Costs associated with invasive Scedosporium and Lomentospora prolificans infections: a case-control study.

BACKGROUND: Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents. METHODS: A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities. RESULTS: Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections. CONCLUSIONS: The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.

Durability of the moderate-to-heavy-intensity transition is related to the effects of prolonged exercise on severe-intensity performance.

PURPOSE: Power output at the moderate-to-heavy-intensity transition decreases during prolonged exercise, and resilience to this has been termed 'durability'. The purpose of this study was to assess the relationship between durability and the effect of prolonged exercise on severe-intensity performance, and explore intramuscular correlates of durability. METHODS: On separate days, 13 well-trained cyclists and triathletes (V̇O2peak, 57.3 ± 4.8 mL kg-1 min-1; training volume, 12 ± 2.1 h week-1) undertook an incremental test and 5-min time trial (TT) to determine power output at the first ventilatory threshold (VT1) and severe-intensity performance, with and without 150-min of prior moderate-intensity cycling. A single resting vastus lateralis microbiopsy was obtained. RESULTS: Prolonged exercise reduced power output at VT1 (211 ± 40 vs. 198 ± 39 W, ∆ -13 ± 16 W, ∆ -6 ± 7%, P = 0.013) and 5-min TT performance (333 ± 75 vs. 302 ± 63 W, ∆ -31 ± 41 W, ∆ -9 ± 10%, P = 0.017). The reduction in 5-min TT performance was significantly associated with durability of VT1 (rs = 0.719, P = 0.007). Durability of VT1 was not related to vastus lateralis carnosine content, citrate synthase activity, or complex I activity (P > 0.05). CONCLUSION: These data provide the first direct support that durability of the moderate-to-heavy-intensity transition is an important performance parameter, as more durable athletes exhibited smaller reductions in 5-min TT performance following prolonged exercise. We did not find relationships between durability and vastus lateralis carnosine content, citrate synthase activity, or complex I activity.

PrEP Demographics and Disparity: The Race, Ethnicity, Gender Identity, Sex Assigned at Birth, Sexual Orientation and Age of Current PrEP Use.

PURPOSE: Identification of disparity in preexposure prophylaxis (PrEP) prescription by demographic group. DESIGN: Exploratory descriptive study. METHODS: Secondary data analysis of 1114 patients who received PrEP from Planned Parenthood League of Massachusetts (PPLM) between 2017 and 2020. FINDINGS: Persons of Asian racial-identity had a higher mean PrEP prescription than the other racial groups. Persons over 30 had a higher mean PrEP prescription than those 18-29. CONCLUSIONS: Discrepancy of PrEP prescription reveals opportunities to improve PrEP delivery. CLINICAL EVIDENCE: Providers of PrEP delivery and community health nurses can enhance delivery by better electronic medical charting regarding PrEP discussion and nonadherence.

Colonisation with toxigenic Corynebacterium diphtheriae in a Scottish burns patient, June 2015.

On 12 June 2015, Corynebacterium diphtheriae was identified in a skin swab from a burns patient in Scotland. The isolate was confirmed to be genotypically and phenotypically toxigenic. Multilocus sequence typing of three patient isolates yielded sequence type ST 125. The patient was clinically well. We summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for C. diphtheriae.

"I Didn't Realize How Common it Was:" A Mixed-Methods Study Examining Changes in Perceptions of Sexual Assault, Sex and Consent, and Sexual Behavior as a Function of the #Metoo Movement.

This mixed-methods study examined awareness and perceived legitimacy of the #MeToo movement and how #MeToo changed perceptions of sexual assault and consent, as well as sexual interactions, in the United States. Adults residing in the U.S. were recruited through CloudResearch to complete an online survey in 2021. Quantitative data from 680 participants (M age = 45.8, 60% women, 77.4% White) indicated moderate awareness and perceived legitimacy of the #MeToo movement; Black, LGBQ+, and more politically liberal respondents had greater #MeToo awareness while younger, more liberal respondents, and those with greater rejection of rape myths rated #MeToo more legitimate. Among 354 participants (M age = 45.0, 65.3% women, 76.4% White) who answered at least one open-ended question with regard to changes resulting from the #MeToo movement, thematic analysis revealed nine primary themes: (1) Describing change; (2) Change in understanding; (3) More cautious; (4) Wrong or requires reporting/punishment; (5) Gendered social norms; (6) Easier to talk about; (7) #MeToo rhetoric; (8) Consequences for survivors, and (9) Empowerment. Several sub-themes were identified among the primary themes and implications for sexual assault prevention and response were discussed. The study findings are contextualized by social constructionism, with a particular focus on gender-based power dynamics, contributing to a growing literature documenting the cultural impact of the #MeToo movement.

Invasive Scedosporium and Lomentospora prolificans Infections in Australia: A Multicenter Retrospective Cohort Study.

Background: Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure. Methods: We conducted a retrospective Australian-based observational study of proven/probable Scedosporium/L prolificans infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed. Results: Of 61 infection episodes, 37 (60.7%) were attributable to L prolificans. Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) L prolificans infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) Scedosporium spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post-IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both P < .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%. Conclusions: Outcomes associated with Scedosporium/L prolificans infections is poor, particularly with L prolificans infections or in the highly immunosuppressed population.

Clostridioides difficile Infection: Clinical Practice and Health Outcomes in 6 Large Tertiary Hospitals in Eastern Australia.

Background: Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality in both healthcare and community settings. We aimed to define the predisposing factors, risks for severe disease, and mortality determinants of CDI in eastern Australia over a 1-year period. Methods: This is an observational retrospective study of CDI in hospitalized patients aged ≥18 years in 6 tertiary institutions from 1 January 2016 to 31 December 2016. Patients were identified through laboratory databases and medical records of participating institutions. Clinical, imaging, and laboratory data were input into an electronic database hosted at a central site. Results: A total of 578 patients (578 CDI episodes) were included. Median age was 65 (range, 18-99) years and 48.2% were male. Hospital-onset CDI occurred in 64.0%. Recent antimicrobial use (41.9%) and proton pump inhibitor use (35.8%) were common. Significant risk factors for severe CDI were age <65 years (P < .001), malignancy within the last 5 years (P < .001), and surgery within the previous 30 days (P < .001). Significant risk factors for first recurrence included severe CDI (P = .03) and inflammatory bowel disease (P = .04). Metronidazole was the most common regimen for first episodes of CDI with 65.2% being concordant with Australian treatment guidelines overall. Determinants for death at 60 days included age ≥65 years (P = .01), severe CDI (P < .001), and antibiotic use within the prior 30 days (P = .02). Of those who received metronidazole as first-line therapy, 10.1% died in the 60-day follow-up period, compared to 9.8% of those who received vancomycin (P = .86). Conclusions: Patients who experience CDI are vulnerable and require early diagnosis, clinical surveillance, and effective therapy to prevent complications and improve outcomes.

Invasive aspergillosis in adult patients in Australia and New Zealand: 2017-2020.

Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice. Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM). Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria - 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51-69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04-3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93-8.17, p < 0.001) but not neutropenia (HR 1.45; 95% CI 0.88-2.39, p = 0.135) were associated with mortality. Chronic kidney disease was also a significant predictor of death in the HM subgroup (HR 3.94; 95% CI 1.15-13.44, p = 0.028). Interpretation: IA is identified in high number of patients with mild/no immunosuppression in our study. The relatively high proportion of non-A. fumigatus species complex isolates and 6.5% azole-resistance rate amongst A. fumigatus sensu stricto necessitates accurate species identification and susceptibility testing for optimal patient outcomes. Funding: This work is unfunded. All authors' financial disclosures are listed in detail at the end of the manuscript.

Viridans Group Streptococci in Pediatric Leukemia and Stem Cell Transplant: Review of a Risk-stratified Guideline for Empiric Vancomycin in Febrile Neutropenia.

Viridans group streptococci (VGS) are an important cause of sepsis in immunosuppressed children. We reviewed the effectiveness of risk-stratified addition of vancomycin to empiric febrile neutropenia therapy among 107 children with leukemia or undergoing an allogeneic transplant. Of 19 VGS bacteremia episodes, 78.9% were susceptible to risk-stratified antibiotics including 100% from high-risk patients. All blood cultures were flagged positive within 24 hours.

The epidemiology of overfeeding in mechanically ventilated intensive care patients.

BACKGROUND AND AIMS: Nutrition research in the Intensive Care Unit (ICU) typically focusses on the epidemiology of underfeeding, particularly early in the ICU admission. Once the acute phase of critical illness has resolved, patients may be at risk of overfeeding. We assessed for the frequency and consequences of potential overfeeding in ICU patients mechanically ventilated (MV) for at least 10 days. METHODS: Retrospective analysis of 105 MV patients including caloric input, estimated caloric requirements using the Schofield equation, and association between caloric input and several pre-defined clinical outcomes. To increase likelihood of detecting overfeeding, we conducted a post-hoc sensitivity analysis for sub-groups of patients who received on average < 25 kcal/kg/day (N = 55) and >30 kcal/kg/day (N = 17) between day 7-10 and performed repeat ANOVA. RESULTS: There were no differences in the pre-defined outcomes for those given over, and below 25 kcal/kg/day. On each study day, approximately 25% of patients received >30 kcal/kg/day. Higher caloric delivery was statistically associated with increased minute ventilation on each study day (Spearman Rho approx 0.27;p ≤ 0.007) and also in sub-group analysis (p< 0.001). Higher caloric delivery was also associated with more frequent diarrhoea (p= 0.02) and greater insulin requirement. However, these differences did not translate into increased duration of mechanical ventilation, length of stay, or increased mortality. Higher caloric intake was less strongly associated with serum urea and creatinine, but not associated with agitation, abnormal liver function tests, fever, or antibiotic prescription. CONCLUSIONS: Delivery of more than 25 kcal/kg/day was not associated with adverse outcomes. On post-hoc analysis, delivery of more than 30 kcal/kg/day was associated with increased minute ventilation, diarrhoea and insulin requirements but no differences in length of ventilation or in-hospital mortality.

High amylase resistant starch to decrease stool output in people with short bowel syndrome: A pilot trial.

Short bowel syndrome (SBS) is defined as having less than 200 cm of functional small bowel. Malabsorptive diarrhoea and dehydration are difficult to manage despite medical therapy and dietary manipulations. Evidence shows that supplementing the diet with High Amylase Resistant Starch (HARS) can reduce diarrhoea from a number of causes including gastroenteritis. It is hypothesised HARS will decrease stool output via the production of short chain fatty acids and the resultant increased water reabsorption. This study aimed to determine if the addition of HARS can reduce diarrhoea in patients with SBS. METHODS: Patients with SBS with colon in continuity were recruited from the intestinal rehabilitation clinic at Austin Health. The study was a 2 week crossover trial. Each participant completed the control and the intervention (addition of 50 g HARS to usual diet). Total daily stool weight and number of bowel actions per day were compared between groups using paired t-tests. RESULTS: Eight adults (58% male, mean age 55.7 yrs) were recruited. Five participants completed the trial. Total daily stool weight was reduced in all participants when consuming HARS. Mean daily stool output was significantly decreased 1049 ± 519 g/d to 804 ± 585 g/d (p = 0.023). Number of bowel actions per day showed a trend to reduction. CONCLUSION: This study gives some support to the hypothesis that the addition of HARS into the diet of patients with short bowel syndrome reduces stool output. Longer trials are required to confirm the effect on nutritional/hydration status.

Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.

PURPOSE: Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. EXPERIMENTAL DESIGN: Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. RESULTS: Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. CONCLUSIONS: Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

Transmission of Salmonella enteritidis after endoscopic retrograde cholangiopancreatography because of inadequate endoscope decontamination.

We report a historic nosocomial outbreak of Salmonella enteritidis affecting 4 inpatients who underwent endoscopic retrograde cholangiopancreatography. The cause was attributed to inadequate decontamination of an on-loan endoscope used over a weekend. This report highlights the risks of using on-loan endoscopes, particularly regarding their commissioning and adherence to disinfection protocols. In an era of increasing antibiotic resistance, transmission of Enterobacteriaceae by endoscopes remains a significant concern.

Cognitive therapy of depression: pretreatment patient predictors of outcome.

This review examines the role of patient predictors of outcome in cognitive therapy of depression. Studies that meet eligibility criteria are reviewed for demonstrated linkage between various predictors (i.e., pretreatment severity, historical features, demographic predictors, dysfunctional attitudes and other cognitive features, and treatment acceptability) and outcome, and several effects are found. Notably, high pretreatment severity scores are associated with poorer response to cognitive therapy, as are high chronicity, younger age at onset, an increased number of previous episodes, and marital status. High pretreatment levels of dysfunctional attitudes and certain beliefs about the nature of depression were also found to predict differential response to cognitive therapy of depression. Limitations of the research and directions for further investigations of patient predictors of outcome in cognitive therapy of depression are provided.

Contamination of a purified water system by Aspergillus fumigatus in a new endoscopy reprocessing unit.

Use of purified water for the final rinse stage of disinfected endoscopes is an important element of quality control. We describe the detection and management of Aspergillus fumigatus contamination of a new reverse osmosis unit supplying 10 automated endoscope reprocessor basins. Prompt detection and reaction to this contaminant were possible because of the introduction of a comprehensive program for microbiological monitoring of rinse waters, which included total viable counts, endotoxin, conductivity, and Pseudomonas spp.

Inclusion as a focus of employment-related research in intellectual disability from 2000 to 2010: a scoping review.

PURPOSE: This paper presents the results of a scoping review of the research literature on community-based employment for individuals with intellectual disabilities from 2000 to 2010. The review examined the variables studied in each paper, and considered the degree to which elements of social inclusion were addressed. METHOD: The search strategy identified a total of 245 articles, the total pool of which was reduced to 42 following abstract and text review. Two researchers reviewed the final set of articles and extracted information relevant to the study goals. Independent and dependent measures used in the studies were categorized relative to a conceptual model of social inclusion. The frequency with which each aspect of inclusion was addressed in the studies was totalled, and the resulting pattern analyzed qualitatively. RESULTS: The analysis revealed that the majority of papers identified the work role achieved (i.e. employment and pay rates, job titles) as the primary construct of interest, while fewer than 5 articles focused on central aspects of inclusion, such as sense of belonging, reciprocity, and need fulfillment. CONCLUSIONS: This study profiles the evidence base relative to inclusive employment for people with intellectual disabilities. The lack of evidence on the degree to which social inclusion is being achieved through community-based employment highlights a critical area requiring attention.