Acceptance and Commitment Therapy for people living with motor neuron disease: an uncontrolled feasibility study

Background: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND. Methods: PlwMND aged ≥ 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (≥ 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (≥ 70% completing ≥ 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months. Results: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended ≥ 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status. Conclusions: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway

REVEALS—a longitudinal cohort study of multifaceted respiratory assessment in ALS

Objective To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression. Methods The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected. Data were analyzed using a Bayesian multiple outcomes random effects model. Results Two hundred and eighty participants had a median of three assessments (IQR 2.0, 5.0) over a median of 8 months (IQR 2.3, 14.1). There were 974 data collection timepoints. Differences in respiratory measures and rates of decline between disease-onset and sex subgroups were identified. Females had lower scores in all respiratory measures and females with bulbar onset ALS had faster decline compared with other sub-groups. These differences were not detected by the ALSFRS-r respiratory subscale. Dyspnea, orthopnea, and a higher King’s stage at baseline were associated with lower respiratory scores throughout follow-up, while having a regular productive cough at baseline was associated with lower peak cough flow scores. Conclusion Respiratory function declines more quickly in females with ALS compared with males when measured by FVC, SVC, SNIP, or PCF, but not the ALSFRS-R respiratory sub-score. Higher baseline King’s staging and the presence of clinical respiratory symptoms at baseline were associated with worse respiratory function. The ALSFRS-R respiratory sub-score is poorly correlated with objective respiratory measurements

National survey of variations in practice in the prevention of surgical site infections in adult cardiac surgery, United Kingdom and Republic of Ireland

Background: Currently no national standards exist for the prevention of surgical site infection (SSI) in cardiac surgery. SSI rates range from 1% to 8% between centres. Aim: The aim of this study was to explore and characterize variation in approaches to SSI prevention in the UK and the Republic of Ireland (ROI). Methods: Cardiac surgery centres were surveyed using electronic web-based questionnaires to identify variation in SSI prevention at the level of both institution and consultant teams. Surveys were developed and undertaken through collaboration between the Cardiothoracic Interdisciplinary Research Network (CIRN), Public Health England (PHE) and the National Cardiac Benchmarking Collaborative (NCBC) to encompass routine pre-, intra- and postoperative practice. Findings: Nineteen of 38 centres who were approached provided data and included responses from 139 consultant teams. There was no missing data from those centres that responded. The results demonstrated substantial variation in over 40 aspects of SSI prevention. These included variation in SSI surveillance, reporting of SSI infection rates to external bodies, utilization of SSI risk prediction tools, and the use of interventions such as sternal support devices and gentamicin impregnated sponges. Conclusion: Measured variation in SSI prevention in cardiac centres across the UK and ROI is evidence of clinical uncertainty as to best practice, and has identified areas for quality improvement as well as knowledge gaps to be addressed by future research

Acceptance and commitment therapy for people living with motor neuron disease: an uncontrolled feasibility study

Background Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND. Methods PlwMND aged ≥ 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (≥ 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (≥ 70% completing ≥ 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months. Results Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended ≥ 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status. Conclusions There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway

The use of biotelemetry to explore disease progression markers in amyotrophic lateral sclerosis

Objective: To explore novel, real-world biotelemetry disease progression markers in patients with amyotrophic lateral sclerosis (ALS) and to compare with clinical gold-standard measures. Methods: This was an exploratory, non-controlled, non-drug 2-phase study comprising a variable length Pilot Phase (n = 5) and a 48-week Core study Phase (n = 25; NCT02447952). Patients with mild or moderate ALS wore biotelemetry sensors for ∼3 days/month at home, measuring physical activity, heart rate variability (HRV), and speech over 48 weeks. These measures were assessed longitudinally in relation to ALS Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC); assessed by telephone [monthly] and clinic visits [every 12 weeks]). Results: Pilot Phase data supported progression into the Core Phase, where a decline in physical activity from baseline followed ALS progression as measured by ALSFRS-R and FVC. Four endpoints showed moderate or strong between-patient correlations with ALSFRS-R total and gross motor domain scores (defined as a correlation coefficient of ≥0.5 or >0.7, respectively): average daytime active; percentage of daytime active; total daytime activity score; total 24-hour activity score. Moderate correlations were observed between speech endpoints and ALSFRS-R bulbar domain scores; HRV data quality was insufficient for reliable assessment. The sensor was generally well tolerated; 6/25 patients reported mostly mild or moderate intensity skin and subcutaneous tissue disorder adverse events. Conclusions: Biotelemetry measures of physical activity in this Pilot Study tracked ALS progression over time, highlighting their potential as endpoints for future clinical trials. A larger, formally powered study is required to further support activity endpoints as novel disease progression markers.</p

Objectively monitoring amyotrophic lateral sclerosis patient symptoms during clinical trials with sensors: Observational study

BACKGROUND:Objective symptom monitoring of patients with Amyotrophic Lateral Sclerosis (ALS) has the potential to provide an important source of information to evaluate the impact of the disease on aspects of real-world functional capacity and activities of daily living in the home setting, providing useful objective outcome measures for clinical trials. OBJECTIVE:This study aimed to investigate the feasibility of a novel digital platform for remote data collection of multiple symptoms-physical activity, heart rate variability (HRV), and digital speech characteristics-in 25 patients with ALS in an observational clinical trial setting to explore the impact of the devices on patients' everyday life and to record tolerability related to the devices and study procedures over 48 weeks. METHODS:In this exploratory, noncontrolled, nondrug study, patients attended a clinical site visit every 3 months to perform activity reference tasks while wearing a sensor, to conduct digital speech tests and for conventional ALS monitoring. In addition, patients wore the sensor in their daily life for approximately 3 days every month for the duration of the study. RESULTS:The amount and quality of digital speech data captured at the clinical sites were as intended, and there were no significant issues. All the home monitoring sensor data available were propagated through the system and were received as expected. However, the amount and quality of physical activity home monitoring data were lower than anticipated. A total of 3 or more days (or partial days) of data were recorded for 65% of protocol time points, with no data collected for 24% of time points. At baseline, 24 of 25 patients provided data, reduced to 13 of 18 patients at Week 48. Lower-than-expected quality HRV data were obtained, likely because of poor contact between the sensor and the skin. In total, 6 of 25 patients had mild or moderate adverse events (AEs) in the skin and subcutaneous tissue disorders category because of skin irritation caused by the electrode patch. There were no reports of serious AEs or deaths. Most patients found the sensor comfortable, with no or minimal impact on daily activities. CONCLUSIONS:The platform can measure physical activity in patients with ALS in their home environment; patients used the equipment successfully, and it was generally well tolerated. The quantity of home monitoring physical activity data was lower than expected, although it was sufficient to allow investigation of novel physical activity end points. Good-quality in-clinic speech data were successfully captured for analysis. Future studies using objective patient monitoring approaches, combined with the most current technological advances, may be useful to elucidate novel digital biomarkers of disease progression

Comparison of King’s clinical staging in multinational amyotrophic lateral sclerosis cohorts

Background: Amyotrophic lateral sclerosis (ALS) shows considerable clinical heterogeneity, which affects clinical trials. A clinical staging system has been proposed for ALS with potential applications in patient care, research, trial design and health economic analyses. The King’s system consists of five stages. We have previously shown that progressive clinical stages were reached at predictable proportions through the disease course, but this needs to be validated in other independent samples. Objectives: We aimed to compare King’s clinical staging in ALS in four patient groups, located in different regions and countries and using different health care systems from the original study population in South London. Methods: Clinical data were extracted from two European phase 3 randomized controlled trials (MitoTarget and LiCALS) and from two databases predominately from the United States: the PRO-ACT Consortium Database and a database of patients from the PatientsLikeMe website. Clinical stage was estimated using an algorithm, and standardized time to each clinical stage was calculated in deceased patients. Results: 8,796 patients were included, of whom 1,959 had died by the end of follow-up. Stages occurred in the same order as in the original study for all cohorts. Median standardized times to stages (interquartile range) were Stage 2: 0.61 (0.47–0.75), Stage 3: 0.68 (0.56–0.81), Stage 4A: 0.82 (0.71–0.91), Stage 4B: 0.82 (0.69–0.92) and Stage 4 0.80 (0.67–0.91). Discussion: Timings for all stages were similar to those reported in the original study, except Stage 2 which occurred later in the clinical trial databases due to recruitment occurring after diagnosis

National survey of variations in practice in the prevention of surgical site infections in adult cardiac surgery, United Kingdom and Republic of Ireland

BackgroundCurrently no national standards exist for the prevention of surgical site infection (SSI) in cardiac surgery. SSI rates range from 1% to 8% between centres.AimThe aim of this study was to explore and characterize variation in approaches to SSI prevention in the UK and the Republic of Ireland (ROI).MethodsCardiac surgery centres were surveyed using electronic web-based questionnaires to identify variation in SSI prevention at the level of both institution and consultant teams. Surveys were developed and undertaken through collaboration between the Cardiothoracic Interdisciplinary Research Network (CIRN), Public Health England (PHE) and the National Cardiac Benchmarking Collaborative (NCBC) to encompass routine pre-, intra- and postoperative practice.FindingsNineteen of 38 centres who were approached provided data and included responses from 139 consultant teams. There was no missing data from those centres that responded. The results demonstrated substantial variation in over 40 aspects of SSI prevention. These included variation in SSI surveillance, reporting of SSI infection rates to external bodies, utilization of SSI risk prediction tools, and the use of interventions such as sternal support devices and gentamicin impregnated sponges.ConclusionMeasured variation in SSI prevention in cardiac centres across the UK and ROI is evidence of clinical uncertainty as to best practice, and has identified areas for quality improvement as well as knowledge gaps to be addressed by future research.</div