. Results There were 153 (6.2%) patients who met the inclusion criteria from a total of 2461 diagnosed rectal cancers. There was significant variability between the three centres with surgical intervention ranging from 59.2% to 84.4%, P = 0.015. There were 81 patients who had neoadjuvant chemoradiotherapy prior to surgery; of these 67 (82.7%) still had positive PSW nodes on the restaging MRI, but only 13 (19.4%) had LLND. There was no difference in local recurrence (15.3% vs 11.8%, P = 0.66), 5-year overall survival (69.2% vs 80.1%, P = 0.16) or 5-year disease-free survival (69.2% vs 79.4%, P = 0.72) between patients having LLND and those receiving standard neoadjuvant treatment followed by total mesorectal excision surgery. Conclusions This study has demonstrated that rectal cancer patients with PSW positive nodal disease have advanced disease, mostly of the lower rectum, and receive a highly heterogeneous spectrum of therapies, even within a relatively small geographical area. Greater accuracy in our preoperative staging is needed to select those patients who will benefit from LLND surgery.

Background Approximately 30,000 people per annum undergo major, emergency abdominal, gastrointestinal surgery, of which 36% (~10,800) are carried out for emergency colorectal pathology. Approximately 14% of all patients requiring emergency surgery undergo laparoscopic surgery. Aims The aims of the LaCeS feasibility trial (Laparoscopic versus Open Colorectal Surgery in the Acute Setting) were to assess the feasibility, safety and acceptability of performing a large-scale definitive phase III randomised controlled trial with a comparison of emergency laparoscopic with open surgery for acute colorectal pathology. Methods LaCeS was designed as a prospective, multicentre, single blind, parallel group, pragmatic, randomised controlled feasibility trial with an integrated qualitative study. Randomisation was performed centrally with patients being randomised on a 1:1 basis between laparoscopic or open surgery. Results A total of 64 patients were recruited across 5 centres. The overall average steady state recruitment rate was 1.2 patients/month. Baseline compliance for clinical and HrQoL data was 99.8% and 93.8% respectively. The conversion rate from laparoscopic to open surgery was 39.4% (95% CI 22.9% – 57.9%). The 30 day post-operative complication rate was 27.3% (95% CI 13.3- 45.5) in the laparoscopic arm and 41.9% (95% CI 24.6 – 60.9) in the open arm. Discussion The LaCeS feasibility trial has demonstrated that it is possible to evaluate laparoscopic surgery in the emergency colorectal setting within the context of a randomised controlled trial. LaCeS has demonstrated that it is possible to recruit to a surgical trial in the emergency setting, with good compliance to trial procedures and processes, and overall acceptability by patients and clinicians. The safety data obtained for laparoscopic emergency colorectal surgery indicate an acceptable safety profile, particularly when considering it to that observed in the open arm. Trial Registration ISRCTN15681041 https://doi.org/10.1186/ISRCTN15681041. Funding body: National Institute of Health Research – Research for Patient Benefit

Multistate modelling is a strategy for jointly modelling related time-to-event outcomes that can handle complicated outcome relationships, has appealing interpretations, can provide insight into different aspects of disease development and can be useful for making individualized predictions. A challenge with using multistate modelling in practice is the large number of parameters, and variable selection and shrinkage strategies are needed in order for these models to gain wider adoption. Application of existing selection and shrinkage strategies in the multistate modelling setting can be challenging due to complicated patterns of data missingness, inclusion of highly correlated predictors and hierarchical parameter relationships. In this article, we discuss how to modify and implement several existing Bayesian variable selection and shrinkage methods in a general multistate modelling setting. We compare the performance of these methods in terms of parameter estimation and model selection in a multistate cure model of recurrence and death in patients treated for head and neck cancer. We can view this work as a case study of variable selection and shrinkage in a complicated modelling setting with missing data.

Addressing the widespread problem of sexual assault in college environments requires both prevention programming and policies addressing sexual misconduct in institutions of higher education. Through the Campus Sexual Assault Policy and Prevention Initiative, nine programs funded by the Office on Women’s Health approached this problem within a network of eight to 13 campuses apiece, supported by national organizations and local task forces. Near the close of the 3-year project period (June 2016–June 2019), key informant interviews were conducted with project directors and campus representatives. Contextual factors elucidating the project approaches, challenges, and successes were investigated through 31 interviews (nine grantee interviews and 22 campus representative interviews). Analyses across all interview content contributed to the development of several key themes related to staffing efforts to strengthen campus policies and prevention programs, working within institutions of varying structural characteristics, infusing efforts with trauma-informed perspectives, attending to cultural differences across campuses, and seeking to follow recommended guidelines in the context of campus-specific factors. Overall, the interviewees reported specific progress toward the program goals.

Despite substantial theoretical and empirical work examining the relation between attention-deficit/hyperactivity disorder (ADHD) and cortisol response, mixed results across studies suggest there are potential moderators in this link that have been previously unexplored. Emotion dysregulation (ED) and sluggish cognitive tempo (SCT) commonly co-occur with ADHD, with one another, and have yet to be included together in investigations exploring this relation. The current study examined the moderating effects of ED and SCT on the relation between symptoms of ADHD and cortisol response. Salivary cortisol response after participation in a novel social group was examined in 102 children (Mage = 8.75 years, 69.6% male), approximately half with ADHD. A significant three-way interaction of ADHD, ED, and SCT on cortisol response (p = .014) indicated the strongest association between ADHD and cortisol response when ED and SCT were low (p = .047), with children low in ADHD showing greater cortisol response in the presence of elevated ED (p = .033) or SCT (p = .021). These findings point to a pattern of cortisol responding that is specific to ADHD symptomatology, possibly indicating attenuated hypothalamic-pituitary-adrenal axis activity, and demonstrate the effect of ED and SCT on social functioning. Other clinical implications based on the findings across different levels of ADHD, ED, and SCT symptoms are discussed. Future research should seek to explore the mechanisms underlying the different patterns of responding.

In 2015, Guglielmi and Badia discussed optimal strategies in a particular type of service system with two strategic servers. In their setup, each server can be either active or inactive and an active server can be requested to transmit a sequence of packets. The servers have varying probabilities of successfully transmitting when they are active, and both servers receive a unit reward if the sequence of packets is transmitted successfully. Guglielmi and Badia provided an analysis of optimal strategies in four scenarios: where each server does not know the other’s successful transmission probability; one of the two servers is always inactive; each server knows the other’s successful transmission probability and they are willing to cooperate. Unfortunately, the analysis by Guglielmi and Badia contained some errors. In this paper we correct these errors. We discuss three cases where both servers (I) communicate and cooperate; (II) neither communicate nor cooperate; (III) communicate but do not cooperate. In particular, we obtain the unique Nash equilibrium strategy in Case II through a Bayesian game formulation, and demonstrate that there is a region in the parameter space where there are multiple Nash equilibria in Case III. We also quantify the value of communication or cooperation by comparing the social welfare in the three cases, and propose possible regulations to make the Nash equilibrium strategy the socially optimal strategy for both Cases II and III. doi:10.1017/S1446181120000048

In the US, mortality in sickle cell disease (SCD) increases after age 18–20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3–20 years into an observational study in 2006–2010 and followed 497 patients for a median of 88 months (range 1–105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P = .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 μg/L (observed in 60% of patients who died vs 7.8% of survivors, P < .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC)

Objective: Cauda Equina Syndrome (CES) is a challenging condition to diagnose due to such variability in clinical features and poor correlation with MRI findings. It requires surgery within hours to avoid damage to the bowel, bladder, sexual organs and lower limbs. There are empirical studies exploring patients’ perspectives of having CES, however, there is no literature to review NHS staff perceptions of managing this neurosurgical emergency. The aim is to explore perceptions of senior clinical staff who commonly manage patients with suspected CES in secondary care within the Emergency Department (ED) and Trauma and Orthopaedics (T&O) to improve the management of CES. The main objective is to identify barriers to successful management and possible solutions to improve care. Methods: A self-administered non-validated questionnaire was designed to identify barriers experienced and potential solutions. In addition, a Nominal Group Technique (NGT) was used to gain a greater insight. The qualitative data obtained was analysed by thematic analysis. Results: The questionnaire generated a 73% response rate. Six senior clinicians attended the NGT with representation from the three clinical specialities; ED, T&O and Advanced Physiotherapy Practitioner (APP). The challenges and potential solutions were categorised into themes and subthemes. The barriers highlighted included; staff confidence in clinical diagnosis; fear of litigation and inter-professional relations; patient psychosocial factors, expectations and comorbidities; lack of agreed local pathway. The solutions raised include; staff training; standardising local/national pathway; access to daily Magnetic Resonance Imaging (MRI) slots. Conclusion: Patient safety and accurate diagnosis of CES is at the forefront of decision-making despite organisation barriers and limitations of existing pathways. A shift away from admission to expedite an urgent MRI requires a change to traditional clinical practice and expectations. In times of rising pressures and financial constraints, collaborative working is essential to implement and sustain the required changes highlighted in this study.

Background Blood loss during adult spinal deformity surgery is multifactorial. Anesthetic-related factors, such as mode of mechanical ventilation, may contribute to intraoperative blood loss. The aim of this study was to determine the influence of ventilator mode and ventilator parameters on intraoperative blood loss and transfusion requirements in patients undergoing prone position spine surgery. Methods This single-center retrospective study examined electronic medical records of patients ≥18 years of age who underwent elective prone position spine surgery between May 2015 and June 2016. Associations between ventilator mode and ventilator parameters with intraoperative estimated blood loss (EBL), packed red blood cells (PRBCs), fresh-frozen plasma (FFP), cryoprecipitate and platelet transfusions, and subfascial drain output were examined using multiple linear regression models controlling for age, sex, American Society of Anesthesiologist (ASA) physical status score, body mass index (BMI), preoperative blood coagulation parameters and laboratory values, operative levels, cage constructs, osteotomies, transforaminal lumbar interbody fusions, laminectomies, reoperation, spine surgery invasiveness index, and operative time. In a secondary analysis, EBL, blood product transfusions, and postoperative drain output were compared between pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) propensity score-matched cohorts. Results Nine hundred forty-six records were reviewed, and 822 were included in the analysis. After adjusting for confounding, no statistically significant associations were observed between mode of ventilation and intraoperative EBL (estimate, -2; 95% confidence interval [CI], -248 to 245; P = .99) or blood product transfusions (PRBC: estimate, -9; 95% CI, -154 to 135; P = .90; FFP: estimate, -3; 95% CI, -59 to 54; P = .93; cryoprecipitate: estimate, -14; 95% CI, -70 to 43; P = .63; platelets: -7; 95% CI, -39 to 24; P = .64). After propensity score matching (n = 27 per group), no significant differences were observed in EBL (mean difference, 525 mL; 95% CI, -15 to 1065; P = .056) or blood transfusions (PRBC: mean difference, 208 mL; 95% CI, -23 to 439; P = .077; FFP (mean difference, 34 mL; 95% CI, -17 to 84; P = .19); cryoprecipitate (mean difference, 55 mL; 95% CI, -24 to 133; P = .17); or platelets (mean difference, 26 mL; 95% CI, -12 to 64; P = .18) between PCV and VCV groups. Conclusions In prone position spine surgery, neither mode of mechanical ventilation nor airway pressure is associated with intraoperative blood loss or need for allogeneic transfusion. Use of modern ventilation strategies using lung protective techniques may mitigate differences in blood loss previously observed between PCV and VCV modes.

Summary Dynamic prediction uses patient information collected during follow-up to produce individualized survival predictions at given time points beyond treatment or diagnosis. This allows clinicians to obtain updated predictions of a patient’s prognosis that can be used in making personalized treatment decisions. Two commonly used approaches for dynamic prediction are landmarking and joint modeling. Landmarking does not constitute a comprehensive probability model, and joint modeling often requires strong distributional assumptions and computationally intensive methods for estimation. We introduce an alternative approximate approach for dynamic prediction that aims to overcome the limitations of both methods while achieving good predictive performance. We separately specify the marker and failure time distributions conditional on surviving up to a prediction time of interest and use standard variable selection and goodness-of-fit techniques to identify the best-fitting models. Taking advantage of its analytic tractability and easy two-stage estimation, we use a Gaussian copula to link the marginal distributions smoothly at each prediction time with an association function. With simulation studies, we examine the proposed method’s performance. We illustrate its use for dynamic prediction in an application to predicting death for heart valve transplant patients using longitudinal left ventricular mass index information.

We report 2 infants hospitalized with Cronobacter sakazakii meningitis. Each infant had exposure to powdered infant formula at home. Both infants survived, but 1 infant had a subdural empyema drained and developed left sensorineural hearing loss. Early advanced brain imaging is recommended in infants with C. sakazakii meningitis. Reporting to state and federal public health officials may help identify outbreaks.

Introduction: Rapid prehospital identification of patients with ST-elevation myocardial infarction (STEMI) is a critical step to reduce time to treatment. Broad screening with field 12-lead ECGs can lead to a high rate of false positive STEMI activations due to low prevalence. One strategy to reduce false positive STEMI interpretations is to limit acquisition of 12-lead ECGs to patients who have symptoms strongly suggestive of STEMI, but this may delay care in patients who present atypically and lead to disparities in populations with more atypical presentations. We sought to assess patient factors associated with atypical STEMI presentation.Methods: We retrospectively analyzed consecutive adult patients for whom Los Angeles Fire Department paramedics obtained a field 12-lead ECG from July 2011 through June 2012. The regional STEMI receiving center registry was used to identify patients with STEMI. Patients were designated as having typical symptoms if paramedics documented provider impressions of chest pain/discomfort, cardiac arrest, or cardiac symptoms, otherwise they were designated as having atypical symptoms. We utilized logistic regression to determine patient factors (age, sex, race) associated with atypical STEMI presentation.Results: Of the 586 patients who had STEMI, 70% were male, 43% White, 16% Black, 20% Hispanic, 5% Asian and 16% were other or unspecified race. Twenty percent of STEMI patients (n = 117) had atypical symptoms. Women who had STEMI were older than men (74 years [IQR 62-83] vs. 60 years [IQR 53-70], p < 0.001). Univariate predictors of atypical symptoms were older age and female sex (p < 0.0001), while in multivariable analysis older age [odd ratio (OR) 1.05 per year, [95%CI 1.04-1.07, p < 0.0001] and black race (OR vs White 2.18, [95%CI 1.20-3.97], p = 0.011) were associated with atypical presentation.Conclusion: Limiting prehospital acquisition of 12-lead ECGs to patients with typical STEMI symptoms would result in one in five patients with STEMI having delayed recognition, disproportionally impacting patients of older age, women, and Black patients. Age, not sex, may be a better predictor of atypical STEMI presentation.

P24 Figure 1CARP trial wearable respiratory rate, respiratory support and outcome data from 3 patients with severe COVID-19[Figure omitted. See PDF]Results156 patients were screened, with 77 recruited to the CARP trial. 32 patients required non-invasive respiratory support, of which 14 were escalated to mechanical intubation. 17 patients died within trial.Bland-Altman analyses of paired RR data confirmed that wearable sensor data shows good agreement with critical care RR monitoring (Phillips Intellivue MX700), and that ward-based intermittent clinician RR measurements were imprecise.From the initial utility review of CARP physiology data visualisations, rising hourly average RR >25/min is associated with subsequent patient deterioration. Improving and stable hourly average RR of

This paper leverages phased array techniques to determine the positions of multiple reflectors in 3-D space using ultrasonic sensing. The design of a low-cost sensor, consisting of a single narrowband ultrasonic transducer and a receiver array consisting of a small number of MEMS microphones, is discussed. Aspects of system design related to the sensor, analog signal chain, and digital processing are presented. A processing algorithm is described to simultaneously determine the 3-D positions of all the reflectors present in the sensor’s workspace. Further, the processing algorithm is implemented on a low-cost microcontroller and requires low memory resources (64-70 kilobytes). Experiments demonstrate the performance achieved and the detection of multiple objects in the sensor’s workspace. A computation cost analysis is performed exhibiting the rapid execution of the algorithm. High processing throughput (20-45 Hz) is achieved making the sensor suitable for applications such as workspace mapping and the tracking of multiple reflectors.

We demonstrate two-photon interference and polarization entanglement at 2090 nm, constituting a crucial leap towards free-space mid-infrared quantum communication systems in a spectral region with high atmospheric transparency and reduced solar background.

Superconducting Nanowire Single photon Detectors (SNSPDs) offer unparalleled performance for IR photon counting, combining close to unity quantum efficiency, low intrinsic noise and ultrafast timing jitter. The ability of SNSPDs to count photons in mid-IR band up to 7 um wavelength opens up new possibilities in quantum optics, laser ranging, free space Quantum Key Distribution (QKD) and astronomy. Here we report on development of mid-IR SNSPDs including device design, fabrication, optimisation of superconducting materials and characterisation. We present a characterisation setup covering 1.5 - 4.2 um spectral region based on tuneable optical parametric oscillator with picosecond long pulses. We then demonstrate the viability of mid infrared SNSPDs for a variety of applications and report the results from single photon light detection and ranging (LIDAR) experiment with 2.3 um photons. This work paves the way for future app in free space QKD, deep space communication and astronomy.

The use of wireless sensor networks to measure soil parameters eliminates the need to remove sensors for field operations, such as tillage, thus allowing long-term measurements without multiple disturbances to soil structure. Wireless sensors also reduce above-ground cables and the risk of undesired equipment damage and potential data loss. However, implementing wireless sensor networks in field studies usually requires advanced and costly engineering knowledge. This study presents a new underground, wireless, open-source, low-cost system for monitoring soil oxygen, temperature, and soil moisture. The process of system design, assembly, programming, deployment, and power management is presented. The system can be left underground for several years without the need to change the battery. Emphasis was given on modularity so that it can be easily duplicated or changed if needed and deployed without previous engineering knowledge. Data from this type of system have a wide range of applications, including precision agriculture and high-resolution modelling.

BACKGROUND: Omega-3 fatty acids, including DHA and α-linolenic acid (ALA), are proposed to improve metabolic health by reducing obesity-associated inflammation. Their effects are mediated in part by conversion to oxylipins. ALA is relatively understudied, and direct comparisons to other omega-3 fatty acids are limited. OBJECTIVES: We compared the effects of equal doses of ALA and DHA on plasma oxylipins and markers of metabolic health in women with obesity. METHODS: We carried out a randomized, double-blind, crossover clinical trial where women aged 20–51 with a BMI of 30–51 kg/m(2) were supplemented with 4 g/day of ALA or DHA for 4 weeks in the form of ALA-rich flaxseed oil or DHA-rich fish oil. The primary outcome, the plasma oxylipin profile, was assessed at Days 0 and 28 of each phase by HPLC-MS/MS. Plasma fatty acids, inflammatory markers, and the monocyte glucose metabolism were key secondary outcomes. Data were analyzed using a mixed model. RESULTS: Compared to the baseline visit, there were higher plasma levels of nearly all oxylipins derived from DHA (3.8-fold overall; P

Modern polymer science is plagued by the curse of multidimensionality; the large chemical space imposed by including combinations of monomers into a statistical copolymer overwhelms polymer synthesis and characterization technology and limits the ability to systematically study structure–property relationships. To tackle this challenge in the context of 19F MRI agents, we pursued a computer-guided materials discovery approach that combines synergistic innovations in automated flow synthesis and machine learning (ML) method development. A software controlled, continuous polymer synthesis platform was developed to enable iterative experimental–computational cycles that resulted in the synthesis of 397 unique copolymer compositions within a six-variable compositional space. The non-intuitive design criteria identified by ML, which was accomplished by exploring less than 0.9% of overall compositional space, upended conventional wisdom in the design of 19F MRI agents and lead to the identification of >10 copolymer compositions that outperformed state-of-the-art materials.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is an infectious virus that causes coronavirus disease 2019 (COVID-19) transmitted mainly through droplets and aerosol affecting the respiratory tract and lungs. Little is known regarding why some individuals are more susceptible than others and develop severe symptoms. In this study, we analyzed the nasopharyngeal microbiota profile of aged patients with COVID-19 (asymptomatic vs. symptomatic) vs. healthy individuals. We examined the nasopharynx swab of 84 aged-matched patients, out of which 27 were negative asymptomatic (NegA), 30 were positive asymptomatic (PA), and 27 patients were positive symptomatic (PSY). Our analysis revealed the presence of abundant Cyanobacterial taxa at phylum level in PA (p-value = 0.0016) and PSY (p-value = 0.00038) patients along with an upward trend in the population of Litoricola, Amylibacter, Balneola, and Aeromonas at the genus level. Furthermore, to know the relationship between the nasal microbiota composition and severity of COVID-19, we compared PA and PSY groups. Our data show that the nasal microbiota of PSY patients was significantly enriched with the signatures of two bacterial taxa: Cutibacterium (p-value = 0.045) and Lentimonas (p-value = 0.007). Furthermore, we also found a significantly lower abundance of five bacterial taxa, namely: Prevotellaceae (p-value = 7 × 10−6), Luminiphilus (p-value = 0.027), Flectobacillus (p-value = 0.027), Comamonas (p-value = 0.048), and Jannaschia (p-value = 0.012) in PSY patients. The dysbiosis of the nasal microbiota in COVID-19 positive patients might have a role in contributing to the severity of COVID-19. The findings of our study show that there is a strong correlation between the composition of the nasal microbiota and COVID-19 severity. Further studies are needed to validate our finding in large-scale samples and to correlate immune response (cytokine Strome) and nasal microbiota to identify underlying mechanisms and develop therapeutic strategies against COVID-19.

This paper quantitatively characterises the microstructure in shales across five scales in 3D, builds a multi-scale model of CH 4 and CO 2 flow pathways and storage, and assesses the potential of enhanced gas recovery and CO 2 storage simultaneously. Injection of CO 2 into shale reservoirs to enhance gas recovery and simultaneously sequester greenhouse gases is a potential contributor towards the carbon-neutral target. It offers a low-carbon, low-cost, low-waste and large-scale solution during the energy transition period. A precondition to efficient gas storage and flow is a sound understanding of how the shale's micro-scale impacts on these phenomena. However, the heterogeneous and complex nature of shales limits the understanding of microstructure and pore systems, making feasibility analysis challenging. This study qualitatively and quantitatively investigates the Bowland shale microstructure in 3D at five length scales: artificial fractures at 10–100 μm scale, matrix fabric at 1–10 μm-scale, individual mineral grains and organic matter particles at 100 nm–1 μm scale, macropores and micro-cracks at 10–100 nm scale and organic matter and mineral pores at 1–10 nm-scale. For each feature, the volume fraction variations along the bedding normal orientation, the fractal dimensions and the degrees of anisotropy were analysed at all corresponding scales for a multi-scale heterogeneity analysis. The results are combined with other bulk laboratory measurements, including supercritical CO 2 and CH 4 adsorption at reservoir conditions, pressure-dependent permeability and nitrogen adsorption pore size distribution, to perform a comprehensive analysis on the storage space and flow pathways. A cross-scale pore size distribution, ranging from 2 nm to 3 μm, was calculated with quantified microstructure. The cumulative porosity is calculated to be 8%. The cumulative surface area is 17.6 m 2 g −1 . A model of CH 4 and CO 2 flow pathways and storage with quantified microstructure is presented and discussed. The feasibility of simultaneously enhanced gas recovery and subsurface CO 2 storage in Bowland shale, the largest shale gas potential formation in the UK, was assessed based using multi-scale microstructure analysis. The potential is estimated to store 19.0–21.2 Gt CO 2 as free molecules, together with 18.3–28.5 Gt CO 2 adsorbed onto pore surfaces, implying a theoretical maximum of 47.5–49.5 Gt carbon storage in the current estimate of 38 trillion cubic metres (∼1300 trillion cubic feet) of Bowland shale. Simple estimates suggest 6.0–15.8 Gt CO 2 may be stored in practice.

Gamma delta T-cells are commonly found in response to Listeria monocytogenes infection in mice, whereas this same immunological response has only been reported a few times in vivo in humans. Moreover, gamma delta T-cell response in cerebral spinal fluid samples in conjunction with Listeria meningitis has never been described in medical literature to date. Thus, we describe a 64-year-old male who presented with altered mental status, fever, and neck stiffness. After lumbar puncture revealed elevated glucose, protein, lactate dehydrogenase, and white blood cell count, further cytologic analysis was indicated. The CSF showed a markedly hypercellular sample with a lymphocytic pleocytosis, including some enlarged forms with irregular nuclear contours, and rare macrophage containing intracytoplasmic bacteria. Lymphocyte immunophenotyping was performed via flow cytometric analysis, which ultimately revealed a prominent CD4/CD8 negative T-cell population, suggestive of a gamma delta T-cell population. Thus, an initial suspicion of malignancy was considered but was ruled out due to the absence of mass lesion on imaging and overall features including heterogenous lymphocyte morphology. Shortly after, gram stain and cultures were obtained revealing Listeria monocytogenes. Unfortunately, the patient rapidly succumbed to disease following the diagnosis of Listeria meningitis. Studies suggest that gamma delta T-cells are activated by the protein components of Listeria and thus have been found to be an important mediator of resistance to Listeria infection. Studies have also discovered that the level of activation for these T-cells appears to be tissue specific and dose dependent, with most cases occurring within visceral organs. Hence, we herein present the first case of gamma delta T-cell activation due to Listeria monocytogenes within the cerebral spinal fluid of a human patient.

Hybrid inertial microwave reflectometry (HIMR) is one of the most promising technologies for achieving the elusive, ultimate goal of wireless localization, i.e., motion-capture grade position tracking at long-range distances. In this paper, we introduce and analyze Kalman filter-based real-time position estimators for HIMR systems. Results from measured data show that the new approach results in a 5 mm RMS tracking error at a range of several meters—a 25% improvement with enhanced robustness over existing position estimators. Moreover, this performance level is shown to be achievable using only RF signals, without inertial data, thereby potentially simplifying RFID-based motion capture system design in many cases. The technique is scalable to ranges of tens- and hundreds-of-meters.

Background and Objectives In later life, the loss of a spouse due to divorce or widowhood is common and can lead to elevated depressive symptoms and loneliness. Research suggests that companion animal (CA) may be beneficial for psychological health, but limited research has explored whether CA can buffer negative consequences of social losses. Research Design and Methods This study uses data drawn from the Health and Retirement Study (HRS) to examine changes in depressive symptoms and loneliness in relation to a social loss among those with/without a CA. We used inverse-probability weighted regression to adjust for selection factors and isolate effects of CA ownership on changes in psychological health. Results Regardless of CA ownership, spousal loss was associated with psychological health consequences. Facing a social loss without a CA was related to statistically greater increases in depressive symptoms relative to those with a pet (2.580 vs. 1.207 symptoms, respectively). Similarly, experiencing a loss was associated with significantly greater increases in loneliness, with statistically greater increases in loneliness among those without a CA (p < .01). However, those with a CA did not experience greater increases in loneliness than those who did not experience a loss. Discussion and Implications In later life, CA ownership may buffer against the detrimental consequences of major social losses on psychological health. Future research on the therapeutic effects of CA ownership, as well as pet therapy, during other major life stage transitions is needed to help isolate potential mechanisms driving the benefits of human–animal interactions.

OBJECTIVERecent literature describing complications associated with spinopelvic fixation with iliac screws in adult patients has been limited but has suggested high complication rates. The authors’ objective was to report their experience with iliac screw fixation in a large series of patients with a 2-year minimum follow-up.METHODSOf 327 adult patients undergoing spinopelvic fixation with iliac screws at the authors’ institution between 2010 and 2015, 260 met the study inclusion criteria (age ≥ 18 years, first-time iliac screw placement, and 2-year minimum follow-up). Patients with active spinal infection were excluded. All iliac screws were placed via a posterior midline approach using fluoroscopic guidance. Iliac screw heads were deeply recessed into the posterior superior iliac spine. Clinical and radiographic data were obtained and analyzed.RESULTSTwenty patients (7.7%) had iliac screw–related complication, which included fracture (12, 4.6%) and/or screw loosening (9, 3.5%). No patients had iliac screw head prominence that required revision surgery or resulted in pain, wound dehiscence, or poor cosmesis. Eleven patients (4.2%) had rod or connector fracture below S1. Overall, 23 patients (8.8%) had L5–S1 pseudarthrosis. Four patients (1.5%) had fracture of the S1 screw. Seven patients (2.7%) had wound dehiscence (unrelated to the iliac screw head) or infection. The rate of reoperation (excluding proximal junctional kyphosis) was 17.7%. On univariate analysis, an iliac screw–related complication rate was significantly associated with revision fusion (70.0% vs 41.2%, p = 0.013), a greater number of instrumented vertebrae (mean 12.6 vs 10.3, p = 0.014), and greater postoperative pelvic tilt (mean 27.7° vs 23.2°, p = 0.04). Lumbosacral junction–related complications were associated with a greater mean number of instrumented vertebrae (12.6 vs 10.3, p = 0.014). Reoperation was associated with a younger mean age at surgery (61.8 vs 65.8 years, p = 0.014), a greater mean number of instrumented vertebrae (12.2 vs 10.2, p = 0.001), and longer clinical and radiological mean follow-up duration (55.8 vs 44.5 months, p < 0.001; 55.8 vs 44.6 months, p < 0.001, respectively). On multivariate analysis, reoperation was associated with longer clinical follow-up (p < 0.001).CONCLUSIONSPrevious studies on iliac screw fixation have reported very high rates of complications and reoperation (as high as 53.6%). In this large, single-center series of adult patients, iliac screws were an effective method of spinopelvic fixation that had high rates of lumbosacral fusion and far lower complication rates than previously reported. Collectively, these findings argue that iliac screw fixation should remain a favored technique for spinopelvic fixation.

Nonthrombotic intracranial venous occlusive disease (NIVOD) has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH) and various non-IIH headache syndromes. Endovascular stenting of stenotic, dominant transverse sinuses (TSs) may reduce trans-stenosis pressure gradients, decrease intracranial pressure, and alleviate symptoms in a subset of NIVOD patients. We present a case in which concurrent stenting of the occipito-marginal sinus obliterated the residual trans-stenosis pressure gradient across an initially stented dominant TS. We hypothesize that this observation may be explained using an electric-hydraulic analogy, and that this patient’s dominant TS and occipito-marginal sinus may be modeled as a parallel hemodynamic circuit. Neurointerventionalists should be aware of parallel hemodynamic drainage patterns and consider manometry and possibly additional stenting of stenotic, parallel venous outflow pathways if TS stenting alone fails to obliterate the trans-stenosis pressure gradient.

Background Suicidal outcomes, including ideation, attempt, and completed suicide, are an important drug safety issue, though few epidemiological studies address the accuracy of suicidal outcome ascertainment. Our primary objective was to evaluate validated methods for suicidal outcome classification in electronic health care database studies. Methods We performed a systematic review of PubMed and EMBASE to identify studies that validated methods for suicidal outcome classification published 1 January 1990 to 15 March 2016. Abstracts and full texts were screened by two reviewers using prespecified criteria. Sensitivity, specificity, and predictive value for suicidal outcomes were extracted by two reviewers. Methods followed PRISMA-P guidelines, PROSPERO Protocol: 2016: CRD42016042794. Results We identified 2202 citations, of which 34 validated the accuracy of measuring suicidal outcomes using International Classification of Diseases (ICD) codes or algorithms, chart review or vital records. ICD E-codes (E950-9) for suicide attempt had 2–19% sensitivity, and 83–100% positive predictive value (PPV). ICD algorithms that included events with ‘uncertain’ intent had 4–70% PPV. The three best-performing algorithms had 74–92% PPV, with improved sensitivity compared with E-codes. Read code algorithms had 14–68% sensitivity and 0–56% PPV. Studies estimated 19–80% sensitivity for chart review, and 41–97% sensitivity and 100% PPV for vital records. Conclusions Pharmacoepidemiological studies measuring suicidal outcomes often use methodologies with poor sensitivity or predictive value or both, which may result in underestimation of associations between drugs and suicidal behaviour. Studies should validate outcomes or use a previously validated algorithm with high PPV and acceptable sensitivity in an appropriate population and data source.

Background: Ibrance Real World Insights (IRIS) is a multi-country study aimed to describe clinical characteristics, treatment patterns and clinical outcomes of patients receiving palbociclib plus aromatase inhibitor. Previously the results on the overall population within the US have been communicated. The current analysis focuses on subgroups stratified by age, performance status and visceral status. Materials and methods: A retrospective chart review of HR+/HER2- ABC/MBC patients who received palbociclib plus aromatase inhibitor as initial endocrine based therapy for their advanced disease was conducted between June and October 2017. Physicians completed electronic case report forms, extracting data on patient demographics, clinical characteristics, treatment history/patterns and clinical outcomes.Progression free and survival rates at 12 and 24 months were estimated via Kaplan-Meier analysis. Results: Data for the US are reported here. In total 63 physicians completed 360 eCRFs with a mean follow up time since palbociclib initiation of 12 months. Majority of the patients were >65 years (53%), and had ECOG status of 0 (30%) or 1 (56%). Overall 293 (81%) patients had metastatic disease, of which 50% had visceral metastases. Across all sub-groups, majority of patients prescribed an initial palbociclib dose of 125mg did not require a change of dose while on treatment. The 12-month and 24-month progression free and overall survival rates across subgroups are presented in Table 1. Patients with a performance status of ECOG=1 had a slightly lower progression and survival rates at 12 and 24 months compared to those with a score =0. Likewise, patients with visceral disease were observed to have slightly lower progression free and survival rates than others. Table 1:Clinical Outcomes for the different sub-groups.Patient Sub-groups AgeECOG statusVisceral Status Up to 65 n=169Over 65 n=1910 n=1071 n=200Visceral metastases n=147Non-visceral metastases n=146Progression free survival rate at 12 months, %86.382.194.386.580.285.8Progression free survival rate at 24 months, %59.769.071.267.450.780.6Overall survival rate At 12 months, %97.992.8100.099.590.599.3Overall survival rate at 24 months, %95.185.695.796.487.290.7 Conclusions: The analysis indicates consistent trends in different clinical outcomes were observed with palbociclib plus aromatase inhibitor across patients sub-groups based on age, performance status and visceral metastases. Citation Format: Taylor-Stokes G, Mitra D, Waller J, Gibson K, Milligan G, Zhan L, Iyer S. Real world treatment patterns and outcomes of patients receiving palbociclib plus aromatase inhibitor in the United States: Sub-groups analysis based on age, performance status and sites of metastases from the IRIS study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-36.