Placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder.

We searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms.

We included 16 RCTs (n = 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91–1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types.

Placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.

Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.

Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.

Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).

Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

Positive psychological attributes have been associated with better health outcomes and quality of life among people with HIV (PWH). Recently, we identified two latent factors (internal strengths, socioemotional support) among 7 positive psychological attributes through factor analysis (Ham et al., 2022). Depression was inversely associated with both factors. Our current aim was to investigate associations between these latent factors, neurocognition, and daily functioning among PWH.

106 PWH and 90 HIV- participants were included in cross-sectional analyses (Mage = 51.3, 77% men, 60% White). Seven positive psychological questionnaires, a neuropsychological battery covering 7 domains, two daily functioning questionnaires (Patient’s Assessment of Own Functioning (PAOFI); Independent Activities of Daily Living (IADL)), and a depression symptom questionnaire (Center for Epidemiologic Studies Depression Scale) were administered. Internal strengths and socioemotional support composite z-scores were calculated using HIV- participants’ scores as reference. Outcomes included global and domain-specific neurocognitive T-scores (demographically-adjusted), global deficit score (GDS), number of functional impairments (PAOFI), and number of functional declines (IADL). Main effects of HIV status, latent factors, and their interaction were included in linear (neurocognition) and Poisson (daily functioning) regressions. Significant interactions were followed up by simple effects analyses and nonsignificant interactions were removed. Depressive symptoms and demographics associated with daily functioning were included as covariates.

PWH exhibited worse neurocognitive performance (global, executive functioning, processing speed, learning, recall, GDS) and reported greater functional difficulties and depressive symptoms compared to HIV-counterparts (ps < 0.05). For neurocognition, there were socioemotional support x HIV status (B = 2.39, p = 0.04) and internal strengths x HIV status (B = 2.70, p < 0.05) interactions on verbal fluency, accounting for depressive symptoms, such that only PWH had a positive association between socioemotional support and verbal fluency (B = 1.97, p = 0.01). Removing nonsignificant interactions, there was a main effect of socioemotional support on global cognition (B = 1.01, p = 0.04) and psychomotor speed (B = 1.83, p = 0.02), independent of HIV status and depressive symptoms. For daily functioning, there was a socioemotional support x HIV status interaction on IADL declines (B = 0.42, p = 0.02), accounting for depressive symptoms and education, such that only HIV- participants had an inverse relationship between socioemotional support and IADL declines (B = -0.64, p < 0.001). Removing non-significant interactions, there were main effects of internal strengths on PAOFI impairments (B = -0.36, p < 0.001) and IADL declines (B = -0.38, p < 0.001), independent of HIV status and depressive symptoms.

Among PWH, both positive psychological factors were associated with better neurocognition, even after adjusting for depressive symptomatology. Though internal strengths were associated with better daily functioning regardless of HIV status, socioemotional support was not related to daily functioning in PWH. While mechanisms underlying these associations cannot be established cross-sectionally, it is possible that among people with medical illnesses complicated by cognitive disturbance, positive psychological factors relate to improved health-related behaviors (e.g., better disease management). Additionally, better neurocognition, including cognitive reserve, may engender greater resilience and improved ability to marshal social support.

Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper & Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper & Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.

The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).

When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p > .83) or after cannabis administration (all p > .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p > .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p > .7).

When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.

Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH.

Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery.

27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05).

Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH.

People with severe mental illness (SMI) have a greater risk of dying from colorectal cancer (CRC), even though the incidence is lower or similar to that of the general population This pattern is unlikely to be solely explained by lifestyle factors, while the role of differences in cancer healthcare access or treatment is uncertain

We undertook a systematic review and meta-analysis on access to guideline-appropriate care following CRC diagnosis in people with SMI including the receipt of surgery, chemo- or radiotherapy. We searched for full-text articles indexed by PubMed, EMBASE, PsychInfo and CINAHL that compared CRC treatment in those with and without pre-existing SMI (schizophrenia, schizoaffective, bipolar and major affective disorders). Designs included cohort or population-based case–control designs.

There were ten studies (sample size = 3501–591 561). People with SMI had a reduced likelihood of surgery (RR = 0.90, 95% CI 0.92–0.97; p = 0.005; k = 4). Meta-analyses were not possible for the other outcomes but in results from individual studies, people with SMI were less likely to receive radiotherapy, chemotherapy or sphincter-sparing procedures. The disparity in care was greatest for those who had been psychiatric inpatients.

People with SMI, including both psychotic and affective disorders, receive less CRC care than the general population. This might contribute to higher case-fatality rates for an illness where the incidence is no higher than that of the general population. The reasons for this require further investigation, as does the extent to which differences in treatment access or quality contribute to excess CRC mortality in people with SMI.

To describe the epidemiology of patients with nonintestinal carbapenem-resistant Enterobacterales (CRE) colonization and to compare clinical outcomes of these patients to those with CRE infection.

A secondary analysis of Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae 2 (CRACKLE-2), a prospective observational cohort.

A total of 49 US short-term acute-care hospitals.

Patients hospitalized with CRE isolated from clinical cultures, April, 30, 2016, through August 31, 2017.

We described characteristics of patients in CRACKLE-2 with nonintestinal CRE colonization and assessed the impact of site of colonization on clinical outcomes. We then compared outcomes of patients defined as having nonintestinal CRE colonization to all those defined as having infection. The primary outcome was a desirability of outcome ranking (DOOR) at 30 days. Secondary outcomes were 30-day mortality and 90-day readmission.

Of 547 patients with nonintestinal CRE colonization, 275 (50%) were from the urinary tract, 201 (37%) were from the respiratory tract, and 71 (13%) were from a wound. Patients with urinary tract colonization were more likely to have a more desirable clinical outcome at 30 days than those with respiratory tract colonization, with a DOOR probability of better outcome of 61% (95% confidence interval [CI], 53%–71%). When compared to 255 patients with CRE infection, patients with CRE colonization had a similar overall clinical outcome, as well as 30-day mortality and 90-day readmission rates when analyzed in aggregate or by culture site. Sensitivity analyses demonstrated similar results using different definitions of infection.

Patients with nonintestinal CRE colonization had outcomes similar to those with CRE infection. Clinical outcomes may be influenced more by culture site than classification as “colonized” or “infected.”

Intentional vehicular assaults on civilians have become more frequent worldwide, with some resulting in mass casualties, injuries, and traumatized witnesses. Health care costs associated with these vehicular assaults usually fall to compensation agencies. There is, however, little guidance around how compensation agencies should respond to mental and physical injury claims arising from large-scale transport incidents.

A Delphi review methodology was used to establish expert consensus recommendations on the major components of “no fault” injury claim processes for mental and physical injury.

Thirty-three international experts participated in a 3-round online survey to rate their agreement on key statements generated from the literature. Consensus was achieved for 45 of 60 (75%) statements, which were synthesized into 36 recommendations falling within the domains of (1) facilitating claims, (2) eligibility rules, (3) payments and benefits for clients, (4) claims management procedures, (5) making and explaining decisions, (6) support and information resources for clients, (7) managing scheme staff and organizational response, (8) clients with special circumstances, and (9) scheme values and integrity.

The recommendations present an opportunity for agencies to review their existing claims management systems and procedures. They also provide the basis for the development of best practice guidelines, which may be adapted for application to compensation schemes in different contexts worldwide.

Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.

Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.

When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.

The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.

Methamphetamine (MA) dependence contributes to neurotoxicity and neurocognitive deficits. Although combined alcohol and MA misuse is common, how alcohol consumption relates to neurocognitive performance among MA users remains unclear. We hypothesized that alcohol and MA use would synergistically diminish neurocognitive functioning, such that greater reported alcohol consumption would exert larger negative effects on neurocognition among MA-dependent individuals compared to MA-nonusing persons.

Eighty-seven MA-dependent (MA+) and 114 MA-nonusing (MA−) adults underwent neuropsychological and substance use assessments. Linear and logistic regressions examined the interaction between MA status and lifetime average drinks per drinking day on demographically corrected global neurocognitive T scores and impairment rates, controlling for recent alcohol use, lifetime cannabis use, WRAT reading performance, and lifetime depression.

MA+ displayed moderately higher rates of impairment and lower T scores compared to MA−. Lifetime alcohol use significantly interacted with MA status to predict global impairment (ORR = 0.70, p = .003) such that greater lifetime alcohol use increased likelihood of impairment in MA−, but decreased likelihood of impairment in MA+. Greater lifetime alcohol use predicted poorer global T scores among MA− (b = −0.44, p = .030) but not MA+ (b = 0.08, p = .586).

Contrary to expectations, greater lifetime alcohol use related to reduced risk of neurocognitive impairment among MA users. Findings are supported by prior research identifying neurobiological mechanisms by which alcohol may attenuate stimulant-driven vasoconstriction and brain thermotoxicity. Replication and examination of neurophysiologic mechanisms underlying alcohol use in the context of MA dependence are warranted to elucidate whether alcohol confers a degree of neuroprotection.