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Psychosis is often a traumatic experience that can lead to significant suffering. However, people may also experience posttraumatic growth following psychosis. Posttraumatic growth refers to the positive changes that people experience following a struggle with an adversarial event and has been shown to occur in at least five domains, including a greater appreciation for life; improved relationships with others; greater personal strengths; new life possibilities and spiritual/existential growth. Studies have shown that mental health services can play a key role in facilitating posttraumatic growth. However, there are no recommendations that clinicians can follow to best support posttraumatic growth following psychosis specifically. Without guidance, clinicians risk invalidating people’s experiences of, or providing improper support for, posttraumatic growth. To address this knowledge gap, we reflect on current research and clinical guidelines to recommend ways that clinicians can support posttraumatic growth following psychosis.
Obesity indicators are known to predict the presence of type 2 diabetes mellitus (T2DM); however, evidence for which indicator best identifies undiagnosed T2DM in the Indian population is still very limited. In the present study we examined the utility of different obesity indicators to identify the presence of undiagnosed T2DM and determined their appropriate cut point for each obesity measure. Individuals were recruited from the large-scale population-based Kerala Diabetes Prevention Program. Oral glucose tolerance tests was performed to diagnose T2DM. Receiver operating characteristic (ROC) curve analyses were used to compare the association of different obesity indicators with T2DM and to determine the optimal cut points for identifying T2DM. A total of 357 new cases of T2DM and 1352 individuals without diabetes were identified. The mean age of the study participants was 46⋅4 (sd 7⋅4) years and 62 % were men. Waist circumference (WC), waist:hip ratio (WHR), waist:height ratio (WHtR), BMI, body fat percentage and fat per square of height were found to be significantly higher (P < 0⋅001) among those with diabetes compared with individuals without diabetes. In addition, ROC for WHR (0⋅67; 95 % 0⋅59, 0⋅75), WHtR (0⋅66; 95 % 0⋅57, 0⋅75) and WC (0⋅64; 95 % 0⋅55, 0⋅73) were shown to better identify patients with T2DM. The proposed cut points with an optimal sensitivity and specificity for WHR, WHtR and WC were 0⋅96, 0⋅56 and 86 cm for men and 0⋅88, 0⋅54 and 83 cm for women, respectively. The present study has shown that WHR, WHtR and WC are better than other anthropometric measures for detecting T2DM in the Indian population. Their utility in clinical practice may better stratify at-risk patients in this population than BMI, which is widely used at present.
OBJECTIVES/SPECIFIC AIMS: Precise biomarkers are urgently needed to characterize the tumor immune microenvironment in primary melanoma tumors both for prognostication and to predict the benefit of immuno-therapeutic intervention. The goal of this work is to define spatial relationships between CD8+ T cells, CD68+ macrophages and Sox10+ melanoma cells in order to define features correlating with prolonged survival METHODS/STUDY POPULATION: Five micrometer slides from either the primary biopsy or subsequent wide local excision procedure were stained using Opal multiplex IHC for DAPI, CD3 (LN10, Leica), CD8 (4B11, Leica), CD68 (KP1, Biogenex), SOX10 (BC34, Biocare), HLA-DR (LN-3, Abcam), and Ki67 (MIB1, Abcam). Cell phenotypes within representative fields preselected by a trained dermato-pathologist and were visualized using the Mantra quantitative pathology workstation (PerkinElmer), and analysis of spatial distribution of CD3+ CD8+ cells analyzed using inForm® image analysis software (PerkinElmer), and Spotfire software (TIBCO). In order to test whether mIHC can better characterize the tumor immune microenvironment, we screened databases at the Herbert Irving Cancer Center (HICC) at Columbia University for stage II/III melanoma patients diagnosed between 2000 and 2012, with available FFPE of primary melanoma tissue and documented clinical follow-up. We identified a preliminary population of 57 patients to begin our analysis. Clinical follow-up was available on 35 patients of whom 21 patients were alive with no evidence of recurrence or died with no evidence of recurrence and 14 had died of melanoma. Twenty-four patients had more than 24 months of survival information available but no detailed clinical information to determine cause of death. RESULTS/ANTICIPATED RESULTS: First, we evaluated whether density of immune cells in tumor and stroma predicted prognosis in 35 patients with disease specific survival information. We find that high number of CD3+CD8+ cells in tumor correlates with Disease Specific Survival (DSS) (p=0.0323*) and CD3+CD8+ cells in stroma may also correlate with DSS (p=0.0671). This is consistent with what is known in the literature regarding tumor infiltrating lymphocytes (TILs). We also found that CD68+ cells in stroma predict poor prognosis (0.0259*). This is consist with the proposed deleterious role for macrophages in tumor progression. Next, using nearest neighbor analysis we examined the effect of HLA-DR and Ki67 expression on spatial distribution of CD3+CD8+ T cells. We find that CD8+ T cells are closer to myeloid (CD68+) cells expressing HLA-DR. This is consistent with the potential of HLA-DR expressing cells to present antigens to T cells, and suggests that T cells may preferentially interact with HLA-DR expressing myeloid cells. Conversely, we find that Ki67 expression on tumor (SOX10+) cells correlates with increased distance from CD3+CD8+ T cells relative to SOX10+Ki67-tumor cells. This finding is consistent with the observation that more advanced tumors with higher mitotic rates have decreased T cell infiltrates, and suggests that dividing melanoma cells are less likely to interact with T cells. In addition, we performed analysis to determine whether spatial relationships defined above impact prognosis. Clinical oncology follow-up was available on 35 of the 57 patients evaluated above. We compared proximity of CD3+CD8+ cells to both myeloid (CD68+) and tumor (SOX10+) cells in patients who recurred and those with no evidence of recurrence. We found that CD3+CD8+ cells in patients who had recurrence were closer to CD68+ HLA-DR− cells than in patients who had no recurrence (t-test, p=0.0377), this correlated with DSS (p=0.003). Conversely, distance from CD3+CD8+ to CD68+ HLA-DR+ in relationship to recurrence was not significant with a trend towards CD3+CD8+ T cells being closer in nonrecurrent patients (t-test, p=0.1362). DISCUSSION/SIGNIFICANCE OF IMPACT: Consistent with the literature, we find that densities of CD8+ T cells correlates with favorable outcomes in early stage melanoma. We also find that density of CD68+ macrophages in stroma correlates with poor outcome. If proximity is a surrogate for interaction, these data indicate that dividing, Ki67+, melanoma cells interact less with CD8+ T cells than do Ki67+ melanoma cells. Further, HLA-DR expression on CD68+ infiltrating cells likely enhances their interaction with T cells. Interestingly, on further analysis, CD3+CD8+ cells were significantly closer to CD68+ HLA-DR− cells in patients who recurred, implying that interactions between these cell types may not be favorable. This analysis demonstrates that spatial analysis may be useful in predicting prognosis in early stage melanoma, and this is the first report of this type of analysis predicting outcomes in primary tumor specimens to our knowledge. Further staining and analysis of the complete patient cohort (n=120) is ongoing.
Objectives: The aim of this study was to evaluate the reliability and validity of three computerized neurocognitive assessment tools (CNTs; i.e., ANAM, DANA, and ImPACT) for assessing mild traumatic brain injury (mTBI) in patients recruited through a level I trauma center emergency department (ED). Methods: mTBI (n=94) and matched trauma control (n=80) subjects recruited from a level I trauma center emergency department completed symptom and neurocognitive assessments within 72 hr of injury and at 15 and 45 days post-injury. Concussion symptoms were also assessed via phone at 8 days post-injury. Results: CNTs did not differentiate between groups at any time point (e.g., M 72-hr Cohen’s d=−.16, .02, and .00 for ANAM, DANA, and ImPACT, respectively; negative values reflect greater impairment in the mTBI group). Roughly a quarter of stability coefficients were over .70 across measures and test–retest intervals in controls. In contrast, concussion symptom score differentiated mTBI vs. control groups acutely), with this effect size diminished over time (72-hr and day 8, 15, and 45 Cohen’s d=−.78, −.60, −.49, and −.35, respectively). Conclusions: The CNTs evaluated, developed and widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in sport-related concussion studies. Nonspecific injury factors, and other characteristics common in ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs for assessing mTBI in this patient population. (JINS, 2017, 23, 293–303)
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = −.24–.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment. (JINS, 2013, 19, 1–10)
Loring et al. (Journal of Clinical and Experimental Neuropsychology, 2005:27;610–617) observed relationships between VSVT hard item performance and IQ and memory indices in epilepsy surgical candidates, with a potential confound of low FSIQ on VSVT performance. The present study replicated the Loring et al. study in a larger sample and extended their findings by examining the relationships among VSVT performance, FSIQ, and working memory. A total of 404 patients with medically intractable epilepsy completed a comprehensive neuropsychological assessment. Differences in WAIS-III and WMS-III performance were examined as a function of VSVT hard score categories as determined by Grote et al. (2000)—that is, valid, >20/24; questionable, 18–20; or invalid, <18. Quantile regression models were constructed to compare the strength of the relationship between FSIQ and VSVT at various points of the FSIQ distribution. Linear regression analyses examined working memory as a potential mediator between FSIQ and VSVT performance. The invalid group performed more poorly than the valid and questionable groups on multiple measures of intelligence and memory. The strength of the relationship between FSIQ and VSVT hard item performance decreased as FSIQ increased, and working memory mediated this relationship. Results suggest VSVT hard item scores may be impacted by working memory difficulties and/or low intellectual functioning. (JINS, 2013, 19, 1–10)
School-based health services (SBHS) including pastoral care can play a pivotal role in addressing adolescent health and wellbeing; including their tobacco and other drug use. To maximise the benefits of these services, they need to be accessible, useful for, and acceptable to students. This formative, qualitative study involved 12 focus groups within nine lower socio-economic Western Australian Government secondary schools. The purpose was to identify student (n = 59) perceptions of the availability and usefulness of SBHS (and other identified caring staff) to reduce students’ harm associated with tobacco and other drug use. The findings suggest students were aware of the SBHS available to them, but considered them less useful if staff were regularly unavailable; presented a ‘don't care’ attitude; held solely disciplinary roles; and were based in an area of the school unfamiliar to the student. Services were considered useful when staff members built rapport with students; took time to listen; followed-up with students and displayed a general concern for the student's wellbeing. Interestingly, students acknowledged trusting health teachers more than SBHS staff for tobacco information and support. These findings have important implications for school counsellors and other school health/pastoral care staff who want to increase the likelihood of students approaching and using school support services to reduce harm associated with tobacco and other harmful drug (OHD) use.
While longitudinal studies of children treated for brain tumors have consistently revealed declines on measures of intellectual functioning, greater specification of cognitive changes following treatment is imperative for isolating vulnerable neural systems and developing targeted interventions. Accordingly, this cross-sectional study evaluated the performance of childhood brain tumor survivors (n = 50) treated with conformal radiation therapy, solid tumor survivors (n = 40) who had not received central nervous system (CNS) -directed therapy, and healthy sibling controls (n = 40) on measures of working memory [Digit Span and computerized self-ordered search (SOS) tasks]. Findings revealed childhood brain tumor survivors were impaired on both traditional [Digit Span Backward- F(2,127)= 5.98; p < .01] and experimental [SOS-Verbal- F(2,124)= 4.18; p < .05; SOS-Object- F(2,126)= 5.29; p < .01] measures of working memory, and performance on working memory measures correlated with intellectual functioning (Digit Span Backward- r = .45; p < .0001; SOS- r = −.32 to −.26; p < .01). Comparison of performance on working memory tasks to recognition memory tasks (computerized delayed match-to-sample) offered some support for greater working memory impairment. This pattern of findings is consistent with vulnerability in functional networks that include prefrontal brain regions and has implications for the clinical management of children with brain tumors. (JINS, 2012, 18, 1–10)
The issue of detention as a tuberculosis control measure has resurfaced following the prolonged detention of a patient with an extensively drug-resistant strain of tuberculosis in a prison cell in Arizona, and the attempted detention in Italy and subsequent detention in Atlanta, Georgia of an American sufferer thought to have XDR-TB in May 2007. These cases have reignited the debate over the evidence that supports detention policy in the control of tuberculosis, and its associated legal and ethical ramifications. This paper considers whether involuntary detention is justified where voluntary measures have failed or where a patient poses a danger, albeit uncertain, to the public, and discusses the need for strengthening evidencebased assessments of public health risk.
Rates can account for population size and time intervals. To generate a rate, the population from which the counts arose must be defined. Population size is a common choice for a denominator. Many geopolitical regions, such as cities or countries, create estimates of the population during a given year. Cumulative incidence is commonly used when the entire population from which the incident cases arise can be counted and followed to the conclusion of the observation period. Proportional incidence or proportional mortality is sometimes used when an accurate denominator is not available. A more formal statistical test of a difference in two proportions is the chi-squared test; large sample and exact methods are available in virtually any statistical package. To compare the rates of injury in two or more regions, or between time periods, it is sometimes desirable to adjust for other factors, which may confound the comparison.
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