SLCO1B3 polymorphisms and clinical outcomes in kidney transplant recipients receiving mycophenolate.

Aim: Determine the influence of SLCO1B3 polymorphisms on outcomes in kidney transplant recipients. Materials & methods: We retrospectively evaluated 181 adult kidney transplant recipients receiving mycophenolate. Outcomes included treated biopsy-proven acute rejection (tBPAR), de novo donor-specific antibody (dnDSA) formation, graft survival, patient survival and mycophenolate-related adverse effects among SLCO1B3 genotypes. Results: The presence of SLCO1B3 variants was not associated with increased risk of tBPAR (HR: 1.45, 95% CI: 0.76-2.74), dnDSA (HR: 0.46, 95% CI: 0.16-1.36) or composite of tBPAR or dnDSA (HR: 1.14, 95% CI: 0.64-2.03). Graft and patient survival were reduced among variant carriers; however, inconsistent findings with the primary analysis suggest these associations were not due to genotype. Adverse effects were similar between groups. Conclusion: Presence of SLCO1B3 polymorphisms were not predictive of rejection or dnDSA in kidney transplant recipients.

A Prospective Study of the Effects of Sex Hormones on Lung Function and Inflammation in Women with Cystic Fibrosis.

Rationale: Epidemiologic studies demonstrate worse outcomes in women with cystic fibrosis (CF) than men. Women are colonized earlier with respiratory pathogens and have increased rates of pulmonary exacerbations after puberty and near ovulation. The etiology of this disparity is unclear, but sex hormones may contribute to these differences.Objectives: We sought to explore whether natural hormonal fluctuations and hormonal contraception associate with changes in lung function, respiratory symptoms, or inflammatory markers.Methods: We prospectively followed women with CF who were not on hormonal contraceptives and reported regular menstrual cycles. We captured study visits at points that corresponded with menses, ovulation, and the luteal phase. A subset of subjects were subsequently placed on a standard oral estrogen/progesterone combination contraceptive pill, ethinyl estradiol/norethindrone (loestrin), and reevaluated. Measurements included lung function, symptom questionnaires, sweat tests, blood for hormone concentrations, and sputum for inflammatory markers, bacterial density, and cytology.Results: Twenty-three women participated in this study. Hormone concentrations were as expected on and off hormonal contraception. At times of peak estrogen (ovulation), there was a significant increase in sputum proinflammatory cytokines (neutrophil-free elastase) and a corresponding pattern of decrease in lung function. Proinflammatory cytokines (IL-8, TNF-α, and neutrophil-free elastase) improved when placed on hormone contraception.Conclusions: Our results show that there are potentially important fluctuations in inflammatory biomarkers in the lungs that correlate with changes in lung function in women with CF. Larger studies evaluating the impact of sex hormones on airway inflammation and immune response are necessary to better understand the clinical impact of these responses.

Tailored digital behaviour change intervention with e-referral system to increase attendance at NHS stop smoking services (the MyWay project): study protocol for a randomised controlled feasibility trial.

INTRODUCTION: In the UK, smokers who use stop smoking services (SSSs) are four times more likely to stop smoking than smokers who do not. Attendance has declined, warranting the development of interventions to address this. StopApp is a novel, brief online behaviour change intervention designed to address common barriers to SSS attendance. It links to widely commissioned service management software that enables instant appointment booking at a user's location and time of choice. METHODS AND ANALYSIS: A two-arm parallel group, individual participant feasibility randomised controlled trial of StopApp (intervention) compared with the standard promotion of and referral to SSSs (control). The study includes a nested qualitative process evaluation to assess the acceptability of the research processes, with a subsample of participants. Smokers aged over 16 years will be recruited via three routes: General Practice (GP), community settings and online. After consenting and the collection of baseline data, participants will be randomised to control or intervention groups. Participants in the intervention group receive a link to StopApp and those in the control group receive standard web-based information about the SSSs. All participants are told they can book a SSS appointment but are under no obligation to do so. Online follow-up 2 months post randomisation includes data on SSS use and carbon monoxide verified 4-week quit rates. The study aims to recruit 162 smokers. ETHICS AND DISSEMINATION: Ethics approval has been granted by the West Midlands-Edgbaston NHS Research Ethics Committee. The findings will be reported in conferences and peer-reviewed publications; and will be used to design the parameters necessary for a definitive trial to ascertain the effectiveness of StopApp at increasing booking and attendance at SSSs compared with existing methods for encouraging uptake.

Feasibility randomised controlled trial of a guided workbook intervention to support work-related goals among cancer survivors in the UK.

OBJECTIVES: Employment following illness is associated with better physical and psychological functioning. This study aimed to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support patients with cancer returning to work. DESIGN: Parallel-group randomised controlled trial with embedded qualitative interviews. SETTING: Oncology clinics within four English National Health Service Trusts. PARTICIPANTS: Patients who had received a diagnosis of breast, gynaecological, prostate or colorectal cancer and who had been receiving treatment for a minimum of two weeks. INTERVENTION: A self-guided WorkPlan workbook designed to support patients with cancer to return to work with fortnightly telephone support calls to discuss progress. The control group received treatment as usual and was offered the workbook at the end of their 12-month follow-up. OUTCOME MEASURES: We assessed aspects of feasibility including eligibility, recruitment, data collection, attrition, feasibility of the methodology, acceptability of the intervention and potential to calculate cost-effectiveness. RESULTS: The recruitment rate of eligible patients was 44%; 68 participants consented and 58 (85%) completed baseline measures. Randomisation procedures were acceptable, data collection methods (including cost-effectiveness data) were feasible and the intervention was acceptable to participants. Retention rates at 6-month and 12-month follow-up were 72% and 69%, respectively. At 6-month follow-up, 30% of the usual care group had returned to full-time or part-time work (including phased return to work) compared with 43% of the intervention group. At 12 months, the percentages were 47% (usual care) and 68% (intervention). CONCLUSIONS: The findings confirm the feasibility of a definitive trial, although further consideration needs to be given to increasing the participation rates among men and black and ethnic minority patients diagnosed with cancer. TRIAL REGISTRATION NUMBER: ISRCTN56342476; Pre-results.

Usefulness and engagement with a guided workbook intervention (WorkPlan) to support work related goals among cancer survivors.

BACKGROUND: Returning to work after cancer is associated with improved physical and psychological functioning, but managing this return can be a challenging process. A workbook based intervention (WorkPlan) was developed to support return-to-work among cancer survivors. The aim of this study was to explore how participants using the workbook engaged with the intervention and utilised the content of the intervention in their plan to return-to-work. METHODS: As part of a feasibility randomised controlled trial, 23 participants from the intervention group were interviewed 4-weeks post intervention. Interviews focussed on intervention delivery and data was analysed using Framework analysis. RESULTS: Participants revealed a sense of empowerment and changes in their outlook as they transitioned from patient to employee, citing the act of writing as a medium for creating their own return-to-work narrative. Participants found the generation of a return-to-work plan useful for identifying potential problems and solutions, which also served as a tool for aiding discussion with the employer on return-to-work. Additionally, participants reported feeling less uncertain and anxious about returning to work. Timing of the intervention in coordination with ongoing cancer treatments was crucial to perceived effectiveness; participants identified the sole or final treatment as the ideal time to receive the intervention. CONCLUSIONS: The self-guided workbook supports people diagnosed with cancer to build their communication and planning skills to successfully manage their return-to-work. Further research could examine how writing plays a role in this process. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56342476 . Retrospectively registered 14 October 2015.

Agitation Management in Pediatric Males with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

OBJECTIVES: Severe agitation is a common symptom in pediatric cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis-an autoimmune encephalitis with prominent neuropsychiatric symptoms. Agitation is a major barrier to treatment of the underlying disease process and increases patients' risk of harming themselves and others. Furthermore, male patients often have undetectable tumors and are especially at risk for extended hospitalization, but have been infrequently studied. This report presents a case series of four pediatric male patients with anti-NMDAR encephalitis complicated by agitation, the strategies used to address treatment challenges, and a review of the current literature. METHODS: A chart review of four agitated pediatric male patients with anti-NMDAR encephalitis and a PubMed search of the current literature were conducted. RESULTS: A number of first-generation and second-generation antipsychotics (SGAs) have been reported for use in child and adult patients; however, treatment with these antipsychotics often has been complicated by movement disorders and autonomic instability caused by the underlying encephalitis that appears similar to and can be exacerbated by adverse effects of antipsychotics, including neuroleptic malignant syndrome (NMS), extrapyramidal symptoms (EPS), and tardive dyskinesia. The literature shows SGAs to be less likely to cause NMS and quetiapine to be one of the least likely SGAs to cause EPS. However, quetiapine has rarely been reported for use in patients with anti-NMDAR encephalitis. In the four pediatric male patients, quetiapine was generally effective, well tolerated, and not associated with NMS or significant EPS. CONCLUSION: These cases and review of the literature suggest that quetiapine may be particularly beneficial for treating agitation secondary to anti-NMDAR encephalitis in pediatric patients and have fewer adverse effects.

A Guided Workbook Intervention (WorkPlan) to Support Work-Related Goals Among Cancer Survivors: Protocol of a Feasibility Randomized Controlled Trial.

BACKGROUND: Returning to and staying at work following illness is associated with better physical and psychological functioning. Not working has been shown to be associated with reduced self-esteem, lowered self-efficacy, and decreased belief in one's ability to return to the workplace. Although there is a growing body of research looking at what predicts return to work following cancer treatment, there are fewer studies examining interventions targeting return to work. OBJECTIVE: The primary objective is to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support cancer patients in returning to work to inform a fully powered randomized controlled trial (RCT). METHODS: This is a multicenter feasibility RCT where the main analysis uses a qualitative approach. Sixty participants (aged 18-65 years) who have received a diagnosis of cancer and who intend to return to work will be randomized to either the WorkPlan intervention group or a usual care group (ratio 1:1). Participants in the intervention group will receive a guided workbook intervention (which contains activities aimed at eliciting thoughts and beliefs, identifying targets and actions, and concrete steps to achieve goals) and will receive telephone support over a 4-week period. The primary outcome measure is time taken to return to work (in days), and secondary outcome measures include mood, quality of life, illness perceptions, and job satisfaction. Data will be collected through postal questionnaires administered immediately postintervention and at 6- and 12-month follow-ups. In addition, interviews will be undertaken immediately postintervention (to explore acceptability of the intervention and materials) and at 12-month follow-up (to explore perceptions of participation in the trial and experiences of returning to work). RESULTS: Enrollment for the study will be completed in May 2016. Data analysis will commence in April 2017, and the first results are expected to be submitted for publication in late 2017. CONCLUSIONS: Currently no standardized return-to-work intervention based on targeting cancer patient beliefs is in existence. If the intervention is shown to be feasible and acceptable, the results of this study will inform a future full RCT with the potential to provide a valuable and cost-efficient tool in supporting cancer survivors in the return-to-work process. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN56342476; http://www.isrctn.com/ISRCTN56342476 (Archived by WebCite at http://www.webcitation.org/6gblhEPXd).