Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.

The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs.

An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health.

Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general.

The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.

To investigate the frequency of exceptional cognition (cognitive super-aging) in Australian older adults using different published definitions, agreement between definitions, and the relationship of super-aging status with function, brain imaging markers, and incident dementia.

Three longitudinal cohort studies.

Participants recruited from the electoral roll, Australian Twins Registry, and community advertisements.

Older adults (aged 65–106) without dementia from the Sydney Memory and Ageing Study (n = 1037; median age 78), Older Australian Twins Study (n = 361; median age 68), and Sydney Centenarian Study (n = 217; median age 97).

Frequency of super-aging was assessed using nine super-aging definitions based on performance on neuropsychological testing. Levels of agreement between definitions were calculated, and associations between super-aging status for each definition and functioning (Bayer ADL score), structural brain imaging measures, and incident dementia were explored.

Frequency of super-aging varied between 2.9 and 43.4 percent with more stringent definitions associated with lower frequency. Agreement between different criteria varied from poor (K = 0.04, AC1 = .24) to very good (K = 0.83, AC1 = .91) with better agreement between definitions using similar tests and cutoffs. Super-aging was associated with better functional performance (4.7–11%) and lower rates of incident dementia (hazard ratios 0.08–0.48) for most definitions. Super-aging status was associated with a lower burden of white matter hyperintensities (3.8–33.2%) for all definitions.

The frequency of super-aging is strongly affected by the demographic and neuropsychological testing parameters used. Greater consistency in defining super-aging would enable better characterization of this exceptional minority.

There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT.

A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates.

The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective.

Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.

Apathy is a common symptom in mild cognitive impairment (MCI) and may predict progression to dementia. Little research, however, has investigated the longitudinal trajectory of apathy in patients with MCI or controlled for depression, which can mimic apathy, when examining its clinical correlates. The current study sought to address these issues.

A prospective longitudinal study was conducted over 3 years.

Nine memory clinics around Australia

One hundred and eighty-five patients with MCI at baseline.

Measures of cognition, function, neuropsychiatric symptoms, caregiver burden, and medication use were completed annually with additional assessments at 3 and 6 months. Patients were also assessed for dementia by expert clinicians at these time points.

Of 164 patients who completed measures of neuropsychiatric symptoms, 59 (36.0%) had apathy and 61 (37.2%) had depression. The proportion affected by apathy and overall apathy scores increased over time, in contrast to measures of depression, which remained relatively stable. Apathy was associated with incident dementia and worse cognition, function, neuropsychiatric symptoms, and caregiver burden independent of both depression and incident dementia. Depression was associated with worse function, albeit to lesser degree than apathy, and neuropsychiatric symptoms.

Apathy increases in MCI and is associated with worse clinical outcomes. These findings provide further evidence for apathy as a marker of clinical decline in older people and poorer outcomes across neurocognitive disorders.

Health technology reassessment (HTR) is a process to manage existing health technologies to ensure ongoing optimal use. A model to guide HTR was developed; however, there is limited practical experience. This paper addresses this knowledge gap through the completion of a multi-phase HTR of red blood cell (RBC) transfusion practices in the intensive care unit (ICU).

The HTR consisted of three phases and here we report on the final phase: the development, implementation, and evaluation of behavior change interventions aimed at addressing inappropriate RBC transfusions in an ICU.

The interventions, comprised of group education and audit and feedback, were co-designed and implemented with clinical leaders. The intervention was evaluated through a controlled before-and-after pilot feasibility study. The primary outcome was the proportion of potentially inappropriate RBC transfusions (i.e., with a pre-transfusion hemoglobin of 70 g/L or more).

There was marked variability in the monthly proportion of potentially inappropriate RBC transfusions. Relative to the pre-intervention phase, there was no significant difference in the proportion of potentially inappropriate RBC transfusions post-intervention. Lessons from this work include the importance of early and meaningful engagement of clinical leaders; tailoring the intervention modalities; and, efficient access to data through an electronic clinical information system.

It was feasible to design, implement, and evaluate a tailored, multi-modal behavior change intervention in this small-scale pilot study. However, early evaluation of the intervention revealed no change in technology use leading to reflection on the important question of how the HTR model needs to be improved.

Patients with cyanotic heart disease are at an increased risk of developing thrombosis. Aspirin has been the mainstay of prophylactic anticoagulation for shunt-dependent patients with several reports of prevalent aspirin resistance, especially in neonates. We investigate the incidence of aspirin resistance and its relationship to thrombotic events and mortality in a cohort of infants with shunt-dependent physiology.

Aspirin resistance was assessed using the VerifyNow™ test on infants with single-ventricle physiology following shunt-dependent palliation operations. In-hospital thrombotic events and mortality data were collected. Statistical analysis was performed to evaluate the effect of aspirin resistance on in-hospital thrombotic events and mortality risk.

Forty-nine patients were included with 41 of these patients being neonates. Six patients (12%) were aspirin resistant. A birth weight < 2500 grams was a significant factor associated with aspirin resistance (p = 0.04). Following a dose increase or additional dose administration, all patients with initial aspirin resistance had a normal aspirin response. There was no statistically significant difference between aspirin resistance and non-resistance groups with respect to thrombotic events. However, a statistically significant incidence of in-hospital mortality in the presence of thrombotic events was observed amongst aspirin-resistant patients (p = 0.04) in this study.

Low birth weight was associated with a higher incidence of aspirin resistance. Inadequate initial dosing appears to be the primary reason for aspirin resistance. The presence of both thrombotic events and aspirin resistance was associated with significantly higher in-hospital mortality indicating that these patients warrant closer monitoring.

The randomized, controlled, phase 3b ALPINE study evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) initiated with a 1-day regimen during hospitalization for an acute exacerbation of schizophrenia; paliperidone palmitate (PP) was included as an active control. The primary efficacy outcome, within-group change from baseline in PANSS total score at 4 weeks, was previously reported. Here we report additional exploratory PANSS subscale endpoints and patient-reported outcomes (PROs).

Adults aged 18–65 years were enrolled as inpatients and randomized to AL 1064 mg q8wk or PP 156 mg q4wk and discharged after 2 weeks of study treatment if clinically stable. Patients were followed as outpatients through week 25. Exploratory efficacy endpoints were PANSS subscale (Positive, Negative, and General) and Clinical Global Impression-Severity (CGI-S) scores. The Burden Assessment Scale was administered to patients’ nonprofessional caregivers (family member or friend). Exploratory PROs (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form [Q-LES-Q-SF] and Medication Satisfaction Questionnaire) were assessed during the outpatient period. Within-group changes in PANSS subscales and CGI-S scores from baseline through week 25 were analyzed for AL and PP using mixed models with repeated measures. PROs were summarized based on observed data.

In total, 200 patients were randomized (AL, n=99; PP, n=101); 99 (AL, n=56; PP, n=43) completed the 25-week study. PANSS Positive, Negative, and General subscale scores improved with AL treatment as measured by change from baseline to week 25 (least squares [LS] mean [95% CI]: Positive, −7.0 [−8.1, −6.0]; Negative, −3.7 [−4.7, −2.8]; General, −11.1 [−12.7, −9.5]), as did CGI-S scores (LS mean [95% CI] change at week 25: –1.2 [–1.4 –1.0]). Caregiver burden decreased over the treatment period, with the largest decline noted at week 9 for AL patients’ caregivers (mean change from baseline at week 9: −8.4; week 25: −8.9). Over weeks 5, 9, and 17, 70.8%−74.7% of AL-treated patients were somewhat or very satisfied with treatment. Mean Q-LES-Q-SF total scores were stable. With PP, PANSS subscale and CGI-S scores improved from baseline to study end (LS mean [95% CI] changes at week 25: Positive, −7.1 [−8.2, −5.9]; Negative, −3.5 [−4.6, −2.5]; General, −10.4 [−12.1, −8.6]; CGI-S, −1.2 [−1.5, −1.0]). Mean caregiver burden decreased (week 9: −8.8; week 25: −9.2). Most PP patients were satisfied or very satisfied with treatment (64.7%−69.3% at weeks 5, 9, and 17), and mean Q-LES-Q-SF total scores were stable.

In ALPINE, patients who initiated AL or PP in the hospital and continued treatment during outpatient care experienced improvement in schizophrenia symptoms and reported satisfaction with medication, decreased caregiver burden, and stable quality of life.

Alkermes, Inc.

The patient experience of radiotherapy magnetic resonance (MR) simulation is unknown. This study aims to evaluate the patient experience of MR simulation in comparison to computed tomography (CT) simulation, identifying the quality of patient experience and pathway changes which could improve patient experience outcomes.

MR simulation was acquired for 46 anal and rectal cancer patients. Patient experience questionnaires were provided directly after MR simulation. Questionnaire responses were assessed after 33 patients (cohort one). Changes to the scanning pathway were identified and implemented. The impact of changes was assessed by cohort two (13 patients).

Response rates were 85% (cohort one) and 54% (cohort two). 75% of cohort one respondents found the magnetic resonance imaging (MRI) experience to be better or similar to their CT experience. Implemented changes included routine use of blankets, earplugs and headphones, music and feet-first positioning and further MRI protocol optimisation. All cohort two respondents found the MRI experience to be better or similar to the CT experience.

MR simulation can be a comfortable and positive experience that is comparable to that of standard radiotherapy CT simulation. Special attention is required due to the fundamental differences between CT and MRI scanning.

To describe a pilot project infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal 2-week period when the region became the nation’s epicenter for coronavirus disease 2019 (COVID-19).

A telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity.

SNFs in 14 New York counties, including New York City.

A 3-component remote IPC assessment: (1) screening tool; (2) telephone IPC checklist; and (3) COVID-19 video IPC assessment (ie, “COVIDeo”).

In total, 92 SNFs completed the IPC screening tool and checklist: 52 (57%) were conducted as part COVID-19 investigations, and 40 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26 (28%) of 92 assessments and provided observations that other tools would have missed: personal protective equipment (PPE) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took ∼1 hour each and reached an estimated 4 times as many SNFs as on-site visits in a similar time frame.

Remote IPC assessments by telephone and video were timely and feasible methods of assessing the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across New York State and in various healthcare facility types. Similar methods have been adapted nationally by the Centers for Disease Control and Prevention.