Integrating personalized experience sampling in psychotherapy: A case illustration of the Therap-i module.

Background: The experience sampling methodology (ESM) is increasingly being suggested as a clinical tool in mental health care, as it offers ecologically valid, microlevel information on psychopathological processes. Patients and clinicians have recommended that applications of ESM should be personalized and integrated into the existing clinical process, but there is still much uncertainty about how implementation may look like. Objective: To provide an example of personalized ESM assessment and feedback being integrated into psychotherapy for depression, specifically looking at the collaborative use of ESM in case conceptualization. Methods: George, a 27-year-old man diagnosed with depression, and his therapist participated in the Therap-i randomized controlled trial, which investigates the efficacy of a personalized ESM module added to psychotherapy. Together, they created a personalized ESM questionnaire, aiming to capture their hypotheses and questions regarding George's case conceptualization. George then filled out his ESM questionnaire five times per day, for 8 weeks. During this period, ESM data were discussed and interpreted by George, his therapist, and a researcher, in three feedback sessions. In these sessions, data were visualized in a flexible feedback interface that allowed for collaborative exploration of George's data. Both patient and therapist evaluated the module through questionnaires and George also participated in a semi-structured evaluation interview. Results: George's ESM questionnaire included personalized items on the topics of self-esteem and open versus withdrawn behavior. He completed 241 (89.3%) assessments. Discussions during the feedback sessions focused on two core themes: First, George's low energy level, which was further explored with regard to his sleep, medication, and activity patterns. Second, his low sense of self-esteem, which led to an in-depth exploration of his thinking patterns and social interactions. The ESM module was seen as useful and insightful by both George and therapist. Conclusions: This case shows how ESM and ESM-based feedback can stimulate the collaborative exploration of the patient's complaints, and how it can provide useful insights for treatment. We discuss how our personalized ESM module relates to current clinical principles and practices, and make suggestions for further implementation.

A clinical PREMISE for personalized models: Toward a formal integration of case formulations and statistical networks.

Over the past decade, the idiographic approach has received significant attention in clinical psychology, incentivizing the development of novel approaches to estimate statistical models, such as personalized networks. Although the notion of such networks aligns well with the way clinicians think and reason, there are currently several barriers to implementation that limit their clinical utility. To address these issues, we introduce the Prior Elicitation Module for Idiographic System Estimation (PREMISE), a novel approach that formally integrates case formulations with personalized network estimation via prior elicitation and Bayesian inference. PREMISE tackles current implementation barriers of personalized networks; incorporating clinical information into personalized network estimation systematically allows theoretical and data-driven integration, supporting clinician and patient collaboration when building a dynamic understanding of the patient's psychopathology. To illustrate its potential, we estimate clinically informed networks for a patient suffering from obsessive-compulsive disorder. We discuss open challenges in selecting statistical models for PREMISE, as well as specific future directions for clinical implementation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cannabidiol enhancement of exposure therapy in treatment refractory patients with social anxiety disorder and panic disorder with agoraphobia: A randomised controlled trial.

Preclinical research suggests that enhancing CB1 receptor agonism may improve fear extinction. In order to translate this knowledge into a clinical application we examined whether cannabidiol (CBD), a hydrolysis inhibitor of the endogenous CB1 receptor agonist anandamide (AEA), would enhance the effects of exposure therapy in treatment refractory patients with anxiety disorders. Patients with panic disorder with agoraphobia or social anxiety disorder were recruited for a double-blind parallel randomised controlled trial at three mental health care centres in the Netherlands. Eight therapist-assisted exposure in vivo sessions (weekly, outpatient) were augmented with 300 mg oral CBD (n = 39) or placebo (n = 41). The Fear Questionnaire (FQ) was assessed at baseline, mid- and post-treatment, and at 3 and 6 months follow-up. Primary analyses were on an intent-to-treat basis. No differences were found in treatment outcome over time between CBD and placebo on FQ scores, neither across (ß = 0.32, 95% CI [-0.60; 1.25]) nor within diagnosis groups (ß = -0.11, 95% CI [-1.62; 1.40]). In contrast to our hypotheses, CBD augmentation did not enhance early treatment response, within-session fear extinction or extinction learning. Incidence of adverse effects was equal in the CBD (n = 4, 10.3%) and placebo condition (n = 6, 15.4%). In this first clinical trial examining CBD as an adjunctive therapy in anxiety disorders, CBD did not improve treatment outcome. Future clinical trials may investigate different dosage regimens.

Anxiety in Late-Life Depression: Determinants of the Course of Anxiety and Complete Remission.

OBJECTIVE: Studies on the course of depression often ignore comorbid anxiety disorders or anxiety symptoms. We explored predictors of complete remission (no depression nor anxiety diagnoses at follow-up) and of the course of comorbid anxiety symptoms. We additionally tested the hypothesis that the course of anxiety disorders and symptoms in depressed patients is explained by negative life-events in the presence of high neuroticism or a low sense of mastery. METHODS: An observational study of 270 patients (≥60 years) diagnosed with major depressive disorder and 2-year follow-up data, who participated in the Netherlands Study of Depression in Older persons (NESDO). Sociodemographic, somatic, psychiatric, and treatment variables were first explored as possible predictors. A multiple logistic regression analysis was used to examine their predictive value concerning complete remission. Subsequently, negative life-events, personality and their interaction were tested as potential predictors. Linear Mixed Models were used to assess whether the personality traits modified the effect of early and recent life-events, and time and their interactions on the course of the anxiety symptoms. RESULTS: A total of 135 of 270 patients achieved complete remission. Depressed patients with a comorbid anxiety disorder at baseline less often achieved complete remission: 38 of 103 (37.0%) versus 97 of 167 (58.1%). The severity of depressive and anxiety symptomatology, the presence of a comorbid anxiety disorder, and a poorer physical health at baseline predicted nonremission. In line with our hypothesis, a less favorable course of self-reported anxiety symptoms was associated with more recent negative life-events, but only among patients with a high level of neuroticism or a low level of mastery. CONCLUSION: Comorbid anxiety in depression as a negative impact on complete remission at 2-year follow-up. The course of anxiety severity seems dependent on the interaction of personality traits and life-events.

ESMvis: a tool for visualizing individual Experience Sampling Method (ESM) data.

PURPOSE: The experience sampling method (ESM) is used for intensive longitudinal time-series data collection during normal daily life. ESM data give information on momentary affect, activities and (social) context of, for example, patients suffering from mental disorders, and allows for person-specific feedback reports. However, current personalized feedback reports only display a selection of measured variables, and typically involve only summary statistics, thus not reflecting the dynamic fluctuations in affect and its influencing factors. To address this shortcoming, we developed a tool for dynamically visualizing ESM data. METHODS: We introduce a new framework, ESMvis, for giving descriptive feedback, focusing on direct visualization of the dynamic nature of raw data. In this ESM feedback approach, raw ESM data are visualized using R software. We applied ESMvis to data collected for over 52 weeks on a patient diagnosed with an obsessive-compulsive disorder with comorbid depression. RESULTS: We provided personalized feedback, in which both the overall trajectory and specific time moments were captured in a movie format. Two relapses during the study period could be visually determined, and subsequently confirmed by the therapist. The therapist and patient evaluated ESMvis as an insightful add-on tool to care-as-usual. CONCLUSION: ESMvis is a showcase on providing personalized feedback by dynamic visualization of ESM time-series data. Our tool is freely available and adjustable, making it widely applicable. In addition to potential applications in clinical practice, ESMvis can work as an exploratory tool that can lead to new hypotheses and inform more complex statistical techniques.

Using person-specific networks in psychotherapy: challenges, limitations, and how we could use them anyway.

BACKGROUND: The complexity of psychopathology is evident from its multifactorial etiology and diversity of symptom profiles and hampers effective treatment. In psychotherapy, therapists approach this complexity by using case conceptualization. During this process, patients and therapists closely collaborate on a personalized working theory of the patient's psychopathology. This is a challenging process and shows low reliability between therapists. With the experience sampling method (ESM), time-series data-valuable for case conceptualization-can be systematically gathered in a patient's normal daily life. These data can be analyzed and visualized in person-specific networks (PSNs). PSNs may support case conceptualization by providing a schematic representation of association patterns between affective, cognitive, behavioral, and context variables. MAIN TEXT: We adopt a clinical perspective in considering how PSNs might be implemented to serve case conceptualization and what their role could be in psychotherapy. We suggest PSNs to be based on personalized ESM assessment to capture the unique constellation of variables in each patient. We reflect on the lack of a gold standard for creating PSNs, which may result in substantially different PSNs and thereby disparate information for case conceptualization. Moreover, even if PSNs are created in a consistent manner, results remain ambiguous as they are subject to multiple interpretations. Therefore, associations in PSNs do not allow for firm conclusions about a patient's psychopathology, but they may nevertheless be valuable in the process of case conceptualization. PSNs are based on systematically gathered, ecologically valid ESM data and provide a unique personalized perspective. When used responsibly, PSNs may be able to support case conceptualization by generating questions that serve as a starting point for a dialog between therapists and patients. Well-targeted questions are an essential tool for therapists to gain insight into the patients' psychopathology patterns and improve the quality of case conceptualization. CONCLUSIONS: PSNs have limitations in terms of the reliability of the insights they provide directly. However, taking these challenges into account, we believe they have potential as a tool to help therapists and patients in their collaborative exploration of a patient's psychopathology. Clearly, this would need to be validated in future clinical research.

Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology.

OBJECTIVE: One of the promises of the experience sampling methodology (ESM) is that a statistical analysis of an individual's emotions, cognitions and behaviors in everyday-life could be used to identify relevant treatment targets. A requisite for clinical implementation is that outcomes of such person-specific time-series analyses are not wholly contingent on the researcher performing them. METHODS: To evaluate this, we crowdsourced the analysis of one individual patient's ESM data to 12 prominent research teams, asking them what symptom(s) they would advise the treating clinician to target in subsequent treatment. RESULTS: Variation was evident at different stages of the analysis, from preprocessing steps (e.g., variable selection, clustering, handling of missing data) to the type of statistics and rationale for selecting targets. Most teams did include a type of vector autoregressive model, examining relations between symptoms over time. Although most teams were confident their selected targets would provide useful information to the clinician, not one recommendation was similar: both the number (0-16) and nature of selected targets varied widely. CONCLUSION: This study makes transparent that the selection of treatment targets based on personalized models using ESM data is currently highly conditional on subjective analytical choices and highlights key conceptual and methodological issues that need to be addressed in moving towards clinical implementation.

Bridging the gap between complexity science and clinical practice by formalizing idiographic theories: a computational model of functional analysis.

BACKGROUND: The past decades of research have seen an increase in statistical tools to explore the complex dynamics of mental health from patient data, yet the application of these tools in clinical practice remains uncommon. This is surprising, given that clinical reasoning, e.g., case conceptualizations, largely coincides with the dynamical system approach. We argue that the gap between statistical tools and clinical practice can partly be explained by the fact that current estimation techniques disregard theoretical and practical considerations relevant to psychotherapy. To address this issue, we propose that case conceptualizations should be formalized. We illustrate this approach by introducing a computational model of functional analysis, a framework commonly used by practitioners to formulate case conceptualizations and design patient-tailored treatment. METHODS: We outline the general approach of formalizing idiographic theories, drawing on the example of a functional analysis for a patient suffering from panic disorder. We specified the system using a series of differential equations and simulated different scenarios; first, we simulated data without intervening in the system to examine the effects of avoidant coping on the development of panic symptomatic. Second, we formalized two interventions commonly used in cognitive behavioral therapy (CBT; exposure and cognitive reappraisal) and subsequently simulated their effects on the system. RESULTS: The first simulation showed that the specified system could recover several aspects of the phenomenon (panic disorder), however, also showed some incongruency with the nature of panic attacks (e.g., rapid decreases were not observed). The second simulation study illustrated differential effects of CBT interventions for this patient. All tested interventions could decrease panic levels in the system. CONCLUSIONS: Formalizing idiographic theories is promising in bridging the gap between complexity science and clinical practice and can help foster more rigorous scientific practices in psychotherapy, through enhancing theory development. More precise case conceptualizations could potentially improve intervention planning and treatment outcomes. We discuss applications in psychotherapy and future directions, amongst others barriers for systematic theory evaluation and extending the framework to incorporate interactions between individual systems, relevant for modeling social learning processes. With this report, we hope to stimulate future efforts in formalizing clinical frameworks.

Differential associations of locus of control with anxiety, depression and life-events: A five-wave, nine-year study to test stability and change.

BACKGROUND: The locus of control (LOC) construct has been associated with onset, course, and severity of anxiety and depression. We investigated the stability of LOC, the bidirectional relationships between LOC and symptom severity of anxiety and depression over nine years, and the influence of intermediate positive and negative life-events on these associations. METHODS: Data came from five assessment waves over nine years of 2052 subjects with an anxiety or depressive disorder or healthy controls. First, the stability of LOC (assessed with 5-item Mastery Scale) was tested. Next, associations between LOC, anxiety severity (Beck Anxiety Inventory), depression severity (Inventory of Depressive Symptomatology), and intermediate positive and negative life-events (20-item List of Threatening Experience Questionnaire) were determined with structural equation modeling. RESULTS: LOC was rather stable over nine years (r = 0.62), and scores increased slightly with age (i.e. became more internal). LOC yielded equal stability estimates as symptom levels of anxiety and depression did over nine years. A more external LOC predicted higher anxiety and depression severity, but did not influence the incidence of positive and negative life-events. Higher depression severity and more negative life-events predicted the development of a more external LOC, whereas more positive life-events predicted a more internal LOC. Anxiety severity had no effect on LOC. LIMITATIONS: Life-events were assessed with self-report measures. CONCLUSIONS: The prospective associations between LOC and meaningful changes in anxiety and depressive symptom severity and experienced life-events may yield important new insights for clinical interventions.

Anxiety sensitivity, its stability and longitudinal association with severity of anxiety symptoms.

Anxiety sensitivity is associated with the onset of panic attacks, anxiety, and other common mental disorders. Anxiety sensitivity is usually seen as a relative stable trait. However, previous studies were inconclusive regarding the longitudinal stability of anxiety sensitivity and differed in study designs and outcomes. The current study examines the stability of anxiety sensitivity over time and its longitudinal associations with severity of anxiety symptoms. Participants from the Netherlands Study of Depression and Anxiety with and without an anxiety, depressive, or comorbid anxiety-depressive disorder diagnosis were included (N = 2052). Stability in anxiety sensitivity over two year follow-up and the longitudinal association between the change in anxiety sensitivity and change in severity of anxiety symptoms were tested. Results indicated that two-year stability of anxiety sensitivity was high (r = 0.72), yet this test-retest estimate leaves room for changes in anxiety sensitivity in some individuals as well. Change in anxiety sensitivity was positively associated with change in severity of anxiety symptoms (B = 0.64 in univariable analysis and B = 0.52 in multivariable analysis). The longitudinal association of anxiety sensitivity with severity of anxiety symptoms indicates that targeting anxiety sensitivity may be of additional benefit in clinical practice.

Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial.

BACKGROUND: Phobic anxiety disorders are among the most prevalent psychiatric disorders and are burdensome in terms of loss of quality of life and work productivity. Evidence-based treatments are relatively successful in the majority of patients, especially exposure therapy. However, a substantial subset of patients fails to achieve or stay in remission. Preclinical and genetic research have yielded evidence that the cannabinoid system is involved in the extinction of fear, presumed to underlie the beneficial effects of exposure therapy in phobic disorders. A cannabinoid constituent that may enhance endocannabinoid signaling is cannabidiol (CBD), a non-psychoactive component of cannabis. Hence, the addition of CBD to exposure therapy is expected to strengthen effects of treatment. To determine the added benefit of CBD on exposure therapy, we conduct a randomized controlled trial, in which patients in whom previous treatment as usual has not yielded sufficient response receive either CBD or placebo preceding 8 exposure sessions in a double-blind fashion. A subsidiary aim is to explore which (combination of) clinical, behavioral and genetic profiles of patients are related to treatment response. METHODS/DESIGN: This is an 8-week multicenter, randomized, double-blind, placebo-controlled trial. Seventy-two patients with social phobia or panic disorder with agoraphobia with incomplete response to earlier treatment will be included from outpatient clinics in the Netherlands. Patients are randomized to augmentation of exposure therapy with 300 mg CBD or placebo. The study medication is administered orally, 2 h preceding each of the eight 90 min exposure sessions. Measurements will take place at baseline, first administration of medication, every session, mid-treatment, last administration of medication, post-treatment and at 3 and 6 months' follow-up. The primary outcome measure is the score on the Fear Questionnaire (FQ). In addition, determinants of the expected treatment enhancing effect of CBD will be explored. DISCUSSION: This is the first trial to investigate whether the addition of CBD to exposure therapy is effective in reducing phobic symptoms in treatment refractory patients with social phobia or panic disorder with agoraphobia. TRIAL REGISTRATION: Netherlands Trial Register NTR5100 . Registered 13 March 2015. Protocol version: issue date 17 Jan 2018, protocol amendment number 7.

Personalized Network Modeling in Psychopathology: The Importance of Contemporaneous and Temporal Connections.

Recent literature has introduced (a) the network perspective to psychology and (b) collection of time series data to capture symptom fluctuations and other time varying factors in daily life. Combining these trends allows for the estimation of intraindividual network structures. We argue that these networks can be directly applied in clinical research and practice as hypothesis generating structures. Two networks can be computed: a temporal network, in which one investigates if symptoms (or other relevant variables) predict one another over time, and a contemporaneous network, in which one investigates if symptoms predict one another in the same window of measurement. The contemporaneous network is a partial correlation network, which is emerging in the analysis of cross-sectional data but is not yet utilized in the analysis of time series data. We explain the importance of partial correlation networks and exemplify the network structures on time series data of a psychiatric patient.

The importance of personality and life-events in anxious depression: from trait to state anxiety.

OBJECTIVES: Anxious depression is associated with severe impairment and bad prognoses. We hypothesize that recent life-events are associated with more anxiety in late-life depression and that this is conditional upon the level of certain personality traits. METHOD: Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used. In 333 patients (≥60 years) suffering from a major depressive disorder, anxiety was assessed with the BAI, personality traits with the NEO-FFI and the Mastery Scale, and life-events with the Brugha questionnaire. Multiple linear regression analyses were applied with anxiety severity as dependent and life-events and personality traits as independent variables. RESULTS: 147 patients (44.1%) had recently experienced one or more life-events. The presence of a life-event is not associated with anxiety (p = .161) or depression severity (p = .440). However, certain personality traits interacted with life-events in explaining anxiety severity. Stratified analyses showed that life-events were associated with higher anxiety levels in case of high levels of neuroticism and openness and low levels of conscientiousness or mastery. CONCLUSIONS: In the face of a life-event, personality traits may play a central role in increased anxiety levels in late-life depression.

Personalized Feedback on Symptom Dynamics of Psychopathology: A Proof-of-Principle Study.

BACKGROUND AND OBJECTIVES: In the proposed symptom network approach to psychopathology, psychiatric disorders are assumed to result from the (causal) interplay between symptoms. By implementing this approach we explored whether individual feedback on symptom dynamics complements current categorical classification and treatment. The aim of this proof-of-principle case-study was to explore the feasibility, acceptability and usability of this transdiagnostic approach. METHODS: A female patient, aged 67, suffering from treatment resistant anxious and depressive symptoms was treated in our tertiary outpatient clinic for old age psychiatry. She participated in ecological momentary assessments (EMA), which involved intensive repeated measurements of mood and context-related items during two weeks. Visualizations of the interplay between the items were provided by network graphs and were discussed with the patient. RESULTS: Network graphs were discussed with the patient. For example, it was hypothesized and discussed with the patient that feeling relaxed increased physical activity, causing physical discomfort in the following hours. Physical discomfort caused stress as its symptoms resembled her feared somatic anxiety symptoms. This increased the patient's insight that stress, expressed as somatic symptoms, played a central role in her panic disorder. This started a dialogue on how to cope with stress caused by somatic (anxiety) symptoms and provided a rationale for the patient to start an interoceptive exposure intervention she had repeatedly refused before. LIMITATIONS: The observed symptom dynamics may not be generalizable to any other random two weeks. CONCLUSIONS: Personalized diagnosis of psychopathology incorporating complex symptom dynamics is feasible and a promising addition to current categorical diagnostic systems and could guide intervention selection. This merits further exploration.

Breast cancer molecular subtypes: from TNBC to QNBC.

Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

Low stability of diagnostic classifications of anxiety disorders over time: A six-year follow-up of the NESDA study.

BACKGROUND: Stability of diagnosis was listed as an important predictive validator for maintaining separate diagnostic classifications in DSM-5. The aim of this study is to examine the longitudinal stability of anxiety disorder diagnoses, and the difference in stability between subjects with a chronic versus a non-chronic course. METHODS: Longitudinal data of 447 subjects with a current pure anxiety disorder diagnosis at baseline from the Netherlands Study of Depression and Anxiety were used. At baseline, 2-, 4-, and 6-year follow-up mental disorders were assessed and numbers (and percentages) of transitions from one anxiety disorder diagnosis to another were determined for each anxiety disorder diagnosis separately and for subjects with a chronic (i.e. one or more anxiety disorder at every follow-up assessment) and a non-chronic course. RESULTS: Transition percentages were high in all anxiety disorder diagnoses, ranging from 21.1% for social anxiety disorder to 46.3% for panic disorder with agoraphobia at six years of follow-up. Transition numbers were higher in the chronic than in the non-chronic course group (p=0.01). LIMITATIONS: Due to the 2 year sample frequency, the number of subjects with a chronic course may have been overestimated as intermittent recovery periods may have been missed. CONCLUSIONS: These data indicate that anxiety disorder diagnoses are not stable over time. The validity of the different anxiety disorder categories is not supported by these longitudinal patterns, which may be interpreted as support for a more pronounced dimensional approach to the classification of anxiety disorders.

Suicide in late-life depression with and without comorbid anxiety disorders.

OBJECTIVE: Comorbid anxiety in depression increases the risk of suicidal ideation and behavior, although data on death by suicide are scarce. We compared characteristics of depressed elderly patients with and without anxiety disorders who died by suicide. METHODS: From a 16-year clinical survey of all suicides in the UK (n = 25,128), we identified 1909 cases aged ≥60 years with a primary diagnosis of depression and no comorbidity other than anxiety disorders. Clinical characteristics of cases with (n = 333, 17.4%) and without (n = 1576) comorbid anxiety disorders were compared by logistic regression adjusted for demographic differences. RESULTS: Compared with cases without comorbid anxiety disorders, cases with comorbid anxiety disorders were more likely to have a duration of illness over 1 year (OR(1-5 years) = 1.4 [95% CI: 1.0-1.9], p = 0.061; OR(≥5 years) = 1.4 [95% CI: 1.6-2.8], p < 0.001), were more frequently prescribed psychotropic drugs other than antidepressants, lithium, and antipsychotics (OR = 2.1 [95% CI: 1.6-2.7], p < 0.001) and were more distressed during their last contact with services (OR = 1.3 [95% CI: 1.0-1.7], p = 0.037). In contrast, clinicians estimated the immediate and long-term suicidal risks lower in those with comorbid anxiety disorders (OR = 0.6 [95% CI: 0.3-0.9], p = 0.011 and OR = 0.7 [95% CI: 0.6-1.0], p = 0.028, respectively). CONCLUSION: Among depressed suicide cases, a comorbid anxiety disorder was identified in one out of six cases and associated with a higher prevalence of several suicide risk factors. This is important, as the detection of anxiety disorders comorbid to depression seems rather low and even when recognized clinicians rated such individuals as at low suicide risk.

Hepatocellular Carcinoma Without Cirrhosis Presenting With Hypercalcemia: Case Report and Literature Review.

BACKGROUND: Hepatocellular carcinoma (HCC) in non-cirrhotic livers is an uncommon finding and can present insidiously in patients. Another uncommon finding in HCC, and one of poor prognosis, is the presence of paraneoplastic diseases such as hypercalcemia. We report a case of a 66-year-old previous healthy Filipina woman who after routine laboratory evaluation was discovered to have hypercalcemia as the first sign of an advanced HCC without underlying cirrhosis. Because of the patient's relative lack of symptoms, healthy liver function, lack of classical HCC risk factors, and unexpected hypercalcemia, the diagnosis of a paraneoplastic syndrome caused by a noncirrhotic HCC was unanticipated. METHODS: Case Analysis with Pubmed literature review. RESULTS: It is unknown how often hypercalcemia is found in association with HCC in a non-cirrhotic liver. However, paraneoplastic manifestations of HCC, particularly hypercalcemia, can be correlated with poor prognosis. For this patient, initial management included attempts to lower calcium levels via zoledronate, which wasn't completely effective. Tumor resection was then attempted however the patient expired due to complications from advanced tumor size. CONCLUSIONS: Hypercalcemia of malignancy can be found in association with non-cirrhotic HCC and should be considered on the differential diagnosis during clinical work-up.

The influence of season and air temperature on water intake by food groups in a sample of free-living Japanese adults.

BACKGROUND/OBJECTIVES: To examine the influence of season and climate (air temperature and humidity) on water intake by the food group in a sample of free-living Japanese adults. SUBJECTS/METHODS: Four-nonconsecutive-day, semi-weighed dietary records were collected from each of the four seasons in a single 12-month period (16 days in total). The influence of season and climate on individual water intake by the food group was analyzed using a mixed linear model. Participants were 242 healthy adults (121 women aged 30-69 years and 121 men aged 30-76 years) from four areas in Japan. RESULTS: For women and men together, the mean total water intake was 2230 g/day (highest in summer: 2331 g/day; lowest in winter: 2134 g/day). Fifty-one percent of water was derived from foods and the rest from beverages. In a mixed linear model adjusted for sex, age and body mass index, intake of water from foods decreased by 3.1 g/day and that from beverages increased by 8.4 g/day, with an increase in the mean outdoor air temperature on the survey day of 1 °C (both P < 0.0001). The influence of humidity was nonsignificant. CONCLUSIONS: In contrast to previous findings in Western countries, half of water intake in Japanese adults was derived from foods. Water intake from beverages was positively associated with air temperature, whereas that from foods was inversely associated with air temperature.

Renal Leiomyosarcoma: Case Report and Review of the Literature.

Leiomyosarcoma of the kidney is a rare entity, and our understanding of this type of renal sarcomas is limited. A 46-year-old Caucasian male presented with a chief complaint of right flank pain for one month. He came to our facility for an additional opinion regarding the management of his renal mass. Computed tomography (CT) of the abdomen showed an enhancing, heterogeneous right renal mass, consistent with the features of renal cell carcinoma (RCC). Robotic-assisted total nephrectomy of the right kidney revealed a tan mass with central necrosis that involved the upper pole of the kidney. Based on gross specimen observation and immunochemical analysis, the patient was diagnosed with high-grade leiomyosarcoma. While the prognosis is poor, radical nephrectomy remains the treatment of choice. The potential benefits of adjuvant therapy should be discussed with selected patients.