Loneliness partially mediates the relation between substance use and suicidality in Veterans.

America has experienced a rapid increase in loneliness, substance use, and suicidality. This increase is particularly deleterious for Veterans, who, as compared to nonmilitary-connected civilians, experience elevated rates of loneliness, substance use, and suicidality. In this project we investigated the link between loneliness, substance use, and suicidality, paying particular attention to the mediational role of loneliness between substance use and suicidality. 1,469 Veterans (male, n = 1004, 67.2%; female, n = 457, 32.3%; transgender/non-binary/prefer not to say, n = 8, 0.5%) answered online surveys in the Mental Health and Well-Being Project. Items assessed participants on psychosocial antecedents of health and wellness. Pearson correlations and mediational models were used to determine if loneliness, substance use, and suicidality were related and if loneliness mediated the link between substance use and suicidality. Results indicated that loneliness, substance use, and suicidality were significantly and positively related (rs = .33-.42, ps < .01). Additionally, loneliness partially mediated the link between substance use and suicidality (ß = .08 [.06-.10]), suggesting that, within the context of substance use in Veterans, loneliness may account for significant variance in suicidality. Together findings suggest the Veterans Health Administration should support, fund, and study community engagement activities that could reduce the development or intensity of substance use, loneliness, and suicidality in Veterans.

Examining Blunted Initial Response to Reward and Recent Suicidal Ideation in Children and Adolescents Using Event-Related Potentials: Failure to Conceptually Replicate Across Two Independent Samples.

A recent study by Tsypes and colleagues (2019) found that children with recent suicidal ideation had blunted neural reward processing, as measured by the reward positivity (RewP), compared to matched controls, and that this difference was driven by reduced neural responses to monetary loss, rather than to reward. Here, we aimed to conceptually replicate and extend these findings in two samples (n = 264, 27 with suicidal ideation; and n = 314, 49 with suicidal ideation at baseline) of children and adolescents (11 to 15 years and 8 to 15 years, respectively). Results from both samples showed no evidence that children and adolescents with suicidal ideation have abnormal reward or loss processing, nor that reward processing predicts suicidal ideation two years later. The results highlight the need for greater statistical power, as well as continued research examining the neural underpinnings of suicidal thoughts and behaviors.

Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.

Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy for hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; however, few have assessed long-term hepatic function. This study aimed to evaluate a clinical real-world experience of Y90 effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with Child-Pugh (CP) class A or B who received Y90 for primary HCC between 2008 and 2016. Model for end-stage liver disease (MELD) and CP scores were calculated on the day of treatment and 1, 3, 6, 12, and 24 months post-procedure. Results: Of the 134 patients included, the mean age was 60 years old and median overall survival (OS) from date of diagnosis was 28 months [95% confidence interval (CI): 22.21-38.05]. Patients with CP class A (85%) had a median progression-free survival (PFS) of 3 months (95% CI: 2.99-5.55) and median OS of 17 months (95% CI: 9.59-23.10) from date of Y90 treatment compared to a median PFS of 4 months (95% CI: 2.07-8.28) and OS of 8 months (95% CI: 4.60-15.64) for patients with CP class B. MELD scores were significantly higher post-treatment than pre-treatment, with significant recovery at 24 months. No significant differences were seen between cancer stage and OS, while PFS and cancer stage did show difference between cancer stage 1 and 3 with longer median PFS seen in stage 1. Conclusions: While our study supports the literature for OS in Y90-treated patients, we found a shorter PFS in this population. This may reflect the differences between the utilization of RECIST in clinical trials and clinical radiology practice in determining progression. Significant factors associated with OS were age, MELD, CP scores and portal vein thrombosis (PVT). For PFS, CP score and stage at diagnosis were significant. Increasing MELD scores over time likely reflected a combination of radioembolization-induced liver disease, liver decompensation or progression of HCC. The downtrend at 24 months is likely due to long term survivors with significant benefit from therapy with no long-term complications from Y90.

Refractory Immune Thrombocytopenic Purpura with Abdominal Splenosis: A Complex Case.

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia resulting from immune-mediated platelet destruction via antiplatelet antibodies and T cells. Medical management of ITP includes corticosteroids and multiple other adjunct therapies, with splenectomy generally being reserved for severe, refractory cases. In this clinical case report, we describe the evaluation of a 35-year-old male with a history of prior traumatic splenic injury who presented to the emergency department endorsing easy bruising and a petechial rash, ultimately found to have severe thrombocytopenia. The patient was diagnosed with primary ITP that proved to be refractory to a number of first- and second-line medical therapies. His course was complicated by the presence of abdominal splenosis discovered at the time of planned splenectomy and intra-abdominal hemorrhage requiring splenic artery embolization thereafter. To our knowledge, this is one of few published cases of ITP complicated by abdominal splenosis, highlighting the need to consider splenosis and the presence of accessory splenic tissue in cases of refractory ITP.

Extreme hyperferritinemia without associated HLH in a patient with T-cell lymphoma.

Extreme hyperferritinemia has historically been associated with a short list of rare diagnoses, including hemophagocytic lymphohistiocytosis (HLH). However, hyperferritinemia is not specific for HLH in the adult population. Among other more common causes, T-cell lymphoma and other malignancies warrant evaluation prior to considering more rare diagnoses.

Understanding Differences in Health Care Spending: A Comparative Study of Prices and Volumes Across OECD Countries.

Variations across OECD countries in the prices of health care and hospital services can be vast. These price differences mean that comparisons of such services should be adjusted to reflect the 'real' volumes consumed. Purchasing power parities (PPPs) can be used to make such comparisons more accurately, going beyond simple GDP-based comparisons, by aggregating the prices of actual individual consumption of health items. These health and hospital PPPs demonstrate that GDP PPPs are a weak substitute, as price structures vary widely. Moreover, there is tentative evidence that higher relative prices for health care tend to bloat health expenditure and are associated with lower life expectancy.

And as things have been they remain: Enteric disease and differential mortality among ethnic groups in early twentieth century Milwaukee.

OBJECTIVE: This project aims to document enteric disease mortality differentials between German, Irish and Polish communities in Milwaukee, Wisconsin during the early twentieth century. At that time, residential segregation by ethnicity was common as was access to gainful employment. The Polish had the least access to adequately paid jobs and consequently resided in the area of the city adjacent to waterways used for waste disposal. MATERIALS: A total of 14,573 death certificates were examined for the years 1901 through 1905. The certificates include name, places of birth and death, age, sex and cause of death. METHODS: Deaths from enteric diseases have been compiled for each ethnic group along with age and sex. Incomplete certificates were excluded from the analysis. RESULTS: A total of 1038 enteric disease deaths were noted. All ethnic groups were affected with the greatest impact in the Polish community. The highest risk was among infants and children in all ethnic groups. CONCLUSIONS: Mortality differentials resulted from unequal access to safe water and sewage systems in neighborhoods segregated by ethnicity. SIGNIFICANCE: The data demonstrate variation in the timing of the epidemiologic transition among communities separated by only a few kilometers. LIMITATIONS: Water- and food borne sources of enteric disease could not be differentiated. SUGGESTIONS FOR FURTHER RESEARCH: The effect of living conditions in these communities can be further studied by analyses of respiratory diseases. This can be expanded by detailed analyses of infant and child mortality.

The impact of decentralisation on the performance of health care systems: a non-linear relationship.

This paper examines the role of institutions-notably the degree of administrative decentralisation across levels of government-in health care decision-making and health spending as well as life expectancy. The empirical analysis builds on a new methodology to analyse health sector performance. In particular, the present analysis examines the impact of centralisation versus decentralisation of responsibilities across levels of government, making use of newly collected data on governance and expenditure assignment, as well as non-linear empirical specifications. An interlocking U-shaped relationship is found with respect to expenditure and life expectancy. Under moderate decentralisation, public spending in health care is lower, while life expectancy is higher, compared with more centralised systems; however, in highly decentralised systems, public spending is higher and life expectancy is lower. This finding of a "fish-shaped" relationship for decentralisation and outcomes also helps to understand recent reforms of OECD health systems, which have often reverted towards more moderate degrees of administrative decentralisation.

IgA Nephropathy Secondary to Ipilimumab Use.

Ipilimumab is a human monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 approved for the treatment of non-small-cell lung cancer (NSCLC) and other malignancies. Despite a high prevalence of other immune-related adverse events (irAEs), checkpoint inhibitor (CPI)-related nephrotoxicity has been reported less frequently. In this clinical case report, we describe the evaluation of a 70-year-old female with stage IV NSCLC who presented with nephrotic range proteinuria 4 weeks after receiving her first cycle of ipilimumab. She underwent a renal biopsy and was found to have IgA nephropathy that was presumed to be secondary to ipilimumab use, given recent initiation of therapy and clinical history. Unfortunately, despite prompt initiation of corticosteroids, her acute kidney injury progressed and she required hemodialysis, later transitioning to hospice. To our knowledge, this is one of few reported cases of IgA nephropathy secondary to CPI use. With increasing use of CPIs, this case further emphasizes the need for continued surveillance for irAEs, which can occur at any point in a patient's treatment course.

Are all pain tolerance tasks the same? Convergent validity of four behavioral pain tolerance tasks, self-reported capability for suicide, and lifetime self-injurious behaviors.

OBJECTIVES: Discrepancies persist regarding the extent to which different pain measures provide similar information and relate to capability for suicide and self-injurious behaviors. This study examined pain threshold, tolerance, and persistence across four modalities (cold, heat, pressure, shock) and assessed associations with self-reported capability for suicide, non-suicidal self-injury (NSSI), and suicide attempts. METHODS: A sample of 211 students who reported lifetime suicidal ideation completed four behavioral pain tasks and self-reported on capability for suicide, NSSI, and self-injurious behaviors. RESULTS: All pain thresholds, tolerances, and persistences were positively correlated across the four tasks. Pain facets were related to self-reported capability for suicide with small effect sizes but generally did not differ across suicide attempt or NSSI histories. CONCLUSIONS: Pain thresholds, tolerances, and persistences demonstrated convergent validity across the four modalities, suggesting that these tasks provide similar information. Although the relation between pain and self-injurious behaviors remains unclear, these tasks can generally be used interchangeably.

Suicidal thoughts, behaviors, and event-related potentials: A systematic review and meta-analysis.

Suicidal thoughts and behaviors (STBs) are thought to result from, at least in part, abnormalities in various neural systems. Event-related potentials (ERPs) are a useful method for studying neural activity and can be leveraged to study neural deficits related to STBs; however, it is unknown how effective ERPs are at differentiating various STB groups. The present meta-analysis examined how well ERPs can differentiate (a) those with and without suicidal ideation, (b) those with and without suicide attempts, (c) those with different levels of suicide risk, and (d) differences between those with suicide attempts versus those with suicidal ideation only. This meta-analysis included 208 effect sizes from 2,517 participants from 27 studies. We used a random-effects meta-analysis using a restricted maximum likelihood estimator with robust variance estimation. We meta-analyzed ERP-STB combinations that had at least three effect sizes across two or more studies. A qualitative review found that for each ERP and STB combination, the literature is highly mixed. Our meta-analyses largely did not find significant relationships between STBs and ERPs. We also found that the literature is likely severely underpowered, with most studies only being sufficiently powered to detect unrealistically large effect sizes. Our results provided little-to-no support for a reliable relationship between the ERPs assessed and STBs. However, the current literature is severely underpowered, and there are many methodological weaknesses that must be resolved before making this determination. We recommend large-scale collaboration and improvements in measurement practices to combat the issues in this literature.

On prediction, refutation, and explanatory reach: A consideration of the Interpersonal Theory of Suicidal Behavior.

Theory proposition, empirical evaluation, and resulting support or refutation are core pieces of the scientific process. These steps of theory-testing, however, can be complicated by relative rigidity and dogmatism, in combination with the logistical challenges inherent in conducting comprehensive, real-world tests of theories explicating complex scientific phenomena, especially rare ones. It may be argued that suicide is one such phenomenon, and one for which the field of psychology has struggled to develop satisfactory understanding. One leading theory of suicide, the Interpersonal Theory of Suicide, has garnered attention and, to a considerable degree, has weathered substantial scrutiny. Still, it is arguable that the theory has yet to be tested in full-that is, in accordance with all propositions originally put forth. In this effort, we sought to evaluate the current state of knowledge regarding the Interpersonal Theory of Suicide, as well as to suggest potential directions via which future work may proceed. We draw from the fields of philosophy, psychology, physics, and engineering in the hopes of engendering curiosity and critical thought about the assumptions researchers (ourselves included) bring to their work. We direct particular attention to the role of refutation in theory-testing; the supposed dichotomy of explanatory vs. algorithmic approaches; and the categorization of research programs as progressive vs. degenerative. In doing so, we hope not only to promote these ideas in the study of suicidal behavior but also to empiricists of all creeds and foci. We also include implications for suicide prevention efforts.

Interoception, Pain Tolerance, and Self-Injurious Behaviors: A Multidimensional Assessment.

Impairments in interoception have been linked to self-injurious behaviors, and capability for suicide may account for this relationship. However, past studies have relied primarily on self-report and unidimensional measures. The present study aimed to replicate and extend previous findings by examining the relationship between interoceptive dysfunction, pain tolerance, and self-injurious behaviors using a multidimensional and multi-method approach. A sample of 245 undergraduate students (Mage = 19.27 years, SD = 2.81; 73.7% female, 72.% White/European American), who reported lifetime suicidal ideation on a screening survey completed a battery of self-report measures, four counterbalanced pain tolerance tasks, and a clinical interview assessing their self-injurious behaviors. A tendency to stay attuned to bodily sensations was significantly related to decreased pain tolerance. Only trust in one's body was significantly related to decreased presence of lifetime suicide attempts. No other facets of interoception or pain tolerance were significantly associated with self-injurious behaviors. Overall, these findings contrast with previous findings that capability for suicide may account for relations between interoceptive dysfunction and self-injurious behaviors. Nonetheless, the results of this study provide important information on the factor structure of interoceptive dysfunction and pain tolerance, and highlight the importance of careful selection of measures and operationalization of key constructs, particularly interoceptive dysfunction and pain tolerance.

Drug-induced immune-mediated thrombocytopenia secondary to durvalumab use.

Immunotherapy is an expanding area of cancer treatment with significant promise. Despite their efficacy, checkpoint inhibitors are associated with a number of immune-related adverse events; here, we described thrombocytopenia secondary todurvalumab.

Myeloid Cell Infiltration Correlates With Prognosis in Cholangiocarcinoma and Varies Based on Tumor Location.

Cholangiocarcinoma (CC) is an uncommon malignancy with increasing incidence and dismal prognosis. We conducted a comprehensive analysis of the CC tumor immune microenvironment (TIME) based on tumor location to identify therapeutic targets. We hypothesized that the TIME of CC would vary by primary tumor location and that high tumor infiltration by CD8+ T cells and low infiltration by M2 macrophages would be associated with improved survival. A retrospective analysis was conducted of 99 CC tumor samples surgically resected between 2000 and 2014. Tissue microarrays were constructed from each tumor and stained by immunohistochemistry for 24 markers of immune cells, immune activation or inhibition, programmed cell death-ligand 1, and mesothelin. Most tumors were amply infiltrated with by CD4+, CD8+, and FoxP3+ T cells, as well as by myeloid cells. Mesothelin expression ≥1+ by immunohistochemistry was found in 68% of tumors. We identified higher densities of M1 macrophages in primary distal extrahepatic CC, as well as metastatic lesions. Mesothelin expression was also significantly higher in distal extrahepatic CC. There was no association with survival of infiltration by CD4+, CD8+, or FoxP3+ T cells, mesothelin expression, or programmed cell death-ligand 1 percentage expression, however, high CD14+ myeloid cells and high CD163+ M2 macrophages were associated with worse survival. In conclusion, the CC TIME is a heterogenous milieu highly infiltrated by innate and adaptive immune cells, which differs based on primary tumor location and between primary tumors and metastatic lesions. The correlation of intratumoral M2 macrophages and myeloid cells with a worse prognosis may suggest promising immunotherapeutic targets in CC.

Global transcriptomic analysis of a murine osteocytic cell line subjected to spaceflight.

Bone loss is a major health concern for astronauts during long-term spaceflight and for patients during prolonged bed rest or paralysis. Growing evidence suggests that osteocytes, the most abundant cells in the mineralized bone matrix, play a key role in sensing mechanical forces applied to the skeleton and integrating the orchestrated response into subcellular biochemical signals to modulate bone homeostasis. However, the precise molecular mechanisms underlying both mechanosensation and mechanotransduction in late-osteoblast-to-osteocyte cells under microgravity (µG) have yet to be elucidated. To unravel the mechanisms by which late osteoblasts and osteocytes sense and respond to mechanical unloading, we exposed the osteocytic cell line, Ocy454, to 2, 4, or 6 days of µG on the SpaceX Dragon-6 resupply mission to the International Space Station. Our results showed that µG impairs the differentiation of osteocytes, consistent with prior osteoblast spaceflight experiments, which resulted in the downregulation of key osteocytic genes. Importantly, we demonstrate the modulation of critical glycolysis pathways in osteocytes subjected to microgravity and discovered a set of mechanical sensitive genes that are consistently regulated in multiple cell types exposed to microgravity suggesting a common, yet to be fully elucidated, genome-wide response to microgravity. Ground-based simulated microgravity experiments utilizing the NASA rotating-wall-vessel were unable to adequately replicate the changes in microgravity exposure highlighting the importance of spaceflight missions to understand the unique environmental stress that microgravity presents to diverse cell types. In summary, our findings demonstrate that osteocytes respond to µG with an increase in glucose metabolism and oxygen consumption.

Attitudes towards and use of cannabis in New Zealand patients with inflammatory bowel disease: an exploratory study.

AIMS: We aimed to assess the use of and attitudes towards cannabis use (medicinal and recreational) by people with IBD in New Zealand. METHODS: People with IBD were invited to complete an anonymous online questionnaire. Participants were recruited via postal mail using a hospital database of patients with IBD (developed by the Gas-troenterology Department at Dunedin Public Hospital) and via online recruitment (advertised on the Crohn's and Colitis New Zealand website, Facebook page and e-mail list). Inclusion criteria were ages 18+ and self-reported confirmed IBD diagnosis. RESULTS: In total, 378 participants completed the questionnaire, with 334 eligible responses. Partici-pants were predominantly New Zealand European (84%) and female (71%). Sixty-one percent of re-spondents had CD and 34% UC. Overall, 51% of respondents reported having ever used cannabis. Of those, 63% reported use as recreational and 31% for reduction of IBD symptoms. Users were more likely to be younger (on average by 6.4 years), with on-going symptoms, unemployed or self-employed and current or ex-smokers. There were no differences by disease status or severity. Symp-toms most reported as improved by cannabis use were abdominal pain/cramping, nausea/vomiting and loss of appetite. Fifty-four percent of participants reported that if cannabis were legal, they would request it for medicinal use to help manage their symptoms. CONCLUSIONS: Overall, our research aligns with previous observational research that reports im-provements in symptoms of IBD with cannabis use. Studies of a higher evidence level (eg, RCTs) would be needed to guide prescribing. In the meantime, this research provides useful background to clini-cians about patients' views and experiences.

Routinized categorization of suicide risk into actionable strata: Establishing the validity of an existing suicide risk assessment framework in an outpatient sample.

OBJECTIVE: The Suicide Risk Assessment and Management Decision Tree (DT) is a clinician-administered assessment that leads to risk categorizations that correspond with actionable strata. This study investigated the construct validity and test-retest reliability of the DT risk categories across two time points. METHOD: Outpatients (N = 731) completed a battery of self-report measures. Spearman's correlations were used to examine the relationships between DT suicide risk level and suicidal symptoms, theory-based risk factors, psychiatric correlates, and DT suicide risk level at Timepoint 2. Correlations were analyzed for significant differences to examine the divergent validity of the DT. RESULTS: Results, overall, were in line with hypotheses, with the exception of depression and thwarted belongingness. CONCLUSIONS: Findings provide evidence for the reliability, convergent validity, and discriminant validity of the DT. This clinician-administered suicide risk assessment may be useful for standardization of the assessment and management of suicide risk in outpatient clinical settings.