Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.

RATIONALE: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility. OBJECTIVES: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults. METHODS: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts. MEASUREMENTS AND MAIN RESULTS: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity. CONCLUSIONS: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

Outbreak of Gastroenteritis in Adults Due to Rotavirus Genotype G12P[8].

BACKGROUND: Rotavirus infection in adults is poorly understood and few rotavirus outbreaks among US adults have been reported in the literature. We describe an outbreak due to genotype G12P[8] rotavirus among medical students, faculty, and guests who attended a formal dinner event in April 2013. METHODS: A web-based questionnaire was distributed to event attendees to collect symptom and exposure data. A clinical case was defined as a person who developed diarrhea after attending the formal event. A laboratory-confirmed case was defined as a clinical case who attended the formal event, with rotavirus detected in stool by enzyme immunoassay or reverse transcription-polymerase chain reaction (RT-PCR) assay. RESULTS: Among 334 dinner attendees, 136 (41%) completed the web-based questionnaire; 58 (43%) respondents reported illness. Symptom onset ranged from 1 to 8 days, with peak onset 3 days after the event. In addition to diarrhea, predominant symptoms included fever (91%), abdominal pain (84%), and vomiting (49%). The median duration of illness was 2.5 days. Thirteen (22%) of 58 cases sought medical attention; none were hospitalized. Analysis of food exposures among questionnaire respondents did not identify significant associations between any specific food or drink item and illness. Stool specimens were negative for bacterial pathogens by culture and negative for norovirus by RT-PCR assay; 4 specimens were positive for rotavirus by enzyme immunoassay or PCR. G12P[8]-R1-C1-M1-A1-N1-T1-E1-H1 was identified as the causative full-genome genotype. CONCLUSIONS: Rotavirus outbreaks can occur among adults, including young adults. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults.

Reduction of airborne and surface-borne bacteria in a medical center burn intensive care unit using active, upper-room, germicidal ultraviolet (GUV) disinfection.

OBJECTIVE: To determine the effectiveness of active, upper-room, germicidal ultraviolet (GUV) devices in reducing bacterial contamination in patient rooms in air and on surfaces as a supplement to the central heating, ventilation, and air conditioning (HVAC) air handling unit (AHU) with MERV 14 filters and UV-C disinfection. METHODS: This study was conducted in an academic medical center, burn intensive care unit (BICU), for 4 months in 2022. Room occupancy was monitored and recorded. In total, 402 preinstallation and postinstallation bacterial air and non-high-touch surface samples were obtained from 10 BICU patient rooms. Airborne particle counts were measured in the rooms, and bacterial air samples were obtained from the patient-room supply air vents and outdoor air, before and after the intervention. After preintervention samples were obtained, an active, upper-room, GUV air disinfection system was deployed in each of the patient rooms in the BICU. RESULTS: The average levels of airborne bacteria of 395 CFU/m3 before GUV device installation and 37 CFU/m3 after installation indicated an 89% overall decrease (P < .0001). Levels of surface-borne bacteria were associated with a 69% decrease (P < .0001) after GUV device installation. Outdoor levels of airborne bacteria averaged 341 CFU/m3 in March before installation and 676 CFU/m3 in June after installation, but this increase was not significant (P = .517). CONCLUSIONS: Significant reductions in air and surface contamination occurred in all rooms and areas and were not associated with variations in outdoor air concentrations of bacteria. The significant decrease of surface bacteria is an unexpected benefit associated with in-room GUV air disinfection, which can potentially reduce overall bioburden.

Recommendations for quantitative uncertainty consideration in ecology and evolution.

Ecological and evolutionary studies are currently failing to achieve complete and consistent reporting of model-related uncertainty. We identify three key barriers - a focus on parameter-related uncertainty, obscure uncertainty metrics, and limited recognition of uncertainty propagation - which have led to gaps in uncertainty consideration. However, these gaps can be closed. We propose that uncertainty reporting in ecology and evolution can be improved through wider application of existing statistical solutions and by adopting good practice from other scientific fields. Our recommendations include greater consideration of input data and model structure uncertainties, field-specific uncertainty standards for methods and reporting, and increased uncertainty propagation through the use of hierarchical models.

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation.

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Granulomatous hepatitis due to Bartonella henselae infection in an immunocompetent patient.

BACKGROUND: Bartonella henselae (B. henselae) is considered a rare cause of granulomatous hepatitis. Due to the fastidious growth characteristics of the bacteria, the limited sensitivity of histopathological stains, and the non-specific histological findings on liver biopsy, the diagnosis of hepatic bartonellosis can be difficult to establish. Furthermore, the optimal treatment of established hepatic bartonellosis remains controversial. CASE PRESENTATION: We present a case of hepatic bartonellosis in an immunocompetent woman who presented with right upper quadrant pain and a five cm right hepatic lobe mass on CT scan. The patient underwent a right hepatic lobectomy. Surgical pathology revealed florid necrotizing granulomatous hepatitis, favoring an infectious etiology. Despite extensive histological and serological evaluation a definitive diagnosis was not established initially. Thirteen months after initial presentation, hepatic bartonellosis was diagnosed by PCR studies from surgically excised liver tissue. Interestingly, the hepatic granulomas persisted and Bartonella henselae was isolated from the patient's enriched blood culture after several courses of antibiotic therapy. CONCLUSION: The diagnosis of hepatic bartonellosis is exceedingly difficult to establish and requires a high degree of clinical suspicion. Recently developed, PCR-based approaches may be required in select patients to make the diagnosis. The optimal antimicrobial therapy for hepatic bartonellosis has not been established, and close follow-up is needed to ensure successful eradication of the infection.

Native range estimates for red-listed vascular plants.

Besides being central for understanding both global biodiversity patterns and associated anthropogenic impacts, species range maps are currently only available for a small subset of global biodiversity. Here, we provide a set of assembled spatial data for terrestrial vascular plants listed at the global IUCN red list. The dataset consists of pre-defined native regions for 47,675 species, density of available native occurrence records for 30,906 species, and standardized, large-scale Maxent predictions for 27,208 species, highlighting environmentally suitable areas within species' native regions. The data was generated in an automated approach consisting of data scraping and filtering, variable selection, model calibration and model selection. Generated Maxent predictions were validated by comparing a subset to available expert-drawn range maps from IUCN (n = 4,257), as well as by qualitatively inspecting predictions for randomly selected species. We expect this data to serve as a substitute whenever expert-drawn species range maps are not available for conducting large-scale analyses on biodiversity patterns and associated anthropogenic impacts.

A Scoping Review on Use of Drugs Targeting the JAK/STAT Pathway in Psoriasis.

Introduction: The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway are known to be involved in inflammatory immune-mediated skin diseases, including psoriasis. The development of drugs targeting the JAK/STAT signaling pathway presents new treatment opportunities for psoriasis. However, the application of JAK inhibitors for the treatment of dermatological disorders is still in its early stages of development. This review summarizes available evidence in an attempt to identify knowledge gaps for conducting further research studies and improving clinical decision-making. Objective: The objective of this study is to conduct a scoping review of the use of drugs targeting the JAK/STAT pathway in the treatment of psoriasis. Methods: A priori protocol for scoping review was published in 2019. The Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Review were used for the review. MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science databases and ClinicalTrials registry were referred to in April 2019 and March 2021, respectively. References in English involving evidence on the use of drugs targeting the JAK/STAT pathway in patients with psoriasis were included. Data charting was performed by two authors using tables and figures. Results: The evidence found on the efficacy and safety of drugs targeting the JAK/STAT pathway in patients with psoriasis comes from 118 articles reporting the results of 34 randomized clinical trials (RCTs). Nine different drugs administered through various routes were identified (systemic: peficitinib, baricitinib, solcitinib, itacitinib, abrocitinib, deucravacitinib, and brepocitinib; topical: ruxolitinib; and both: tofacitinib). Knowledge articles are mainly created and published by pharmaceutical companies and authors through their own funding or by those related to them. Only tofacitinib and deucravacitinib have undergone phase III clinical trials, being the only ones tested with active comparators etanercept and apremilast, respectively. Proportions of Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) were the efficacy variables most frequently studied in systemic treatments. Only two RCTs declared the safety data collected by systematic assessment; the only systemic drug with phase III data was tofacitinib. Tofacitinib 5 mg two times daily (BID)/10 mg BID efficacy was compared with etanercept 50 mg/week and a placebo. At 12-16 weeks, PASI 75/PGA 01 ranges were as follows: 38.07-80%/37.16-67.4% for tofacitinib 5 mg BID; 54.79-100%/50-75.6% for tofacitinib 10 mg BID; 58.8/66.8% for etanercept, date from one only study; and 0-33.3%/9.04-33.3% for the placebo group. Other drugs in earlier stages of development showed values within these ranges. The most frequent adverse events (AEs) were nasopharyngitis and upper respiratory tract infections in all treatment groups. Conclusion: There is increasing evidence on the use of drugs targeting the JAK/STAT pathway as a treatment for psoriasis, although they are in the early phases of development. The trials conducted to date have been financed directly or indirectly by the pharmaceutical industry, which must be taken into account when interpreting the results of the trials. Psoriasis treatment is currently symptomatic and could potentially present a significant risk of toxicity. Therefore, the design of principal efficacy outcome measures considering the impact of the outcome on quality of life and a drug assessment methodology aimed at improving safety would probably strengthen the evidence and decision-making process.

Insights into the quantification and reporting of model-related uncertainty across different disciplines.

Quantifying uncertainty associated with our models is the only way we can express how much we know about any phenomenon. Incomplete consideration of model-based uncertainties can lead to overstated conclusions with real-world impacts in diverse spheres, including conservation, epidemiology, climate science, and policy. Despite these potentially damaging consequences, we still know little about how different fields quantify and report uncertainty. We introduce the "sources of uncertainty" framework, using it to conduct a systematic audit of model-related uncertainty quantification from seven scientific fields, spanning the biological, physical, and political sciences. Our interdisciplinary audit shows no field fully considers all possible sources of uncertainty, but each has its own best practices alongside shared outstanding challenges. We make ten easy-to-implement recommendations to improve the consistency, completeness, and clarity of reporting on model-related uncertainty. These recommendations serve as a guide to best practices across scientific fields and expand our toolbox for high-quality research.

Coexistence of large mammals and humans is possible in Europe's anthropogenic landscapes.

A critical question in the conservation of large mammals in the Anthropocene is to know the extent to which they can tolerate human disturbance. Surprisingly, little quantitative data is available about large-scale effects of human activity and land use on their broad scale distribution in Europe. In this study, we quantify the relative importance of human land use and protected areas as opposed to biophysical constraints on large mammal distribution. We analyze data on large mammal distribution to quantify the relative effect of anthropogenic variables on species' distribution as opposed to biophysical constraints. We finally assess the effect of anthropogenic variables on the size of the species' niche by simulating a scenario where we assumed no anthropogenic pressure on the landscape. Results show that large mammal distribution is primarily constrained by biophysical constraints rather than anthropogenic variables. This finding offers grounds for cautious optimism concerning wildlife conservation in the Anthropocene.

Effectiveness of a Standardized External Ventricular Drain Placement Protocol for Infection Control.

INTRODUCTION: Placement of an external ventricular drain (EVD) is a common procedure routinely completed at bedside by neurosurgical residents. A standardized protocol for placement and maintenance of an EVD is potentially useful. METHODS: This single-institution retrospective review analyzed all patients who underwent placement of an EVD over a 5-year span using a standardized protocol. RESULTS: A total of 428 EVDs in 381 patients were placed as per this protocol. Overall compliance with the practice protocol was 98.7%. Overall, our infection rate was 1.86% (8 external ventricular drain-related infection [ERIs] over 428 EVDs). There was no difference in age for the ERI cases (median 55, range (50.5-60.5), compared with the non-ERI cases (median of 53, range [38-65]) (P = 0.512). Indications for placement of EVD were hemorrhage (51.9%, n = 198), tumor (16.2%, n = 62), trauma (12.8%, n = 49), hydrocephalus (11.5%, n = 44), cerebellar stroke (2.8%, n = 11), infection (3.1%, n = 12), unknown (1.3%, n = 5). Most EVDs (77.6%, n = 296) were placed bedside by second-year residents (median PGY level 2, interquartile range 1-2.75). Computed tomography confirmed placement in the ipsilateral frontal horn in 72% (n = 277) of EVDs. EVD-related complications were noted in 8.3% of EVDs (n = 32, with 8 infections and 24 tract hemorrhages). The median EVD duration was 10 days; duration of EVD had no statistically significant impact on the risk of an ERI (P = 1). Only replacement of an EVD was associated with an increased risk of infection. CONCLUSIONS: Adherence to a standard EVD placement protocol is useful in maintaining a low risk of ERI regardless of the duration of catheter utilization. Replacement of the catheter through the same access hole as the original catheter is associated with an increased risk of ERI.

Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review.

IMPORTANCE: Type I interferon (IFN)-mediated monogenic autoinflammatory disorders (interferonopathies) are childhood-onset rare multisystemic diseases with limited treatment options. The Janus kinase (JAK) inhibitors are promising potential therapeutic candidates for immune-mediated chronic inflammatory skin diseases. OBJECTIVE: To review the use of JAK inhibitors to improve decision-making when treating interferonopathies with cutaneous manifestations. EVIDENCE REVIEW: The MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science databases were searched for studies that used JAK protein inhibitors to treat IFN-related monogenic diseases with cutaneous manifestations in humans. The search results are reported using the scoping review approach. FINDINGS: Seventeen open-label studies assessing the efficacy of ruxolitinib, baricitinib, or tofacitinib reported variable responses in patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) and related syndromes, stimulator of IFN genes [STING]-associated vasculopathy with onset in infancy (SAVI), familial chilblain lupus (FCh-L), gain-of-function mutations of STAT1 (GOF-STAT1), or Aicardi-Goutiéres syndrome. JAK inhibitors improved clinical and analytical parameters and decreased flare numbers, plasma inflammatory markers, and expression of IFN-stimulated genes. BK viremia and upper respiratory infections were the most frequent and severe adverse events. Significant heterogeneity in efficacy assessment methods and poor reporting of safety events were detected. CONCLUSIONS AND RELEVANCE: Evidence of the use of JAK inhibitors in patients with interpheronopathies is scarce and of low methodological quality. Future clinical trials should use validated scales and report drug safety in a more accurate way.

Antimicrobial susceptibility of biliary stents do not predict infectious complications after whipple.

BACKGROUND: Postoperative infectious complications after a pancreaticoduodenectomy remain a significant cause of morbidity. Studies have demonstrated that a preoperative biliary stent increases the risk of postoperative infectious complications. Few studies have investigated the specific preoperative biliary stent bacterial sensitivities to preoperative antibiotics and the effect on infectious complications. The goal of this study was to investigate if the presence of a preoperative biliary stent increases the risk of postoperative infectious complications in patients undergoing a pancreaticoduodenectomy. Additionally, we aimed to investigate biliary stent culture sensitivities to preoperative antibiotics and determine if those sensitivities impacted postoperative infectious complications after a pancreaticoduodenectomy. METHODS: A retrospective chart review of patients who had undergone a pancreaticoduodenectomy at a single institution tertiary care center from 2007 to 2018 was performed. Perioperative variables including microbiology cultures from biliary stents were collected and analyzed. RESULTS: A total of 244 patients underwent a pancreaticoduodenectomy. A preoperative biliary stent was present in 45 (18%) patients. Infectious complications occurred in 25% of those patients with a preoperative biliary stent, and 19% of those without (P = .37). Of those patients with a stent that was cultured intraoperatively, 92% grew bacteria and 61% of those were resistant to the preoperative antibiotics administered. Of the patients with a preoperative biliary stent and bacteria resistant to the preoperative antibiotics, 17% developed a postoperative infectious complication, compared with 20% if the bacteria cultured was susceptible to the preoperative antibiotics (P = .64). CONCLUSION: Infectious complications after pancreaticoduodenectomy are a significant cause of morbidity. Stent bacterial sensitivities to preoperative antibiotics did not reduce the postoperative infectious complications in the preoperative biliary stent group suggesting a multifactorial cause of infections.

Molecular epidemiology of Clostridium difficile over the course of 10 years in a tertiary care hospital.

BACKGROUND: The molecular epidemiology of endemic and outbreak Clostridium difficile strains across time is not well known. METHODS: HindIII restriction endonuclease analysis (REA) typing was performed on available clinical C. difficile isolates from 1982 to 1991. RESULTS: The annual incidence of C. difficile infection (CDI) ranged from 3.2 to 9.9 cases per 1000 discharges and was significantly higher in 1982, 1983, 1985, and 1991 (high-incidence years) than in other years (mean standard deviation number of cases for the high- vs the low-incidence years, 121.8 +/-20.4 and 70.0 +/-15.0; P =.002). A total of 696 (76.6%) of 908 C. difficile isolates were available for REA typing over the 10-year period. Large clusters (>or=10 CDI cases in consecutive months) were caused by REA types B1 and B2 in 1982 and 1983, F2 and B1 in 1985, and K1 in 1991 (high-incidence years). Small clusters of 4-9 CDI cases in consecutive months were caused by REA types G1 (1984), Y4 and Y6 (1987), Y2 (1988), L1 (1989), Y1 (1990), and K1 (1991). Current epidemic REA group BI (unrelated to type B1) was isolated 6 times, twice in 1984, 1988, and 1990. CONCLUSIONS: Years with a high incidence of CDI were associated with large clusters of specific REA types that changed yearly. The molecular epidemiology of CDI in this hospital was characterized by a wide diversity of C. difficile types and an ever-changing dominance of specific C. difficile types over time. The current epidemic BI group was found sporadically on 6 occasions. A changing CDI molecular epidemiology should be expected in the future.

Mupirocin resistance among methicillin-resistant Staphylococcus aureus-colonized patients at admission to a tertiary care medical center.

All patients admitted to our tertiary care hospital from 1 December 2007 to 10 June 2008 were screened for methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) nasal colonization, and the isolates were tested for mupirocin susceptibility by using Etest. Mupirocin resistance (MR) was noted to occur in 3.4% of MRSA carriers, and high-level MR was noted to occur in 0.62% of carriers.

Hepatotoxicity associated with long- versus short-course HIV-prophylactic nevirapine use: a systematic review and meta-analysis from the Research on Adverse Drug events And Reports (RADAR) project.

BACKGROUND AND OBJECTIVE: The antiretroviral nevirapine can cause severe hepatotoxicity when used 'off-label' for preventing mother-to-child HIV transmission (PMTCT), newborn post-exposure prophylaxis and for pre- and post-exposure prophylaxis among non-HIV-infected individuals. We describe the incidence of hepatotoxicity with short- versus long-course nevirapine-containing regimens in these groups. METHODS: We reviewed hepatotoxicity cases among non-HIV-infected individuals and HIV-infected pregnant women and their offspring receiving short- (or=5 days) nevirapine prophylaxis. Sources included adverse event reports from pharmaceutical manufacturers and the US FDA, reports from peer-reviewed journals/scientific meetings and the Research on Adverse Drug events And Reports (RADAR) project. Hepatotoxicity was scored using the AIDS Clinical Trial Group criteria. RESULTS: Toxicity data for 8216 patients treated with nevirapine-containing regimens were reviewed. Among 402 non-HIV-infected individuals receiving short- (n=251) or long-course (n=151) nevirapine, rates of grade 1-2 hepatotoxicity were 1.99% versus 5.30%, respectively, and rates of grade 3-4 hepatotoxicity were 0.00% versus 13.25%, respectively (p<0.001 for both comparisons). Among 4740 HIV-infected pregnant women receiving short- (n=3031) versus long-course (n=1709) nevirapine, rates of grade 1-2 hepatotoxicity were 0.62% and 7.04%, respectively, and rates of grade 3-4 hepatotoxicity were 0.23% versus 4.39%, respectively (p<0.001 for both comparisons). The rates of grade 3-4 hepatotoxicity among 3074 neonates of nevirapine-exposed HIV-infected pregnant women were 0.8% for those receiving short-course (n=2801) versus 1.1% for those receiving long-course (n=273) therapy (p<0.72). CONCLUSIONS: Therapy duration appears to significantly predict nevirapine hepatotoxicity. Short-course nevirapine for HIV prophylaxis is associated with fewer hepatotoxic reactions for non-HIV-infected individuals or pregnant HIV-infected women and their offspring, but administration of prophylactic nevirapine for >or=2 weeks appears to be associated with high rates of hepatotoxicity among non-HIV-infected individuals and HIV-infected pregnant mothers. When full highly active antiretroviral therapy (HAART) regimens are not available, single-dose nevirapine plus short-course nucleoside reverse transcriptase inhibitors to decrease the development of HIV viral resistance is an essential therapeutic option for PMTCT and these data support the safety of single-dose nevirapine in this setting.

Variability in catheter-associated asymptomatic bacteriuria rates among individual nurses in intensive care units: An observational cross-sectional study.

Catheter-associated asymptomatic bacteriuria (CAABU) is frequent in intensive care units (ICUs) and contributes to the routine use of antibiotics and to antibiotic-resistant infections. While nurses are responsible for the implementation of CAABU-prevention guidelines, variability in how individual nurses contribute to CAABU-free rates in ICUs has not been previously explored. This study's objective was to examine the variability in CAABU-free outcomes of individual ICU nurses. This observational cross-sectional study used shift-level nurse-patient data from the electronic health records from two ICUs in a tertiary medical center in the US between July 2015 and June 2016. We included all adult (18+) catheterized patients with no prior CAABU during the hospital encounter and nurses who provided their care. The CAABU-free outcome was defined as a 0/1 indicator identifying shifts where a previously CAABU-free patient remained CAABU-free (absence of a confirmed urine sample) 24-48 hours following end of shift. The analytical approach used Value-Added Modeling and a split-sample design to estimate and validate nurse-level CAABU-free rates while adjusting for patient characteristics, shift, and ICU type. The sample included 94 nurses, 2,150 patients with 256 confirmed CAABU cases, and 21,729 patient shifts. Patients were 55% male, average age was 60 years. CAABU-free rates of individual nurses varied between 94 and 100 per 100 shifts (Wald test: 227.88, P<0.001) and were robust in cross-validation analyses (correlation coefficient: 0.66, P<0.001). Learning and disseminating effective CAABU-avoidance strategies from top-performers throughout the nursing teams could improve quality of care in ICUs.

Use of high-power diode laser at 1060 nm for the treatment of vascular lesions.

The use of 1060-nm wavelength light emitted from a high-power diode laser is a novel method for the removal of vascular lesions. Two Caucasian women with Fitzpatrick skin phototype II, who had various vascular lesions, were treated with a 1060-nm high-power diode laser, applying a fluence of 120 J/cm2 and a single pulse duration of 74 milliseconds. Immediate results were that the cherry angiomas became dark and a scab was formed (that remitted 2 weeks after treatment); the telangiectasias and venulectasias disappeared immediately. This technology has reported effective and safe results for removing different types of vascular lesions in the two patients treated. Side effects were those expected for this technique.

Scoping Review on the Use of Drugs Targeting JAK/STAT Pathway in Atopic Dermatitis, Vitiligo, and Alopecia Areata.

INTRODUCTION: The JAK/STAT signaling pathway is involved in the immune-mediated inflammatory skin diseases atopic dermatitis (AD), vitiligo, and alopecia areata (AA), and represents a potential target when developing treatments. So far, no drugs targeting this pathway have been approved for the treatment of dermatological diseases. We reviewed the use of drugs blocking the JAK/STAT pathway in the aforementioned diseases. METHODS: An a priori protocol was published. We used Joanna Briggs Institute Reviewer's Manual methodology to conduct the review and PRISMA Extension for Scoping Review (PRISMA-ScR) to report results. MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science databases were searched in a three-step approach on April 2019 by two researchers. RESULTS: Ninety-six mainly multicenter observational studies were included (66, 10, and 20 studies on AA, vitiligo, and AD, respectively). Tofacitinib and ruxolitinib were mainly used for the three diseases, and also upadacitinib, abrocitinib, baricitinib, cerdulatinib, delgocitinib, gusacitinib for AD, and baricitinib, PF-06700841, and PF-06651600 for AA. All patients with AD improved, whereas patients with vitiligo and patients with AA showed varied responses, including unresponsive cases. The safety profiles were similar for all drugs and diseases, mainly comprising mild or no adverse events. CONCLUSIONS: Evidence on the efficacy and safety of drugs targeting the JAK/STAT pathway for the treatment of patients with AD, vitiligo, or AA is increasing but is still of low quality.

Physician agreement on the diagnosis of sepsis in the intensive care unit: estimation of concordance and analysis of underlying factors in a multicenter cohort.

BACKGROUND: Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting. METHODS: We conducted a post hoc analysis of previously collected data from a prospective, observational trial (N = 249 subjects) in intensive care units at seven US hospitals, in which physicians at different stages of patient care were asked to make diagnostic calls of either SIRS, sepsis, or indeterminate, based on varying amounts of available clinical information (clinicaltrials.gov identifier: NCT02127502). The overall percent agreement and the free-marginal, inter-observer agreement statistic kappa (κ free) were used to quantify agreement between evaluators (attending physicians, site investigators, external expert panelists). Logistic regression and machine learning techniques were used to search for significant variables that could explain heterogeneity within the indeterminate and SIRS patient subgroups. RESULTS: Free-marginal kappa decreased between the initial impression of the attending physician and (1) the initial impression of the site investigator (κ free 0.68), (2) the consensus discharge diagnosis of the site investigators (κ free 0.62), and (3) the consensus diagnosis of the external expert panel (κ free 0.58). In contrast, agreement was greatest between the consensus discharge impression of site investigators and the consensus diagnosis of the external expert panel (κ free 0.79). When stratified by infection site, κ free for agreement between initial and later diagnoses had a mean value + 0.24 (range - 0.29 to + 0.39) for respiratory infections, compared to + 0.70 (range + 0.42 to + 0.88) for abdominal + urinary + other infections. Bioinformatics analysis failed to clearly resolve the indeterminate diagnoses and also failed to explain why 60% of SIRS patients were treated with antibiotics. CONCLUSIONS: Considerable uncertainty surrounds the differential clinical diagnosis of sepsis vs. SIRS, especially before organ damage has become highly evident, and for patients presenting with respiratory clinical signs. Our findings underscore the need to provide physicians with accurate, timely diagnostic information in evaluating possible sepsis.