Non-invasive molecular imaging of inflammatory macrophages in allograft rejection.

BackgroundMacrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin (Sn, Siglec 1 or CD169) using anti-Sn mAb (SER-4) directly radiolabelled with (99m)Tc pertechnetate.MethodsWe used a heterotopic heart transplantation model where allogeneic or syngeneic heart grafts were transplanted into the abdomen of recipients. In vivo nanosingle-photon emission computed tomography (SPECT/CT) imaging was performed 7 days post transplantation followed by biodistribution and histology.ResultsIn wild-type mice, the majority of (99m)Tc-SER-4 monoclonal antibody cleared from the blood with a half-life of 167 min and was located predominantly on Sn(+) tissues in the spleen, liver and bone marrow. The biodistribution in the transplantation experiments confirmed data derived from the non-invasive SPECT/CT images, with significantly higher levels of (99m)Tc-SER-4 observed in allogeneic grafts (9.4 (±2.7) %ID/g) compared to syngeneic grafts (4.3 (±10.3) %ID/g) (p = 0.0022) or in mice which received allogeneic grafts injected with (99m)Tc-IgG isotype control (5.9 (±0.6) %ID/g) (p = 0.0185). The transplanted heart to blood ratio was also significantly higher in recipients with allogeneic grafts receiving (99m)Tc-SER-4 as compared to recipients with syngeneic grafts (p = 0.000004) or recipients with allogeneic grafts receiving (99m)Tc-IgG isotype (p = 0.000002).ConclusionsHere, we demonstrate that imaging of Sn(+) macrophages in inflammation may provide an important additional and non-invasive tool for the monitoring of the pathophysiology of cellular immunity in a transplant model

Cognitive or behavioural interventions (or both) to prevent or mitigate loneliness in adolescents, adults, and older adults

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To examine the effects of structured psychological interventions, based on cognitive behavioural therapy (CBT) techniques, compared to all comparators on loneliness in adolescents, adults, and older adults with diagnoses of common mental disorders, or at risk of loneliness. To examine the effects of structured psychological interventions, based on CBT techniques, compared to all comparators on depression severity, anxiety severity, social connectedness, or quality of life in adolescents, adults, and older adults, with diagnoses of common mental disorders, or at risk of loneliness

A systematic review and meta-analysis of the prevalence of common mental disorders in people with non-communicable diseases in Bangladesh, India, and Pakistan

Background: The prevalence of mental and physical comorbidities is unknown in South Asia, as estimates of mental ill health in patients with non-communicable diseases (NCDs) have predominantly come from studies based in the United States, Europe and Australasia. This systematic review and meta-analysis summarises evidence and provides pooled estimates of the prevalence of common mental disorders in adults with non-communicable diseases in South Asia. Methods: We included prevalence studies of depression and anxiety in adults with diabetes, cancer, cardiovascular disease, and chronic respiratory conditions in Bangladesh, India, and Pakistan, published from 1990 onwards in international and country-specific databases. Results: Out of 96 included studies, 83 provided data for random effects meta-analyses. The pooled prevalence of depression was 44% (95% confidence interval (CI) = 26 to 62) for patients with COPD, 40% (95% CI = 34 to 45) for diabetes, 39% (95% CI = 23 to 56) for stroke, 38% (95% CI = 32 to 45) for hypertension, and 37% (95% CI = 30 to 45) for cancer. The pooled prevalence of anxiety based on 28 studies was 29% (95% CI = 22 to 36). Many quality issues were identified in a critical appraisal of included studies, mostly relating to the sampling frame and selection process, the description of the methods and basic data, and the description of non-responders. Conclusions: Depression and anxiety are prevalent and underdiagnosed in people with physical comorbidities in Bangladesh, India, and Pakistan

Behavioural activation therapy for depression in adults (Review)

This is the final version. Available from Cochrane Collaboration via the DOI in this record. BACKGROUND: Behavioural activation is a brief psychotherapeutic approach that seeks to change the way a person interacts with their environment. Behavioural activation is increasingly receiving attention as a potentially cost-effective intervention for depression, which may require less resources and may be easier to deliver and implement than other types of psychotherapy. OBJECTIVES: To examine the effects of behavioural activation compared with other psychological therapies for depression in adults. To examine the effects of behavioural activation compared with medication for depression in adults. To examine the effects of behavioural activation compared with treatment as usual/waiting list/placebo no treatment for depression in adults. SEARCH METHODS: We searched CCMD-CTR (all available years), CENTRAL (current issue), Ovid MEDLINE (1946 onwards), Ovid EMBASE (1980 onwards), and Ovid PsycINFO (1806 onwards) on the 17 January 2020 to identify randomised controlled trials (RCTs) of 'behavioural activation', or the main elements of behavioural activation for depression in participants with clinically diagnosed depression or subthreshold depression. We did not apply any restrictions on date, language or publication status to the searches. We searched international trials registries via the World Health Organization's trials portal (ICTRP) and ClinicalTrials.gov to identify unpublished or ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of behavioural activation for the treatment of depression or symptoms of depression in adults aged 18 or over. We excluded RCTs conducted in inpatient settings and with trial participants selected because of a physical comorbidity. Studies were included regardless of reported outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all titles/abstracts and full-text manuscripts for inclusion. Data extraction and 'Risk of bias' assessments were also performed by two review authors in duplicate. Where necessary, we contacted study authors for more information. MAIN RESULTS: Fifty-three studies with 5495 participants were included; 51 parallel group RCTs and two cluster-RCTs. We found moderate-certainty evidence that behavioural activation had greater short-term efficacy than treatment as usual (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.10 to 1.78; 7 RCTs, 1533 participants), although this difference was no longer evident in sensitivity analyses using a worst-case or intention-to-treat scenario. Compared with waiting list, behavioural activation may be more effective, but there were fewer data in this comparison and evidence was of low certainty (RR 2.14, 95% CI 0.90 to 5.09; 1 RCT, 26 participants). No evidence on treatment efficacy was available for behavioural activation versus placebo and behavioural activation versus no treatment. We found moderate-certainty evidence suggesting no evidence of a difference in short-term treatment efficacy between behavioural activation and CBT (RR 0.99, 95% CI 0.92 to 1.07; 5 RCTs, 601 participants). Fewer data were available for other comparators. No evidence of a difference in short term-efficacy was found between behavioural activation and third-wave CBT (RR 1.10, 95% CI 0.91 to 1.33; 2 RCTs, 98 participants; low certainty), and psychodynamic therapy (RR 1.21, 95% CI 0.74 to 1.99; 1 RCT,60 participants; very low certainty). Behavioural activation was more effective than humanistic therapy (RR 1.84, 95% CI 1.15 to 2.95; 2 RCTs, 46 participants; low certainty) and medication (RR 1.77, 95% CI 1.14 to 2.76; 1 RCT; 141 participants; moderate certainty), but both of these results were based on a small number of trials and participants. No evidence on treatment efficacy was available for comparisons between behavioural activation versus interpersonal, cognitive analytic, and integrative therapies. There was moderate-certainty evidence that behavioural activation might have lower treatment acceptability (based on dropout rate) than treatment as usual in the short term, although the data did not confirm a difference and results lacked precision (RR 1.64, 95% CI 0.81 to 3.31; 14 RCTs, 2518 participants). Moderate-certainty evidence did not suggest any difference in short-term acceptability between behavioural activation and waiting list (RR 1.17, 95% CI 0.70 to 1.93; 8 RCTs. 359 participants), no treatment (RR 0.97, 95% CI 0.45 to 2.09; 3 RCTs, 187 participants), medication (RR 0.52, 95% CI 0.23 to 1.16; 2 RCTs, 243 participants), or placebo (RR 0.72, 95% CI 0.31 to 1.67; 1 RCT; 96 participants; low-certainty evidence). No evidence on treatment acceptability was available comparing behavioural activation versus psychodynamic therapy. Low-certainty evidence did not show a difference in short-term treatment acceptability (dropout rate) between behavioural activation and CBT (RR 1.03, 95% CI 0.85 to 1.25; 12 RCTs, 1195 participants), third-wave CBT (RR 0.84, 95% CI 0.33 to 2.10; 3 RCTs, 147 participants); humanistic therapy (RR 1.06, 95% CI 0.20 to 5.55; 2 RCTs, 96 participants) (very low certainty), and interpersonal, cognitive analytic, and integrative therapy (RR 0.84, 95% CI 0.32 to 2.20; 4 RCTs, 123 participants). Results from medium- and long-term primary outcomes, secondary outcomes, subgroup analyses, and sensitivity analyses are summarised in the text. AUTHORS' CONCLUSIONS: This systematic review suggests that behavioural activation may be more effective than humanistic therapy, medication, and treatment as usual, and that it may be no less effective than CBT, psychodynamic therapy, or being placed on a waiting list. However, our confidence in these findings is limited due to concerns about the certainty of the evidence. We found no evidence of a difference in short-term treatment acceptability (based on dropouts) between behavioural activation and most comparison groups (CBT, humanistic therapy, waiting list, placebo, medication, no treatment or treatment as usual). Again, our confidence in all these findings is limited due to concerns about the certainty of the evidence. No data were available about the efficacy of behaioural activation compared with placebo, or about treatment acceptability comparing behavioural activation and psychodynamic therapy, interpersonal, cognitive analytic and integrative therapies. The evidence could be strengthened by better reporting and better quality RCTs of behavioural activation and by assessing working mechanisms of behavioural activation.National Institute for Health Research (NIHR