Evaluation of a young adult renal and transplant transition clinic in a regional setting: Supporting young adults and parents' transition to self-management.

OBJECTIVE: This study evaluated the impact of establishing a transition clinic in a regional Australian setting on the lives of young adults living with severe chronic kidney disease and their families. DESIGN: A qualitative design using the experience-based co-design framework. SETTING: Interviews were held at the Royal Hobart Hospital or the Menzies Institute for Medical Research. The co-design workshop was held at the Royal Hobart Hospital. PARTICIPANTS: Young people aged 17-29 years living with a kidney transplant or stage 4-5 chronic kidney disease, parents/carers and health professionals. INTERVENTIONS: Establishment of a young adult renal and transplant clinic. MAIN OUTCOME MEASURE: Impact of a transition clinic in a regional setting on the lives of young adults living with chronic kidney disease and their families and suggestions for improvement. RESULTS: Four key themes were identified as follows: The Model of Care; Peer support; Transition towards self-management: Building life skills; Suggestions for improvement and limitations of the service model. The non-institutional, informal clinic setting and social/educational activities facilitated engagement, self-management and peer support for young people and parents. Suggestions for improvement included involvement of older peers, additional life skills sessions and a youth worker. CONCLUSION: This regional transition clinic is valued by the young people and their parents for generating peer support, building self-management and life skills. Sustainability of the clinic depends upon having the appropriate expertise available, access to a suitable venue and offering a program that meets the needs of young people.

Acute kidney injury, stroke and death after cardiopulmonary bypass surgery: the role of perfusion flow and pressure.

INTRODUCTION: Acute kidney injury after cardiopulmonary bypass surgery is associated with morbidity and mortality. This study aims to evaluate the role of low perfusion flow and pressure in the development of cardiopulmonary bypass-associated acute kidney injury, stroke and death, using multicentre registry data. METHODS: We identified patients from the Australian and New Zealand Collaborative Perfusion Registry who underwent coronary artery bypass grafting and/or valvular surgery between 2008 and 2018. Primary predictor variables were the length of time the perfusion flow was <1.6 L/min/m2 and the length of time perfusion pressure was < 50mmHg. The primary outcome was new postoperative acute kidney injury defined by the risk-injury-failure-loss-end stage criteria. Secondary outcomes were stroke and in-hospital death. The influence of perfusion flow and pressure during cardiopulmonary bypass on the primary and secondary outcomes was estimated using separate multivariate models. RESULTS: A total of 16,356 patients were included. The mean age was 66 years and 75% were male. Acute kidney injury was observed in 1,844 patients (11%), stroke in 204 (1.3%) and in-hospital death in 286 (1.8%). Neither the duration of the time spent for perfusion flow (<1.6 L/minute/m2) nor the duration of the time spent for perfusion pressure (<50 mmHg) was associated with postoperative acute kidney injury, stroke or death in adjusted models. CONCLUSIONS: Neither low perfusion pressure nor low perfusion flow during cardiopulmonary bypass were predictive of postoperative acute kidney injury, stroke or death.

Motivational Enhancement as a Pretreatment to a Transdiagnostic Intervention for Emerging Adults with Emotion Dysregulation: A Pilot Randomized Controlled Trial.

OBJECTIVE: New approaches are needed to help the large number of emerging adults (EA) presenting with early-stage mental health problems. The goal of this pilot study was to carry out a randomized controlled trial to investigate whether motivational enhancement therapy (MET) improved the treatment effects of a 12-week psychological intervention, Dialectical Behaviour Therapy Skills Training (DBT-ST), for EA presenting in the early stages of mental health difficulties. Participants were recruited from the Youth Wellness Centre at St. Joseph's Healthcare Hamilton and McMaster University's Student Wellness Centre in Hamilton, Canada. METHODS: Seventy-five participants were randomized to receive MET followed by DBT-ST or to DBT-ST alone. We assessed psychological distress, emotion dysregulation, and depression and anxiety symptoms as outcomes. RESULTS: We found that both treatment groups had significant reductions in emotional dysregulation, psychological distress, depression, and anxiety at post-treatment and at the three-month follow-up. Participants assigned to MET pre-treatment experienced greater improvement in psychological distress at the end of treatment. CONCLUSION: This pilot study provides preliminary evidence of the potential augmentation of DBT-ST using MET in a real-world setting. Future studies should examine whether MET uniquely augments DBT-ST through the use of a comparable pre-treatment control group.

OBJECTIF: De nouvelles approches sont nécessaires pour aider le grand nombre d'adultes émergeants (AE) qui présentent des problèmes de santé mentale au stade précoce. La présente étude pilote avait pour but d'exécuter un essai randomisé contrôlé afin de rechercher si la thérapie d'amélioration motivationnelle (TAM) améliorait les effets du traitement d'une intervention psychologique de 12 semaines, soit la formation technique à la thérapie comportementale dialectique (FT-TCD), pour les AE qui présentent les premiers stades de difficultés de santé mentale. Les participants ont été recrutés au centre Youth Wellness de St. Joseph's Healthcare Hamilton et au centre Student Wellness de l'Université McMaster, à Hamilton, Canada. MÉTHODES: Soixante-quinze participants ont reçu au hasard la TAM suivie de la FT-TCD ou uniquement la FT-TCD. Nous avons évalué la détresse psychologique, la dérégulation émotionnelle, et les symptômes dépressifs et anxieux comme résultats. RÉSULTATS: Nous avons constaté que les deux groupes du traitement avaient des réductions significatives de la dérégulation émotionnelle, de la détresse psychologique, de la dépression et de l'anxiété au post-traitement et au suivi de 3 mois. Les participants affectés à la TAM de prétraitement ont eu une plus grande amélioration de la détresse psychologique en fin de traitement. CONCLUSION: Cette étude pilote offre des données probantes préliminaires de l'augmentation potentielle de la FT-TCD utilisant la TAM dans une situation réelle. Les futures études devraient examiner si la TAM n'augmente seulement la FT-TCD que par le recours à un groupe témoin prétraitement comparable.

Rethinking service design for youth with mental health needs: The development of the Youth Wellness Centre, St. Joseph's Healthcare Hamilton.

AIM: This article describes the development and design of the Youth Wellness Centre (YWC), an innovative, youth-friendly centre providing mental health and addiction services for emerging adults aged 17 to 25 in Hamilton, Canada. We also report on demographic and clinical characteristics of clients to evaluate how the YWC is serving populations at increased risk of developing mental disorders. METHODS: Data were extracted from clinic databases for 1520 youth at the YWC between March 2015 and 2018 to report on demographic characteristics, clinical profiles, primary presenting problems, service use and overall satisfaction with services. RESULTS: Marginalized groups, particularly street-involved individuals and LGBTQ+ youth, are highly represented at the YWC, keeping with the centre's mandate of reaching at-risk populations. Youth at the YWC carry significant mental health burdens, with 80.8% having a history of suicidal ideation and 32.8% having a history of a substance use disorder. The primary route of referral is self-referral and the number of new clients has increased by nearly 20% in the first 3 years of operations. Overall satisfaction with the centre is on par with or slightly above provincial averages. CONCLUSIONS: The YWC was developed to meet the mental health needs of transition-aged youth in Hamilton by providing early intervention, system navigation and transition services. The success of the YWC in reaching high-risk youth is demonstrated by the significant proportion of clients reporting demographic and clinical risk factors associated with increased risk for development of mental disorders. The increasing referrals to the YWC highlight the ongoing need for similar services.

Investigating service features to sustain engagement in early intervention mental health services.

AIM: To understand what service features would sustain patient engagement in early intervention mental health treatment. METHODS: Mental health patients, family members of individuals with mental illness and mental health professionals completed a survey consisting of 18 choice tasks that involved 14 different service attributes. Preferences were ascertained using importance and utility scores. Latent class analysis revealed segments characterized by distinct preferences. Simulations were carried out to estimate utilization of hypothetical clinical services. RESULTS: Overall, 333 patients and family members and 183 professionals (N = 516) participated. Respondents were distributed between a Professional segment (53%) and a Patient segment (47%) that differed in a number of their preferences including for appointment times, individual vs group sessions and mode of after-hours support. Members of both segments shared preferences for many of the service attributes including having crisis support available 24 h per day, having a choice of different treatment modalities, being offered help for substance use problems and having a focus on improving symptoms rather than functioning. Simulations predicted that 60% of the Patient segment thought patients would remain engaged with a Hospital service, while 69% of the Professional segment thought patients would be most likely to remain engaged with an E-Health service. CONCLUSIONS: Patients, family members and professionals shared a number of preferences about what service characteristics will optimize patient engagement in early intervention services but diverged on others. Providing effective crisis support as well as a range of treatment options should be prioritized in the future design of early intervention services.

Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET Trial.

PURPOSE: CDK4/6 inhibitors are used to treat estrogen receptor (ER)-positive metastatic breast cancer (BC) in combination with endocrine therapy. PALLET is a phase II randomized trial that evaluated the effects of combination palbociclib plus letrozole as neoadjuvant therapy. PATIENTS AND METHODS: Postmenopausal women with ER-positive primary BC and tumors greater than or equal to 2.0 cm were randomly assigned 3:2:2:2 to letrozole (2.5 mg/d) for 14 weeks (A); letrozole for 2 weeks, then palbociclib plus letrozole to 14 weeks (B); palbociclib for 2 weeks, then palbociclib plus letrozole to 14 weeks (C); or palbociclib plus letrozole for 14 weeks. Palbociclib 125 mg/d was administered orally on a 21-days-on, 7-days-off schedule. Core-cut biopsies were taken at baseline and 2 and 14 weeks. Coprimary end points for letrozole versus palbociclib plus letrozole groups (A v B + C + D) were change in Ki-67 (protein encoded by the  MKI67 gene; immunohistochemistry) between baseline and 14 weeks and clinical response (ordinal and ultrasound) after 14 weeks. Complete cell-cycle arrest was defined as Ki-67 less than or equal to 2.7%. Apoptosis was characterized by cleaved poly (ADP-ribose) polymerase. RESULTS: Three hundred seven patients were recruited. Clinical response was not significantly different between palbociclib plus letrozole and letrozole groups ( P = .20; complete response + partial response, 54.3% v 49.5%), and progressive disease was 3.2% versus 5.4%, respectively. Median log-fold change in Ki-67 was greater with palbociclib plus letrozole compared with letrozole (-4.1 v -2.2; P < .001) in the 190 evaluable patients (61.9%), corresponding to a geometric mean change of -97.4% versus -88.5%. More patients on palbociclib plus letrozole achieved complete cell-cycle arrest (90% v 59%; P < .001). Median log-fold change (suppression) of cleaved poly (ADP-ribose) polymerase was greater with palbociclib plus letrozole versus letrozole (-0.80 v -0.42; P < .001). More patients had grade 3 or greater toxicity on palbociclib plus letrozole (49.8% v 17.0%; P < .001) mainly because of asymptomatic neutropenia. CONCLUSION: Adding palbociclib to letrozole significantly enhanced the suppression of malignant cell proliferation (Ki-67) in primary ER-positive BC, but did not increase the clinical response rate over 14 weeks, which was possibly related to a concurrent reduction in apoptosis.

Hypercalcaemia preceding diagnosis of Pneumocystis jirovecii pneumonia in renal transplant recipients.

BACKGROUND: The overall incidence of Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients is 5-15%. A timely diagnosis of PJP is difficult and relies on imaging and detection of the organism. METHODS: We present a case series of four patients displaying hypercalcaemia with an eventual diagnosis of PJP and document the management of the outbreak with a multidisciplinary team approach. We discuss the underlying pathophysiology and previous reports of hypercalcaemia preceding a diagnosis of PJP. We also reviewed the evidence concerning PJP diagnosis and treatment. RESULTS: Within our renal transplant cohort, four patients presented within 7 months with hypercalcaemia followed by an eventual diagnosis of PJP. We measured their corrected calcium, parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D] levels at admission and following treatment of PJP. All four patients diagnosed with PJP were 4-20 years post-transplantation. Three of the four patients demonstrated PTH-independent hypercalcaemia (corrected calcium >3.0 mmol/L). The presence of high 1,25(OH)2D3 and low 25(OH)D levels suggest negation of the negative feedback mechanism possibly due to an extrarenal source; in this case, the alveolar macrophages. All four patients had resolution of their hypercalcaemia after treatment of PJP. CONCLUSIONS: Given the outbreak of PJP in our renal transplant cohort, and based on previous experience from other units nationally, we implemented cohort-wide prophylaxis with trimethoprim-sulphamethoxazole for 12 months in consultation with our local infectious diseases unit. Within this period there have been no further local cases of PJP.

Modeling the mental health service utilization decisions of university undergraduates: A discrete choice conjoint experiment.

OBJECTIVE: We modeled design factors influencing the intent to use a university mental health service. PARTICIPANTS: Between November 2012 and October 2014, 909 undergraduates participated. METHOD: Using a discrete choice experiment, participants chose between hypothetical campus mental health services. RESULTS: Latent class analysis identified three segments. A Psychological/Psychiatric Service segment (45.5%) was most likely to contact campus health services delivered by psychologists or psychiatrists. An Alternative Service segment (39.3%) preferred to talk to peer-counselors who had experienced mental health problems. A Hesitant segment (15.2%) reported greater distress but seemed less intent on seeking help. They preferred services delivered by psychologists or psychiatrists. Simulations predicted that, rather than waiting for standard counseling, the Alternative Service segment would prefer immediate access to E-Mental health. The Usual Care and Hesitant segments would wait 6 months for standard counseling. CONCLUSIONS: E-Mental Health options could engage students who may not wait for standard services.

Preferences for Early Intervention Mental Health Services: A Discrete-Choice Conjoint Experiment.

OBJECTIVE: Early intervention services (EISs) for mental illness may improve outcomes, although treatment engagement is often a problem. Incorporating patients' preferences in the design of interventions improves engagement. A discrete-choice conjoint experiment was conducted in Canada to identify EIS attributes that encourage treatment initiation. METHODS: Sixteen four-level attributes were formalized into a conjoint survey, completed by patients, family members, and mental health professionals (N=562). Participants were asked which EIS option people with mental illness would contact. Latent-class analysis identified respondent classes characterized by shared preferences. Randomized first-choice simulations predicted which hypothetical options, based on attributes, would result in maximum utilization. RESULTS: Participants in the conventional-service class (N=241, 43%) predicted that individuals would contact traditional services (for example, hospital location and staffed by psychologists or psychiatrists). Membership was associated with being a patient or family member and being male. Participants in the convenient-service class (N=321, 57%) predicted that people would contact services promoting easy access (for example, self-referral and access from home). Membership was associated with being a professional. Both classes predicted that people would contact services that included short wait times, direct contact with professionals, patient autonomy, and psychological treatment information. The convenient-service class predicted that people would use an e-health model, whereas the conventional-service class predicted that people would use a primary care or clinic-hospital model. CONCLUSIONS: Provision of a range of services may maximize EIS use. Professionals may be more apt to adopt EISs in line with their beliefs regarding patient preferences. Considering several perspectives is important for service design.

Viral RNA in the influenza vaccine may have contributed to the development of ANCA-associated vasculitis in a patient following immunisation.

A number of large studies have demonstrated influenza vaccinations to be safe and effective. However, there have been some sporadic case reports, describing a temporal association of influenza vaccination with onset or relapse of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The nature of this association, beyond time of occurrence, remains unknown. The presentation of a previously healthy patient who developed ANCA-associated vasculitis (AAV) shortly after influenza vaccination provided us with the rare opportunity to study the possible mechanisms behind this observation. We tested the ability of different types and batches of influenza vaccines to stimulate proteinase-3 ANCA (PR3-ANCA) production in vitro. We found that only some influenza vaccines stimulated PR3-ANCA production in this patient. We demonstrated that this unusual response was associated with those vaccines that contained viral ribonucleic acid (RNA), the natural ligand for Toll-like receptor-7. Exome sequencing of the patient's DNA did not show any mutation in any of the molecules associated with Toll-like receptor signalling. We propose that hyper-reaction to viral RNA in the influenza vaccine may have contributed to the development of AAV following influenza vaccination in this patient.

Randomized trial investigating the safety and efficacy of influenza vaccination in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

AIM: This study evaluated the safety and efficacy of influenza vaccination in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. METHODS: Thirty-one patients who were in remission were randomized to receive either a trivalent influenza vaccine or no vaccine. Vaccine efficacy was assessed at 28 days. Patients were followed for 6 months for signs of reactivation of disease. In addition, 67 healthy individuals were randomized to receive either the influenza vaccine or no vaccine to assess its potential for triggering the formation of autoantibodies. RESULTS: Compared with patients who did not receive the vaccine, vaccinated patients achieved effective responses to all three influenza vaccine antigens. There was no significant change in levels of anti-neutrophil cytoplasmic antibody post-vaccination. There was no significant change in disease activity in vaccinated patients compared with non-vaccinated patients. Among vaccinated healthy individuals, we did not observe any significant change in the level of autoantibodies measured. CONCLUSION: This study shows that the administration of influenza vaccine to patients in remission with anti-neutrophil cytoplasmic antibody-associated vasculitis is both safe and modestly efficacious.

Antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: the evidence for treatment.

Antineutrophil cytoplasmic antibody-associated vasculitis is an autoimmune disease involving small to medium blood vessels. It is an uncommon illness, but can have devastating consequences, particularly on kidney function and other vital organs. Exciting progress has been made in the treatment of the disease largely because of international collaboration in randomised clinical trials. Patient survival has improved dramatically with advancements in disease diagnosis and medical treatment. The long-term morbidity from the disease, although improving, remains substantial with up to 10% of survivors requiring dialysis or kidney transplantation. Clinical trials are underway using more specifically targeted immunosuppressants in the hope to improve the long-term patient outcomes. Advancements are also being made in understanding the pathogenesis of the disease and this will further assist disease treatment and outcomes in the future.

CpG oligodeoxynucleotide stimulates production of anti-neutrophil cytoplasmic antibodies in ANCA associated vasculitis.

BACKGROUND: Wegener's Granulomatosis and Microscopic Polyangiitis are life-threatening systemic necrotizing vasculitides of unknown aetiology. The appearance of circulating antibodies to neutrophil cytoplasmic antigens (ANCA) is strongly associated with the development of the disease. A link between infection and disease has long been suspected, and the appearance of ANCA antibodies has been reported following bacterial and viral infections. The depletion of circulating B cells with monoclonal antibody therapy can induce remission, and this observation suggests a pathogenic role for B cells in this disease. As bacterial DNA is known to induce B cell proliferation and antibody production via TLR-9 stimulation, we have explored the possibility that unmethylated CpG oligodeoxynucleotide, as found in bacterial and viral DNA, may play a role in stimulating circulating autoreactive B cells to produce ANCA in patients with vasculitis. RESULTS: We have confirmed that unmethylated CpG oligonucleotide is a potent stimulator of antibody production by PBMC in vitro. The stimulation of PBMC with CpG oligonucleutides resulted in the production of similar amounts of IgG in both ANCA+ patients and normal controls. In spite of this, PR3 ANCA+ patients synthesised significantly higher amount of IgG ANCA than normal controls. In MPO ANCA+ patients, there was a tendency for patients to produce higher amount of ANCA than controls, however, the difference did not reach significance. Furthermore, we were able to detect circulating MPO-reactive B cells by ELISpot assay from the peripheral blood of 2 MPO+ ANCA vasculitis patients. Together, this indicates that circulating anti-neutrophil autoreactive B cells are present in ANCA+ vasculitis patients, and they are capable of producing antibodies in response to CpG stimulation. Of note, CpG also induced the production of the relevant autoantibodies in patients with other types of autoimmune diseases. CONCLUSION: Circulating ANCA autoreactive B cells are present in patients with ANCA+ vasculitis. The production of ANCA from these cells in response to unmethylated CpG stimulation lead us to propose that stimulation of these cells by immunostimulatory DNA sequences such as CpG oligodeoxynucleotide during infection may provide a link between infection and ANCA associated vasculitis. This phenomenon may also apply to other antibody mediated autoimmune diseases.

Effect of pravastatin on markers of endothelial activation in dialysis patients.

AIM: The aim of this pilot study was to test the effect of pravastatin on serum levels of high-sensitivity CRP (hs-CRP), IL-6 and the soluble adhesion molecules sVCAM-1, sICAM-1 and sE-selectin in chronic dialysis patients. METHODS: At the commencement of the study, serum levels of lipids, liver function tests and endothelial markers (CRP, IL-6, sICAM-1, sVCAM-1, sE-selectin) were measured. Patients then commenced 1 month of 10 mg of pravastatin per day, and if tolerated, then 4 months of 40 mg of pravastatin per day. Serum levels of lipids, liver function tests and endothelial markers were repeated after the total of 5 months of pravastatin therapy. RESULTS: Thirty-nine patients were enrolled, and 25 (male/female 17/8; 21 haemodialysis, 4 peritoneal dialysis) patients completed the study. Pravastatin therapy significantly improved the patients' lipid profiles, but had no significant effect on the levels of CRP, IL-6, sICAM-1, sVCAM-1, or sE-selectin. CONCLUSION: Short-term (5 months) treatment with pravastatin in patients receiving chronic dialysis improved their lipid profile, but had no significant effect on surrogate markers of endothelial activation.