Remembering for Relationships: Brief Cognitive-Reminiscence Therapy Improves Young Adults’ Perceptions About Self and Others in Relationships

Reminiscence-based interventions involve the guided recall and interpretation of autobiographical memories to promote adaptive thinking. This study involved secondary analyses of a recent trial of a positively focused, three-session version of cognitive-reminiscence therapy (CRT) on generalised perceptions of relationship quality and interpersonally related psychological resources in young adults. A community sample (N = 62, Mage = 24.6 [SD = 3.1], 71% females) of young adults were randomised into a CRT and wait-list condition. Participants completed assessments measuring perceived relationship quality (relationship satisfaction, emotional intimacy, commitment, and trust) and perceptions of self and others within relationships (relationship self-esteem, relationship self-efficacy, relationship optimism and meaning in relationships). The CRT group, relative to the control group, scored significantly higher on perceived relationship quality (d = 0.62), and higher on generalized relationship self-efficacy (d = 0.70), relationship self-esteem (d = 0.59), and relationship optimism (d = 0.57) at the follow-up. Group differences for relationship meaning were non-trivial (small to moderate), but not statistically significant. A brief, positive-focused, intervention of guided recall of autobiographical memories was generally effective in improving perceptions about self and others within the context of relationships in young adults. Replication studies with larger samples are needed. Future research may expand CRT to target other relationship variables, assess the impacts of different doses, explore relationships in specific populations, and better understand the mechanisms for change.

Ignoring transmission dynamics leads to underestimation of the impact of a novel intervention against mosquito-borne disease

Wolbachia is an intracellular bacterium that many hope could have a major impact on dengue and other mosquito-borne diseases that are notoriously difficult to control. The balance of future investments in Wolbachia versus other public health needs will be informed to a great extent by efficacy estimates from large-scale trials, which can be affected by multiple sources of bias. We used mathematical models to quantify the possible magnitude of these biases, finding that efficacy would have been severely underestimated in a recent trial in Indonesia if the spatial scale of clusters had been smaller than it was. We also identified a previously unrecognized source of bias owing to the coupled nature of transmission dynamics across clusters. This too led to a consistent underestimate of the protection afforded by Wolbachia. Taken together, our findings suggest that this intervention may be even more promising than currently recognized.

Stimulating the Facial Nerve to Treat Ischemic Stroke: A Systematic Review

Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation of the sphenopalatine ganglion, but have suffered from operational limitations and non-significant clinical findings. Regardless, the potential of ganglion stimulation to treat AIS or elongate the window-of-efficacy for current stroke treatments remains extremely promising. This review aims to summarize results from recent trial publications, highlight current innovations, and discuss future directions for the field. Importantly, this review comes after the release of four important clinical trials that were published in mid 2019.

Relevance of Frequency-Domain Analyses to Relate Shoe Cushioning, Ground Impact Forces and Running Injury Risk: A Secondary Analysis of a Randomized Trial With 800+ Recreational Runners

Cushioning systems in running shoes are used assuming that ground impact forces relate to injury risk and that cushioning materials reduce these impact forces. In our recent trial, the more cushioned shoe version was associated with lower injury risk. However, vertical impact peak force was higher in participants with the Soft shoe version. The primary objective of this study was to investigate the effect of shoe cushioning on the time, magnitude and frequency characteristics of peak forces using frequency-domain analysis by comparing the two study groups from our recent trial (Hard and Soft shoe group, respectively). The secondary objective was to investigate if force characteristics are prospectively associated with the risk of running-related injury. This is a secondary analysis of a double-blinded randomized trial on shoe cushioning with a biomechanical running analysis at baseline and a 6-month follow-up on running exposure and injury. Participants (n = 848) were tested on an instrumented treadmill at their preferred running speed in their randomly allocated shoe condition. The vertical ground reaction force signal for each stance phase was decomposed into the frequency domain using the discrete Fourier transform. Both components were recomposed into the time domain using the inverse Fourier transform. An analysis of variance was used to compare force characteristics between the two study groups. Cox regression analysis was used to investigate the association between force characteristics and injury risk. Participants using the Soft shoes displayed lower impact peak force (p < 0.001, d = 0.23), longer time to peak force (p < 0.001, d = 0.25), and lower average loading rate (p < 0.001, d = 0.18) of the high frequency signal compared to those using the Hard shoes. Participants with low average and instantaneous loading rate of the high frequency signal had lower injury risk [Sub hazard rate ratio (SHR) = 0.49 and 0.55; 95% Confidence Interval (CI) = 0.25–0.97 and 0.30–0.99, respectively], and those with early occurrence of impact peak force (high frequency signal) had greater injury risk (SHR = 1.60; 95% CI = 1.05–2.53). Our findings may explain the protective effect of the Soft shoe version previously observed. The present study also demonstrates that frequency-domain analyses may provide clinically relevant impact force characteristics.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: 9NCT03115437.

Comparison of Long‐Term Outcomes for Responders Versus Non‐Responders Following Renal Denervation in Resistant Hypertension

Background Recent trial results support the efficacy of renal sympathetic denervation in lowering blood pressure (BP). While BP reduction in general is associated with a clinically meaningful reduction in cardiovascular events and mortality, such a relationship has not been described for patients undergoing renal sympathetic denervation. Methods and Results Clinical events were assessed in patients who underwent renal sympathetic denervation at our center using telephone‐ and clinical follow‐up, interviews with general practitioners, as well as review of hospital databases. Event rates were compared between BP responders (≥5 mm Hg 24‐hour ambulatory BP reduction) and non‐responders; 296 patients were included. Compared with baseline, 24‐hour systolic ambulatory BP was reduced by 8.3±12.2 mm Hg and diastolic BP by 4.8±7.0 mm Hg ( P <0.001 for both) after 3 months. One hundred eighty patients were classified as BP responders and 116 as non‐responders. During a median follow‐up time of 48 months, significantly less major adverse cardiovascular events (cardiovascular death, stroke, myocardial infarction, critical limb ischemia, renal failure) occurred in responders than in non‐responders (22 versus 23 events, hazard ratio [HR], 0.53 [95% CI, 0.28 to 0.97], P =0.041). This was consistent after adjustment for potential confounders as well as confirmed by propensity‐score matching. A proportional relationship was found between BP reduction after 3 months and frequency of major adverse cardiovascular events (HR, 0.75 [95% CI, 0.58 to 0.97] per 10 mm Hg 24‐hour systolic ambulatory BP reduction). Conclusions Based on these observational data, blood pressure response to renal sympathetic denervation is associated with improved long‐term clinical outcome.

Proportion of Conflict, Contingency Learning, and Recency Effects in a Stroop Task

Recent research on the relation between learning and cognitive control has assumed that conflict modulates learning, either by increasing arousal and hence improving learning in high conflict situations (Verguts & Notebaert, 2008), or by inducing control, and hence inhibiting the processing of distracters and their eventual association with the imperative responses (Whitehead et al., 2018). We analyze whether the amount of conflict, manipulated through the proportion of congruency in a set of Stroop inducer trials, affects learning of contingencies established on diagnostic trials composed by neutral words associated with color responses. The results reproduced the list-wide proportion of congruency effect on the inducer trials, and showed evidence of contingency learning on the diagnostic trials, but provided no indication that this learning was modulated by the level of conflict. Specific analyses conducted to control for the impact of episodic effects on the expression of learning indicated that contingency effects were not driven by the incremental processes that could be expected by associative learning, but rather they were due to the impact of the most recent trial involving the same distracter. Accordingly, these effects disappeared when tested selectively on trials that required a non-matching response with respect to the previous occurrence of the distracter. We interpret this result in the context of the debate on how learning and memory interact with the processes of cognitive control.

SGLT2i agonist plus GLP-1 receptor COMBination therapy in type 2 diabetes: a renal (KIDney) endpoints real world study-(COMBi-KID Study). (Preprint)

BACKGROUND Sodium-glucose co-transporter-2 inhibitor (SGLT2i)s and glucagon-like peptide-1 receptor agonist (GLP-1RA)s are both considered to be standard care in the management of glycaemia in type 2 diabetes. Recent trial evidence has indicated benefits on primary renal endpoints for individual drugs within each medication class. Despite potential benefits of combining SGLT2i and GLP-1RA for glycaemia management according to national/international guideline recommendations, there is currently limited data on renal endpoints for this drug combination. OBJECTIVE To assess the real-world effects of combining SGLT2i and GLP-1 RA therapies on renal end-points, glycaemic control and weight in people with type 2 diabetes currently treated with renin-angiotensin system (RAS) blockade medication. METHODS This retrospective cohort study will utilise electronic health records of people with type 2 diabetes registered with general practices covering over 15million people in England and Wales and included in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. A propensity score matched cohort of new users of SGLT2is, GLP-1 RAs, and those prescribed SGLT2is and GLP-1 RAs in combination, will be identified. These will be matched on drug history, comorbidities and demographics. A repeated measures multilevel, linear regression analysis will be performed to compare mean change (from baseline) in estimated glomerular filtration rate (eGFR) at 12 and 24 months between those switched onto combined therapy and those prescribed monotherapy of SGLT2i or GLP-1 RA. Secondary end points will be albuminuria, serum creatinine, glycated haemoglobin, body mass index will be similarly assessed for change at follow up. RESULTS The study proposal was approved by the Medical Sciences Interdivisional Research Ethics Committee, University Oxford in August 2021 (R76885/RE001). The study is due to be commenced October 2021 and expected completion by March 2020 CONCLUSIONS The present study will be one of the first to assess the combination of SGLT2i and GLP-1RA therapy for type 2 diabetes management and renal effects as primary endpoint in type 2 diabetes from a real-world perspective.

Tedizolid: new data and experiences for clinical practice

The most relevant information on the clinical uses of tedizolid from studies published in the last 18 months is presented in this brief review. The most important data indicate better tolerance and safety profile of long-term therapeutic regimes in off-label indications, such as osteoarticular infections and those caused by mycobacteria. Its lower risk of hazardous interactions compared to linezolid should be emphasized. Furthermore, tedizolid in its combination with rifampicin shows a more favourable way of acting as demonstrated in vitro and in vivo studies. A recent trial also opens the door for its potential use in nosocomial pneumonia caused by Gram-positive bacteria.

IMMU-03. MULTICENTER RANDOMIZED PLACEBO CONTROLLED PHASE III TRIAL OF AN AUTOLOGOUS FORMALINFIXED TUMOR VACCINE (CELLM-001) FOR NEWLY DIAGNOSED GLIOBLASTOMAS

INTRODUCTION The development of novel treatments for glioblastoma is desired and immunotherapy is theoretically expected for highly invasive glioblastoma. An autologous formalin-fixed vaccine (AFTV) derived from resected tumor tissue is stable, contains multiple tumor peptides, and could induce specific immunity. We have conducted three clinical trials in patients with glioblastoma, and the most recent trial was a double-blind, multicenter, phase IIb trial with 63 case enrollments. Although this Phase IIb study revealed no vaccine effects in the whole cohort (mOS: 25.6 months of AFTV group, 31.5 months of the placebo group), the 3-year PFS for patients with total tumor removal was 81% in the AFTV group versus 46% in the placebo group (P=0.067). AFTV vaccine (Cellm-001) may have an effect on certain patient subgroups, and a Phase III study has started in November 2021 (jRCT2031200153). Based on Phase IIb, the enrolled patients were those who could be completely resected on MRI. Cellm-001 administration to a patient in the placebo group at recurrence (crossover) was prohibited. In addition, photodynamic therapy (PDT) was added as a stratification factor because our retrospective study showed a good prognosis of 19 patients who underwent both PDT and AFTV (mOS 47.7 months). PATIENTS AND METHODS Trial design: double-blind (1: 1), phase III multicenter, registration 4 years, observation 2 years. ESTIMATED ENROLLMENT: 112 patients with primary glioblastoma (18-75 years old) whose contrast-enhanced lesion could be completely removed on the image and who received standard local radiotherapy and temozolomide chemotherapy. STRATIFICATION FACTORS: presence or absence of PDT, age, KPS. ADMINISTRATION METHOD: Intradermal administration 3 times before radiochemotherapy and 6 times in parallel with maintenance chemotherapy after completion. PRIMARY ENDPOINT: OS, secondary endpoints: PFS and adverse events. https://jrct.niph.go.jp/en-latest-detail/jRCT2031200153. CONCLUSION An investigator-initiated phase III trial will investigate the efficacy and safety of unique AFTV immunotherapy.

Combining malaria vaccination with chemoprevention: a promising new approach to malaria control

Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria, such as those with sickle cell disease, and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations, and the potential of this approach to malaria control needs to be explored.