Latent Trajectories of Persistence of Cannabis Use Across Four Decades in 329 Men From the San Diego Prospective Study.

OBJECTIVE: These analyses use data from a 40-year prospective study to extend information into the sixth and seventh decades of life regarding latent trajectory classes of cannabis use and predictors of those classes. METHOD: Data from the San Diego Prospective Study were analyzed for 329 men of European and Hispanic ethnicity who had used cannabis at about age 23 at study entry (Time 1) and who were interviewed about every 5 years through about age 60 to 70. Latent classes of cannabis use trajectories were evaluated using latent class growth analyses, baseline predictors of class membership were determined, and significant predictors of each class were established using logistic regression analyses. RESULTS: Four latent classes were identified ranging from 12.5% with cannabis use at every follow-up to 25.8% with no use after Time 1. Eight of 14 Time 1 predictors differed significantly across the trajectory classes, including five (age, marital status, religious identity, intensity of cannabis use, and sensation seeking) that significantly contributed to regression analyses when all significant predictors were considered together. DISCUSSION: Forty-two percent of participants continued using cannabis long-term, including one in eight who used it at every follow-up. Predictors of continued use and identification of those most likely to stop required gathering information on a range of demographic, prior substance use, and personality characteristics. CONCLUSIONS: Considering the potential enhanced dangers of cannabis use in later life, the high rate of continued use over four decades implies that clinicians should ask all older patients about recent cannabis use, especially if they had used it in their 20s.

Symptom Burden and Shared Care Planning in an Oncology Nurse-Led Primary Palliative Care Intervention (CONNECT) for Patients with Advanced Cancer.

Purpose: Primary palliative care (PPC) interventions are needed to address unmet symptom needs within standard oncology care. We designed an oncology nurse-led PPC intervention using shared care planning to facilitate patient engagement. This analysis examines the prevalence and severity of symptoms reported by patients and how symptoms were addressed on shared care plans (SCPs). Methods: Secondary analysis of a cluster randomized PPC intervention trial. Adult patients with metastatic solid tumors whose oncologist "would not be surprised if the patient died within a year" were included. Twenty-three oncology nurses received PPC training and conducted up to three monthly visits with patients. Symptom prevalence and severity were assessed before each visit using the Edmonton Symptom Assessment Scale (ESAS). Nurses collaboratively developed treatment strategies with patients, targeting the most bothersome symptoms for improvement. Results: Among 571 nurse-led PPC visits with 235 patients, the most prevalent and severe symptoms were tiredness (reported at 86% of visits; ESAS ≥4 in 55% of visits), low sense of wellbeing (78%; ESAS ≥4 in 38%), and poor appetite (69%; ESAS ≥4 in 42%). Moderately severe symptoms were addressed on SCPs ranging from 4% (drowsiness) to 35% (tiredness) of the time. Symptom management plans developed by PPC-trained oncology nurses primarily focused on nonpharmaceutical interventions (70%) compared with pharmaceutical interventions (30%). Conclusion: The symptoms that patients report most frequently and as most severe on SCPs were addressed less frequently than expected. Further research is needed to understand how PPC interventions can be designed to more effectively target and improve bothersome symptoms for patients with advanced cancer. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02712229.

Low versus high level of response to alcohol affects amygdala functional connectivity during processing of emotional stimuli.

BACKGROUND: Low levels of response (low LR) to alcohol predict heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies of emotion processing have shown that low LR individuals exhibit lower activation in task-related brain regions following both placebo and alcohol administration, but these studies did not examine functional brain networks that might contribute to the phenomena. The current study expands upon the earlier results by evaluating whether functional connectivity differences between the amygdala and other brain regions modulated by emotional face processing are associated with LR. Based on prior findings, we hypothesized that low LR is related to lower functional connectivity in fronto-amygdalar functional circuits, which underlie the processing of emotional stimuli. METHODS: Secondary analyses were conducted on data from a double-blind, placebo-controlled, within-subjects, cross-over study in 108 18-to-25-year-old low and high LR sex-matched pairs without alcohol use disorder at baseline. Participants performed modified emotional faces processing tasks after receiving placebo or approximately 0.7 ml/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between left and right amygdalae and related brain circuits using LR-by-alcohol general linear models. The data included 54 sex-matched pairs with 216 fMRI scans comprising alcohol and placebo conditions. RESULTS: Compared with individuals with high LR, low LR subjects demonstrated lower functional connectivity between the amygdala and the frontal lobes, insula, and parietal regions, while processing angry and happy faces. Interactions showed lower connectivity following alcohol in low LR and higher connectivity in high LR groups. CONCLUSIONS: Low LR individuals demonstrated lower functional connectivity in response both to placebo and a modest dose of ethanol. Attenuated connectivity among low LR individuals when processing emotional faces may contribute to an impaired ability to recognize alcohol intoxication in social situations and to appraise angry and happy emotions irrespective of whether alcohol is consumed.

Relationship between level of response to alcohol and acute tolerance.

BACKGROUND: A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session. METHODS: Data were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7 ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway. RESULTS: Contrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures. CONCLUSION: These data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Low Referral Rates for Genetic Assessment of Patients With Multiple Adenomas in United Kingdom Bowel Cancer Screening Programs.

BACKGROUND: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. OBJECTIVE: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas. DESIGN: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained. SETTING: Data were obtained from 3 centers in London, United Kingdom. PATIENTS: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test. MAIN OUTCOME MEASURES: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening. RESULTS: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment. LIMITATIONS: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population. CONCLUSIONS: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630. TASAS BAJAS DE DERIVACIN PARA LA EVALUACIN GENTICA DE PACIENTES CON ADENOMAS MLTIPLES EN LOS PROGRAMAS DE DETECCIN DEL CNCER DE INTESTINO DEL REINO UNIDO: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630.

Explant rates of electrical neuromodulation devices in 1177 patients in a single center over an 11-year period.

INTRODUCTION: The publication of explant rates has established risk factors and a definitive objective outcome of failure for spinal cord stimulation (SCS) treating neuropathic pain. We present a UK study analyzing explants of electrical neuromodulation devices for different conditions over 11 years in a single center specializing in neuromodulation. METHODS: A retrospective analysis was performed using a departmental database between 2008 and 2019. Explants were analyzed according to condition, mode of stimulation and other demographics using logistic regression and Kaplan-Meier graphs with log-rank (Mantel-Cox) test. RESULTS: Out of a total of 1177 patients, the explant rate was 17.8% at 5 years and 25.2% at 10 years. Loss of efficacy was the most frequent reason for explant 119/181 (65%). Multivariant regression analysis indicated patients with back pain without prior surgery had a reduced risk of explant (p=0.03). Patients with SCS systems that had 10 kHz, options of multiple waveforms, and rechargeable batteries also had a decreased risk of explant (p<0.001). None of these findings were confirmed when comparing Kaplan-Meier graphs, however. Contrary to other studies, we found gender and age were not independent variables for explant. CONCLUSION: These data contribute to a growing list of explant data in the scientific literature and give indications of what factors contribute to long-term utilization of electrical neuromodulation devices.

Should we be talking about guidelines with patients? A qualitative analysis in metastatic breast cancer.

BACKGROUND: Little data exist on perceptions of guideline-based care in oncology. This qualitative analysis describes patients' and oncologists' views on the value of guideline-based care as well as discussing guidelines when making metastatic breast cancer (MBC) treatment decisions. PATIENTS AND METHODS: In-person interviews completed with MBC patients and community oncologists and focus groups with academic oncologists were audio-recorded and transcribed. Two coders utilized a content analysis approach to analyze transcripts independently using NVivo. Major themes and exemplary quotes were extracted. RESULTS: Participants included 20 MBC patients, 6 community oncologists, and 5 academic oncologists. Most patients were unfamiliar with the term "guidelines." All patients desired to know if they were receiving guideline-discordant treatment but were often willing to accept this treatment. Five themes emerged explaining this including trusting the oncologist, relying on the oncologist's experiences, being informed of rationale for deviation, personalized treatment, and openness to novel therapies. Physician discussions regarding the importance of guidelines revealed three themes: consistency with scientific evidence, insurance coverage, and limiting unusual practices. Oncologists identified three major limitations in using guidelines: lack of consensus, inability to "think outside the box" to personalize treatment, and lack of guideline timeliness. Although some oncologists discussed guidelines, it was often not considered a priority. CONCLUSIONS: Patients expressed a desire to know whether they were receiving guideline-based care but were amenable to guideline-discordant treatment if the rationale was made clear. Providers' preference to limit discussions of guidelines is discordant with patients' desire for this information and may limit shared decision-making.

"I'd Want to Know, Because a Year's Not a Long Time to Prepare for a Death": Role of Prognostic Information in Shared Decision Making among Women with Metastatic Breast Cancer.

Context: Increasing emphasis on patient-centered care has led to highlighted importance of shared decision making, which better aligns medical decisions with patient care preferences. Effective shared decision making in metastatic breast cancer (MBC) treatment requires prognostic understanding, without which patients may receive treatment inconsistent with personal preferences. Objectives: To assess MBC patient and provider perspectives on the role of prognostic information in treatment decision making. Methods: We conducted semi-structured interviews with MBC patients and community oncologists and separate focus groups involving lay navigators, nurses, and academic oncologists. Qualitative analysis utilized a content analysis approach that included a constant comparative method to generate themes. Results: Of 20 interviewed patients with MBC, 30% were African American. Academic oncologists were mostly women (60%), community oncologists were all Caucasian, and nurses were all women and 28% African American. Lay navigators were all African American and predominately women (86%). Five emergent themes were identified. (1) Most patients wanted prognostic information but differed in when they wanted to have this conversation, (2) Emotional distress and discomfort was a critical reason for not discussing prognosis, (3) Religious beliefs shaped preferences for prognostic information, (4) Health care professionals differed on prognostic information delivery timing, and (5) Providers acknowledged that an individualized approach taking into account patient values and preferences would be beneficial. Conclusion: Most MBC patients wanted prognostic information, yet varied in when they wanted this information. Understanding why patients want limited or unrestricted prognostic information can inform oncologists' efforts toward shared decision making.

What Is Important When Making Treatment Decisions in Metastatic Breast Cancer? A Qualitative Analysis of Decision-Making in Patients and Oncologists.

BACKGROUND: Metastatic breast cancer (MBC) is an ideal environment for shared decision-making because of the large number of guideline-based treatment options with similar efficacy but different toxicity profiles. This qualitative analysis describes patient and provider factors that influence decision-making in treatment of MBC. MATERIALS AND METHODS: Patients and community oncologists completed in-person interviews. Academic medical oncologists participated in focus groups. Interviews and focus groups were audio-recorded, transcribed, and analyzed using NVivo. Using an a priori model based on the Ottawa Framework, two independent coders analyzed transcripts using a constant comparative method. Major themes and exemplary quotes were extracted. RESULTS: Participants included 20 patients with MBC, 6 community oncologists, and 5 academic oncologists. Analysis of patient interviews revealed a decision-making process characterized by the following themes: decision-making style, contextual factors, and preferences. Patient preference subthemes include treatment efficacy, physical side effects of treatment, emotional side effects of treatment, cognitive side effects of treatment, cost and financial toxicity, salience of cutting-edge treatment options (clinical trial or newly approved medication), treatment logistics and convenience, personal and family responsibilities, treatment impact on daily activities, participation in self-defining endeavors, attending important events, and pursuing important goals. Physician decisions emphasized drug-specific characteristics (treatment efficacy, side effects, cost) rather than patient preferences, which might impact treatment choice. CONCLUSION: Although both patients with MBC and oncologists considered treatment characteristics when making decisions, patients' considerations were broader than oncologists', incorporating contextual factors such as the innovative value of the treatment and life responsibilities. Differences in perspectives between patients and oncologists suggests the value of tools to facilitate systematic communication of preferences in the setting of MBC. IMPLICATIONS FOR PRACTICE: Both patients with metastatic breast cancer (MBC) and oncologists emphasized importance of efficacy and physical side effects when making treatment decisions. However, other patient considerations for making treatment decisions were broader, incorporating contextual factors such as the logistics of treatments, personal and family responsibilities, and ability to attend important events. Furthermore, individual patients varied substantially in priorities that they want considered in treatment decisions. Differences in perspectives between patients and oncologists suggest the value of tools to facilitate systematic elicitation of preferences and communication of those preferences to oncologists for integration into decision-making in MBC.

Combining LOPIT with differential ultracentrifugation for high-resolution spatial proteomics.

The study of protein localisation has greatly benefited from high-throughput methods utilising cellular fractionation and proteomic profiling. Hyperplexed Localisation of Organelle Proteins by Isotope Tagging (hyperLOPIT) is a well-established method in this area. It achieves high-resolution separation of organelles and subcellular compartments but is relatively time- and resource-intensive. As a simpler alternative, we here develop Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) and compare this method to the density gradient-based hyperLOPIT approach. We confirm that high-resolution maps can be obtained using differential centrifugation down to the suborganellar and protein complex level. HyperLOPIT and LOPIT-DC yield highly similar results, facilitating the identification of isoform-specific localisations and high-confidence localisation assignment for proteins in suborganellar structures, protein complexes and signalling pathways. By combining both approaches, we present a comprehensive high-resolution dataset of human protein localisations and deliver a flexible set of protocols for subcellular proteomics.

Comprehensive identification of RNA-protein interactions in any organism using orthogonal organic phase separation (OOPS).

Existing high-throughput methods to identify RNA-binding proteins (RBPs) are based on capture of polyadenylated RNAs and cannot recover proteins that interact with nonadenylated RNAs, including long noncoding RNA, pre-mRNAs and bacterial RNAs. We present orthogonal organic phase separation (OOPS), which does not require molecular tagging or capture of polyadenylated RNA, and apply it to recover cross-linked protein-RNA and free protein, or protein-bound RNA and free RNA, in an unbiased way. We validated OOPS in HEK293, U2OS and MCF10A human cell lines, and show that 96% of proteins recovered were bound to RNA. We show that all long RNAs can be cross-linked to proteins, and recovered 1,838 RBPs, including 926 putative novel RBPs. OOPS is approximately 100-fold more efficient than existing methods and can enable analyses of dynamic RNA-protein interactions. We also characterize dynamic changes in RNA-protein interactions in mammalian cells following nocodazole arrest, and present a bacterial RNA-interactome for Escherichia coli. OOPS is compatible with downstream proteomics and RNA sequencing, and can be applied in any organism.

Alcohol-related blackouts among college students: impact of low level of response to alcohol, ethnicity, sex, and environmental characteristics

Objective: To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs). Methods: Structural equation models (SEMs) were used to evaluate how baseline variables related to ARB patterns in 462 college students over 55 weeks. Data were extracted from a longitudinal study of heavy drinking and its consequences at a U.S. university. Results: In the SEM analysis, female sex and Asian ethnicity directly predicted future ARBs (beta weights 0.10 and -0.11, respectively), while all other variables had indirect impacts on ARBs through alcohol quantities (beta weights ~ 0.23 for European American ethnicity and low LR, 0.21 for cannabis use and COPE, and 0.44 for PEER). Alcohol quantities then related to ARBs with beta = 0.44. The SEM explained 23% of the variance. Conclusion: These data may be useful in identifying college students who are more likely to experience future ARBs over a 1-year period. They enhance our understanding of whether the relationships of predictors to ARBs are direct or mediated through baseline drinking patterns, information that may be useful in prevention strategies for ARBs.

Immune Checkpoint Inhibitor Toxicity Review for the Palliative Care Clinician.

Immune checkpoint inhibitors (ICIs) have opened an exciting chapter in the treatment of patients with advanced cancer. For the palliative care clinician, however, ICIs present several new challenges, including new ways to define treatment success, as well as treatment-related toxicities that differ in nature and timing from traditional chemotherapy. In this article, we review the mechanism of action of ICIs, as well as selected published data supporting the efficacy of ICIs in patients with advanced cancer. In addition, we summarize existing data of ICI toxicity prevalence, patterns of severity, and timing of onset. Finally, we briefly review key principles from published guidelines on the management of ICI toxicities.

Risk factors and short-term outcomes of postoperative pulmonary complications after VATS lobectomy.

BACKGROUND: Postoperative pulmonary complications (PPCs) are associated with poor outcomes following thoracotomy and lung resection. Video-assisted thoracoscopic surgery (VATS) for lobectomy is now frequently utilised as an alternative to thoracotomy, however patients remain at risk for development of PPC. There is little known of the short-term outcome associated with PPC following VATS lobectomy and if there are any potential risk factors that could be modified to prevent PPC development; our study aimed to investigate this. METHODS: A prospective observational study of consecutive patients undergoing VATS lobectomy for lung cancer over a 4-year period in a regional centre was performed (2012-2016). Exclusion criteria included re-do VATS or surgery for pulmonary infection. All patients received physiotherapy as necessary from postoperative day 1 (POD1) and PPC was determined using the Melbourne Group Scale. Outcomes included hospital LOS, intensive therapy unit (ITU) admission and hospital mortality. RESULTS: Of the 285 patients included in the study, 137 were male (48.1%), the median (IQR) age was 69 (13) years and the mean (±SD) FEV1% predicted was 87% (±19). Patients that developed a PPC (n = 21; 7.4%) had a significantly longer hospital LOS (4 vs. 3 days), higher frequency of ITU admission (23.8% vs. 0.5%) and higher hospital mortality (14.3% vs. 0%) (p < 0.001). PPC patients also required more physiotherapy contacts/time, emergency call-outs and specific pulmonary therapy (p < 0.05). Current smoking and COPD diagnosis were significantly associated with development of PPC on univariate analysis (p < 0.05), however only current smoking was a significant independent risk factor on multivariate analysis (p = 0.015). CONCLUSIONS: Patients undergoing VATS lobectomy remain at risk of developing a PPC, which is associated with an increase in physiotherapy requirements and a worse short-term morbidity and mortality. Current smoking is the only independent risk factor for PPC after VATS lobectomy, thus vigorous addressing of preoperative smoking cessation is urgently needed.

Correlates of Patterns of Health Values of African Americans Living With HIV/AIDS: Implications for Advance Care Planning and HIV Palliative Care.

CONTEXT: Advance care planning rates remain low, especially among people who are HIV positive, disadvantaged, and African American. Although advance care planning can be a sensitive topic for clinicians and patients to discuss, health values clarification can be an important initial step. OBJECTIVES: The purpose of the study was to explore health values of African Americans living with HIV/AIDS and to examine correlates of these values. METHODS: Data were from the first 325 participants in the AFFIRM Care study, which enrolled adults living with HIV/AIDS in Baltimore, Maryland, who had histories of illicit drug use. Respondents were asked whether (yes/no) they thought any of six health states would be worse than death: severe unremitting pain, total dependency on others, irreversible coma, being on mechanical ventilation, nursing home residence, and severe dementia. Latent class analysis was used to group individuals by their pattern of responses, interpretable as preference for aggressive (life-sustaining) or nonaggressive (palliative) end-of-life care. Latent class regression analysis was used to examine associations between class membership and background, health status, and social variables. RESULTS: We found statistical support for a three-class latent class analysis model: 1) the nonaggressive treatment class, comprising 43% of cases, in which members perceived that every state was worse than death; 2) the aggressive treatment class, comprising 33% of cases, in which members perceived that none of the states was worse than death; and 3) the mixed class (24% of cases), in which members perceived that only four of the six states were worse than death. CONCLUSION: Three-quarters of participant response patterns had clear preferences for treatment decisions. Further research is needed to ensure inclusion of end-of-life scenarios relevant to this population.

Alcohol-related blackouts among college students: impact of low level of response to alcohol, ethnicity, sex, and environmental characteristics.

Objective: To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs). Methods: Structural equation models (SEMs) were used to evaluate how baseline variables related to ARB patterns in 462 college students over 55 weeks. Data were extracted from a longitudinal study of heavy drinking and its consequences at a U.S. university. Results: In the SEM analysis, female sex and Asian ethnicity directly predicted future ARBs (beta weights 0.10 and -0.11, respectively), while all other variables had indirect impacts on ARBs through alcohol quantities (beta weights ~ 0.23 for European American ethnicity and low LR, 0.21 for cannabis use and COPE, and 0.44 for PEER). Alcohol quantities then related to ARBs with beta = 0.44. The SEM explained 23% of the variance. Conclusion: These data may be useful in identifying college students who are more likely to experience future ARBs over a 1-year period. They enhance our understanding of whether the relationships of predictors to ARBs are direct or mediated through baseline drinking patterns, information that may be useful in prevention strategies for ARBs.

Estimation of malaria parasite reservoir coverage using reactive case detection and active community fever screening from census data with rapid diagnostic tests in southern Zambia: a re-sampling approach.

BACKGROUND AND METHODS: In areas where malaria transmission has been suppressed by vector control interventions many malaria control and elimination programmes are actively seeking new interventions to further reduce malaria prevalence, incidence and transmission. Malaria infection prevalence and incidence has been shown to cluster geographically, especially at lower transmission levels, and as such a reactive strategy is frequently used, by which index cases presenting to a passive surveillance system are used to target small areas for testing and treatment, reactive case detection (RCD), or focal drug administration (fDA). This study utilizes geo-located data from a census with parasitological testing with rapid diagnostic tests (RDTs) and treatment-seeking data collection conducted in southern Zambia to estimate the coverage of RCD or fDA in terms of the population and parasite reservoir as well as the operational requirements of such strategies, using a re-sampling algorithm developed exclusively for this purpose. This re-sampling algorithm allows for the specification of several parameters, such that different operational variants of these reactive strategies can be examined, including varying the search radius, screening for fever, or presumptive treatment (fDA). RESULTS: Results indicate that RCD, fDA and active fever screening followed by RCD, even with search radii over several hundered meters will only yield limited coverage of the RDT positive parasite reservoir during a short period. Long-term use of these strategies may increase this proportion. Reactive strategies detect a higher proportion of the reservoir of infections than random searches, but this effect appears to be greater in areas of low, but not moderate malaria prevalence in southern Zambia. DISCUSSION: Increases in the sensitivity of RDTs could also affect these results. The number of individuals and households that need to be searched increase rapidly, but approximately linearly with search radius. CONCLUSIONS: Reactive strategies in southern Zambia yield improved identification of the parasite reservoir when targeted to areas with prevalence less than 10%. The operational requirements of delivering reactive strategies routinely are likely to prevent their uptake until prevalence falls far below this level.

Predictors of Patterns of Alcohol-Related Blackouts Over Time in Youth From the Collaborative Study of the Genetics of Alcoholism: The Roles of Genetics and Cannabis.

OBJECTIVE: Alcohol-related blackouts (ARBs) are anterograde amnesias related to heavy alcohol intake seen in about 50% of drinkers. Although a major determinant of ARBs relates to blood alcohol concentrations, additional contributions come from genetic vulnerabilities and possible impacts of cannabis use disorders (CUDs). We evaluated relationships of genetics and cannabis use to latent class trajectories of ARBs in 829 subjects from the Collaborative Study of the Genetics of Alcoholism (COGA). METHOD: The number of ARBs experienced every 2 years from subjects with average ages of 18 to 25 were entered into a latent class growth analysis in Mplus, and resulting class membership was evaluated in light of baseline characteristics, including CUDs. Correlations of number of ARBs across assessments were also compared for sibling pairs versus unrelated subjects. RESULTS: Latent class growth analysis identified ARB-based Classes 1 (consistent low = 42.5%), 2 (moderate low = 28.3%), 3 (moderate high = 22.9%), and 4 (consistent high = 6.3%). A multinomial logistic regression analysis within latent class growth analysis revealed that baseline CUDs related most closely to Classes 3 and 4. The number of ARBs across time correlated .23 for sibling pairs and -.10 for unrelated subjects. CONCLUSIONS: Baseline CUDs related to the most severe latent ARB course over time, even when considered along with other trajectory predictors, including baseline alcohol use disorders and maximum number of drinks. Data indicated significant roles for genetic factors for alcohol use disorder patterns over time. Future research is needed to improve understanding of how cannabis adds to the ARB risk and to find genes that contribute to risks for ARBs among drinkers.

Aspirin in the 21st century-common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK.

Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV.

Development and validation of the BRIGHTLIGHT Survey, a patient-reported experience measure for young people with cancer.

BACKGROUND: Patient experience is increasingly used as an indicator of high quality care in addition to more traditional clinical end-points. Surveys are generally accepted as appropriate methodology to capture patient experience. No validated patient experience surveys exist specifically for adolescents and young adults (AYA) aged 13-24 years at diagnosis with cancer. This paper describes early work undertaken to develop and validate a descriptive patient experience survey for AYA with cancer that encompasses both their cancer experience and age-related issues. We aimed to develop, with young people, an experience survey meaningful and relevant to AYA to be used in a longitudinal cohort study (BRIGHTLIGHT), ensuring high levels of acceptability to maximise study retention. METHODS: A three-stage approach was employed: Stage 1 involved developing a conceptual framework, conducting literature/Internet searches and establishing content validity of the survey; Stage 2 confirmed the acceptability of methods of administration and consisted of four focus groups involving 11 young people (14-25 years), three parents and two siblings; and Stage 3 established survey comprehension through telephone-administered cognitive interviews with a convenience sample of 23 young people aged 14-24 years. RESULT: Stage 1: Two-hundred and thirty eight questions were developed from qualitative reports of young people's cancer and treatment-related experience. Stage 2: The focus groups identified three core themes: (i) issues directly affecting young people, e.g. impact of treatment-related fatigue on ability to complete survey; (ii) issues relevant to the actual survey, e.g. ability to answer questions anonymously; (iii) administration issues, e.g. confusing format in some supporting documents. Stage 3: Cognitive interviews indicated high levels of comprehension requiring minor survey amendments. CONCLUSION: Collaborating with young people with cancer has enabled a survey of to be developed that is both meaningful to young people but also examines patient experience and outcomes associated with specialist cancer care. Engagement of young people throughout the survey development has ensured the content appropriately reflects their experience and is easily understood. The BRIGHTLIGHT survey was developed for a specific research project but has the potential to be used as a TYA cancer survey to assess patient experience and the care they receive.