Effectiveness of computer-mediated interventions for informal carers of people with dementia—a systematic review

ABSTRACT Background: Caring for a friend or relative with dementia can be burdensome and stressful, and puts carers at increased risk of physical and psychological problems. A number of psychosocial interventions, some delivered by computer, have been developed to support carers. This review evaluates the outcomes of computer-mediated interventions. Methods: PsychINFO, MEDLINE, and CINAHL Plus were searched for papers published between January 2000 and September 2012. Study quality was evaluated using a modified version of Downs and Black's (1998) checklist. Results: Fourteen empirical studies, evaluating a range of complex, multifaceted interventions, met inclusion criteria. The most commonly measured variables were carer burden/stress and depression. In general, higher quality studies found that interventions did have an effect on these variables. Two higher quality studies also found that anxiety was reduced following intervention. Most studies found that positive aspects of caring were increased through these interventions, as was carer self-efficacy. There were mixed results in relation to social support, and physical aspects of caring did not seem to be affected. Program impact measures indicated general acceptability of these interventions. Conclusions: The findings support the provision of computer-mediated interventions for carers of people with dementia. Future studies would benefit from design improvements, such as articulating clearly defined aims, having a control group, having adequate statistical power, and measuring a greater range of factors important to carers themselves

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: A British birth cohort study

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study, a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44–45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time

Associations between psychological intervention for anxiety disorders and risk of dementia: a prospective cohort study using national health-care records data in England

BACKGROUND: Meta-analyses support an association between anxiety in older adulthood and dementia. The aim of this study was to use routinely collected health data to test whether treatment of anxiety disorders through psychological intervention is associated with a lower incidence of dementia. METHODS: In this prospective cohort study, data from nationally provided psychological therapy services in England termed Improving Access to Psychological Therapies from 2012 to 2019 were linked to medical records, including dementia diagnoses as defined by the tenth edition of the International Classification of Diseases, up to 8 follow-up years later. Inclusion criteria were as follows: (1) patients who were aged 65 years and older; (2) patients with a probable anxiety disorder; and (3) those with no previous or current diagnosis of dementia. Cox proportional hazards models were constructed to test whether reliable improvement in anxiety following psychological intervention was associated with future dementia incidence. The primary outcome was all-cause dementia and cases were identified using ICD-10 dementia codes from Hospital Episode Statistics, Mental Health Services Dataset, and mortality data. For main analyses, hazards ratios (HRs) are presented. FINDINGS: Data from 128 077 people aged 65 years and older attending a nationally provided psychological intervention service in England were linked to medical records. 88 019 (69·0%) of 127 064 participants with available gender data were women and 39 585 (31·0%) were men. 111 225 (95·9%) of 115 989 with available ethnicity data were of White ethnicity. The mean age of the sample was 71·55 years (SD 5·69). Fully adjusted models included data from 111 958 people after 16 119 were excluded due to missing data on key variables or covariates. 4510 (4·0%) of 111 958 participants had a dementia diagnosis. The remaining 107 448 (96·0%) were censored either at date of death or when the final follow-up period available for analyses was reached. People who showed reliable improvement in anxiety had lower rates of later dementia diagnosis (3·9%) than those who did not show reliable improvement (5·1%). Reliable improvement in anxiety following psychological intervention was associated with reduced incidence of all-cause dementia (HR 0·83 [95% CI 0·78-0·88]), Alzheimer's disease (HR 0·85 [0·77-0·94]), and vascular dementia (HR 0·80 [0·71-0·90]). Effects did not differ depending on anxiety disorder diagnosis. INTERPRETATION: Results showed that reliable improvement in anxiety from psychological therapy was associated with reduced incidence of future dementia. There are multiple plausible explanations for this finding and further research is needed to distinguish between these possibilities. Missing data in the sample limit reliability of findings. FUNDING: Alzheimer's Society, Medical Research Council, Wellcome Trust, and UCLH National Institute for Health and Care Research Biomedical Research Centre

Associations between psychological therapy outcomes for depression and incidence of dementia

BACKGROUND: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. METHODS: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. RESULTS: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83-0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77-0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83-1.00). CONCLUSIONS: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: a British birth cohort study

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study (NCDS), a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44–45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time

Is social support pre-treatment associated with prognosis for adults with depression in primary care?

OBJECTIVE: Depressed patients rate social support as important for prognosis, but evidence for a prognostic effect is lacking. We aimed to test the association between social support and prognosis independent of treatment type, and the severity of depression, and other clinical features indicating a more severe illness. METHODS: Individual patient data were collated from all six eligible RCTs (n=2858) of adults seeking treatment for depression in primary care. Participants were randomized to any treatment and completed the same baseline assessment of social support and clinical severity factors. Two-stage random effects meta-analyses were conducted. RESULTS: Social support was associated with prognosis independent of randomized treatment but effects were smaller when adjusting for depressive symptoms and durations of depression and anxiety, history of antidepressant treatment, and co-morbid panic disorder: percentage decrease in depressive symptoms at 3-4 months per z-score increase in social support =-4.14(95%CI: -6.91 to -1.29).Those with a severe lack of social support had considerably worse prognoses than those with no lack of social support: increase in depressive symptoms at 3-4 months =14.64%(4.25% to 26.06%). CONCLUSIONS: Overall, large differences in social support pre-treatment were associated with differences in prognostic outcomes. Adding the Social Support scale to clinical assessments may be informative, but after adjusting for routinely assessed clinical prognostic factors the differences in prognosis are unlikely to be of a clinically important magnitude. Future studies might investigate more intensive treatments and more regular clinical reviews to mitigate risks of poor prognosis for those reporting a severe lack of social support

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Worry and ruminative brooding: associations with cognitive and physical health in older adults

IntroductionMental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health.MethodsWe used baseline data from 282 participants from the SCD-Well and Age-Well trials (178 female; agemean = 71.1 years). We measured worry and ruminative brooding using the Penn State Worry Questionnaire and the Ruminative Response Scale-brooding subscale. We assessed subjective physical health using the WHOQOL-Bref physical subscale, and objective physical health via blood pressure and modified versions of the Framingham Risk Score and Charlson Comorbidity Index. With subjective and objective cognition, we utilized the Cognitive Difficulties Scale and a global composite (modified Preclinical Alzheimer’s Cognitive Composite, PACC5, with the Wechsler Adult Intelligence Scale-IV, category fluency, Mattis Dementia Rating Scale-2, and either the California Verbal Learning Test or the Rey Auditory Verbal Learning Test). We conducted linear regressions, adjusted for education, age, sex and cohort.ResultsWorry and ruminative brooding were negatively associated with subjective physical health (worry: β = −0.245, 95%CI −0.357 to −0.133, p < 0.001; ruminative brooding: β = −0.224, 95%CI −0.334 to −0.113, p < 0.001) and subjective cognitive difficulties (worry: β = 0.196, 95%CI 0.091 to 0.302, p < 0.001; ruminative brooding: β = 0.239, 95%CI 0.133 to 0.346, p < 0.001). We did not observe associations between worry or ruminative brooding and any measure of objective health.DiscussionWorry and ruminative brooding may be common mechanisms associated with subjective but not objective health. Alternatively, cognitively unimpaired older adults may become aware of subtle changes not captured by objective measures used in this study. Interventions reducing worry and ruminative brooding may promote subjective physical and cognitive health; however, more research is needed to determine causality of the relationships

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population