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ABSTRACT IMPACT: The results of this research may influence NCCN guidelines on PET/CT surveillance for this population of patients for whom the guidelines are currently vague. OBJECTIVES/GOALS: We aim to quantify and describe the yield of surveillance PET/CT for detecting asymptomatic recurrence of melanoma after primary surgical treatment for stages IIB, IIC, and IIIA. Our goal is to provide evidence to inform appropriate guidelines for scheduling surveillance PET/CT for this population. METHODS/STUDY POPULATION: This is a retrospective study of patients who have undergone a PET/CT at Barnes-Jewish Hospital. Data will be collected in our Research Electronic Data Capture (REDCap) database. The sample size is 158. Data analysis will be explanatory for the yield of imaging and description of false positives and additional unnecessary workup. Survival endpoints will be reported and multivariate analysis with subgroups will be performed for predictors of PET/CT results. Cost-efficiency analysis will be conducted in collaboration with the Center for Health Economics and Policy (CHEP), with emphasis on a patient-oriented perspective. RESULTS/ANTICIPATED RESULTS: To date, we have collected data for 158 patients, with approximately equal numbers of each stage (56 IIB, 54 IIC, 48 IIIA). Due to lack of clear guidelines for this population, there is significant variation of imaging schedules and results between similar patients or groups of patients. This makes it difficult to anticipate results. Based on clinical experience, literature review, and preliminary data, we may anticipate lower yield of routine PET/CT for the detection of asymptomatic recurrence, with frequent false negatives and occasional false positives, in addition to detection and further workup of benign processes. DISCUSSION/SIGNIFICANCE OF FINDINGS: The high-risk stages IIB, IIC, and IIIA currently occupy a gray area where surveillance PET/CT remains controversial. For this group of patients, it is important to weigh the benefits of early detection and risks of false positives, unnecessary workup and anxiety, and cost.
ABSTRACT IMPACT: This work may provide new targets for vaccine and immunotherapeutic development against MRSA infections. OBJECTIVES/GOALS: Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Patients with SA SSSI have a high 1-year recurrence. We have shown innate memory protects mice against SA SSSI. The goal of this project is to determine epigenetic mechanisms of protective memory against SA SSSI. METHODS/STUDY POPULATION: We have shown macrophages (Mf) afford protective memory against recurrent SA SSSI in mice. Priming by prior infection reduced skin lesion size and MRSA burden, which correlated with increased Mf in abscesses and lymph nodes. Priming potentiated the opsonophagocytic killing of SA by bone-marrow derived Mf (BMDM) in vitro, and their adoptive transfer into naive skin afforded protective efficacy in vivo. Here, we investigated epigenetic mechanisms of anti-SA efficacy in BMDMs. BMDM from naive (uninfected) or primed (SA SSSI) wild-type C57Bl/6 mice were cultured ex vivo. DNA from BMDM groups were isolated and analyzed for methylation changes using reduced representation bisulfite sequencing (RRBS). Pathway analyses of methylation changes were determined with Panther. RESULTS/ANTICIPATED RESULTS: Present findings indicate the protective memory afforded by BMDM was mediated by epigenetic modifications of the DNA. Using RRBS, we profiled differentially methylated regions (DMR) in DNA from naive vs. primed BMDM. Primed BMDM exhibited significantly different DMRs as compared to naive BMDM. Proximity to known genes were mapped using GREAT. Pathway analyses revealed DMRs predominant in genes integral to immune modulation, such as integrin signaling, cytokine/chemokine networks, and growth regulation. For example, SA-primed BMDM were hypermethylated proximate to GIMAP8 versus naive BMDM, suggesting repression of this protein. Gimap family ligands are small GTPase immune-associated proteins expressed in immune cells known to regulate macrophage lysosomal fusion during parasite infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: These findings reveal epigenetic mechanisms of macrophage innate memory against recurrent MRSA infection. Functional testing of these genes in response to SA infection is needed to confirm their protective role. These insights may provide new targets for vaccine and immunotherapeutic development against MRSA.
To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.
Pilot prospective multicenter surveillance study.
The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.
All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.
In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.
Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).
Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Hearing loss affects over 1.3 billion individuals worldwide, with the greatest burden among adults. Little is known regarding the association between adult-onset hearing loss and employment.
Seven databases (PubMed, Embase, Cochrane Library, ABI/Inform Collection, Business Source Ultimate, Web of Science and Scopus) were searched through to October 2018. The key word terms used related to hearing loss and employment, excluding paediatric or congenital hearing loss and deaf or culturally deaf populations.
The initial search resulted in 13 144 articles. A total of 7494 articles underwent title and abstract screening, and 243 underwent full-text review. Twenty-five articles met the inclusion criteria. Studies were set in 10 predominantly high-income countries. Seven of the 25 studies analysed regionally or nationally representative datasets and controlled for key variables. Six of these seven studies reported associations between hearing loss and employment.
The highest quality studies currently available indicate that adult-onset hearing loss is associated with unemployment. However, considerable heterogeneity exists, and more rigorous studies that include low- and middle-income countries are needed.
Dans le cadre du développement de la classification internationale des maladies (CIM-11), les groupes de travail ont développé des propositions avec pour objectif d’améliorer l’utilité clinique de la classification. Ces propositions sont testées via la plateforme internet « Réseau Mondial de Pratique Clinique (RMPC) » permettant de conduire à des études cliniques électroniques dans les langues officielles de l’OMS, dont le français. Cette étude s’intéresse aux catégories diagnostiques des troubles de l’alimentation et des conduites alimentaires (TCA). Des nouveaux diagnostics ont été proposés tels que le trouble d’hyperphagie et le trouble d’évitement et de restriction de l’apport alimentaire.
– évaluer l’impact des changements spécifiques des TCA entre la CIM-10 et la CIM-11 auprès des membres francophones du RMPC ;
– évaluer la validité, l’utilité clinique des nouvelles propositions et l’accord inter-juges des participants.
Étude mixte, internationale, conduite par internet auprès des membres francophones du RMPC.
Membres du RMPC maîtrisant le français (environ 1000 professionnels) et exerçant une activité clinique.
La population cible recevra un email d’invitation. Les participants seront amenés à lire deux vignettes puis à poser des diagnostics et à répondre à des questions complémentaires, en se basant sur la CIM-10 ou la CIM-11 qu’ils auront reçu de façon aléatoire.
Les vignettes représenteront des cas cliniques réels et reflèteront les changements spécifiques entre la CIM-10 et la CIM-11. Elles seront ainsi présentées par pair (8 pairs possibles).
– interparticipants portant sur l’utilisation du système diagnostique (10 ou 11) et l’attribution du diagnostic en fonction des changements spécifiques ;
– intra-participant sur l’évaluation des pairs de vignettes.
Cette étude doit permettre d’évaluer les nouvelles propositions CIM en français, en tenant compte des spécificités culturelles et linguistiques de la francophonie.
To explore factors associated with work impairment at 2 years following an acute episode.
European Mania in Bipolar disorder Longitudinal Evaluation of Medication (EMBLEM) is a prospective, observational study on the outcomes of patients with a manic/mixed episode. Work impairment was measured using a Longitudinal Interval Follow-up Evaluation (slice of LIFE) item and patients were categorised with either low or high work impairment at each observation. Baseline factors associated with work impairment at 2 years were assessed using multivariate modelling.
At baseline (n = 2289), 69% of patients had high work impairment. At 2 years (n = 1393), high impairment reduced to 41%. Modelling identified rapid cycling as the strongest disease-related factor associated with high work impairment at 2 years, although high work impairment at baseline had the strongest association overall. Lower levels of education, recent admissions, CGI-BP overall severity in the 12 months prior to baseline and CGI-BP mania at baseline all predicted higher work impairment. Living together in a relationship and independent housing were both significantly associated with having low work impairment at 2 years.
Work impairment in bipolar disorder is maintained over long periods, and is strongly associated with relationship status, living conditions and various disease-related factors.
Research suggests that cannabis use negatively impacts on onset and outcome of schizophrenia. Possible effects in mood disorders have received little investigation. The first study analysing the influence of cannabis exposure on clinical and social treatment outcomes within a bipolar disorder (BP) population during 1 year of treatment is presented.
3684 patients were enrolled in an observational study when psychotropic treatment for mania was initiated/changed. The influence of cannabis exposure on baseline-corrected clinical and social treatment outcome measures was examined. Mediating effects of six variables on associations between cannabis and outcome measures were investigated further.
Over 12 months of treatment, cannabis users exhibited higher levels of BP overall illness severity, mania and psychosis, and less severe depression symptoms compared to non-users. These associations were most frequently mediated by abuse of alcohol and other substances. Users more frequently abused alcohol and other substances; these associations were not mediated by other variables. Cannabis users engaged in more social activities but had a higher probability of not having a relationship and fewer dependents to care for. Associations with activities and dependents to care for were mediated by various variables, whereas no variables mediated the association with not having a relationship.
Cannabis use impacts on clinical outcomes in patients with BP, with a modest impact on social outcomes. More research is required to further elucidate the mechanism by which cannabis exerts its influence. Understanding the associations between cannabis use and outcome measures may offer valuable insights into treatment strategies.
The objective is to describe the prevalence and nature of painful symptoms among depressive outpatients and how are they related with depressive symptoms and somatic non painful symptoms at baseline.
The FINDER study, conducted in 12 European countries in depressed outpatients in routine primary and specialist care settings provides a unique opportunity to answer these questions.
Painful symptoms were evaluated among 3468 patients enrolled by 437 investigators, using the 28-item Somatic Symptom Inventory (SSI-28) and 6 Visual Analogue Scales (1 item on overall pain and 5 items on pain characteristics: headaches, back pain, shoulder pain, interferences with daily activities and pain while awake). There was a strong correlation between the VAS overall pain score and the pain sub score of the SSI-28. The threshold score of 30 mm on the overall pain severity in combination with selected comorbidities was used to divide patients in three pain cohorts: (1) those with no/mild pain; (2) those with moderate/severe œmedically explained pain and (3) those with moderate/severe medically unexplained pain.
Results showed that 1447 (43.7%) patients had no/mild pain, 550 (16,6%) had moderate/severe medically explained pain, and 1311 (39,6%) had moderate/severe medically unexplained pain. Of the different locations of pain symptoms (from the SSI-28), headaches were the most common, followed by muscle soreness and lower back pain. The mean depression score (HADS-D) was higher in patients with pain-related symptoms.
We studied the correlations between the measures of pain and depression. These results and their implications will be discussed.
Antidepressants are recommended to be withdrawn during a manic episode. This analysis explored the characteristics of patients receiving antidepressants during an acute manic episode in the context of a large, observational study.
EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year prospective observational study of acute mania/mixed mania. Of 2416 patients, 345 (14%) were taking an antidepressant (AD) and 2071 (86%) were not (NAD) during acute mania. Demographic and clinical variables were collected at baseline and at outpatient visits up to 2 years. Illness severity was measured using Clinical Global Impressions–Bipolar Disorder (CGI-BP), 5-item Hamilton Depression Rating Scale (HAM-D-5), and Young Mania Rating Scale (YMRS). Logistic regression analysis was used to identify variables associated with AD use.
AD use varied across countries (p<0.05), more use with mixed episodes (p<0.001), rapid cyclers (p=0.02), more previous depressive episodes (p<0.001) and higher HAM-D-5 severity at baseline (p<0.001) but less use with higher education (p=0.029), YMRS (p=0.022), CGI-BP overall (p=0.006) severity and inpatients at baseline (p<0.001). There were no differences in alcohol abuse or suicide attempts. Depression recurrence rates were significantly higher with AD (p<0.001).
The EMBLEM study suggests that patients with mania receiving antidepressants are more likely to be outpatients with mixed mania or rapid cycling, and have a higher risk of depressive recurrence during follow-up. Clinicians seem to maintain antidepressants in manic patients to address depressive features during mania and prevent further depressive episodes.
To describe 12 month outcomes of French patients enrolled in EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication).
EMBLEM is a prospective, observational study on outcomes of manic/mixed episode. Adult patients were enrolled within the standard course of care if they initiated/changed oral medication for treatment of acute mania. All treatment decisions were at the discretion of the treating psychiatrist. 530 psychiatrists (126 French) enrolled 3459 eligible patients (771 French). 12 months results of the French cohort will be presented.
At baseline, mean age was 45.5 years (sd 13.6) and 59% were female. 68% were outpatients and 34% had a mixed episode. 76% of French patients were eligible for follow-up at 12 months. 80% improved (CGI-BP overall decrease >2) during follow-up whereas 47% patients never achieved recovery (two consecutive CGI-BP overall <2). 37% of patients presented with no medication at baseline. 41.6% were started on monotherapy and 58.4% on combination therapy; of those 54% and 28% respectively remained on their initial medication throughout the 12 months. 25% were treated with antidepressants in addition to their new oral medication, which increased to 35% at 12 months.
In this naturalistic study, less than half of French patients achieved recovery during 12 months follow-up. Antidepressant was frequent at baseline and use increased during follow-up. Twice as many patients remained on the same monotherapy as those on the same combination therapy
To contrast the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a RCT assessing the same treatments (Tohen et al., 2002).
EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with treatment of mania. Severity of mania and depression was assessed at baseline and 6 weeks using the YMRS and 5-item version of the HAMD, respectively. The RCT was a 3-week, randomised, double-blind comparison of olanzapine (n=125) and divalproate-treated (n=123) patients hospitalised for acute manic or mixed episodes. The YMRS and HAMD were used to quantify manic and depressive symptoms, respectively.
621 EMBLEM patients were analysed (n=107 valproate, n=514 olanzapine). Both observed groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with significantly greater mean improvements in the olanzapine compared with the valproate group using linear regression to adjust for baseline differences. The RCT reported significantly greater mean YMRS improvement (but not HAMD) in the olanzapine-treated group. EMBLEM patients treated with olanzapine experienced significantly greater weight gain than patients treated with valproate, similar to RCT results. There was a significantly greater incidence of treatment-emergent gastrointestinal adverse events in EMBLEM patients treated with valproate.
The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy may be more effective than valproate monotherapy in the treatment of acute mania. Contrasting observational and RCT results present methodological challenges but can provide important complementary information.
The PAtient SAtisfaction with Psychotropic (PASAP) scale is a self-completed questionnaire measuring satisfaction with psychotropic medication. The aim of the study was to describe its development in French and its psychometric properties.
Materials and methods:
Scale construction was based on an extensive search of the literature. The item reduction process required semi-structured interviews of psychiatric outpatients (n = 30). The final version of the PASAP is a 9-item, 5-point Likert-type scale, covering the scope of effectiveness and adherence. To assess the psychometric properties of the scale, French patients with an acute manic episode (n = 314) from a large European observational cohort completed the PASAP scale 3 months after psychotropic treatment initiation/change. Internal validity and reliability were assessed using principal component analysis (PCA). Concurrent validity was assessed using comparisons to physician-rated satisfaction with life, illness severity, mood relapse, compliance and side effects.
Participation rate was 68.4%. PCA was in favour of uni-dimensionality. Cronbach's α coefficient was 0.85 (95%CI 0.83–0.88). All five concurrent measures were significantly associated with the PASAP score.
The PASAP scale showed good psychometric properties in a large bipolar population and thus seems adequate for evaluating treatment satisfaction. Its short length and good acceptability makes it suitable for clinical research.
To examine the associations between overall diet quality and hearing function among middle–older aged adults in the USA.
Cross-sectional analysis. Diet quality was examined using the Mediterranean Diet Score (MDS), using data from a single 24 h dietary recall. Hearing function was objectively measured by audiometry assessments and hearing loss, including high- and low-frequency hearing loss, was defined as pure-tone averages at specific ranges of hearing frequencies >25 dB. Weighted logistic regression analyses were performed to examine the associations of MDS (scored 0–9, categorized at the median as ≤3 or >3) with hearing loss and high- and low-frequency hearing loss.
National Health and Nutrition Examination Surveys 2000–2006 and 2009–2012.
Adults aged ≥50 years (n 1639) with valid dietary and audiometry assessments.
After adjusting for potential confounders, a non-significant trend for a protective association of higher MDS was observed for hearing loss (OR = 0·78; 95 % CI 0·49, 1·23). A significant inverse association was observed for high-frequency hearing loss (OR = 0·64; 95 % CI 0·43, 0·95). No association was found for low-frequency hearing loss among women; however, higher MDS was significantly associated with higher odds of low-frequency hearing loss among men (OR = 2·63; 95 % CI 1·39, 4·95).
Among middle–older aged adults, adherence to a Mediterranean-style diet was inversely associated with hearing loss, including those at high hearing frequencies, among older adults. However, a detrimental association was observed at low hearing frequencies among men. Future investigations with a longitudinal design are needed to clarify the associations between diet quality and hearing loss.
Maternal pre-pregnancy weight has been related with young singletons’ cognitive and behavioral development, but it is not clear if it has an effect on temperament. We used a twin cohort to evaluate the association between maternal pre-pregnancy body mass index (BMI) and infants’ temperament. The mothers of 834 twins answered questions regarding their pre-pregnancy BMI and their 0- to 18-month-old children’s temperament using the Revised Infant Behavior Questionnaire. Three temperamental dimensions were examined: activity level, distress to limitation and duration of orienting. The relationship between maternal pre-pregnancy BMI and each temperamental component was investigated by means of multilevel mixed-effects linear regression analysis. We found no clear evidence of an association of maternal pre-pregnancy BMI with twins’ temperament. The development of temperament is influenced by a large number of factors, probably different from those influencing children’s emotional and behavioral development.
We evaluated provider adherence to practice guidelines for inpatients diagnosed with Clostridoides difficile infection (CDI) before and after implementation of a best practice alert (BPA) linking a positive test result to guideline-based orders. After implementation of the BPA, guideline-based prescribing increased from 39.4% in 2013 to 67.7% in 2016 (P = .014).
When Hurricane Harvey landed along the Texas coast on August 25, 2017, it caused massive flooding and damage and displaced tens of thousands of residents of Harris County, Texas. Between August 29 and September 23, Harris County, along with community partners, operated a megashelter at NRG Center, which housed 3365 residents at its peak. Harris County Public Health conducted comprehensive public health surveillance and response at NRG, which comprised disease identification through daily medical record reviews, nightly “cot-to-cot” resident health surveys, and epidemiological consultations; messaging and communications; and implementation of control measures including stringent isolation and hygiene practices, vaccinations, and treatment. Despite the lengthy operation at the densely populated shelter, an early seasonal influenza A (H3) outbreak of 20 cases was quickly identified and confined. Influenza outbreaks in large evacuation shelters after a disaster pose a significant threat to populations already experiencing severe stressors. A holistic surveillance and response model, which consists of coordinated partnerships with onsite agencies, in-time epidemiological consultations, predesigned survey tools, trained staff, enhanced isolation and hygiene practices, and sufficient vaccines, is essential for effective disease identification and control. The lessons learned and successes achieved from this outbreak may serve for future disaster response settings. (Disaster Med Public Health Preparedness. 2019;13:97-101)
The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015–2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015–2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015–2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.
Little is known about the social and emotional well-being of children whose fathers have been deployed to the conflicts in Iraq/Afghanistan or who have post-traumatic stress disorder (PTSD).
To examine the emotional and behavioural well-being of children whose fathers are or have been in the UK armed forces, in particular the effects of paternal deployment to the conflicts in Iraq or Afghanistan and paternal PTSD.
Fathers who had taken part in a large tri-service cohort and had children aged 3–16 years were asked about the emotional and behavioural well-being of their child(ren) and assessed for symptoms of PTSD via online questionnaires and telephone interview.
In total, 621 (67%) fathers participated, providing data on 1044 children. Paternal deployment to Iraq or Afghanistan was not associated with childhood emotional and behavioural difficulties. Paternal probable PTSD were associated with child hyperactivity. This finding was limited to boys and those under 11 years of age.
This study showed that adverse childhood emotional and behavioural well-being was not associated with paternal deployment but was associated with paternal probable PTSD.
Declaration of interest
N.T.F. is a trustee of the Warrior Programme, a charity supporting ex-service personnel and their families. She is also a member of the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee of Combat Stress, a charity supporting ex-service personnel and their families, and President of the Royal Society of Medicine. S.W. is partially funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England (PHE), in collaboration with the University of East Anglia and Newcastle University.