Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study)

Background. The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD) complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD) by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design. This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH) or Rockhampton Base Hospital (RBH) who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection) after initiation of PD. Discussion. The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter

Long-term psychological outcomes following stroke: the OX-CHRONIC study

Background: Stroke survivors rate longer-term (> 2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown. Methods: N = 105 long-term stroke survivors (M [SD] age = 72.92 [13.01]; M [SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male; M [SD] years post-stroke = 4.57 [2.12]) were recruited (potential N = 208). Participants completed 3 remote assessments, including a comprehensive set of standardized cognitive neuropsychological tests comprising domains of memory, attention, language, and executive function, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen’s d effect size estimates and percent Minimal Clinically Important Difference changes between time points. Results: On the Montreal Cognitive Assessment 65.3% scored  Conclusion: Nearly half of participants > 2 years post-event exhibited psychological difficulties including domains of cognition, mood, and fatigue, which impact long-term quality of life. Stroke is a chronic condition with highly prevalent psychological needs, which require monitoring and intervention development

DMAPT inhibits NF-κB activity and increases sensitivity of prostate cancer cells to X-rays in vitro and in tumor xenografts in vivo

Constitutive activation of the pro-survival transcription factor NF-κB has been associated with resistance to both chemotherapy and radiation therapy in many human cancers, including prostate cancer. Our lab and others have demonstrated that the natural product parthenolide can inhibit NF-κB activity and sensitize PC-3 prostate cancers cells to X-rays in vitro; however, parthenolide has poor bioavailability in vivo and therefore has little clinical utility in this regard. We show here that treatment of PC-3 and DU145 human prostate cancer cells with dimethylaminoparthenolide (DMAPT), a parthenolide derivative with increased bioavailability, inhibits constitutive and radiation-induced NF-κB binding activity and slows prostate cancer cell growth. We also show that DMAPT increases single and fractionated X-ray-induced killing of prostate cancer cells through inhibition of DNA double strand break repair and also that DMAPT-induced radiosensitization is, at least partially, dependent upon the alteration of intracellular thiol reduction-oxidation chemistry. Finally, we demonstrate that the treatment of PC-3 prostate tumor xenografts with oral DMAPT in addition to radiation therapy significantly decreases tumor growth and results in significantly smaller tumor volumes compared to xenografts treated with either DMAPT or radiation therapy alone, suggesting that DMAPT might have a potential clinical role as a radiosensitizing agent in the treatment of prostate cancer

Dopamine D1 receptor stimulation modulates the formation and retrieval of novel object recognition memory: role of the prelimbic cortex

Previous studies have shown that dopamine D1 receptor antagonists impair novel object recognition memory but the effects of dopamine D1 receptor stimulation remain to be determined. This study investigated the effects of the selective dopamine D1 receptor agonist SKF81297 on acquisition and retrieval in the novel object recognition task in male Wistar rats. SKF81297 (0.4 and 0.8mg/kg s.c.) given 15 min before the sampling phase impaired novel object recognition evaluated 10 min or 24h later. The same treatments also reduced novel object recognition memory tested 24h after the sampling phase and when given 15min before the choice session. These data indicate that D1 receptor stimulation modulates both the encoding and retrieval of object recognition memory. Microinfusion of SKF81297 (0.025 or 0.05 μg/side) into the prelimbic sub-region of the medial prefrontal cortex (mPFC) in this case 10 min before the sampling phase also impaired novel object recognition memory, suggesting that the mPFC is one important site mediating the effects of D1 receptor stimulation on visual recognition memory

Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study)

Background. The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD) complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD) by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design. This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH) or Rockhampton Base Hospital (RBH) who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection) after initiation of PD. Discussion. The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter

Re-reading of OraQuick HIV-1/2 rapid antibody test results: quality assurance implications for HIV self-testing programmes.

INTRODUCTION: Scale-up of HIV self-testing (HIVST) will play a key role in meeting the United Nation's 90-90-90 targets. Delayed re-reading of used HIVST devices has been used by early implementation studies to validate the performance of self-test kits and to estimate HIV positivity among self-testers. We investigated the stability of results on used devices under controlled conditions to assess its potential as a quality assurance approach for HIVST scale-up. METHODS: 444 OraQuick® HIV-1/2 rapid antibody tests were conducted using commercial plasma from two HIV-positive donors and HIV-negative plasma (high-reactive n = 148, weak-reactive n = 148 and non-reactive n = 148) and incubated them for six months under four conditions (combinations of high and low temperatures and humidity). Devices were re-read daily for one week, weekly for one subsequent month and then once a month by independent readers unaware of the previous results. We used multistage transition models to investigate rates of change in device results, and between storage conditions. RESULTS AND DISCUSSION: There was a high incidence of device instability. Forty-three (29%) of 148 initially non-reactive results became false weak-reactive results. These changes were observed across all incubation conditions, the earliest on Day 4 (n = 9 kits). No initially HIV-reactive results changed to a non-reactive result. There were no significant associations between storage conditions and hazard of results transition. We observed substantial statistical agreement between independent re-readers over time (agreement range: 0.74 to 0.96). CONCLUSIONS: Delayed re-reading of used OraQuick® HIV-1/2 rapid antibody tests is not currently a valid methodological approach to quality assurance and monitoring as we observed a high incidence (29%) of true non-reactive tests changing to false weak-reactive and therefore its use may overestimate true HIV positivity

Enhancing legacy in palliative care: study protocol for a randomized controlled trial of Dignity Therapy focused on positive outcomes

BACKGROUND: Dignity Therapy is a brief psychotherapy that can enhance a sense of legacy while addressing the emotional and existential needs of patients receiving hospice or palliative care. In Dignity Therapy, patients create a formalized “legacy” document that records their most cherished memories, their lessons learned in life, as well as their hopes and dreams for loved ones in the future. To date, this treatment has been studied for its impact on mitigating distress within hospice and palliative care populations and has provided mixed results. This study will instead focus on whether Dignity Therapy enhances positive outcomes in this population. METHODS/DESIGN: In this study, 90 patients with cancer receiving hospice or palliative care will complete a mixed-methods randomized controlled trial of Dignity Therapy (n = 45) versus Supportive Attention (n = 45). The patients will be enrolled in the study for 3 weeks, receiving a total of six study visits. The primary outcomes examine whether the treatment will quantitatively increase levels of positive affect and a sense of life closure. Secondary outcomes focus on gratitude, hope, life satisfaction, meaning in life, resilience, and self-efficacy. Using a fixed, embedded dataset design, this study will additionally use qualitative interviews to explore patients’ perceptions regarding the use of positive outcome measures and whether these outcomes are appropriately matched to their experiences in therapy. DISCUSSION: Dignity Therapy has shown mixed results when evaluating its impact on distress, although no other study to date has solely focused on the potential positive aspects of this treatment. This study is novel in its use of mixed methods assessments to focus on positive outcomes, and will provide valuable information about patients’ direct experiences in this area. TRIAL REGISTRATION: ISRCTN9138919

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A pilot validation of a modified Illness Perceptions Questionnaire designed to predict response to cognitive therapy for psychosis

Background and objectives: Clinical responsiveness to cognitive behavioural therapy for psychosis (CBTp) varies. Recent research has demonstrated that illness perceptions predict active engagement in therapy, and, thereby, better outcomes. In this study, we aimed to investigate the psychometric properties of a modification of the Illness Perceptions Questionnaire (M-IPQ) designed to predict response following CBTp. Methods: Fifty-six participants with persistent, distressing delusions completed the M-IPQ; forty before a brief CBT intervention targeting persecutory ideation and sixteen before and after a control condition. Additional predictors of outcome (delusional conviction, symptom severity and belief inflexibility) were assessed at baseline. Outcomes were assessed at baseline and at follow-up four to eight weeks later. Results: The M-IPQ comprised two factors measuring problem duration and therapy-specific perceptions of Cure/Control. Associated subscales, formed by summing the relevant items for each factor, were reliable in their structure. The Cure/Control subscale was also reliable over time; showed convergent validity with other predictors of outcome; predicted therapy outcomes; and differentially predicted treatment effects. Limitations: We measured outcome without an associated measure of engagement, in a small sample. Findings are consistent with hypothesis and existing research, but require replication in a larger, purposively recruited sample. Conclusions: The Cure/Control subscale of the M-IPQ shows promise as a predictor of response to therapy. Specifically targeting these illness perceptions in the early stages of cognitive behavioural therapy may improve engagement and, consequently, outcomes

Paediatric acute hepatitis of unknown aetiology : a national investigation and adenoviraemia case-control study in the UK

Funding Information: This work was undertaken as part of a national enhanced incident by UK public health agencies. We thank the parents and guardians of the children who gave up their valuable time to speak to the public health investigation teams; without their support we could not have been able to undertake a thorough investigation. We are grateful to the many paediatricians and liver specialists who reported cases to us and responded to follow-up with further information. We also thank Ezra Linley and Simon Tonge of the UK Health Security Agency Seroepidemiology Unit for rapidly providing serum samples for testing. We would like to thank the Incident Management Teams of the UK nations, members of the incident cells, epidemiology, laboratory, and local Health Protection Teams who supported the investigations, in particular: Katy Sinka, Mike Gent, Suzanna Howes, Eileen Gallagher, Selene Corsini, Eleanor Clarke, Rajani Raghu, Kelsey Mowat, Iain Hayden, Matt Hibbert, Skye Firminger, Catriona Angel, Donna Haskins, Kay Ratcliffe, Hannah Emmett, Alex Elliot, Helen Hughes, Sarah Deeny, Sarah Garner, Sarah Gerver, Flora Stevens, Paula Blomquist, Gabriel Gurmail Kauffman, Kristine Cooper, Hannah Taylor, Giovanni Leonardi, Michelle Dickinson and Michelle Watson from England; Kimberly Marsh, Michael Lockhart, David Yirrell, Sandra Currie, Kate Templeton, Samantha Shepherd, Roisin Ure, Jim McMenamin, Rachel Tayler, Louisa Pollock, Antonia Ho, Chris Cunningham and Hayley Peacock from Scotland; and Katie Binley and Meg Wallace from Northern Ireland.Peer reviewe