Obstetric complications (OCs) are associated with cognitive and brain abnormalities observed in patients with schizophrenia. Gyrification, a measure of cortical integrity sensitive to events occurring during the prenatal and perinatal periods, is also altered in first-episode psychosis (FEP). We examined the relationship between OCs and gyrification in FEP, as well as whether gyrification mediates the relationship between OCs and cognition.

We examined differences in the Local Gyrification Index (LGI) for the frontal, parietal, temporal, occipital, and cingulate cortices between 139 FEP patients and 125 healthy controls (HCs). Regression analyses explored whether OCs and diagnosis interact to explain LGI variation. Parametric mediation analyses were conducted to assess the effect of LGI on the relationship between OCs and cognition for FEP and HC.

Significant LGI differences were observed between FEP patients and HC in the left parietal and bilateral cingulate and occipital cortices. There was a significant interaction between OCs and diagnosis on the left cingulate cortex (LCC) that was specific to males (p = 0.04) and was driven by gestational rather than intrauterine OCs.

In HCs, OCs had a direct effect on working memory (WM) (p = 0.048) in the mediation analysis, whereas in FEP, we observed no significant effect of OCs on either verbal or WM.

OCs interact with diagnosis to predict LCC gyrification, such that males with FEP exposed to OCs exhibit the lowest LGI. OCs influence WM, and LCC gyrification may mediate this relation only in HC, suggesting a differential neurodevelopmental process in psychosis.

Predicting long-term outcome trajectories in psychosis remains a crucial and challenging goal in clinical practice. The identification of reliable neuroimaging markers has often been hindered by the clinical and biological heterogeneity of psychotic disorders and the limitations of traditional case-control methodologies, which often mask individual variability. Recently, normative brain charts derived from extensive magnetic resonance imaging (MRI) data-sets covering the human lifespan have emerged as a promising biologically driven solution, offering a more individualised approach.

To examine how deviations from normative cortical and subcortical grey matter volume (GMV) at first-episode psychosis (FEP) onset relate to symptom and functional trajectories.

We leveraged the largest available brain normative model (N > 100 000) to explore normative deviations in a sample of over 240 patients with schizophrenia spectrum disorders who underwent MRI scans at the onset of FEP and received clinical follow-up at 1, 3 and 10 years.

Our findings reveal that deviations in regional normative GMV at FEP onset are significantly linked to overall long-term clinical trajectories, modulating the effect of time on both symptom and functional outcome. Specifically, negative deviations in the left superior temporal gyrus and Broca’s area at FEP onset were notably associated with a more severe progression of positive and negative symptoms, as well as with functioning trajectories over time.

These results underscore the potential of brain developmental normative approaches for the early prediction of disorder progression, and provide valuable insights for the development of preventive and personalised therapeutic strategies.

There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research.

This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery–Åsberg Depression Rating Scale (MADRS-6).

A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation.

The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set.

The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.

Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances.

We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis–Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups.

FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio.

Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Different components of the endocannabinoid (eCB) system such as their most well-known endogenous ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been implicated in brain reward pathways. While shared neurobiological substrates have been described among addiction-related disorders, information regarding the role of this system in behavioral addictions such as gambling disorder (GD) is scarce.

Fasting plasma concentrations of AEA and 2-AG were analyzed in individuals with GD at baseline, compared with healthy control subjects (HC). Through structural equation modeling, we evaluated associations between endocannabinoids and GD severity, exploring the potentially mediating role of clinical and neuropsychological variables.

The sample included 166 adult outpatients with GD (95.8% male, mean age 39 years old) and 41 HC. Peripheral blood samples were collected after overnight fasting to assess AEA and 2-AG concentrations (ng/ml). Clinical (i.e., general psychopathology, emotion regulation, impulsivity, personality) and neuropsychological variables were evaluated through a semi-structured clinical interview and psychometric assessments.

Plasma AEA concentrations were higher in patients with GD compared with HC (p = .002), without differences in 2-AG. AEA and 2-AG concentrations were related to GD severity, with novelty-seeking mediating relationships.

This study points to differences in fasting plasma concentrations of endocannabinoids between individuals with GD and HC. In the clinical group, the pathway defined by the association between the concentrations of endocannabinoids and novelty-seeking predicted GD severity. Although exploratory, these results could contribute to the identification of potential endophenotypic features that help optimize personalized approaches to prevent and treat GD.

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) play a pivotal role in stimulating motivational behavior toward food and energy metabolism. Aberrant functioning of the endocannabinoid system has been observed in extreme weight conditions (EWCs), suggesting it may influence pathophysiology. Then, we aimed to analyze fasting AEA and 2-AG plasma concentrations among individuals with EWC (i.e., anorexia nervosa [AN] and obesity with and without eating disorders [EDs]) compared with healthy controls (HCs), and its association with clinical variables and body mass index (BMI).

The sample included 113 adult women. Fifty-seven belonged to the obesity group, 37 without EDs (OB-ED) and 20 with ED (OB+ED classified within the binge spectrum disorders), 27 individuals from the AN group, and 29 from the HC group. Peripheral blood samples, several clinical variables, and BMI were evaluated.

Unlike 2-AG, AEA concentrations showed significant differences between groups (p < 0.001). Increased AEA was observed in the OB-ED and OB+ED compared with both HC and AN group, respectively. Likewise, AEA was differentially associated with emotional dysregulation, general psychopathology, food addiction, and BMI in all clinical groups.

These results support the interaction between biological and clinical factors contributing to delineating vulnerability pathways in EWC that could help fit personalized therapeutic approaches.

To investigate the opinion and personal experience of parents of children born with Hypoplastic Left Heart Syndrome and what advice they would give to other parents who have to decide between treatment options.

We conducted a qualitative, descriptive and retrospective study by means of a survey directed to parents of children born with Hypoplastic Left Heart Syndrome in a tertiary hospital in Buenos Aires (Argentina). Their answers and data regarding medical procedures were analysed.

Parents of thirteen out of sixteen patients with Hypoplastic Left Heart Syndrome were surveyed. Norwood surgery had been performed in all the patients, many had received other procedures, and five had died. In relation to the decision-making process, sixty-one percent of parents would recommend other parents to remain at peace after having done everything possible and 54% would suggest to not feel guilt despite the final result. None of the parents would recommend rejecting surgical treatment and choosing comfort care.

The majority of parents of children with Hypoplastic Left Heart Syndrome would recommend continuing with the therapeutic effort in order to feel at peace and reduce feelings of guilt.

Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes.

To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories.

We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases.

Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data.

Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

The coronavirus disease 2019 (COVID-19) pandemic has been a global challenge. High mortality rates have been reported in some risk groups, including patients with pre-existing mental disorders.

We used electronic health records to retrospectively identify people infected due to COVID-19 (between March 2020 and March 2021) in the three territories of the Basque Country. COVID-19 cases were defined as individuals who had tested positive on a reverse transcription-polymerase chain reaction (PCR) test. Univariate and multivariate logistic regression models and multilevel analyses with generalized estimated equations were used to determine factors associated with COVID-19-related mortality and hospital admission.

The COVID-19 mortality rate was increased for patients with psychotic disorders [odds ratio (OR) adjusted: 1.45, 95% confidence interval (CI) (1.09–1.94), p = 0.0114] and patients with substance abuse [OR adjusted: 1.88, 95% CI (1.13–3.14, p < 0.0152)]. The mortality rate was lower for patients with affective disorders [OR adjusted: 0.80, 95% CI (0.61–0.99), p = 0.0407]. Hospital admission rates due to COVID-19 were higher in psychosis [OR adjusted: 2.90, 95% CI (2.36–3.56), p < 0.0001] and anxiety disorder groups [OR adjusted: 1.54, 95% CI (1.37–1.72), p < 0.0001]. Among admitted patients, COVID-19 mortality rate was decreased for those with affective disorders rate [OR adjusted: 0.72, 95% CI (0.55–0.95), p = 0.0194].

COVID-19-related mortality and hospitalizations rates were higher for patients with a pre-existing psychotic disorder.

Although randomized controlled trials (RCTs) are recognized as providing the highest level of clinical evidence, few medical device RCTs are available due to underfunding or inherent challenges associated with trial design. This study examines the extent to which real-world evidence (RWE) supports the recommendations made by the National Institute for Health and Care Excellence Medical Technologies Evaluation Programme (MTEP).

All MTEP guidance documents published online prior to October 2020 were reviewed. The “case for adoption” recommendation, type of clinical data, and clinical critiques for each MTEP submission were extracted and categorized. RWE was defined as studies with neither blinding nor prospective selection or control of patient characteristics.

Of the MTEP submissions reviewed, 34 of 45 (76%) received a positive recommendation. Independent of outcome, all submissions included RWE, but only 19 (42%) utilized RCT evidence (15 were recommended and four were not). Meta-analyses of RWE were used whenever possible. The most common clinical critiques in unsuccessful submissions were the following: (i) not generalizable to the United Kingdom National Health Service (NHS); (ii) low quality; (iii) likelihood of bias; (iv) trial design faults; (v) uncertain benefit; and (vi) evidence unrelated to scope.

This study suggests that while the use of RCTs has not always led to a positive recommendation, RWE can be valuable in decision-making. Evidence that is generalizable to the NHS, is related to the scope, and shows clear indication of benefit is more likely to positively influence MTEP decision-making.

The United Kingdom spends approximately GBP4.2 billion (USD5.6 billion; EUR4.7 billion) each year on medical devices, but healthcare providers receive little health technology assessment (HTA) guidance on cost-effective device procurement. Our objective was to assess the availability of HTA guidance for medical technologies and to identify key challenges related to the economic assessment of these technologies.

National Institute for Health and Care Excellence technology appraisal (TA) and Medical Technologies Evaluation Programme (MTEP) appraisals published online between November 2009 and October 2020 were identified. The “case for adoption” recommendation, type of devices, and critiques of economic analyses for each MTEP appraisal were extracted and categorized.

In comparison to 415 publicly available TAs for pharmaceuticals, only 45 medical technologies have been appraised through the MTEP. MTEP-submitted technologies can be categorized into diagnostic (7), monitoring (3), prophylaxis (5), therapeutic (28), and other (2). Furthermore, 11 were implants, seven were used by patients, and 27 had provider interaction. Major points of MTEP criticism were a failure to model cost consequences, training costs, and organizational impact. There was also the barrier of transferring costs across budgeting divisions.

In comparison to HTA guidance for pharmaceuticals, there is a dearth of medical device guidance. Therapeutic and implantable devices appear to be disproportionately overrepresented in the MTEP process. This may be because their appraisal is most akin to pharmaceuticals, for which HTA processes are well established. To encourage more HTAs of medical devices, HTA guidance should elaborate on issues specifically related to medical devices.

Real-world evidence (RWE) is a useful supplement to a product's evidence base especially for medical devices, which are often unsuitable for randomized controlled trials. Generally, RWE is analyzed retrospectively (for example, healthcare records), which lack granularity for health-economic analysis. Prospective collection of RWE in hospitals can promote device-specific endpoint assessment. The advent of the General Data Protection Regulation (GDPR) requires a privacy-by-design approach. This work describes a workflow for a GDPR-compliant device-specific RWE collection as part of quality improvement initiatives (QII).

A literature review identifies relevant clinical and quality markers as endpoints to the investigated technology. A panel of experts grade these endpoints on their clinical significance, privacy sensitivity, analytic value, and feasibility for collection. Endpoints meeting a predefined cut-off are considered quality markers for the QII. Finally, an RWE data collection app is designed to collect the quality markers using either longitudinal, pseudonymized data or single time-point anonymized data to ensure data protection by design.

Using this approach relevant clinical markers were identified in a GDPR-compliant manner. The data collection app design ensured that patient data were protected, while maintaining minimum requirements on patient information and consent. The pilot QII collected data on over 5,000 procedures, which represents the largest single data set available for the tested technology. Due to its prospective nature this programme was the first to collect patient outcomes in sufficient quantity for analysis, while previous studies only recorded adverse events.

GDPR and RWE can co-exist in harmony. A design approach, which has data protection in mind from the start can combine high quality RWE collection of efficacy and safety data with maximum patient privacy.