The cerebellar cognitive affective syndrome (CCAS) scale has been developed to screen for possible cognitive and affective impairments in cerebellar patients, but previous studies stressed concerns regarding insufficient specificity of the scale. Also, direct comparisons of CCAS scale performance between cerebellar patients with and without CCAS are currently lacking. The aim of this study was to evaluate the validity of the CCAS scale in cerebellar patients.

In this study, cerebellar patients with CCAS (n = 49), without CCAS (n = 30), and healthy controls (n = 32) were included. The Dutch/Flemish version of the CCAS scale was evaluated in terms of validity and reliability using an extensive neuropsychological assessment as the gold standard for CCAS. Correlations were examined between the CCAS scale and possible confounding factors. Additionally, a correction for dysarthria was applied to timed neuropsychological tests to explore the influence of dysarthria on test outcomes.

Cerebellar patients with CCAS performed significantly worse on the CCAS scale compared to cerebellar controls. Sensitivity was acceptable, but specificity was insufficient due to high false-positive rates. Correlations were found between outcomes of the scale and both education and age. Although dysarthria did not affect the validity of the CCAS scale, it may influence timed neuropsychological test outcomes.

Evaluation of the CCAS scale revealed insufficient specificity. Our findings call for age- and education-dependent reference values, which may improve the validity and usability of the scale. Dysarthria might be a confounding factor in timed test items and should be considered to prevent misclassification.

The coronavirus disease 2019 (COVID-19) pandemic has impacted global mental health, with individuals with severe mental illness (SMI) being particularly vulnerable. Research on changes in psychiatric symptoms during this pandemic has yielded inconsistent results, often due to individual heterogeneity and a limited focus on broader outcomes such as psychosocial functioning, societal and personal recovery, and quality of life (QoL). Furthermore, long-term effects remain underexplored. This longitudinal cohort study aimed to assess the COVID-19 pandemic’s impact on mental and psychosocial functioning, QoL, and recovery in individuals with SMI, and to explore individual and treatment characteristics associated with outcome changes.

Two cohorts were included, involving adults (≥18 years) diagnosed with DSM-5 disorders and experiencing long-term impairments. Participants received care between January 1, 2018 and December 31, 2023. Outcomes included the Health of the Nation Outcome Scales, the Manchester Short Assessment of Quality of Life, and the Individual Recovery Outcomes Counter. Changes were analyzed across five pandemic periods using linear mixed models.

Improvements in mental and psychosocial functioning, QoL, and recovery were observed over time, regardless of the COVID-19 pandemic period. However, progress was slower during the COVID-19 pandemic compared to pre-pandemic levels. No individual or treatment characteristics were significantly linked to changes in outcomes.

The findings suggest that the COVID-19 pandemic had a minimal negative impact on individuals with SMI. This may be due to the marginal negative effects of the pandemic on this population, or the mitigating role of stabilizing factors within the current Dutch care models.

Poorer family functioning during childhood is associated with severe mental disorders in adulthood in the general population. However, family functioning is understudied in families with parental schizophrenia or bipolar disorder. We aimed to investigate family functioning in families with 11-year-old children of parents with schizophrenia or bipolar disorder compared with controls. Second, we aimed to examine associations between family functioning and levels of child psychopathology, child global functioning, and parental social functioning.

In this prospective, population-based cohort study, we included 160 families with parental schizophrenia, 95 families with parental bipolar disorder, and 177 control families. Family functioning was measured with the 12-item version of the McMaster Family Assessment Device – General Functional Scale.

Families with parental schizophrenia (Cohen’s d = 0.29; p = .002) and parental bipolar disorder (Cohen’s d = 0.34; p = .004) had significantly poorer family functioning and a significantly higher prevalence of clinically significant family dysfunction (Cohen’s d range = 0.29–0.34; p values = .007) than control families. Across study groups, poorer family functioning was associated with higher levels of child psychopathology and poorer social functioning of the primary caregiver (p values < .001).

Children in families with parental schizophrenia or bipolar disorder are at increased risk of experiencing family dysfunction, and poorer family functioning confers risk for more symptoms of child psychopathology and poorer parental social functioning. Future studies should investigate the potentially predictive value of family dysfunction in relation to later illness onset and other adverse outcomes in these populations.

We aimed to study how hormonal status (oral contraceptive [OC] users vs naturally cycling [NC]) affects different dimensions and variability of psychological well-being, and how they relate to sex hormone levels (estradiol, progesterone, and testosterone).

Twenty-two NC participants and 18 OC users reported daily affective and physical symptoms and collected daily salivary samples across 28 days. Groups were compared using psychological well-being averages (linear mixed models), day-to-day variability (Levene’s test), and network models. Within NC participants, cycle phase effects and time-varying associations between hormones and psychological well-being were assessed using both person-centered mean and change (subtracting mean from daily score) scores.

Lowered variability was found for OC users’ agitation, risk-taking, attractiveness, and energy levels. They showed lower overall ratings of happiness, attractiveness, risk-taking, and energy levels (range R2m = .004: .019) but also reported more relaxation, sexual desire, and better sleep quality (range R2m = .005; .01) compared to the NC group. The impact of sex hormones on psychological well-being varied significantly across cycle phases, with the largest effects for progesterone levels.

Our results confirm that hormonal status is associated with a range of psychological well-being domains beyond mood and sexual desire, including energy levels, feelings of attractiveness, risk taking, and agitation. Lowered variability in OC users versus NC participants fit with ‘emotional blunting’ as a possible mechanism behind OC’s side effects. Our findings that show the menstrual cycle and sex hormones differentially influenced markers of psychological well-being emphasize the need to adequately account for the menstrual cycle.

There is an increasing number of policy and guidance documents on the use and acceptability of real-world evidence (RWE) to support regulatory and health technology assessment (HTA) decision-making. The Innovative Health Initiative Integration of Heterogeneous Data and Evidence towards Regulatory and HTA Acceptance (IDERHA) partnership is undertaking a global landscape review of these documents to understand where there is consensus and divergence, and where further policy development is needed.

A literature search of the MEDLINE and Embase databases was performed, in addition to handsearching the websites of specific HTA and regulatory organizations. All policies, standards, frameworks, and guidance documents on requirements for acceptable RWE data use published from 2017 were included. Two reviewers independently extracted data using a standard data extraction form that was pilot tested before use. Any discrepancies between the reviewers were resolved by consensus. Extracted data are currently being analyzed by researchers with regulatory or HTA expertise. A workshop held in October 2023 sought input from experts on analysis plans.

The initial literature search yielded 3,184 results. After screening against the inclusion criteria, a total of 87 documents were selected for full-text review (21 HTA and 62 regulatory documents). Of these, 32 were identified as key documents and prioritized for initial review. Key themes in the documents, including transparency, data collection, study design, and data quality, were identified and validated in a workshop with five regulatory or HTA experts. Data extraction is ongoing for the remaining documents and any further themes identified will be added. Any gaps and areas of divergence will be identified, so they can be addressed by future IDERHA work.

This review assessed the increasingly complex global landscape of regulatory and HTA policies and guidance on the use of RWE. Through the exploration of similarities, differences, and gaps in these policies, this work will extend the current understanding of best practice and identify areas that need development of further guidance.

Tetralogy of Fallot patients face an elevated risk of developing chylothorax and pleural effusions post-surgery. This patient group exhibits risk factors known to compromise the lymphatic system, such as elevated central venous pressure, pulmonary flow changes, and hypoxia. This study investigates the morphology and function of the lymphatic system in tetralogy of Fallot patients through lymphatic magnetic resonance imaging and near-infrared fluorescence imaging, respectively.

Post-repair tetralogy of Fallot patients aged 6–18 years were recruited, along with age and gender-matched controls. Magnetic resonance imaging was used to assess the morphology of the thoracic lymphatic vessels and the thoracic, while near-infrared fluorescence imaging was used to assess lymphatic activity utilising lymph rate, velocity, and pressure.

Nine patients and 10 controls were included. Echocardiography revealed that 2/3 of the patients had moderate-severe pulmonary regurgitation, while none displayed signs of elevated central venous pressure. Magnetic resonance imaging identified three patients with type 3 (out of 4 types) lymphatic abnormalities, while controls had none. The thoracic ducts showed severe (one patient) and moderate (one patient) tortuosity. Mean thoracic duct diameters were 3.3 mm ±1.1 in patients and 3.0 mm ± 0.8 in controls (p-value = 0.53). Near-infrared fluorescence imaging revealed no anomalous patterns.

Despite no presence of clinical lymphatic disease, 3/9 of the repaired tetralogy of Fallot patients exhibited lymphatic morphological abnormalities. The significance of these anomalies remains uncertain currently. Further research is needed to determine whether these lymphatic alterations in this patient cohort are a result of congenital malformations, haemodynamic shifts, or prenatal and early-life saturation levels.

High cognitive activity possibly reduces the risk of cognitive decline and dementia.

To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.

Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.

Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.

A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.

Hospitals in England experience extremely high levels of bed occupancy in the winter. In these circumstances, vaccine-preventable hospitalizations due to seasonal respiratory infections, have a high cost because of the missed opportunity to treat other patients on the waiting list.

This study sought to generate evidence on the hospitalizations that vaccines for older adults against seasonal influenza (flu), pneumococcal disease (PD), respiratory syncytial virus (RSV) and COVID-19 may prevent during the winter season (October-March) in England. The monetary value of the vaccine-preventable hospitalizations was estimated using a conventional reference costing method and a novel opportunity costing approach.

Based on retrospective analysis of Hospital Episode Statistics data on hospitalizations in England, and efficacy and observed coverage rates per vaccination program, we estimated the number of bed-days that current vaccines against flu, PD and COVID-19, and a hypothetical RSV vaccine, could free up by preventing hospitalizations in the winter among older adults. We valued the freed-up bed-days (1) as the cost of prevented hospitalizations (reference cost); (2) as the Net Monetary Benefit (NMB) generated by alternative uses of the freed-up bed-days. The opportunity cost of vaccines-preventable hospitalizations is (2) when they would be an optimal use of beds or (1)+(2) when they would be a suboptimal use.

In the winter months, vaccination programs targeting flu, PD and RSV for older adults could collectively prevent 72,813 bed days and save over £45million (USD56 million) in hospitalization costs. The COVID-19 vaccine could prevent over 2 billion bed days and save GBP1.3 billion. Importantly, the value of hospital beds freed up by vaccination is likely to be 1.1–2 times larger (£48–£93 million [USD60-116 million] for flu, PD and RSV; £1.4–£2.8 billion [USD1.8-3.5 billion] for COVID-19) when quantified in opportunity cost terms. Scenario analysis replacing the current vaccine used in the adult PD program with the newly licensed pneumococcal conjugate 20-valent vaccine (PCV20), would increase the impact of each modelled outcome for this program by approximately 38 times.

Vaccines for flu, PD, RSV and COVID-19 could prevent a significant number of hospitalizations in the winter. The value of the associated freed-up bed capacity is likely to be underestimated by conventional reference costing methods.