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Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Neurostimulation Treatments” is the fourth of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance. Conclusions: There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments.

Purpose Electroconvulsive therapy (ECT) is effective for treating several psychiatric disorders. However, only a minority of patients are treated with ECT. It is of primary importance to characterize their profile for epidemiological purposes and to inform clinical practice. We aimed to characterize the longitudinal profile of psychopathology and services utilization of patients first treated with ECT. Methods We conducted a population-based comparative study using data from a national administrative database in Quebec. Patients who received a first ECT between 2002 and 2016 were compared to controls who were hospitalized in psychiatry but did not receive ECT. We performed descriptive analyses to compare psychiatric diagnoses, domains of psychopathology (internalizing, externalizing and thought/psychotic disorders), medical services and medication use in the 5 years prior to the ECT or hospitalization. Results 5 080 ECT patients were compared with 179 594 controls. Depressive, anxiety, bipolar and psychotic disorders were more frequent in the ECT group. 96.2% of ECT patients had been diagnosed with depression and 53.8% with a primary psychotic disorder. In the ECT group, 1.0% had been diagnosed exclusively with depression and 47.0% had disorders from that belong to all three domains of psychopathology. Having both internalizing and thought/psychotic disorders was associated with an increased likelihood of receiving ECT vs having internalizing disorders alone (unadjusted OR = 2.93; 95% CI = 2.63, 3.26). All indicators of mental health services utilization showed higher use among ECT patients. Conclusion Our results provide robust evidence of complex longitudinal psychopathology and extensive services utilization among ECT patients.

Objective: To report the results of the policies and procedures subsection of a nationwide electroconvulsive therapy (ECT) survey: Canadian Electroconvulsive Therapy Survey/Enquête canadienne sur les electrochocs. Method: We contacted 1273 registered health care institutions in Canada and invited the 175 centres identified as providing ECT to complete a comprehensive postal questionnaire. Nonresponding sites were repeatedly reminded and then eventually contacted by telephone. Results: Sixty-one per cent (107/175) of the institutions returned survey questionnaires. Most (84%) of the responding sites have a written general policy for the delivery of ECT. Only 27% of respondents indicated having some written policy for managing concurrent medications during ECT, and practice was quite variable regarding individual psychotropics. Informed consent was usually obtained by the attending physician (88%), and most sites indicated conveying information before ECT by using interdisciplinary and multimodal means. Almost all of the sites (93%) discharged outpatients with accompaniment home by a responsible adult. Conclusions: It is reassuring to note that general ECT policies and procedures do exist in most Canadian ECT centres. Wider variations in practice were observed in several areas, such as the elements of consent provided to patients and families, the use of concurrent medications, and the degree of supervision on discharge home after outpatient ECT. However, adherence to these policies was not captured by the results of the survey. Based on experiences in other countries, establishing a Canadian ECT accreditation service could further improve standards of practice.

Background Multidrug resistance has been identified in the fungal pathogen responsible for Septoria leaf blotch, Zymoseptoria tritici, since 2011. It has been linked to the overexpression of the gene encoding the MFS1 transporter due to inserts in the promoter region of MFS1 (PMFS1), namely types I-III. Recently, two new inserts were discovered in PMFS1 that were not linked to MDR, interrogating about whether PMFS1 inserts are the only drivers of MDR in Z. tritici. The goal of our study was to gain a more complete view of MDR in Z. tritici by examining the genotypic diversity associated with the MDR phenotype in a large sample of the modern population. Results We isolated 384 potential MDR strains between 2020 and 2021 in northern Europe for PMFS1 genotype and MDR assessment. We discovered six new inserts in PMFS1, bringing the total count to 13 including one insertion-deletion in the 5' UTR region. Of these, 11 display similarities with transposable elements, and 3 are not linked to MDR. Some field strains were significantly more resistant than their respective reference of the same PMFS1 genotype and some strains without insert displayed MDR phenotype. Conclusion We described the landscape of the MDR in modern Z. tritici population and postulate that PMFS1 is a hotspot for insertions involving transposition events. Our study shows that MDR cannot be solely explained by inserts found in PMFS1, and that additional mechanisms might be at work.Competing Interest StatementThe authors have declared no competing interest.

Disease modifying therapies (DMTs) reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS). Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA) or interferon-β 1a/1b (IFN-β) between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches) was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2%) were lost to follow-up and 160 (11%) moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54%) started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

Background Even when older people are discharged directly home after an emergency department (ED) visit, the risk of deterioration of health status and loss of independence persists. We hypothesize that among older adults discharged from the ED, hospital-community transition care provided by geriatric mobile teams (GMTs) may reduce the early readmission rate and level of disability. Such approaches have rarely been evaluated and cannot be generalized yet. Providing evidence of the positive impact of these strategies may influence public health policies. Methods We will conduct a national, multicentre, prospective, controlled, quasi-experimental study. All participating centres have an ED and a GMT, some of which provide transitional care. Participants recruited from hospitals where GMT provide transitional care form the “intervention group”, whereas participants recruited from hospitals where GMT provide standard in-hospital management are the “control group”. Inclusion criteria are age ≥ 75 years, returning to personal home after the ED visit (exclusion of nursing home residents) and having a significant risk for early readmission and/or loss of independence after discharge according to a Triage Risk Screening Tool score ≥ 2. The primary objective of this study is to compare hospital ED readmission rates within 30 days. Among secondary objectives, disability scores at 3 and 6 months will be compared between groups. We estimated that 1322 participants, i.e., 661 per group, is required for the main analysis. Discussion By conducting this study, we aim to provide more evidence of the effectiveness of transitional care on reducing ED readmissions for older adults, and particularly highlight determinants and effects of hospital-community GMT-led interventions. These strategies can be cost-effective while preserving independence and quality of life. We expect that the results will provide a basis to generalize effective strategies to address the challenges of demographic ageing for healthcare systems. Trial registration The study protocol was registered on ClinicalTrial.org (ID NCT05814328 Date 20230414).

BackgroundA growing body of evidence defines inflammation as a hallmark feature of disease pathogenesis of Duchenne muscular dystrophy. To tailor potential immune modulatory interventions, a better understanding of immune dysregulation in Duchenne muscular dystrophy is needed. We now asked whether dystrophin deficiency affects the cascade of leukocyte recruitment.MethodsWe performed intravital microscopy on the cremaster muscle of wild-type and dystrophin-deficient mdx mice. Recruitment was triggered by preparation alone (traumatic inflammation) or in combination with scrotal TNFα injections. Neutrophilic infiltration of the cremaster muscle was assessed on tissue sections. Integrin expression on circulating neutrophils and serum levels of pro-inflammatory cytokines were measured by flow cytometry.ResultsMdx mice show increased rolling and adhesion at baseline (traumatic inflammation) and a more profound response upon TNFα injection compared with wild-type animals. In both models, neutrophilic infiltration of the cremaster muscle is increased. Upregulation of the integrins LFA-1 and Mac-1 on circulating leukocytes and pro-inflammatory cytokines IL-6 and CCL2 in the serum points toward systemically altered immune regulation in mdx mice.ConclusionWe are the first to show exaggerated activation of the leukocyte recruitment cascade in a dystrophin-deficient organism in vivo.

Background This study by the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) was designed to determine the incidence, risk factors, current management strategies, and outcomes of antibody-mediated rejection (ABMR) in pediatric kidney transplant recipients (pKTR). Methods We performed an international, multicenter, longitudinal cohort study of data reported to the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry. Three hundred thirty-seven pKTR from 21 European centers were analyzed. Clinical outcomes, including kidney dysfunction, rejection, HLA donor-specific antibodies, BK polyomavirus-associated (BKPyV) nephropathy, and allograft loss, were assessed through 5 years post-transplant. Results The cumulative incidence of de novo donor-specific class I HLA antibodies (HLA-DSA) post-transplant was 4.5% in year 1, 8.3% in year 3, and 13% in year 5; the corresponding data for de novo class II HLA-DSA were 10%, 22.5%, and 30.6%, respectively. For 5 years post-transplant, the cumulative incidence of acute ABMR was 10% and that of chronic active ABMR was 5.9%. HLA-DR mismatch and de novo HLA-DSA, especially double positivity for class I and class II HLA-DSA, were significant risk factors for ABMR, whereas cytomegalovirus (CMV) IgG negative recipient and CMV IgG negative donor were associated with a lower risk. BKPyV nephropathy was associated with the highest risk of graft dysfunction, followed by ABMR, T-cell mediated rejection, and older donor age. Conclusions This study provides an estimate of the incidence of de novo HLA-DSA and ABMR in pKTR and highlights the importance of BKPyV nephropathy as a strong risk factor for allograft dysfunction. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

BackgroundMedical patients are on occasion admitted transiently to surgical wards when more appropriate wards are at capacity, potentially leading to suboptimal care. The aim of this study was to compare 6-month outcomes in older adults diagnosed with medical conditions in the ED then admitted inappropriately to surgical wards (defined as outliers), with outcomes in comparable patients admitted to medical wards (controls).MethodsIn a matched cohort study, 100 consecutive medical outliers from the ED aged 75 years and over were matched according to age, sex and diagnosis to 200 controls. Collected data included number of diagnoses reported in acute care, level of patient illness severity, length of stay, mortality and destination of patients discharged from acute care units (home, rehabilitation facility, nursing home or palliative care facility). An assessment was made of patient vital status and living environment (home, nursing home or hospital) at 6 months post-ED admission.ResultsMean age was 85.6 years. The most common ED diagnoses were gait disorders/falls (18%), neurological disorders (17%) and exhaustion (16%). Outliers displayed lower illness severity levels (0.001) and shorter lengths of stay from ED admission to acute care discharge (p=0.040). Subsequent to acute care, outliers were less commonly discharged home (45% vs 59%) and more commonly discharged to rehabilitation facilities (42% vs 28%). At 6 months post-ED admission, multivariable regression analysis showed that outlier status (OR=0.44 (0.25–0.83); p=0.011) and numbers of diagnoses reported in acute care (OR=0.87 (0.76–0.98); p=0.028) were independently associated with lower probability of living at home.ConclusionOutlying of older patients to surgical wards negatively affects their prospects of living at home at 6 months after hospital admission. Older patients hospitalised via the ED are entitled to appropriate medical care.