Endoscopic radiofrequency Stretta therapy reduces proton pump inhibitor dependency and the need for anti-reflux surgery for refractory gastroesophageal reflux disease.

BACKGROUND/AIMS: Radiofrequency treatment of the gastroesophageal junction using the Stretta procedure for treating gastroesophageal reflux disease (GERD) is observed to improve the symptoms and proton pump inhibitor (PPI) dependence and reduce the need for anti-reflux operations. As one of the largest studies in Europe, we evaluated the clinical outcomes of Stretta in patients with medically refractory GERD. METHODS: A tertiary UK center evaluated all patients with refractory GERD who underwent Stretta between 2014 and 2022. Patients and primary care professionals were contacted to obtain information regarding the initiation of PPI and reintervention after Stretta. RESULTS: Of the 195 patients (median age, 55 years; 116 women [59.5%]) who underwent Stretta, PPI-free period (PFP) data were available for 144 (73.8%) patients. Overall, 66 patients (45.8%) did not receive PPI after a median follow-up of 55 months. Six patients (3.1%) underwent further interventions. The median PFP after Stretta was 41 months. There was a significant negative correlation between PFP and age (p=0.007), with no differences between sexes (p=0.96). Patients younger than 55 years of age had a longer PFP than their older counterparts (p=0.005). Younger males had a significantly longer PFP than older males (p=0.021). However, this was not observed in the female cohort (p=0.09) or between the younger men and women (p=0.66). CONCLUSION: Our findings suggest that Stretta is a safe and feasible option for treating refractory GERD, especially in younger patients. It prevents further anti-reflux interventions in most patients and increases the lead-time to surgery in patients with refractory GERD.

Posterior Rectus Sheath Hernia Causing Chronic Abdominal Pain.

Posterior rectus sheath hernias are rare hernias that can be difficult to diagnose due to unreliable physical exam characteristics and subtle radiological findings. We present an interesting case of an elderly female found to have a posterior rectus sheath hernia during a diagnostic laparoscopy for chronic abdominal pain. CT evaluation revealed possible appendicitis and laxity of the abdominal wall of the right lower quadrant. Intraoperatively, a 4 cm hernia defect in the right lateral abdominal wall was appreciated. Appendectomy and herniorrhaphy with mesh repair were performed. Postoperative review of CT imaging and intraoperative photographs determined that this hernia defect is a posterior rectus sheath hernia likely caused by trocar placement from previous laparoscopic surgery. This report contributes to the limited body of the literature for this rare type of hernia. Posterior rectus sheath hernias should be considered in differential diagnoses for patients presenting with chronic abdominal pain without clear etiology.

A randomized, controlled proof-of-concept trial evaluating durable effects of memory flexibility training (MemFlex) on autobiographical memory distortions and on relapse of recurrent major depressive disorder over 12 months.

Low-intensity psychological interventions that target cognitive risk factors for depressive relapse may improve access to relapse prevention programs and thereby reduce subsequent risk. This study provides the first evaluation of an autobiographical memory-based intervention for relapse prevention, to establish whether memory-training programs that are efficacious for acute depression may also aid those currently in remission. We also provide the longest follow-up to-date of the effects of autobiographical memory training on autobiographical memory processes themselves. This pre-registered randomized-controlled proof-of-concept trial (N = 74) compared an autobiographical Memory Flexibility (MemFlex) intervention to Psychoeducation about cognitive-behavioral mechanisms which maintain depression. Both interventions were primarily self-guided, and delivered via paper workbooks completed over four weeks. The key cognitive outcome was ability to retrieve and alternate between specific and general autobiographical memories. Co-primary clinical outcomes were time until depressive relapse and depression-free days in the twelve-months following intervention. Results indicated a small-moderate effect size (d = 0.35) in favor of MemFlex for the cognitive outcome. A small Hazard Ratio (1.08) was observed for time until depressive relapse, along with a negligible effect size for depression-free days (d = 0.11). Although MemFlex produced long-term improvement in memory retrieval skills, there was little support for MemFlex as a relapse prevention program for depression.

The global impact of Aspergillus infection on COPD.

BACKGROUND: Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication. Aspergillus sensitisation may worsen symptoms in COPD. METHODS: We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC < 70% and FEV1 < 80%) using standardised criteria in multiple countries, to re-estimate the prevalence of COPD. Hospitalised COPD patients develop IA in 1.3-3.9%, based on positive cultures of Aspergillus spp. and radiological findings. Given limited data on per-patient annual hospitalisation rates, we assumed a conservative 10.5% estimate. Annual IA mortality in COPD was estimated using the literature rates of 43-72%. A separate literature search assessed the impact of Aspergillus sensitisation on severity of COPD (by FEV1). RESULTS: We re-estimated the global prevalence of COPD GOLD stages II-IV at 552,300,599 people (7.39% of the population) with 339,206,893 (8.58%) in Asia, 85,278,783 (8.52%) in the Americas, 64,298,051 (5.37%) in Africa, 59,484,329 (7.77%) in Europe and 4,032,543 (10.86%) in Oceania. An estimated 57,991,563 (10.5%) people with COPD are admitted to hospital annually and of these 753,073 (1.3%) - 2,272,322 (3.9%) develop IA and 540,451-977,082 deaths are predicted annually. Aspergillus sensitisation prevalence in COPD was 13.6% (7.0-18.3%) and not related to lower predicted FEV1% (P > 0.05). CONCLUSIONS: The prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality.

Emotional complexity across the life story: Elevated negative emodiversity and diminished positive emodiversity in sufferers of recurrent depression.

BACKGROUND: Greater diversity in the experience of negative and positive emotions - emodiversity - is associated with better mental health outcomes in the general population (Quoidbach et al. 2014). However, conceptual accounts of depression suggest this might differ in clinical depression. In this study, the diversity of negative and positive emotion experiences as remembered by a recurrently depressed sample and a never-depressed control group were compared. METHODS: Emodiversity was assessed using a life structure card sort task which allowed for the assessment of memory for emotional experience over the life course. Depressed (n=34) and non-depressed (n=34) participants completed the card sort task, from which emodiversity metrics were calculated for negative and positive emotion experience. RESULTS: Depressed individuals showed recollections of enhanced emodiversity across negative emotion but reduced emodiversity across positive emotion, relative to never-depressed individuals. LIMITATIONS: This study involved a relatively small sample size. DISCUSSION: This study indicates that greater diversity of negative emotion experience, which has been interpreted as a protective factor against depressed mood in community samples (Quoidbach et al., 2014), instead characterises the remembered experience of recurrent clinical depression. The finding that positive emodiversity is adaptive in depression suggests that therapeutic outcomes may be improved by facilitating exposure to a diverse range of positive emotions. These findings indicate that the relationship between emotion diversity and mental health is more complex than hitherto assumed.

Longitudinal phenotype development in a minipig model of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant disease with variable clinical presentations. Large animal models are useful to help dissect molecular mechanisms, determine relevant biomarkers, and develop effective therapeutics. Here, we studied a NF1 minipig model (NF1+/ex42del) for the first 12 months of life to evaluate phenotype development, track disease progression, and provide a comparison to human subjects. Through systematic evaluation, we have shown that compared to littermate controls, the NF1 model develops phenotypic characteristics of human NF1: [1] café-au-lait macules, [2] axillary/inguinal freckling, [3] shortened stature, [4] tibial bone curvature, and [5] neurofibroma. At 4 months, full body computed tomography imaging detected significantly smaller long bones in NF1+/ex42del minipigs compared to controls, indicative of shorter stature. We found quantitative evidence of tibial bowing in a subpopulation of NF1 minipigs. By 8 months, an NF1+/ex42del boar developed a large diffuse shoulder neurofibroma, visualized on magnetic resonance imaging, which subsequently grew in size and depth as the animal aged up to 20 months. The NF1+/ex42del minipig model progressively demonstrates signature attributes that parallel clinical manifestations seen in humans and provides a viable tool for future translational NF1 research.

Organizational learning in hospitals: A realist review.

AIM: To establish a middle-range theory of organizational learning in hospitals. DESIGN: A realist review of the literature, conducted according to established standards for realist and meta-narrative evidence syntheses. Middle-range theory development was performed according to Smith and Liehr's recommendations. DATA SOURCES: Two comprehensive scientific databases and six discipline-focused databases spanning health care, life sciences, business, sociology, and psychology were searched from inception to 12 May 2016. REVIEW METHODS: Citations meeting the inclusion criteria were appraised using the Mixed Methods Appraisal Tool. Data extraction was guided by a focus on the contextual factors, mechanisms, and outcomes associated with organizational learning. RESULTS: The initial search yielded 2,332 citations, 147 of which were ultimately included in the review. The included citations were generally of high quality. Reviewed evidence indicates certain aspects of organizational context can be conducive to mechanisms of organizational learning, leading to a range of positive organizational outcomes. CONCLUSION: This review updates and expands on a previous review of the literature on organizational learning in hospitals, refines the concept of organizational learning in hospitals, and provides a middle-range theory of organizational learning in hospitals. IMPACT: This updated review provides a strong evidence base for future work on the topic of organizational learning in hospitals. The refined concept of organizational learning makes it possible to develop reliable, valid research instruments that better reflect of the full scope of organizational learning. Finally, the middle-range theory guides researchers and clinical leaders as they advance the science and practice of organizational learning.

Post-imaging pulmonary nodule mathematical prediction models: are they clinically relevant?

OBJECTIVES: Post-imaging mathematical prediction models (MPMs) provide guidance for the management of solid pulmonary nodules by providing a lung cancer risk score from demographic and radiologists-indicated imaging characteristics. We hypothesized calibrating the MPM risk score threshold to a local study cohort would result in improved performance over the original recommended MPM thresholds. We compared the pre- and post-calibration performance of four MPM models and determined if improvement in MPM prediction occurs as nodules are imaged longitudinally. MATERIALS AND METHODS: A common cohort of 317 individuals with computed tomography-detected, solid nodules (80 malignant, 237 benign) were used to evaluate the MPM performance. We created a web-based application for this study that allows others to easily calibrate thresholds and analyze the performance of MPMs on their local cohort. Thirty patients with repeated imaging were tested for improved performance longitudinally. RESULTS: Using calibrated thresholds, Mayo Clinic and Brock University (BU) MPMs performed the best (AUC = 0.63, 0.61) compared to the Veteran's Affairs (0.51) and Peking University (0.55). Only BU had consensus with the original MPM threshold; the other calibrated thresholds improved MPM accuracy. No significant improvements in accuracy were found longitudinally between time points. CONCLUSIONS: Calibration to a common cohort can select the best-performing MPM for your institution. Without calibration, BU has the most stable performance in solid nodules ≥ 8 mm but has only moderate potential to refine subjects into appropriate workup. Application of MPM is recommended only at initial evaluation as no increase in accuracy was achieved over time. KEY POINTS: • Post-imaging lung cancer risk mathematical predication models (MPMs) perform poorly on local populations without calibration. • An application is provided to facilitate calibration to new study cohorts: the Mayo Clinic model, the U.S. Department of Veteran's Affairs model, the Brock University model, and the Peking University model. • No significant improvement in risk prediction occurred in nodules with repeated imaging sessions, indicating the potential value of risk prediction application is limited to the initial evaluation.

Organisational learning in hospitals: A concept analysis.

AIM: To provide a clear definition and description of organisational learning in hospitals. BACKGROUND: Organisational learning is a promising strategy nurse managers, and leaders can use to improve organisational performance. A clear definition and description of organisational learning is necessary to advance theory, research and practice in this field. METHODS: Walker & Avant's method was used to conduct a concept analysis of organisational learning in hospitals. Data sources included 147 empirical studies, 16 review articles, three dictionary entries and three book chapters. RESULTS: Organisational learning occurs when experiences are translated into positive changes in the organisation's collective knowledge, cognition and actions. Organisational context plays a key role in the learning process. Other manifestations of the concept are identified. CONCLUSIONS: This concept analysis provides a clear definition of organisational learning and a description of its defining attributes, antecedents, empirical referents and consequences. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers and leaders can improve patient and organisational outcomes by creating an environment conducive to translating experiences into organisational learning. Further research is needed to continue advancing the science of organisational learning in hospitals.

A randomised controlled trial of memory flexibility training (MemFlex) to enhance memory flexibility and reduce depressive symptomatology in individuals with major depressive disorder.

Successful navigation within the autobiographical memory store is integral to daily cognition. Impairment in the flexibility of memory retrieval can thereby have a detrimental impact on mental health. This randomised controlled phase II exploratory trial (N = 60) evaluated the potential of a novel intervention drawn from basic science - an autobiographical Memory Flexibility (MemFlex) training programme - which sought to ameliorate memory difficulties and improve symptoms of Major Depressive Disorder. MemFlex was compared to Psychoeducation (an evidence-based low-intensity intervention) to determine the likely range of effects on a primary cognitive target of memory flexibility at post-intervention, and co-primary clinical targets of self-reported depressive symptoms and diagnostic status at three-month follow-up. These effect sizes could subsequently be used to estimate sample size for a fully-powered trial. Results demonstrated small-moderate, though as expected statistically non-significant, effect sizes in favour of MemFlex for memory flexibility (d = 0.34, p = .20), and loss of diagnosis (OR = 0.65, p = .48), along with the secondary outcome of depression-free days (d = 0.36, p = .18). A smaller effect size was observed for between-group difference in self-reported depressive symptoms (d = 0.24, p = .35). Effect sizes in favour of MemFlex in this early-stage trial suggest that fully-powered evaluation of MemFlex may be warranted as an avenue to improving low-intensity treatment of depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02371291.

A porcine model of neurofibromatosis type 1 that mimics the human disease.

Loss of the NF1 tumor suppressor gene causes the autosomal dominant condition, neurofibromatosis type 1 (NF1). Children and adults with NF1 suffer from pathologies including benign and malignant tumors to cognitive deficits, seizures, growth abnormalities, and peripheral neuropathies. NF1 encodes neurofibromin, a Ras-GTPase activating protein, and NF1 mutations result in hyperactivated Ras signaling in patients. Existing NF1 mutant mice mimic individual aspects of NF1, but none comprehensively models the disease. We describe a potentially novel Yucatan miniswine model bearing a heterozygotic mutation in NF1 (exon 42 deletion) orthologous to a mutation found in NF1 patients. NF1+/ex42del miniswine phenocopy the wide range of manifestations seen in NF1 patients, including café au lait spots, neurofibromas, axillary freckling, and neurological defects in learning and memory. Molecular analyses verified reduced neurofibromin expression in swine NF1+/ex42del fibroblasts, as well as hyperactivation of Ras, as measured by increased expression of its downstream effectors, phosphorylated ERK1/2, SIAH, and the checkpoint regulators p53 and p21. Consistent with altered pain signaling in NF1, dysregulation of calcium and sodium channels was observed in dorsal root ganglia expressing mutant NF1. Thus, these NF1+/ex42del miniswine recapitulate the disease and provide a unique, much-needed tool to advance the study and treatment of NF1.

How is a specialist depression service effective for persistent moderate to severe depressive disorder?: a qualitative study of service user experience.

BACKGROUND: A specialist depression service (SDS) offering collaborative pharmacological and cognitive behaviour therapy treatment for persistent depressive disorder showed effectiveness against depression symptoms versus usual community based multidisciplinary care in a randomised controlled trial (RCT) in specialist mental health services in England. However, there is uncertainty concerning how specialist depression services effect such change. The current study aimed to evaluate the factors which may explain the greater effectiveness of SDS compared to Treatment as Usual (TAU) by exploring the experience of the RCT participants. METHODS: Qualitative audiotaped and transcribed semi-structured interviews were conducted 12-18 months after baseline with 21 service users (12 SDS, 9 TAU arms) drawn from all three sites. Inductive thematic analysis using a grounded approach contrasted the experiences of SDS with TAU participants. RESULTS: Four themes emerged in relation to service user experience: 1. Specific treatment components of the SDS: which included sub-themes of the management of medication change, explaining and developing treatment strategies, setting realistic expectations, and person-centred and holistic approach; 2. Individual qualities of SDS clinicians; 3. Collaborative team context in SDS: which included sub-themes of communication between healthcare professionals, and continuity of team members; 4. Accessibility to SDS: which included sub-themes of flexibility of locations, frequent consultation as reinforcement, gradual pace of treatment, and challenges of returning to usual care. CONCLUSIONS: The study uncovered important mechanisms and contextual factors in the SDS that service users experience as different from TAU, and which may explain the greater effectiveness of the SDS: the technical expertise of the healthcare professionals, personal qualities of clinicians, teamwork, gradual pace of care, accessibility and managing service transitions. Usual care in other specialist mental health services may share many of the features from the SDS. TRIAL REGISTRATION: "Trial of the Clinical and Cost Effectiveness of a Specialist Expert Mood Disorder Team for Refractory Unipolar Depressive Disorder" was registered in www.ClinicalTrials.gov ( NCT01047124 ) on 12-01-2010 and the ISRCTN registry was registered in www.isrctn.com ( ISRCTN10963342 ) on 25-11-2015 (retrospectively registered).

Study protocol for a randomised, controlled platform trial estimating the effect of autobiographical Memory Flexibility training (MemFlex) on relapse of recurrent major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a chronic condition. Although current treatment approaches are effective in reducing acute depressive symptoms, rates of relapse are high. Chronic and inflexible retrieval of autobiographical memories, and in particular a bias towards negative and overgeneral memories, is a reliable predictor of relapse. This randomised controlled single-blind trial will determine whether a therapist-guided self-help intervention to ameliorate autobiographical memory biases using Memory Flexibility training (MemFlex) will increase the experience of depression-free days, relative to a psychoeducation control condition, in the 12 months following intervention. METHODS AND ANALYSIS: Individuals (aged 18 and above) with a diagnosis of recurrent MDD will be recruited when remitted from a major depressive episode. Participants will be randomly allocated to complete 4 weeks of a workbook providing either MemFlex training, or psychoeducation on factors that increase risk of relapse. Assessment of diagnostic status, self-report depressive symptoms, depression-free days and cognitive risk factors for depression will be completed post-intervention, and at 6 and 12 months follow-up. The cognitive target of MemFlex will be change in memory flexibility on the Autobiographical Memory Test- Alternating Instructions. The primary clinical endpoints will be the number of depression-free days in the 12 months following workbook completion, and time to depressive relapse. ETHICS AND DISSEMINATION: Ethics approval has been granted by the NHS National Research Ethics Committee (East of England, 11/H0305/1). Results from this study will provide a point-estimate of the effect of MemFlex on depressive relapse, which will be used to inform a fully powered trial evaluating the potential of MemFlex as an effective, low-cost and low-intensity option for reducing relapse of MDD. TRIAL REGISTRATION NUMBER: NCT02614326.

Metabolism of Nucleosides and Nucleotides Prodrugs.

BACKGROUND: Modified nucleoside and nucleotide analogs are now the cornerstone of antiviral and anticancer chemotherapies. However, these compounds are not active on their own and need, after entering the cell, to be metabolized to their active 5'-triphosphate form. METHOD: Limitations of these metabolic processes led to development of nucleoside/nucleotide prodrugs in which nucleosides are masked with different groups that can be intracellularly cleaved either chemically or enzymatically. RESULTS: Several prodrug approaches have been successfully developed in order to increase the efficacy, bioavailability, penetration in target organ, and selectivity of nucleoside/nucleotide analogs. CONCLUSION: The concept of nucleoside/nucleotide prodrug is now a well-established approach that led to the approval of numerous drugs for the treatment of HIV, HBV, HCV, HSV and cancer.

Data Management and Data Quality in PERCH, a Large International Case-Control Study of Severe Childhood Pneumonia.

The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for ≥96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity.

Comparison of low- and ultralow-dose computed tomography protocols for quantitative lung and airway assessment.

PURPOSE: Quantitative computed tomography (CT) measures are increasingly being developed and used to characterize lung disease. With recent advances in CT technologies, we sought to evaluate the quantitative accuracy of lung imaging at low- and ultralow-radiation doses with the use of iterative reconstruction (IR), tube current modulation (TCM), and spectral shaping. METHODS: We investigated the effect of five independent CT protocols reconstructed with IR on quantitative airway measures and global lung measures using an in vivo large animal model as a human subject surrogate. A control protocol was chosen (NIH-SPIROMICS + TCM) and five independent protocols investigating TCM, low- and ultralow-radiation dose, and spectral shaping. For all scans, quantitative global parenchymal measurements (mean, median and standard deviation of the parenchymal HU, along with measures of emphysema) and global airway measurements (number of segmented airways and pi10) were generated. In addition, selected individual airway measurements (minor and major inner diameter, wall thickness, inner and outer area, inner and outer perimeter, wall area fraction, and inner equivalent circle diameter) were evaluated. Comparisons were made between control and target protocols using difference and repeatability measures. RESULTS: Estimated CT volume dose index (CTDIvol) across all protocols ranged from 7.32 mGy to 0.32 mGy. Low- and ultralow-dose protocols required more manual editing and resolved fewer airway branches; yet, comparable pi10 whole lung measures were observed across all protocols. Similar trends in acquired parenchymal and airway measurements were observed across all protocols, with increased measurement differences using the ultralow-dose protocols. However, for small airways (1.9 ± 0.2 mm) and medium airways (5.7 ± 0.4 mm), the measurement differences across all protocols were comparable to the control protocol repeatability across breath holds. Diameters, wall thickness, wall area fraction, and equivalent diameter had smaller measurement differences than area and perimeter measurements. CONCLUSIONS: In conclusion, the use of IR with low- and ultralow-dose CT protocols with CT volume dose indices down to 0.32 mGy maintains selected quantitative parenchymal and airway measurements relevant to pulmonary disease characterization.

Characterization of ß-d-N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.

Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been limited to nonspecific antiviral agents, with suboptimal outcomes. Herein, we have identified ß-d-N4-hydroxycytidine (NHC) as a novel inhibitor of CHIKV. NHC behaves as a pyrimidine ribonucleoside and selectively inhibits CHIKV replication in cell culture.

Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors.

A library of 585 compounds built off a 7-azaindole core was evaluated for anti-HIV-1 activity, and ten hits emerged with submicromolar potency and therapeutic index >100. Of these, three were identified as non-nucleoside reverse transcriptase (RT) inhibitors and were assayed against relevant resistant mutants. Lead compound 8 inhibited RT with submicromolar potency (IC50=0.73µM) and also maintained some activity against the clinically important RT mutants K103N and Y181C (IC50=9.2, 3.5µM) in cell-free assays. Free energy perturbation guided lead optimization resulted in the development of a compound with a two-fold increase in potency against RT (IC50=0.36µM). These data highlight the discovery of a unique scaffold with the potential to move forward as next-generation anti-HIV-1 agents.

The effects of autobiographical memory flexibility (MemFlex) training: An uncontrolled trial in individuals in remission from depression.

BACKGROUND AND OBJECTIVES: Impaired cognitive processing is a key feature of depression. Biases in autobiographical memory retrieval (in favour of negative and over-general memories) directly impact depression symptoms, but also influence downstream cognitive factors implicated in the onset and maintenance of the disorder. We introduce a novel cognitive intervention, MemFlex, which aims to correct these biases in memory retrieval and thereby modify key downstream cognitive risk and maintenance factors: rumination, impaired problem solving, and cognitive avoidance. METHOD: Thirty eight adults with remitted Major Depressive Disorder completed MemFlex in an uncontrolled clinical trial. This involved an orientation session, followed by self-guided completion of six workbook-based sessions over one-month. Assessments of cognitive performance and depression symptoms were completed at pre- and post-intervention. RESULTS: Results demonstrated medium-sized effects of MemFlex in improving memory specificity and problem solving, and decreasing rumination, and a small effect in reducing cognitive avoidance. No significant change was observed in residual symptoms of depression. LIMITATIONS: This study was an uncontrolled trial, and has provided initial evidence to support a larger-scale, randomized controlled trial. CONCLUSIONS: These findings provide promising evidence for MemFlex as a cost-effective, low-intensity option for reducing cognitive risk associated with depression.