Behavioural activation for depressive symptoms in adults with severe to profound intellectual disabilities: Modelling and initial feasibility study.

BACKGROUND: Almost no research has been published reporting on evaluations of the effectiveness of psychological interventions for people with severe to profound intellectual disabilities and depression. This paper describes the development and initial feasibility testing of an adapted Behavioural Activation therapy (BeatIt2) for this population. METHOD: Phase 1 of the study examined participant recruitment and willingness to be randomised in the context of a planned Randomised Controlled Trial (RCT). Phase 2 examined the feasibility of delivering the intervention. RESULTS: Twenty adults with a severe or profound intellectual disability and clinically significant depression were recruited to Phase 1 of the study. In Phase 2, there was 100% participant retention for those recruited to the study at 6-month follow-up. The BeatIt2 therapy was reported to be acceptable for participants. CONCLUSION: COVID disruption meant that it was not possible to complete the planned feasibility RCT. The positive findings suggest that additional evaluation of BeatIt2 is warranted.

Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Candida auris PCR for high-throughput infection control screening.

Candida auris has significant implications for infection control due to its multidrug resistance and spread in healthcare settings. Current culture-based screening methods are laborious and risk muco-cutaneous colonisation of laboratory staff. We describe the adaptation of a published real-time PCR for the identification of C. auris in skin swabs for high-throughput infection control screening. Two published primer and probe sets were analysed utilising serial 10-fold dilutions of 15 C. auris strains to assess the PCR limit of detection. One primer and probe set was compatible with our laboratory workflow and was selected for further development yielding a limit of detection of 1 colony forming unit per reaction. Non-C. auris isolates as well as routine skin swabs (n = 100) were tested by culture and PCR to assess specificity, where no cross-reactivity was detected. Skin swabs from a proven C. auris case (n = 6) were all both culture positive and PCR positive, while surveillance swabs from close contacts (n = 46) were all both culture negative and PCR negative. Finally, the use of a lysis buffer comprising 4 m guanidinium thiocyanate rendered swab-equivalent quantities of C. auris non-viable, providing assurance of the safety benefit of PCR over culture. The development of a PCR assay for high-throughput infection control screening is a promising method for rapid detection of C. auris with utility in an outbreak setting. LAY SUMMARY: Candida auris, a difficult to treat yeast-like fungus, has spread through healthcare facilities globally, posing a serious threat to the health of patients. We evaluated a PCR-based method suitable for screening large numbers of patient samples to rapidly and accurately detect C. auris.

Antifungal Susceptibility Testing and Identification.

The requirement for antifungal susceptibility testing is increasing given the availability of new drugs, increasing populations of individuals at risk for fungal infection, and emerging multiresistant fungi. Rapid and accurate fungal identification remains at the forefront of laboratory efforts to guide empiric therapy. Antifungal susceptibility testing methods have greatly improved, but are subject to variation in results between methods. Careful standardization, validation, and extensive training of users is essential to ensure susceptibility results are clinically useful and interpreted appropriately. Interpretive criteria for many drugs and species are still lacking, but this will continue to evolve.

Mycetoma caused by Microsporum canis in a patient with renal transplant: A case report and review of the literature.

Microsporum canis is a dermatophyte known to cause superficial skin infections. In immunocompromised patients, it can lead to invasive dermatophytosis. We present a case of biopsy-proven left knee mycetoma caused by M canis in a renal transplant patient. Identification of M canis was achieved via sequencing of the internal transcribed spacer regions. Treatment involved surgical debridement, oral posaconazole, and reduction in immunosuppression. In addition, we provide a review of current literature on invasive M canis infections.

Respiratory Viruses Cause Late Morbidity in Recipients of Hematopoietic Stem Cell Transplantation.

Common respiratory viral infections (CRVIs) frequently complicate hematopoietic stem cell transplantation (HSCT). We conducted a retrospective, single-center, observational cohort study to determine the incidence of CRVI in patients who received an allogeneic (allo) or autologous (auto) HSCT at the Royal Adelaide Hospital between 2009 and 2017. The median follow-up was 8.9 and 4.5 years for auto- and allo-HSCT recipients, respectively. There were 149 CRVI episodes in 74 patients, with rhinovirus being the most commonly isolated virus (n = 81, 47%). The majority of CRVIs (113/149, 75.8%) occurred more than 100 days post-HSCT and 67% were diagnosed in the outpatient setting. There was evidence of lower respiratory tract infection (LRTI) in 45.6% (68/149) of CRVIs. On multivariate logistic regression analysis, coviral infections and cytomegalovirus viremia were independent risk factors for progression of CRVI to LRTI. Ten (6.7%) CRVI episodes resulted in admission to intensive care for ventilatory support and 8 (5.4%) patients died within 30 days of CRVI diagnosis. In our study, 10.4% of HSCT recipients experienced a CRVI post-transplant, primarily causing late morbidity and potentially mortality. Prevention with strict infection control practices, vaccination, and patient education is essential.

The antibacterial toxin colicin N binds to the inner core of lipopolysaccharide and close to its translocator protein.

Colicins are a diverse family of large antibacterial protein toxins, secreted by and active against Escherichia coli and must cross their target cell's outer membrane barrier to kill. To achieve this, most colicins require an abundant porin (e.g. OmpF) plus a low-copy-number, high-affinity, outer membrane protein receptor (e.g. BtuB). Recently, genetic screens have suggested that colicin N (ColN), which has no high-affinity receptor, targets highly abundant lipopolysaccharide (LPS) instead. Here we reveal the details of this interaction and demonstrate that the ColN receptor-binding domain (ColN-R) binds to a specific region of LPS close to the membrane surface. Data from in vitro studies using calorimetry and both liquid- and solid-state NMR reveal the interactions behind the in vivo requirement for a defined oligosaccharide region of LPS. Delipidated LPS (LPS(Δ) (LIPID) ) shows weaker binding; and thus full affinity requires the lipid component. The site of LPS binding means that ColN will preferably bind at the interface and thus position itself close to the surface of its translocon component, OmpF. ColN is, currently, unique among colicins in requiring LPS and, combined with previous data, this implies that the ColN translocon is distinct from those of other known colicins.