Bayesian estimation of post-test probability of Candida glabrata fungemia by means of serum creatinine.

Fungemia is a life-threatening condition associated with high mortality; the most frequently isolated genus is Candida. Candida glabrata is of particular concern because of its increasing resistance to azoles. We evaluated common lab tests accessible by almost all healthcare professionals to estimate the post-test probability of recovery of C. glabrata from a blood culture collected by venipuncture, positive for fungi identified by microscopic examination. Patients with blood cultures positive for C. glabrata had significantly higher median values of serum creatinine (P=0.006), and a value of ≥1.45 mg/dL was the best cut-off in discriminating C. glabrata from other Candida spp., with 0.67 [95% Confidence Interval (CI): 0.49-0.85] sensitivity and 0.75 (95% CI: 0.66-0.84) specificity; Youden's J statistic: 0.42. The receiver operator characteristic curve analysis showed an area under the curve of 0.718 (95% CI: 0.603-0.833); P=0.001. Therefore, given a pre-test probability of 24% and applying the Bayes' theorem, the post-test probability of C. glabrata fungemia with creatinine values ≥1.45 mg/dL increased to 45.8%. In conclusion, we showed how the probability of recovery of C. glabrata from blood cultures collected by venipuncture and positive for fungi can be better estimated using concurrent creatinine values.

Comparison of TSH Levels with Liquid Formulation Versus Tablet Formulations of Levothyroxine in the Treatment of Adult Hypothyroidism.

OBJECTIVE: A great number of factors can interfere with levothyroxine (LT4) tablet absorption, leading to increased serum thyroid-stimulating hormone (TSH) levels and, accordingly, to increased LT4 requirements. LT4 oral solution (LT4-OS) is a novel formulation with a pharmacokinetics profile different from those of tablets. The aim of this study was to retrospectively evaluate whether serum TSH levels were decreased after switching adult hypothyroid patients from the tablet to LT-OS. METHODS: We retrospectively evaluated 53 outpatients on LT4 replacement therapy (consumed within 1 hour before breakfast) who switched from LT4 tablets to LT4-OS without changing the daily dose. We compared preswitch TSH (TSH1) with TSH level 60 to 90 days after the switch (TSH2) and examined the clinical differences between the patients whose TSH did and did not drop after the switch. RESULTS: After the switch, TSH levels decreased from a median value of 3.04 (interquartile range [IQR] 1.75-6.80) to 2.30 (IQR 1.21-3.81) µIU/mL, and the difference was significant (P = .0034). We observed a TSH reduction (TSH2/TSH1 ratio <1) in 36/53 (67.9%) of patients; the median TSH2/TSH1 ratio was 0.71 (IQR 0.37-1.14). In the group of patients whose TSH dropped, we observed an increased frequency of factors interfering with LT4 absorption (P = .014). The median TSH2/TSH1 ratios were 0.50 (IQR 0.31-0.72) and 0.85 (IQR 0.65-1.36) for patients with and without interfering factors, respectively. CONCLUSION: Our study confirms that LT4-OS could have an increased absorption rate in comparison to LT4 tablets, especially in the presence of other factors interfering with LT4 absorption.

Evaluation of Bacterial Viability for Fecal Microbiota Transplantation: Impact of Thawing Temperature and Storage Time.

Fecal Microbiota Transplantation (FMT) represents a promising therapeutic tool under study for several purposes and is currently applied to the treatment of recurrent Clostridioides difficile infection. However, since the use of fresh stool was affected by several issues linked to donor screening, the development of a frozen stool bank is a reliable option to standardize FMT procedures. Nevertheless, different environmental factors impact microbial viability. Herein, we report the effect of different thawing temperatures and storage conditions on bacterial suspensions in the FMT procedure. In total, 20 stool samples were divided into aliquots and tested across a combination of different storing periods (15, 30; 90 days) and thawing procedures (4 °C overnight, room temperature for 1 h; 37 °C for 5 min). Focusing on storage time, our data showed a significant reduction in viability for aerobic and anaerobic bacteria after thawing for 15 days, while no further reductions were observed until after 90 days. Instead, among the different thawing procedures, no significant differences were observed for aerobic bacteria, while for anaerobes, thawing at 37 °C for 5 min was more effective in preserving the bacterial viability. In conclusion, the frozen fecal microbiota remained viable for at least three months, with an excellent recovery rate in all three thawing conditions.

Application of a SARS-CoV-2 Antigen Rapid Immunoassay Based on Active Microfluidic Technology in a Setting of Children and Young Adults.

To carry out effective and quick identification of SARS-CoV-2 from nasopharyngeal swabs and contain outbreaks, reliable and rapid tools are needed. Herein, we compared a rapid antigen test based on active microfluidic technology to an RT-qPCR assay in pediatric and young adult patients admitted to the Pediatric Emergency Unit of a Children's Hospital. Nasopharyngeal swabs collected from patients with suspected COVID-19 disease and from those without COVID-19 related symptoms, but requiring hospitalization, were performed with both antigen test and RT-qPCR assays. We included 375 patients with a median age of 5 years in the study, with an estimated overall prevalence of 7.2%. Overall, we observed a specificity of 97.4% (95% CI: 94.9-98.7) and a sensitivity of 66.6% (95% CI: 46.0-82.7) with a positive likelihood ratio (LR+) of 25.8 (95% CI: 12.8-51.8). In the subgroup of symptomatic patients, the specificity and the sensitivity were 95.2% (95% CI: 89.4-98.0) and 80.0% (95% CI: 44.2-96.5) respectively; LR+ was 16.6 (95% CI: 7.19-38.6). In the asymptomatic subset, the performance showed a specificity of 98.7% (95% CI: 95.8-99.7), a sensitivity of 58.8% (95% CI: 33.5-80.6), and an LR+ of 43.7 (95% CI: 13.3-144.0). Compared to RT-qPCR, the new microfluidic-based antigen test showed higher specificity (>95%) in the pediatric population, thus representing a suitable point-of-care testing (POCT) in a clinical setting with low prevalence of COVID-19.

The effectiveness and durability of an early insulin pump therapy in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: This study evaluated the predictors of effectiveness and durability of insulin pump therapy in children and adolescents who have initiated continuous subcutaneous insulin infusion (CSII) within 2 years after the diagnosis of type 1 diabetes mellitus (T1DM). SUBJECTS AND METHODS: The charts of individuals with T1DM using insulin pumps who were treated at our center were reviewed, including subjects with age at onset of <22 years, interval between onset and insulin pump commencement (interval onset-commencement) of <2 years, use of pumps of >1 year, and use of glucose sensors for <4 weeks/year. The primary end point was the mean glycosylated hemoglobin (HbA1c) value (MHbA1c) throughout the follow-up. RESULTS: From 684 patients treated with insulin pumps, 119 met the inclusion criteria, and 113 were selected for statistical analysis (60 females; age at diabetes onset, 8.9±5.6 years [mean±SD]; follow-up, 4.0±1.8 years; range, 1-8 years; baseline HbA1c, 9.3±1.8%). Only the interval onset-commencement was a linear predictor of the MHbA1c (P=0.01; R(2)=0.089). A significant reduction of the mean yearly HbA1c from baseline throughout all the follow-up was observed (P<0.001). Categorizing the sample into four quartiles on the basis of an increasing interval onset-commencement resulted in levels of MHbA1c significantly lower in the first and second quartiles in comparison with the fourth quartile (7.6±0.8% and 7.8±1.0%, respectively, versus 8.5±0.8%; P<0.001 and P=0.004, respectively). CONCLUSIONS: The present study suggests that early pump commencement in children and adolescents with T1DM provides lower and more durable HbA1c values than a late commencement. It is possible that an early pump commencement could prolong the honeymoon phase, but we cannot confirm or exclude this hypothesis because the lack of data about C-peptide levels during the follow-up.

Prognostic accuracy of continuous glucose monitoring in the prediction of diabetes mellitus in children with incidental hyperglycemia: receiver operating characteristic analysis.

AIM: The purpose of this study is to evaluate continuous glucose monitoring (CGM) in predicting diabetes mellitus in children with incident hyperglycemia (IH) and negativity for some insular autoantibodies. SUBJECTS AND METHODS: Thirty-one autoantibody-negative children who presented at our center with IH underwent a baseline assessment and were followed up for 23.8 months (range, 6-48 months). At the end of the follow-up, we compared the receiver operating characteristic (ROC) areas under the curve (AUCs) of metabolic markers from 17 children who developed diabetes (Group A; n=17) and 14 children who did not develop diabetes (Group B; n=14). RESULTS: Only two oral glucose tolerance test (OGTT)-derived markers and three CGM-derived markers showed a good prognostic performance, with ROC AUCs indicating significant results (P<0.0001) for the following markers: 2-h glucose, OGTT (0.813; 95% confidence interval [CI] 0.621-0.954); AUC glucose, OGTT (0.832; 95% CI 0.611-0.950); CGM glucose measurement peak (0.803; 95% CI 0.621-0.923); percentage of CGM glucose measurements inside the range 70-125 mg/dL (0.866; 95% CI 0.695-0.961); and percentage of CGM measurements ≥126 mg/dL (0.889; 95% CI 0.724-0.973). The combination of the OGTT-derived markers did not increase the predictive value, but the combination of CGM markers with each other or with the OGTT markers yielded higher ROC AUCs (ranging from 0.828 to 0.945). CONCLUSIONS: This is the first study showing that CGM is useful in predicting diabetes mellitus in children with IH.