This analysis describes the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in patients enrolled in the Prospective Antifungal Therapy Alliance (PATH Alliance) registry from 2004 to 2008. A total of 2,496 patients with non-albicans species of Candida isolates were identified. The identified species were C. glabrata (46.4%), C. parapsilosis (24.7%), C. tropicalis (13.9%), C. krusei (5.5%), C. lusitaniae (1.6%), C. dubliniensis (1.5%) and C. guilliermondii (0.4%); 111 infections involved two or more species of Candida (4.4%). Non-albicans species accounted for more than 50% of all cases of invasive candidiasis in 15 of the 24 sites (62.5%) that contributed more than one case to the survey. Among solid organ transplant recipients, patients with non-transplant surgery, and patients with solid tumors, the most prevalent non-albicans species was C. glabrata at 63.7%, 48.0%, and 53.8%, respectively. In 1,883 patients receiving antifungal therapy on day 3, fluconazole (30.5%) and echinocandins (47.5%) were the most frequently administered monotherapies. Among the 15 reported species, 90-day survival was highest for patients infected with either C. parapsilosis (70.7%) or C. lusitaniae (74.5%) and lowest for patients infected with an unknown species (46.7%) or two or more species (53.2%). In conclusion, this study expands the current knowledge of the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in North America. The variability in species distribution in these centers underscores the importance of local epidemiology in guiding the selection of antifungal therapy.

Introduction: Antimuscarinics are the principal pharmacological treatment for overactive bladder (OAB), but frequently give rise to anticholinergic side effects, such as dry mouth, a factor leading to poor persistence. The ß 3 -adrenoceptor agonist mirabegron is devoid of significant anticholinergic activity, while being effective in OAB. We evaluated persistence and adherence with mirabegron versus antimuscarinics over 12 months. Methods: We obtained retrospective claims from a Canadian Private Drug Plan database for patients 18 years old and over, with a first claim for mirabegron or antimuscarinics during a 6-month index period (April-September 2013). A 6-month look-back identified those with no prior claims for OAB medication (treatmentnaïve) or ≥1 prior OAB drug (treatment-experienced). Time to end of persistence (≥30 day therapy gap or switch of therapy) was evaluated over 12 months; adherence with medication (medication possession ratio) was also measured. Results: Persistence data from 19 485 patients (74% female, 92% naïve, 19.9% aged ≥65 years) showed that for experienced patients the median number of days on mirabegron was 299 days, compared with a range of 96 to 242 days for the different antimuscarinics; for naïve patients, it was 196 versus 70 to 100 days, respectively. Persistence at 12 months was for mirabegron 39% versus 14% to 35% for antimuscarinics, (experienced) and 30% mirabegron versus 14% to 21% antimuscarinics, (naïve). Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics. Conclusion: Patients who received mirabegron remained longer on treatment than those treated with antimuscarinics, and had higher 12-month persistence and adherence rates.

Epidemiological characteristics of 333 proven and probable invasive mould infections (IMIs) among solid organ transplant recipients (SOTRs) identified between 2004 and 2008 from the Prospective Antifungal Therapy Alliance (PATH) registry are presented. Liver transplant recipients (LTRs) had the lowest median time to IMIs (109 days; interquartile range [IQR] 24-611 days), the highest rate of disseminated disease (n/N = 18/33; 55%), and highest mortality (n/N = 21/33; 64%). Lung transplant recipients had highest median time to IMIs (486 days; IQR 117-1358 days) and lowest mortality (n/N = 31/184; 17%). Complete or partial response at week 12 in patients with invasive aspergillosis (IA) was 67% (n/N = 189/281), and 41% (n/N = 9/22) in mucormycosis patients. In the composite outcome of death or no response to therapy, LTRs had the worst outcome. Higher suspicion of mold infection and institution of appropriate antifungal prophylactic strategies are warranted, especially in high risk LTRs.

ObjectivesWe investigated machinelearningbased identification of presymptomatic COVID-19 and detection of infection-related changes in physiology using a wearable device.DesignInterim analysis of a prospective cohort study.Setting, participants and interventionsParticipants from a national cohort study in Liechtenstein were included. Nightly they wore the Ava-bracelet that measured respiratory rate (RR), heart rate (HR), HR variability (HRV), wrist-skin temperature (WST) and skin perfusion. SARS-CoV-2 infection was diagnosed by molecular and/or serological assays.ResultsA total of 1.5 million hours of physiological data were recorded from 1163 participants (mean age 44±5.5 years). COVID-19 was confirmed in 127 participants of which, 66 (52%) had worn their device from baseline to symptom onset (SO) and were included in this analysis. Multi-level modelling revealed significant changes in five (RR, HR, HRV, HRV ratio and WST) device-measured physiological parameters during the incubation, presymptomatic, symptomatic and recovery periods of COVID-19 compared with baseline. The training set represented an 8-day long instance extracted from day 10 to day 2 before SO. The training set consisted of 40 days measurements from 66 participants. Based on a random split, the test set included 30% of participants and 70% were selected for the training set. The developed long short-term memory (LSTM) based recurrent neural network (RNN) algorithm had a recall (sensitivity) of 0.73 in the training set and 0.68 in the testing set when detecting COVID-19 up to 2 days prior to SO.ConclusionWearable sensor technology can enable COVID-19 detection during the presymptomatic period. Our proposed RNN algorithm identified 68% of COVID-19 positive participants 2 days prior to SO and will be further trained and validated in a randomised, single-blinded, two-period, two-sequence crossover trial.Trial registration numberISRCTN51255782; Pre-results.

SummaryInvasive Fusarium infections occur in immunosuppressed patients, especially those with haematological malignancies. We conducted a descriptive analysis of data from patients with invasive fusariosis identified in the Prospective Antifungal Therapy Alliance registry, which collected data on invasive fungal infections in the United States and Canada from 2004 to 2008. In this series of 65 patients with proven (83.1%) and probable (16.9%) invasive fusariosis, the most common underlying condition was haematological malignancy, in which neutropenia and corticosteroid usage frequently occurred. Seven patients with invasive Fusarium infections had cross-reactive galactomannan assay results. The survival rate for all patients at 90 days was 44%, which was an improvement compared with historical data. Disseminated disease occurred frequently (35.4%), and patients with and without disseminated disease had survival rates of 33% and 50%, respectively. Posaconazole and voriconazole were the most frequently employed therapies and may be linked to the improved survival rate observed in this patient series. In summary, patients with invasive Fusarium infections continue to have high fatality rates, especially those with disseminated disease. Fusarium infections should be strongly considered in the absence of Aspergillus isolation in patients at high risk of mould infections with positive galactomannan assay test results.