Functional cognitive disorder is an increasingly recognised subtype of functional neurological disorder for which treatment options are currently limited. We have developed a brief online group acceptance and commitment therapy (ACT)-based intervention.

To assess the feasibility of conducting a randomised controlled trial of this intervention versus treatment as usual (TAU).

The study was a parallel-group, single-blind randomised controlled trial, with participants recruited from cognitive neurology, neuropsychiatry and memory clinics in London. Participants were randomised into two groups: ACT + TAU or TAU alone. Feasibility was assessed on the basis of recruitment and retention rates, the acceptability of the intervention, and signal of efficacy on the primary outcome measure (Acceptance and Action Questionnaire II (AAQ-II)) score, although the study was not powered to demonstrate this statistically. Outcome measures were collected at baseline and at 2, 4 and 6 months post-intervention, including assessments of quality of life, memory, anxiety, depression and healthcare use.

We randomised 44 participants, with a participation rate of 51.1% (95% CI 40.8–61.5%); 36% of referred participants declined involvement, but retention was high, with 81.8% of ACT participants attending at least four sessions, and 64.3% of ACT participants reported being ‘satisfied’ or ‘very satisfied’ compared with 0% in the TAU group. Psychological flexibility as measured using the AAQ-II showed a trend towards modest improvement in the ACT group at 6 months. Other measures (quality of life, mood, memory satisfaction) also demonstrated small to modest positive trends.

It has proven feasible to conduct a randomised controlled trial of ACT versus TAU.

Celiac disease (CD), an autoimmune disorder triggered by gluten, impacts about one percent of the population. Only one-third receive a diagnosis, leaving the majority unaware of their condition. Untreated CD can lead to gut lining damage, resulting in malnutrition, anemia, and osteoporosis. Our primary goal was to identify at-risk groups and assess the cost-effectiveness of active case finding in primary care.

Our methodology involved systematic reviews and meta-analyses focusing on the accuracy of CD risk factors (chronic conditions and symptoms) and diagnostic tests (serological and genetic). Prediction models, based on identified risk factors, were developed for identifying individuals who would benefit from CD testing in routine primary care. Additionally, an online survey gauged individuals’ preferences regarding diagnostic certainty before initiating a gluten-free diet. This information informed the development of economic models evaluating the cost-effectiveness of various active case finding strategies.

Individuals with dermatitis herpetiformis, a family history of CD, migraine, anemia, type 1 diabetes, osteoporosis, or chronic liver disease showed one and a half to two times higher risk of having CD. IgA tTG, and EMA demonstrated good diagnostic accuracy. Genetic tests showed high sensitivity but low specificity. Survey results indicated substantial variation in preference for certainty from a blood test before initiating a gluten-free diet. Cost-effectiveness analyses showed that, in adults, IgA tTG at a one percent pre-test probability (equivalent to population screening) was the most cost effective. For non-population screening strategies, IgA EMA plus HLA was most cost effective. There was substantial uncertainty in economic model results.

While population-based screening with IgA tTG appears the most cost effective in adults, decisions for implementation should not solely rely on economic analyses. Future research should explore whether population-based CD screening aligns with UK National Screening Committee criteria and requires a long-term randomized controlled trial of screening strategies.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Traumatic brain injuries (TBIs) are a common occurrence among Veterans and may increase risk for neurodegenerative diseases, such as Alzheimer's disease (AD). Neuropathological correlates of AD, including buildup of ß-amyloid (Aß) plaques, formation of neurofibrillary tangles, and cortical atrophy, begin years before the onset of noticeable clinical and cognitive symptoms, emphasizing the importance of identifying early risk factors that could be targeted to prevent the development of AD. Of note, Aß ratios (e.g., Aß 42/40) have been shown to efficiently capture brain amyloid accumulation in prodromal AD, and thus may serve as a useful biological marker of preclinical AD. The present study investigates the mechanism by which TBI is associated with AD by examining the synergistic effects of TBI and genetic risk for AD on Aß among aging Veterans without dementia.

Participants included 88 White, Non-Hispanic/Latino male Vietnam War Veterans (Mage = 68.3 years) from the Alzheimer's Disease Neuroimaging Initiative Department of Defense (ADNI DoD) cohort, 49 of whom reported a history of at least one mild, moderate, or severe TBI. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Aß levels were extracted from cerebrospinal fluid and Aß 42/40 ratios were calculated as an index of Aß deposition in the brain. Linear regression models were run to determine if TBI history and polygenic risk influence Aß 42/40 levels. An ANCOVA was implemented to examine the interaction between TBI severity and polygenic risk. Covariates in all models included age, education, and posttraumatic stress disorder symptoms.

Results demonstrated a significant interaction between TBI and genetic risk on Aß 42/40 (B = -0.45, Puncorrected = 0.029, Pcorrected = 0.0495). Specifically, higher polygenic risk was associated with lower Aß 42/40 ratio, suggesting greater Aß burden in the brain, among those with a history of TBI (pr = -0.33, P = 0.024) compared to individuals without a history of TBI (pr = 0.17, P = 0.308). This relationship trended towards being stronger as a function of increasing TBI severity (F(2, 77) = 3.01, P = 0.055).

These results show that, in the context of TBI, higher genetic risk for AD is associated with greater AD-related pathology, particularly with more severe injuries. TBI and polygenic risk may implicate similar biological pathways, notably amyloid precursor protein processing, to increase Aß burden in the brain and likelihood of progression to AD in future years. These findings could inform early intervention techniques to delay or preclude conversion to AD.

The number of studies on digital health technologies (DHTs) for remote treatment and patient self-management is increasing. Existing health technology assessment (HTA) frameworks for DHTs, which guide researchers in generating evidence suitable for HTA, do not cover all domains of the commonly used EUnetHTA Core Model, and DHT-specific considerations have not been informed by a large stakeholder preference study. Our aim was to develop a stakeholder prioritized, literature-informed checklist of DHT-specific considerations that aligns with the EUnetHTA model.

We conducted two systematic reviews to identify: (i) DHT evaluation frameworks published to March 2020 for content; and (ii) primary research on DHTs published from 1 January 2015 to 20 March 2020.

Stakeholder prioritization of issues was performed using a best-worst scaling preference study among a broad cross-section of patients, carers, health professionals, and the general population in Australia, Canada, New Zealand, and the UK. Systematic review issues were prioritized and adapted for use as a practical checklist.

DHT evaluation content was recommended by the 44 identified frameworks for 28 of the 145 issues in the EUnetHTA model and for 22 new DHT-specific issues. A coverage assessment of 112 clinical studies of remote treatment and self-management DHTs for patients with cardiovascular disease or diabetes revealed that less than half covered DHT-specific content in all but one domain, or traditional HTA content in clinical effectiveness and ethical analysis. The preference survey of 1,251 stakeholders identified broad agreement on the 12 most important DHT attributes, six of which were related to safety. The most important attribute was “helps health professionals respond quickly when changes in patient care are needed”, which is not a focus of existing DHT HTA frameworks.

The review identified mismatches in the content generated by DHT clinical studies and that required for DHT-specific HTAs. These findings informed the development of an extended checklist comprising 22 stakeholder-prioritized DHT-specific considerations, which are aligned with the EUnetHTA model and will help ensure the planning of DHT-specific research generates evidence suitable for HTA.

Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.

Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).

The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.

Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.

Health service providers are currently making decisions on the public funding of digital health technologies (DHTs) for managing chronic diseases with limited understanding of stakeholder preferences for DHT attributes. This study aims to understand the community, patient/carer, and health professionals’ preferences to help inform a prioritized list of evaluation criteria.

An online best–worst scaling survey was conducted in Australia, New Zealand, Canada, and the United Kingdom to ascertain the relative importance of twenty-four DHT attributes among stakeholder groups using an efficient incomplete block design. The attributes were identified from a systematic review of DHT evaluation frameworks for consideration in a health technology assessment. Results were analyzed with multinomial models by stakeholder group and latent class.

A total of 1,251 participants completed the survey (576 general community members, 543 patients/carers, and 132 health professionals). Twelve attributes achieved a preference score above 50 percent in the stakeholder group model, predominantly related to safety but also covering technical features, effectiveness, ethics, and economics. Results from the latent class model supported this prioritization. Overall, connectedness with the patient’s healthcare team seemed the most important; with “Helps health professionals respond quickly when changes in patient care are needed” as the most highly prioritized of all attributes.

It is proposed that these prioritized twelve attributes be considered in all evaluations of DHTs that manage chronic disease, supplemented with a limited number of attributes that reflect the specific perspective of funders, such as equity of access, cost, and system-level implementation considerations.

To test a culturally tailored obesity prevention intervention in low-income, minority preschool age children.

A three-group clustered randomised controlled trial.

Twelve Head Start centres were randomly assigned to a centre-based intervention, a combined centre- and home-based intervention, or control using a 1:1:1 ratio. The centre-based intervention modified centre physical activity and nutrition policies, staff practices, and child behaviours, while the home-based intervention supported parents for obesity prevention at home.

The primary end point was change in children’s BMI (kg/m2) at post-test immediately following completion of the 8-month intervention. Secondary end points included standardised scores for BMI (BMIz) and body weight (WAZ), and BMI percentiles (BMI pctl).

Three-year-old children enrolled in Head Start in San Antonio, Texas, with written parent consent (n 325), 87 % Latino, 57 % female with mean age (sd) of 3·58 years (0·29).

Change in BMI at post-test was 1·28 (0·97), 1·28 (0·87) and 1·41 (0·71) in the centre + home-based intervention, centre-based intervention and control, respectively. There was no significant difference in BMI change between centre + home-based intervention and control or centre-based intervention and control at post-test. BMIz (adjusted difference –0·12 (95 % CI, –0·24, 0·01), P = 0·06) and WAZ (adjusted difference, –0·09 (–0·17, –0·002), P = 0·04) were reduced for children in centre + home-based intervention compared with control group.

There was no reduction in BMI at post-test in children who received the intervention. Findings shed light on methodological challenges in childhood obesity research and offer future directions to explore health equity-oriented obesity prevention.

Psychiatric mother and baby units (MBUs) are recommended for severe perinatal mental illness, but effectiveness compared with other forms of acute care remains unknown.

We hypothesised that women admitted to MBUs would be less likely to be readmitted to acute care in the 12 months following discharge, compared with women admitted to non-MBU acute care (generic psychiatric wards or crisis resolution teams (CRTs)).

Quasi-experimental cohort study of women accessing acute psychiatric care up to 1 year postpartum in 42 healthcare organisations across England and Wales. Primary outcome was readmission within 12 months post-discharge. Propensity scores were used to account for systematic differences between MBU and non-MBU participants. Secondary outcomes included assessment of cost-effectiveness, experience of services, unmet needs, perceived bonding, observed mother–infant interaction quality and safeguarding outcome.

Of 279 women, 108 (39%) received MBU care, 62 (22%) generic ward care and 109 (39%) CRT care only. The MBU group (n = 105) had similar readmission rates to the non-MBU group (n = 158) (aOR = 0.95, 95% CI 0.86–1.04, P = 0.29; an absolute difference of −5%, 95% CI −14 to 4%). Service satisfaction was significantly higher among women accessing MBUs compared with non-MBUs; no significant differences were observed for any other secondary outcomes.

We found no significant differences in rates of readmission, but MBU advantage might have been masked by residual confounders; readmission will also depend on quality of care after discharge and type of illness. Future studies should attempt to identify the effective ingredients of specialist perinatal in-patient and community care to improve outcomes.

As health services increasingly make investment decisions in digital health technologies (DHTs), a DHT-specific and comprehensive health technology assessment (HTA) process is crucial in assessing value-for-money. Research in DHTs is ever-increasing, but whether it covers the content required for HTA is unknown.

To summarize current trends in primary research on DHTs that manage chronic disease at home, particularly the coverage of content recommended for DHT-specific and comprehensive HTA.

Medline, Embase, Econlit, CINAHL, and The Cochrane Library (1 January 2015 to 20 March 2020) were searched for primary research studies using keywords related to DHT and HTA domains. Studies were assessed for coverage of the most frequently recommended content to be considered in a nine domain DHT-specific HTA previously developed.

A total of 178 DHT interventions were identified, predominantly randomized controlled trials targeting cardiovascular disease/diabetes in high- to middle-income countries. A coverage assessment of the cardiovascular and diabetes DHT studies (112) revealed less than half covered DHT-specific content in all but the health problem domain. Content common to all technologies but essential for DHTs was covered by more than half the studies in all domains except for the effectiveness and ethical analysis domains.

Although DHT research is increasing, it is not covering all the content recommended for a DHT-specific and comprehensive HTA. The inability to conduct such an HTA may lead to health services making suboptimal investment decisions. Measures to increase the quality of trial design and reporting are required in DHT primary research.

To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI).

We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention.

An academic healthcare system with 4 hospitals.

All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients.

Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing.

Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P < .01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P < .05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P < .01).

Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

A growing number of evaluation frameworks have emerged over recent years addressing the unique benefits and risk profiles of new classes of digital health technologies (DHTs). This systematic review aims to identify relevant frameworks and synthesize their recommendations into DHT-specific content to be considered when performing Health Technology Assessments (HTAs) for DHTs that manage chronic noncommunicable disease at home.

Searches were undertaken of Medline, Embase, Econlit, CINAHL, and The Cochrane Library (January 2015 to March 2020), and relevant gray literature (January 2015 to August 2020) using keywords related to HTA, evaluation frameworks, and DHTs. Included framework reference lists were searched from 2010 until 2015. The EUNetHTA HTA Core Model version 3.0 was selected as a scaffold for content evaluation.

Forty-four frameworks were identified, mainly covering clinical effectiveness (n = 30) and safety (n = 23) issues. DHT-specific content recommended by framework authors fell within 28 of the 145 HTA Core Model issues. A further twenty-two DHT-specific issues not currently in the HTA Core Model were recommended.

Current HTA frameworks are unlikely to be sufficient for assessing DHTs. The development of DHT-specific content for HTA frameworks is hampered by DHTs having varied benefit and risk profiles. By focusing on DHTs that actively monitor/treat chronic noncommunicable diseases at home, we have extended DHT-specific content to all nine HTA Core Model domains. We plan to develop a supplementary evaluation framework for designing research studies, undertaking HTAs, and appraising the completeness of HTAs for DHTs.