Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Association Between a National Behavioral Weight Management Program and Veterans Affairs Health Expenditures.

OBJECTIVE: The association between participation in a behavioral weight intervention and health expenditures has not been well characterized. We compared Veterans Affairs (VA) expenditures of individuals participating in MOVE!, a VA behavioral weight loss program, and matched comparators 2 years before and 2 years after MOVE! initiation. METHODS: Retrospective cohort study of Veterans who had one or more MOVE! visits in 2008-2017 who were matched contemporaneously to up to 3 comparators with overweight or obesity through sequential stratification on an array of patient characteristics, including sex. Baseline patient characteristics were compared between the two cohorts through standardized mean differences. VA expenditures in the 2 years before MOVE! initiation and 2 years after initiation were modeled using generalized estimating equations with a log link and distribution with variance proportional to the standard deviation (gamma). RESULTS: MOVE! participants (n=499,696) and comparators (n=1,336,172) were well-matched, with an average age of 56, average body mass index of 35, and similar total VA expenditures in the fiscal year before MOVE! initiation ($9662 for MOVE! participants and $10,072 for comparators, standardized mean difference=-0.019). MOVE! participants had total expenditures that were statistically lower than matched comparators in the 6 months after initiation but modestly higher in the 6 months to 2 years after initiation, though differences were small in magnitude (1.0%-1.6% differences). CONCLUSIONS: The VA's system-wide behavioral weight intervention did not realize meaningful short-term health care cost savings for participants.

Misuse of Prescribed and Nonprescribed Substances Among U.S. Cancer Survivors.

BACKGROUND: Substance misuse is common among cancer survivors and can negatively impact cancer outcomes. METHODS: We conducted a cross-sectional study using National Survey on Drug Use and Health data for 2015 to 2020. We included adult respondents with a history of solid tumor cancer. We calculated the weighted prevalence and corresponding SEs (both expressed as percentages) of substance (alcohol, opioid, sedative, stimulant, other) misuse for respondents with any history of solid tumor cancer and, in secondary analyses, respondents diagnosed with cancer in the prior 12 months. RESULTS: The study included 6,101 respondents with any history of cancer, 1,437 diagnosed in the prior 12 months. Alcohol was the most commonly misused substance. The average prevalence of alcohol misuse was 14.4% (SE 0.60%) across cancer types; it was markedly more common among people with a history or cervical (24.2% [3.0%]) or head and neck cancer (27.4% [7.1%]). The next most common form of substance misuse was opioid misuse (average prevalence: 2.7% [0.25%]). As with alcohol misuse, the prevalence of opioid misuse was higher among those with a lifetime history of cervical cancer (5% [1%]) or head and neck cancer (5% [3%]). Results were generally consistent among cancer survivors diagnosed in the prior 12 months. CONCLUSIONS: There is a clear opportunity to address substance misuse-particularly alcohol misuse-among cancer survivors. Such efforts should focus on populations with a high prevalence of substance misuse (e.g., cervical and head and neck cancer survivors) and have strong potential to improve cancer-specific and overall health outcomes.

Real World Use of Anti-Obesity Medications and Weight Change in Veterans.

BACKGROUND: Anti-obesity medications (AOMs) can be initiated in conjunction with participation in the VA national behavioral weight management program, MOVE!, to help achieve clinically meaningful weight loss. OBJECTIVE: To compare weight change between Veterans who used AOM + MOVE! versus MOVE! alone and examine AOM use, duration, and characteristics associated with longer duration of use. DESIGN: Retrospective cohort study using VA electronic health records. PARTICIPANTS: Veterans with overweight or obesity who participated in MOVE! from 2008-2017. MAIN MEASURES: Weight change from baseline was estimated using marginal structural models up to 24 months after MOVE! initiation. The probability of longer duration of AOM use (≥ 180 days) was estimated via a generalized linear mixed model. RESULTS: Among MOVE! participants, 8,517 (1.6%) used an AOM within 24 months after MOVE! initiation with a median of 90 days of cumulative supply. AOM + MOVE! users achieved greater weight loss than MOVE! alone users at 6 (3.2% vs. 1.6%, p < 0.001), 12 (3.4% vs. 1.4%, p < 0.001), and 24 months (2.7% vs. 1.5%, p < 0.001), and had a greater probability of achieving ≥ 5% weight loss at 6 (38.8% vs. 26.0%, p < 0.001), 12 (43.1% vs. 28.4%, p < 0.001), and 24 months (40.4% vs. 33.3%, p < 0.001). Veterans were more likely to have ≥ 180 days of supply if they were older, exempt from medication copays, used other medications with significant weight-gain, significant weight-loss, or modest weight-loss side effects, or resided in the West North Central or Pacific regions. Veterans were less likely to have ≥ 180 days of AOM supply if they had diabetes or initiated MOVE! later in the study period. CONCLUSIONS: AOM use following MOVE! initiation was uncommon, and exposure was time-limited. AOM + MOVE! was associated with a higher probability of achieving clinically significant weight loss than MOVE! alone.

Comparing eating disorder treatment outcomes of transgender and gender diverse adolescents with those of cisgender adolescents.

OBJECTIVE: Eating disorder (ED), depression, and anxiety symptoms at admission and discharge were compared, as were admission-to-discharge changes, for transgender and gender diverse (TGD), and cisgender adolescents receiving intensive treatment for EDs. METHOD: Participants were 44 TGD and 573 cisgender adolescents admitted to a treatment facility. Participants completed the Eating Disorder Examination Questionnaire (EDE-Q), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) at admission and discharge. RESULTS: Both groups had elevated EDE-Q scores at admission (TGD: M = 3.78, standard deviation [SD] = 1.70; cisgender: M = 3.33, SD = 1.74) that improved by discharge (TGD: M = 2.27, SD = 1.83, Cohen's d = .98; cisgender: M = 2.10, SD = 1.54, Cohen's d = .79); there were no differences in EDE-Q between groups at admission (p = .09; odds ratio [OR] = 1.18, 95% confidence interval [CI] [.98, 1.44]) or discharge (p = .48; OR = 1.07, 95% CI [.88, 1.30]). On admission, TGD adolescents had higher suicidality, measured by PHQ-9, item 9 (p < .001; OR = 1.94, 95% CI [1.51, 2.52]), and depression (p < .001; OR = 1.10, 95% CI [1.05, 1.16]) than cisgender participants. Severity decreased over treatment for all measures. Both groups showed similar improvement on suicidality (p = .93; OR = .98, 95% CI [.70,1.36]), depression (p = .42; OR = 1.02, 95% CI [.97, 1.07]), and anxiety (p = .14; OR = 1.05, 95% CI [.99, 1.12]). However, at discharge, suicidality (p = .02; OR = 1.40, 95% CI [1.04, 1.85]), depression (p < .01; OR = 1.06, 95% CI [1.02, 1.11]), and anxiety (p = .02; OR = 1.06, 95% CI [1.01, 1.12]) were higher for TGD adolescents than their cisgender peers. DISCUSSION: All participants had similar ED symptom severity and improvement. Depression, anxiety, and suicidality remained elevated for TGD adolescents compared to their cisgender peers at discharge, suggesting the need for targeted treatment. PUBLIC SIGNIFICANCE: Transgender and gender diverse (TGD) adolescents have increased risk of eating disorders (EDs); few studies examine how they respond to ED treatment. We examine treatment outcomes of TGD adolescents receiving ED treatment compared to their cisgender peers. We measured ED symptoms along with depression, anxiety, and suicidality at the beginning and end of treatment. While TGD adolescents showed similar improvement in ED symptoms, measures of depression, anxiety, and suicidality remained elevated at the time of discharge.

An examination of adults with atypical anorexia nervosa at admission to treatment at higher levels of care: An attempt to increase diagnostic clarity.

OBJECTIVE: Anorexia nervosa (AN) is a serious illness with a high mortality rate and multiple physiological complications. The vague definition of atypical AN allows for subjective interpretation. This retrospective study aimed to focus future research on the operational definition of atypical AN by examining four factors associated with atypical AN at admission to higher level of care treatment. METHODS: Adults with atypical AN (n = 69) were examined within sample analyses among four groups: (1) >10% versus ≤10% weight loss; (2) weight loss within the previous 3 months versus >3 months; (3) engaging in purging behaviors versus absence of purging behaviors; and (4) endorsing versus not endorsing significant cognitive aspects of AN. RESULTS: Patients with atypical AN endorsed elevated ED cognitions on the Eating Disorder Examination-Questionnaire and depressive symptoms; a lack of association was found between weight loss severity and weight loss time frame with depressive symptoms, eating concern, and restraint. Purging behavior was associated with a higher expected body weight percentage (%EBW) and dietary restraint, while greater AN cognitions were associated with a higher EBW and weight loss percentage. Few patients demonstrated bradycardia, hypophosphatemia, or amenorrhea. DISCUSSION: This study demonstrated the severity of ED cognitions and depressive symptoms in this atypical AN sample and provided directions for future studies in the nosology of atypical AN. It may be important to distinguish between individuals with atypical AN who are purging and those who are not. Atypical AN was associated with a low frequency of physiological disturbances. PUBLIC SIGNIFICANCE: This study provides further clarification regarding the operational definition of atypical AN; currently, a constellation of symptoms under Other Specified Feeding or Eating Disorders. This study was consistent with previous research in reporting severe eating disorder cognitions in adults with atypical AN, and noted the potential importance of distinguishing a purging distinction. A minority of patients in this study had physiological impairments.

Radioactive Iodine Therapy of Graves' Disease in Patients Pretreated With Methimazole Without Radioiodine Uptake for Dose Estimation.

OBJECTIVE: To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole. METHODS: Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies. RESULTS: In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response. CONCLUSION: RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach.

Patterns of bacterial motility in microfluidics-confining environments.

Understanding the motility behavior of bacteria in confining microenvironments, in which they search for available physical space and move in response to stimuli, is important for environmental, food industry, and biomedical applications. We studied the motility of five bacterial species with various sizes and flagellar architectures (Vibrio natriegens, Magnetococcus marinus, Pseudomonas putida, Vibrio fischeri, and Escherichia coli) in microfluidic environments presenting various levels of confinement and geometrical complexity, in the absence of external flow and concentration gradients. When the confinement is moderate, such as in quasi-open spaces with only one limiting wall, and in wide channels, the motility behavior of bacteria with complex flagellar architectures approximately follows the hydrodynamics-based predictions developed for simple monotrichous bacteria. Specifically, V. natriegens and V. fischeri moved parallel to the wall and P. putida and E. coli presented a stable movement parallel to the wall but with incidental wall escape events, while M. marinus exhibited frequent flipping between wall accumulator and wall escaper regimes. Conversely, in tighter confining environments, the motility is governed by the steric interactions between bacteria and the surrounding walls. In mesoscale regions, where the impacts of hydrodynamics and steric interactions overlap, these mechanisms can either push bacteria in the same directions in linear channels, leading to smooth bacterial movement, or they could be oppositional (e.g., in mesoscale-sized meandered channels), leading to chaotic movement and subsequent bacterial trapping. The study provides a methodological template for the design of microfluidic devices for single-cell genomic screening, bacterial entrapment for diagnostics, or biocomputation.

Association of performance in medical residency selection with a psychiatric diagnosis, and depressive and anxiety symptoms.

OBJECTIVE: Few studies have focused on medical students and residents' mental health impact on medical residency selection (MRS) performance. The authors evaluated the association of performance in MRS with depressive and anxiety symptoms and with a reported psychiatric diagnosis (rPD). METHODS: The authors enrolled candidates after the second round of MRS examinations at a Brazilian Medical School. Performance was assessed by final grade. Depressive and anxiety symptoms were assessed by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the State-Trait Anxiety Inventory (STAI). The authors performed mediation analysis and multiple linear regression analysis to investigate the impact of rPD, state and trait anxiety, and depressive symptom severity on performance. RESULTS: 515 of the 643 MRS candidates (80.1%) participated in the study. Higher age, attending a preparatory course for MRS, rPD, and the number of MRS applications that year were associated with poorer performance. In mediation analysis, trait anxiety was associated with a direct effect on performance and an indirect effect mediated by rPD. CONCLUSION: The data suggest that psychiatric diagnosis is associated with poorer performance on MRS, regardless of current symptoms of anxiety and depression. Additionally, increased levels of trait anxiety may negatively impact performance, directly and indirectly.

A brief examination of treatment outcomes in higher levels of care for individuals with eating disorders across age groups.

OBJECTIVE: Although eating disorders (EDs) occur throughout the lifespan, little research has been conducted with midlife/older adults, particularly those in higher levels of care (HLOC). The current study examined outcomes among 2009 patients with EDs receiving HLOC treatment at a large multisite facility between January 2020 and June 2022, across different age groups (ages <18, 18-25, 26-39 and ≥40). It was hypothesised that patients aged 40+ would exhibit less improvement on measures of ED psychopathology and depression than other age groups. METHOD: Participants completed the eating disorder examination-questionnaire (EDE-Q) and the patient health questionnaire-9 (PHQ-9) at admission and discharge. RESULTS: Changes for all outcomes from admission to discharge were statistically significant at p < 0.001 across all age groups. Changes in the EDE-Q Restraint subscale were significantly less in patients ages 26-39 than in patients ages 18-25 (p < 0.01). Changes in PHQ-9 were significantly greater in patients ages 40+ than patients ages 18-25 (p = 0.03). CONCLUSIONS: Contrary to hypotheses, patients ages 40+ did not show worse outcomes than younger patients, and showed greater improvements in depression than young adults. The therapeutic needs of midlife/older adults with EDs may be favourably met by a HLOC regimen as described in this study.

Weight gain and eating disorder symptoms among individuals with atypical anorexia nervosa.

OBJECTIVE: The purpose of this study was to examine the association between weight gain and eating disorder (ED) symptoms among adults receiving treatment for atypical anorexia nervosa (AAN), to determine whether those who had a higher percent of expected body weight (%EBW) at discharge exhibited lower ED symptoms than those who gained less weight, and to compare this group to a matched sample of patients with anorexia nervosa (AN). METHOD: Participants were 96 adults receiving treatment at an ED treatment facility between December 2020 and May 2023. The Eating Disorder Examination-Questionnaire (EDE-Q) was completed at admission and discharge, and %EBW was obtained at admission and discharge. RESULTS: All EDE-Q subscale scores improved from admission to discharge for patients with AAN and patients with AN. Neither %EBW at discharge nor weight gain were associated with EDE-Q subscale scores for those with AAN. For patients with AN, %EBW at discharge and weight gain were associated with EDE-Q Restraint at discharge. CONCLUSIONS: Weight restoring to a higher level and gaining more weight were not associated with EDE-Q scores at discharge for AAN. Further research is needed to determine how weight restoration using intensive treatment settings affects remission and recovery in patients with AAN.

Characterising use of recovery record among a large, transdiagnostic sample of adults with eating disorders across higher levels of care.

OBJECTIVE: Smartphone applications (i.e., apps) designed to target mental health symptoms have received increasing public and empirical attention, including in eating disorder|eating disorders (EDs) treatment. While some data have begun to characterise app users in non-controlled settings, there is limited information on use of apps in higher levels of care (e.g., partial hospitalisation or residential treatment programs) for EDs. METHOD: This study aimed to explore metrics of use while in treatment for a commonly used ED-focused mobile app (Recovery Record) among individuals enroled in intensive outpatient, partial hospitalisation, residential, or inpatient treatments (N = 2042). RESULTS: Results indicated that older individuals and participants with binge eating disorder demonstrated more frequent app engagement compared to younger participants and other ED diagnoses, respectively. Individuals entering at intensive outpatient and partial hospitalisation levels of care, as well as those with routine discharges engaged more frequently with RR compared to individuals entering in inpatient or residential treatment, and those with non-routine discharges. CONCLUSIONS: Our data provide initial descriptions of how RR may be used within higher levels of care for adults with EDs. Further work is needed to establish the benefit of these apps in clinical settings for EDs over and above standard treatment, better characterise for whom these apps provide benefit, and identify how best to tailor the experience to promote engagement across the full spectrum of ED patients.

Eating disorder virtual intensive outpatient program: patient satisfaction according to age group.

The COVID-19 pandemic has required a shift to telehealth services. However, not all patients are similarly satisfied with this shift, with some studies finding that midlife and older adults are less comfortable with telehealth. The current study examined patient satisfaction with a virtual intensive outpatient program (VIOP) for eating disorders (EDs) among 305 adults (ages 18-25, ages 26-39, and ages 40+), and compared adult satisfaction to satisfaction among children/adolescents (n = 33) receiving VIOP treatment between August 2020 and March 2022 from a large ED treatment facility. It was hypothesized that adults aged 40+ would report lower satisfaction than younger age groups. Patients completed several questions regarding satisfaction with treatment upon discharge, including a question about likelihood of recommending the program, which was used to calculate a Net Promoter Score (NPS). The NPS was 33.3 for children/adolescents, 33.3 for 18-25 year-olds, 57.7 for 26-39 year-olds, and 30.9 for the 40+ year age group. NPS of 31-50 = quality services; 51-70 = excellent customer experiences. Satisfaction was high, with no statistically significant differences between age groups after Bonferroni correction. The current study adds to the limited literature on the treatment experiences of midlife adults with EDs.

A descriptive study of treatment-seeking adults with avoidant/restrictive food intake disorder at residential and inpatient levels of care.

Most research on avoidant/restrictive food intake disorder (ARFID) has been with children and adolescents, while the limited research on adults with ARFID has been in the domain of outpatient treatment. This descriptive study sought to explore psychological characteristics (N = 45; measured with self-report questionnaires) and physiological characteristics (N = 66; e.g. vital signs, bloodwork) at admission for 66 adults with ARFID seeking residential and inpatient levels of care. While adults with ARFID presented with significant food restriction as well as mild depressive symptoms, high anxiety symptoms, and impaired quality of life, patients presented with mostly normal physiology, except for low bone density, and trivial abnormalities in serum creatinine and hepatic enzymes. Patients in this sample were most likely to endorse fear of aversive consequences, especially those for whom ARFID symptoms had first arisen in adulthood. These results note the psychological impairment and relative physiological normalcy of treatment-seeking adults with ARFID at the outset of residential and inpatient treatment, identifying future treatment and outcome research priorities in this understudied population.

An open trial for adults in a residential program for binge eating spectrum disorders.

The current study assessed treatment outcome for 99 adult admissions to a residential program specifically designed for binge eating spectrum disorders (BESD). Participants completed self-report measures at admission, discharge, and 12-month follow-up and were asked to complete blood draws at admission and follow-up. Primary outcomes were eating behaviors; secondary outcomes included comorbid symptoms and physiological variables. Eating behaviors improved significantly from admission to follow-up, as did most comorbid symptoms and quality of life, despite no change in body mass index. Some variables displayed a curvilinear relationship, with some worsening of symptoms from discharge to follow-up, although scores at follow-up remained well below admission values. Participation in the treatment program was associated with reduced problematic eating and comorbid symptoms and increased quality of life up to one year after discharge. Findings from this study may encourage the development of similar residential treatment programs for BESD for those who have not responded to outpatient care or mixed milieu settings, and may prompt randomized studies testing similar treatments versus usual care.

Factors impacting the efficacy of the in-situ vaccine with CpG and OX40 agonist.

BACKGROUND: The in-situ vaccine using CpG oligodeoxynucleotide combined with OX40 agonist antibody (CpG + OX40) has been shown to be an effective therapy activating an anti-tumor T cell response in certain settings. The roles of tumor volume, tumor model, and the addition of checkpoint blockade in the efficacy of CpG + OX40 in-situ vaccination remains unknown. METHODS: Mice bearing flank tumors (B78 melanoma or A20 lymphoma) were treated with combinations of CpG, OX40, and anti-CTLA-4. Tumor growth and survival were monitored. In vivo T cell depletion, tumor cell phenotype, and tumor infiltrating lymphocyte (TIL) studies were performed. Tumor cell sensitivity to CpG and macrophages were evaluated in vitro. RESULTS: As tumor volumes increased in the B78 (one-tumor) and A20 (one-tumor or two-tumor) models, the anti-tumor efficacy of the in-situ vaccine decreased. In vitro, CpG had a direct effect on A20 proliferation and phenotype and an indirect effect on B78 proliferation via macrophage activation. As A20 tumors progressed in vivo, tumor cell phenotype changed, and T cells became more involved in the local CpG + OX40 mediated anti-tumor response. In mice with larger tumors that were poorly responsive to CpG + OX40, the addition of anti-CTLA-4 enhanced the anti-tumor efficacy in the A20 but not B78 models. CONCLUSIONS: Increased tumor volume negatively impacts the anti-tumor capability of CpG + OX40 in-situ vaccine. The addition of checkpoint blockade augmented the efficacy of CpG + OX40 in the A20 but not B78 model. These results highlight the importance of considering multiple preclinical model conditions when assessing the efficacy of cancer immunotherapy regimens and their translation to clinical testing.

BMI Trends for Veterans Up to 10 Years After VA Enrollment Following Military Discharge.

BACKGROUND: Obesity (body mass index [BMI]≥30kg/m2) among US adults has tripled over the past 45 years, but it is unclear how this population-level weight change has occurred. OBJECTIVE: We sought to identify distinct long-term BMI trajectories and examined associations with demographic and clinical characteristics. DESIGN: The design was latent trajectory modeling over 10 years of a retrospective cohort. Subgroups were identified via latent class growth mixture models, separately by sex. Weighted multinomial logistic regressions identified factors associated with subgroup membership. PARTICIPANTS: Participants were a retrospective cohort of 292,331 males and 62,898 females enrolled in VA. MAIN MEASURES: The main outcome measure was 6-month average VA-measured BMI over the course of 10 years. Additional electronic health record measures on demographic, clinical, and services utilization characteristics were also used to characterize latent trajectories. KEY RESULTS: Four trajectories were identified for men and for women, corresponding to standard BMI categories "normal weight" (BMI <25), "overweight" (BMI 25-29.99), and "with obesity" (BMI ≥30): "normal weight" and increasing (males: 28.4%; females: 22.8%), "overweight" and increasing (36.4%; 35.6%), "with obesity" and increasing (33.6%; 40.0%), and "with obesity" and stable (males: 1.6%) or decreasing (females: 1.6%). Race, ethnicity, comorbidities, mental health diagnoses, and mental health service utilization discriminated among classes. CONCLUSIONS: BMI in the 10 years following VA enrollment increased modestly. VA should continue prioritizing weight management interventions to the large number of veterans with obesity upon VA enrollment, because the majority remain with obesity.

Pliocene hominins from East Turkana were associated with mesic environments in a semiarid basin.

During the middle Pliocene (∼3.8-3.2 Ma), both Australopithecus afarensis and Kenyanthropus platyops are known from the Turkana Basin, but between 3.60 and 3.44 Ma, most hominin fossils are found on the west side of Lake Turkana. Here, we describe a new hominin locality (ET03-166/168, Area 129) from the east side of the lake, in the Lokochot Member of the Koobi Fora Formation (3.60-3.44 Ma). To reconstruct the paleoecology of the locality and its surroundings, we combine information from sedimentology, the relative abundance of associated mammalian fauna, phytoliths, and stable isotopes from plant wax biomarkers, pedogenic carbonates, and fossil tooth enamel. The combined evidence provides a detailed view of the local paleoenvironment occupied by these Pliocene hominins, where a biodiverse community of primates, including hominins, and other mammals inhabited humid, grassy woodlands in a fluvial floodplain setting. Between <3.596 and 3.44 Ma, increases in woody vegetation were, at times, associated with increases in arid-adapted grasses. This suggests that Pliocene vegetation included woody species that were resilient to periods of prolonged aridity, resembling vegetation structure in the Turkana Basin today, where arid-adapted woody plants are a significant component of the ecosystem. Pedogenic carbonates indicate more woody vegetation than other vegetation proxies, possibly due to differences in temporospatial scale and ecological biases in preservation that should be accounted for in future studies. These new hominin fossils and associated multiproxy paleoenvironmental indicators from a single locale through time suggest that early hominin species occupied a wide range of habitats, possibly including wetlands within semiarid landscapes. Local-scale paleoecological evidence from East Turkana supports regional evidence that middle Pliocene eastern Africa may have experienced large-scale, climate-driven periods of aridity. This information extends our understanding of hominin environments beyond the limits of simple wooded, grassy, or mosaic environmental descriptions.

Relationships between interoceptive sensibility and resting-state functional connectivity of the insula in obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) exhibit abnormality in their subjective perception of internal sensation, a process known as interoceptive sensibility (IS), as well as altered functioning of the insula, a key neural structure for interoception. We investigated the multivariate structure of IS in 77 OCD patients and 53 controls and examined associations of IS with resting-state functional connectivity (FC) of the insula within the OCD group. For each group, principal component analysis was performed on 8 subscales of the Multidimensional Assessment of Interoceptive Awareness assessing putatively "adaptive" and "maladaptive" aspects of IS. Associations between IS components and insula FC in the OCD group were evaluated using seed regions placed in each of 3 subdivisions of the insula (posterior, anterior dorsal, and anterior ventral). Behaviorally, controls showed a 2-component solution broadly categorized into "adaptive" and "maladaptive" IS, while OCD patients exhibited a 3-component solution. The general tendency to notice or be aware of sensation loaded onto an "adaptive" IS component in controls but loaded onto both "adaptive" and "maladaptive" IS components in OCD. Within OCD, insula FC was differentially associated with distinct aspects of IS, identifying network connections that could serve as future targets for the modulation of IS in OCD.

Health-related quality of life profiles in adolescents and young adults with chronic conditions.

PURPOSE: To assess health-related quality of life (HRQOL) among adolescents and young adults (AYAs) with chronic conditions. METHODS: AYAs (N = 872) aged 14-20 years completed NIH's Patient-Reported Outcomes Measurement Information System® (PROMIS®) measures of physical function, pain interference, fatigue, social health, depression, anxiety, and anger. Latent profile analysis (LPA) was used to group AYAs into HRQOL profiles using PROMIS T-scores. The optimal number of profiles was determined by model fit statistics, likelihood ratio test, and entropy. Multinomial logistic regression models were used to examine how LPA's HRQOL profile membership was associated with patient demographic and chronic conditions. The model prediction accuracy on profile membership was evaluated using Huberty's I index with a threshold of 0.35 for good effect. RESULTS: A 4-profile LPA model was selected. A total of 161 (18.5%), 256 (29.4%), 364 (41.7%), and 91 (10.4%) AYAs were classified into Minimal, Mild, Moderate, and Severe HRQOL Impact profiles. AYAs in each profile had distinctive mean scores with over a half standard deviation (5-points in PROMIS T-scores) of difference between profiles across most HRQOL domains. AYAs who were female or had conditions such as mental health condition, hypertension, and self-reported chronic pain were more likely to be in the Severe HRQOL Impact profile. The Huberty's I index was 0.36. CONCLUSIONS: Approximately half of AYAs with a chronic condition experience moderate to severe HRQOL impact. The availability of risk prediction models for HRQOL impact will help to identify AYAs who are in greatest need of closer clinical care follow-up.