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Background Practice in the simulated environment can improve surgical skills. However, the transfer of open complex surgical skills to the operating room is unclear. This study evaluated the effect of resident operative performance following a simulation experience on a hand-sewn small bowel anastomosis and determined the impact of utilizing proficiency-based training. Methods Nine categorical interns performed a hand-sewn small bowel anastomosis in the operating room prior to (pre-test) and following (post-test) a 3-h simulation training session with an assessment at the end. Participants were randomly assigned to 1of 2 simulation training groups: proficiency-based or standard. Operative performance was videotaped. 2 independent, blinded faculty surgeons assessed performances by a global rating scale. Pre- and post-confidence levels were obtained on a 5-point Likert scale. Results Overall, pre-test and post-test operative performance was similar (3 [IQR, 2.5 -3.5] versus 3 [IQR, 3 -3], P = 0.59). Furthermore, no difference was observed in the post-test performance with proficiency-based or standard training (3 [IQR, 3 -3] versus 3 [IQR, 3 -3], P = 0.73). Self-reported confidence with the skills, however, significantly improved (median 1 versus 4, P = 0.007). Conclusions In this prospective, randomized study, we did not observe an improvement in operative performance following simulation instruction and assessment, with both training groups. Overcoming barriers to skills transfer will be paramount in the future to optimize simulation training in general surgery. These findings highlight the importance of continued study for the ideal conditions and timing of technical skills training.

In this paper, we propose a novel mobility model providing train traffic traces essential for train-to-train communication models. As the proposed mobility model works only based on trip timetables and train timetables are currently available in real-time, the produced mobility traces will be also in real-time. Additionally, as no GPS module is used in this method, our proposed model can provide a practical solution when signal from GPS or Assisted GPS is poor or unavailable such as in urban area or inside tunnels. Furthermore, as we used an energy optimization function, the proposed mobility model will provide a guidance trajectory for trains to have an energy-optimized operation. We also develop an algorithm that can determine the specifications of contacts between trains based on the traffic traces obtained from the mobility model. Such specifications includes duration, rate and location of train contacts used for estimation of data exchange capacity between trains through train-to-train communications. We validate our proposed model using data collected from Sydney Trains of Australia. The results obtained from our proposed model show over 98 percent accuracy in comparison with the real data collected via a GPS module from Sydney Trains.

Objective This study aims to define an effective senior resident and understand the process of leadership and nontechnical skill development in the transition from junior to senior surgery resident. Summary background General surgery residents are responsible for patient care, technically demanding operations, and diverse care team management. However, leadership skill development for the transition from junior to senior resident roles is often overlooked. Methods We conducted 15 semi-structured focus groups with surgery residents from an urban, academic institution. Focus group transcripts were inductively coded. Using content analysis and constant comparative methodology, primary codes were refined into categories and organized into higher-level themes. Results Thirty-three general surgery residents completed fifteen focus groups. Six themes were identified. Three themes describe the process of becoming an effective senior resident: how to define a senior resident's scope of practice, the transition process, and the importance of personal investment. Three themes were identified regarding effective seniors: ideal traits, teachable skills, and the team and patient impact. Conclusions Surgery residents define an effective senior resident as the team member with the highest level of experience who manages the big picture of patient care. The transition is improved by personal engagement and acknowledgement of the transition. Ideal traits of effective seniors, including emotional intelligence and inherent personality traits, allow a resident to more naturally assume this role; however, teachable skills, such as communication, expectation setting and competence, can be taught to improve one's effectiveness. The actions of a senior resident impact the team and patient care, underscoring the importance of understanding this role.

Background In the present study, the authors aimed to compare the pharmacokinetics (PK) of micafungin in critically ill patients receiving continuous veno-venous hemofiltration (CVVH, 30 mL/kg/h) with those of patients receiving equidoses of hemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h) and determine the optimal dosing regimen using the developed model. Methods Patients with septic shock undergoing continuous renal replacement therapy (CRRT) and receiving a conventional dose of 100 mg micafungin once daily were eligible for inclusion. Total micafungin plasma concentrations from eight CVVH sessions and eight CVVHDF sessions were subjected to a population PK analysis using Pmetrics. Validation of the model performance was reinforced by external validation. Monte Carlo simulations were performed considering the total ratio of free drug area under the curve (AUC) over 24 h to the minimum inhibitory concentration (MIC) (AUC0-24/MIC) in plasma. Results The median total body weight (min-max) was 94.8 (66-138) kg. Micafungin concentrations were best described by a two-compartmental PK model. No covariates, including CRRT modality (CVVH or CVVHDF), were retained in the final model. The mean parameter estimates (standard deviation) were 0.96 (0.32) L/h for clearance and 14.8 (5.3) L for the central compartment volume. External validation confirmed the performance of the developed PK model. Dosing simulations did not support the use of standard 100 mg daily dosing, except for Candida albicans on the second day of therapy. A loading dose of 150 mg followed by 100 mg daily reached the probability of target attainment for all C. albicans and C. glabrata, but not for C. krusei and C. parapsilosis. Conclusions No difference was observed in micafungin PK between equidoses of CVVH and CVVHDF. A loading dose of 150 mg is required to achieve the PK/PD target for less susceptible Candida species from the first day of therapy.

Introduction We present our experience developing and embedding a registry-based module for resident feedback. Methods At our institution, entering operative data into the institutional quality collaborative registry is standard practice. In February 2019, a surgical education module was embedded into the registry to capture procedure-specific resident operative assessments. Faculty engagement with the sugical education module was assessed during its first year in existence (February 2019-February 2020). Results In total, 1074 of 1269 (85%) operative assessments were completed by 27 faculty via the surgical education registry module. Median faculty engagement rate with the module following resident-assisted procedures was 91% [IQR 76%-100%]. Residents received a median of 7 operative assessments [IQR 2-19] over the study period. Conclusion By embedding a surgical education module into an existing surgical quality collaborative registry, procedure-specific operative assessments can be routinely captured.

Non-tuberculous mycobacterial pulmonary disease is on the rise globally. It is often missed, and causes significant morbidity and even mortality. Here, members of a clinical research network and a patient support group discuss some of the current key issues in NTM management. In addition to the need for research into epidemiology, immunology and treatment, we recommend greater use of patient and clinician networks to: (i) educate primary and secondary care clinicians to develop a high index of suspicion when investigating and treating at risk populations. (ii) promote a multidisciplinary team. (iii) promote shared patient-clinician decision making throughout care. (iv) incorporate use of patient self-report measures to assess progress and outcomes. (v) increase education of patients on their illness and its management. (vi) recruit patients into research projects and registries to improve the clinical evidence base. (vii) increase co-production of research with key stakeholders such as patients and their families, using expert patients and patient groups. (viii) understand more about the psychological, social and economic consequences of the disease.

Objective U.S. disparities in pediatric type 1 diabetes treatment and outcomes are increasing disproportionately among Black youth and compounded for youth from single parent homes. Despite worsened outcomes, Black youth from single parent homes and their caregivers are underrepresented in pediatric type 1 diabetes research. The purpose of this study was to understand the social determinants of health (SDOH) barriers that may contribute to health disparities and family management in Black youth with type 1 diabetes from single parent homes. Methods A three-phase mixed methods study with self-identified Black single parents of youth with type 1 diabetes from an urban U.S. pediatric diabetes center was conducted. Focus groups and interviews informed development of a parent-generated survey of SDOH barriers to diabetes management. Survey results are presented. Results A resulting 71 item parent-generated survey was administered to 105 parents. Among all items, most problematic SDOH barriers included lack of social support, managing parent/child diabetes-related stress, difficulties accessing diabetes supplies, pain management, cost of food and diabetes camp, need to take time off from work, lack of skilled school staff, school absences and unsafe neighborhoods. Structural racism related to child welfare reporting, and police targeting were also notable concerns. Conclusions There is a critical need for clinical, community, and policy-related research and interventions, designed to reduce type 1 diabetes racial health disparities by addressing the impacts of SDOH as drivers of family management outcomes among Black youth from single parent families. This article is protected by copyright. All rights reserved.

OBJECTIVES To describe micafungin pharmacokinetic (PK) alterations of sepsis induced in piglets and to determine whether the porcine septic model is able to predict the PK of micafungin in septic patients at the plasma and peritoneal sites. METHODS From healthy (n = 8) and septic piglet group (n = 16), total micafungin concentrations were subject to a population PK analysis using Monolix®. Data from 16 septic humans patients from others studies was used to compare micafungin PK between septic piglets and septic patients. RESULTS Sepsis induced in piglets slightly alters the total clearance and the volume of distribution, while inter-compartment clearance is increased (from 3.88 to 5.74 L/h) as well as the penetration into peritoneal cavity (from 61 to 90%). In septic human patients, PK parameters are similar except for the Vd, which is corrected by an allometric factor based on the body weight of each species. Micafungin penetration into peritoneal cavity of humans is lower than in septic piglets (40 versus 90%). CONCLUSIONS The sepsis induced in the porcine model alters the PK of micafungin comparable to that in humans. In addition, micafungin PK is similar between these two species at the plasma level taking into account the allometric relationship of the body weight of these species on the central volume of distribution. The porcine septic plasma model would be able to predict the micafungin PK in the septic patients. However, further studies on peritoneal penetration are necessary to characterize this inter-species difference.

Ileocolic resection for Crohn's disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn's disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion.This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn's disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented.Twenty-two patients with ileocolic Crohn's disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak.Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn's disease.

Adolescents with type 1 diabetes are vulnerable to suboptimal glycemic control, generally due to insufficient self-care behaviors (1,2). Because they have some of the highest rates of mobile communication technology use (3), this modality may hold promise for providing reminders or encouragement to adolescents to engage in self-care. However, the effects of text messaging interventions on self-care and glycemic outcomes are mixed, with some reports favoring improvements in teen self-care behaviors such blood glucose monitoring frequency or medication adherence (4–7). In an alternative attempt to reach this high-risk age-group, researchers have explored the use of financial incentives to promote self-care behaviors, which yielded some glycemic benefit in the short term (8,9). However, there is limited research on the combination of a financial incentive and a mobile health intervention (10,11) and the potential benefits that could accrue from blending these approaches. Nonetheless, use of either a unimodal or a bimodal intervention requires that adolescent recipients remain engaged with the program. In this report, we describe adolescent engagement during a 6-month study of a psychoeducational text messaging intervention that incorporated financial incentives. The primary study included adolescents with type 1 diabetes in suboptimal control and showed a potential increase in self-reported self-care in those receiving the intervention as intended (10). This analysis of the primary study’s intervention group described patterns of adolescent engagement with the intervention and identified factors associated with responsiveness. We also evaluated the potential impact of engagement on glycemic outcomes and self-care. This study analyzed 6 months of data from teenagers with type 1 diabetes receiving an incentivized text messaging intervention aimed at increasing education and support for diabetes self-care. Youths were eligible for inclusion if they were 12–18 years of age, had a duration of type 1 diabetes of …

BACKGROUND: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis. OBJECTIVE: To describe a statistical analysis plan for the BLING III study. METHODS: The statistical analysis plan was designed by the trial statistician and chief investigators and approved by the BLING III management committee before the completion of data collection. Statistical analyses for primary, secondary and tertiary outcomes and planned subgroup analyses are described in detail. Interim analysis by the Data Safety and Monitoring Committee (DSMC) has been conducted in accordance with a pre-specified DSMC charter. RESULTS AND CONCLUSIONS: The statistical analysis plan for the BLING III study is published before completion of data collection and unblinding to minimise analysis bias and facilitate public access and transparent analysis and reporting of study findings. TRIAL REGISTRATION: ClinicalTrials.gov Registry NCT03212990.

Although tuberculosis (TB) incidence has significantly declined in high-income, low-incidence (HILI) countries, challenges remain in managing TB in vulnerable populations who may struggle to stay on anti-TB treatment (ATT). Factors associated with non-adherence to ATT are well documented; however, adherence is often narrowly conceived as a fixed binary variable that places emphasis on individual agency and the act of taking medicines, rather than on the demands of being on treatment more broadly. Further, the mechanisms through which documented factors act upon the experience of being on treatment are poorly understood. Adopting a relational approach that emphasizes the embeddedness of individuals within dynamic social, structural, and health systems contexts, this scoping review aims to synthesize qualitative evidence on experiences of being on ATT and mechanisms through which socio-ecological factors influence adherence in HILI countries. Six electronic databases were searched for peer-reviewed literature published in English between January 1990 and May 2020. Additional studies were obtained by searching references of included studies. Narrative synthesis was used to analyze qualitative data extracted from included studies. Of 28 included studies, the majority (86%) reported on health systems factors, followed by personal characteristics (82%), structural influences (61%), social factors (57%), and treatment-related factors (50%). Included studies highlighted three points that underpin a relational approach to ATT behavior: 1) individual motivation and capacity to take ATT is dynamic and intertwined with, rather than separate from, social, health systems, and structural factors; 2) individuals’ pre-existing experiences of health-seeking influence their views on treatment and their ability to commit to long-term regular medicine-taking; and 3) social, cultural, and political contexts play an important role in mediating how specific factors work to support or hinder ATT adherence behavior in different settings. Based on our analysis, we suggest that person-centered clinical management of tuberculosis should 1) acknowledge the ways in which ATT both disrupts and is managed within the everyday lives of individuals with TB; 2) appreciate that individuals' circumstances and the support and resources they can access may change over the course of treatment; and 3) display sensitivity towards context-specific social and cultural norms affecting individual and collective experiences of being on ATT.

SUMMARY Background Lateral intercostal artery perforator (LICAP) flap for breast volume augmentation provides the benefits of addressing axillary tissue excess and avoiding intramuscular dissection. Previous experience with the LICAP flap in patients with prior breast conservation therapy (BCT) has led to the development of an extended version for massive weight loss (MWL) patients as well. Methods A retrospective review of all cases of LICAP flaps was performed by a single surgeon. Data were subsequently extracted and analyzed including patient demographics, indication and timing of volume augmentation, complications, and follow-up length. Results From 2016 to 2020, 12 patients underwent 16 LICAP flaps for volume augmentation. Indications for volume augmentation included deficits from prior oncologic surgery (ten patients) and loss of volume due to MWL (two patients). The average BMI was 29.9 kg/m2. Among the oncologic group, eight patients had delayed reconstruction, while two were immediate. Nine patients underwent radiation prior to volume augmentation. Eight of the 14 patients simultaneously received fat grafting. There were 4 cases of delayed wound healing that improved with local wound care. There were no statistically significant differences in complication rates between the oncologic and MWL groups. The average length of follow-up was 11.4 months. Conclusions This study supports that the application of the LICAP flap can be effectively broadened from the oncologic population to the MWL population. If needed, extending the flap provides an option to simultaneously address excess axillary and back tissue.

Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Autoimmune progesterone dermatitis (AIPD) is a cyclical, cutaneous reaction to endogenous progesterone that occurs throughout the menstrual cycle. The cutaneous manifestations of AIPD vary greatly from patient to patient, ranging anywhere from urticaria to erythema multiforme to anaphylaxis. As such, recognition, diagnosis, and management of this condition are difficult for clinicians. In the present article, we conducted a systematic review of 112 articles and 132 individual cases to summarize the clinical features and presentation of AIPD while also summarizing the successes and failures of different treatment plans. Despite the great variety in clinical presentations, it is clear from the data that ovulation-suppressing medical therapies and surgery have the greatest success in treating AIPD, whereas more commonly used therapies such as antihistamines and systemic corticosteroids frequently fail in providing any relief. Further research is necessary to determine the exact pathogenesis of AIPD and allow for more targeted treatment.

Standardized testing remains a cornerstone of assessment in surgical education. Summative standardized tests make up a bulk of the certification requirements that encompasses demonstration of efficient, safe application of clinically relevant surgical knowledge and skills. Formative standardized tests serve similar role to guide teaching endeavors for the programs and comparison of individual trainees on a national level. Ongoing rigorous psychometric evaluations of the standardized tests ensure reliability and validity; however, standardized tests are not without their limitations and biases.

Pruritus is the most burdensome and prevalent symptom in patients suffering from atopic dermatitis. Treating atopic itch has historically been a challenge due to multiple underlying mechanisms within its pathogenesis and an incomplete understanding of them. In recent years, our understanding of these mechanisms have increased tremendously and subsequently, new treatments have reached the market that target the pathophysiology of atopic itch from different angles. In addition, there are several promising new treatments currently in development and trials. In the current article, we discuss these currently available treatment options, their available evidence and efficacy, and highlight some of the more recent advancements in the field.

Component alignment in total knee arthroplasty is a determining factor for implant longevity. Mechanical alignment, which provides balanced load transfer, is the most common alignment strategy. However, a retrospective review found that varus alignment, which could lead to unbalanced loading, can happen in up to 18% of tibial baseplates. This may be particularly burdensome for cementless tibial baseplates, which require low bone-implant micromotion and avoidance of bone overload to obtain bone ingrowth. Our aim was to assess the effect of varus alignment on the bone-implant interaction of cementless baseplates. We virtually implanted 11 patients with knee OA with a modern cementless tibial baseplate in mechanical alignment and in 2° of tibial varus alignment. We performed finite element simulations throughout gait, with loading conditions derived from literature. Throughout the stance phase, varus alignment had greater micromotion and percentage of bone volume at risk of failure than mechanical alignment. At mid-stance, when the most critical conditions occurred, the average increase in peak micromotion and amount of bone at risk of failure due to varus alignment were 79% and 59%, respectively. Varus alignment also resulted in the decrease of the surface area with micromotion compatible with bone ingrowth. However, for both alignments, this surface area was larger than the average area of ingrowth reported for well-fixed implants retrieved post-mortem. Our findings suggest that small varus deviations from mechanical alignment can adversely impact the biomechanics of the bone-implant interaction for cementless tibial baseplates during gait; however, the clinical implications of such changes remain unclear.

Network slicing is emerging as a promising solution for end-to-end resource management and orchestration together with Software Defined Networking (SDN) and Network Function Virtualization (NFV) technologies. In this paper, a comprehensive network slicing framework is presented to achieve end-to-end (E2E) QoS provisioning among customized services in 5G-driven VANETs. The proposed scheme manages the cooperation of both RAN and Core Network (CN), using SDN, NFV and Edge Computing technologies. Furthermore, a dynamic radio resource slice optimization scheme is formulated mathematically, that handles a mixture of mission-critical and best effort traffic, by delivering the QoS provisioning of Ultra-reliability and low latency. The proposed scheme adjusts the optimal bandwidth slicing and dynamically adapts to instantaneous network load conditions in a way that a targeted performance is guaranteed. The problem is solved using a Genetic Algorithm (GA) and results are compared with the previously proposed 5 G VANET architecture. Simulation reveal that the proposed slicing framework is able to optimize resources and deliver on the key performance metrics for mission critical communication.

Chronic pruritus (itch lasting ≥6 weeks) is a bothersome chief complaint that may present in a broad variety of diseases. Most itch-causing diagnoses fit into 1 of 5 categories (inflammatory, secondary to systemic disease, neuropathic, chronic pruritus of undetermined origin, and psychogenic itch) and this broad differential can be narrowed using key findings in the history and physical. In this article, we discuss which key findings are most pertinent for narrowing this differential and guiding further workup and treatment, as well as how to treat many itchy conditions.

The strategy to eliminate tuberculosis (TB) in low-incidence countries includes the investigation of the contacts of TB cases [1]. This recognises that whilst most TB disease in these settings is due to reactivation [2], local transmission also occurs [3]. In the UK, TB networks (TBN), which support and coordinate local and regional TB services, typically follow the National Institute of Health and Care Excellence guidance which recommends screening close contacts (predominantly household) but not routinely for social or non-household contacts [4]. Many studies from low TB burden countries report contact investigation for specific congregate settings including outbreaks in childcare centres [5], homeless facilities [6] and methadone treatment clinics [7]. However, the comprehensive application of contact investigation across multiple non-household locations is rarely reported. Therefore, we evaluated a systematic approach to managing people potentially exposed to TB in congregate settings., A systematic approach to nonhousehold TB contact identified a similar number of LTBI cases to household screening over the same time period https://bit.ly/2Tq96LN

While there is a vast array of aetiologies that may lead to chronic pruritus, recent data suggests that many of these conditions share similar interactions between keratinocytes, nerves, and the immune system. Specifically, the type 2 immune response, including Th2 T Cells and their related cytokines, has been noted to play a major role in the development of pruritus in a variety of itchy conditions. To date, atopic dermatitis is the most striking example of this pathogenesis. However, the body of literature supporting its role in many other itchy conditions, including other inflammatory, bullous, as well as systemic diseases, continues to grow. In addition, new treatments targeting this type 2 immune system continue to be developed and investigated. In the current review, we present the current body of literature supporting the role of the type 2 immune response in itchy conditions beyond atopic dermatitis as well as potential therapeutic options that target this pathway for chronic itch.

Despite efforts to enhance serious illness communication, patients with advanced heart failure (HF) lack prognostic understanding.To determine rate of concordance between HF patients' estimation of their prognosis and their physician's estimate of the patient's prognosis, and to compare patient characteristics associated with concordance.Cross-sectional analysis of a cluster randomized controlled trial with 24-month follow-up and analysis completed on 09/01/2020. Patients were enrolled in inpatient and outpatient settings between September 2011 to February 2016 and data collection continued until the last quarter of 2017.Six teaching hospitals in the U.S.Patients with advanced HF and implantable cardioverter defibrillators (ICDs) at high risk of death. Of 537 patients in the parent study, 407 had complete data for this analysis.A multi-component communication intervention on conversations between HF clinicians and their patients regarding ICD deactivation and advance care planning.Patient self-report of prognosis and physician response to the "surprise question" of 12-month prognosis. Patient-physician prognostic concordance (PPPC) measured in percentage agreement and kappa. Bivariate analyses of characteristics of patients with and without PPPC.Among 407 patients (mean age 62.1 years, 29.5% female, 42.4% non-white), 300 (73.7%) dyads had non-PPPC; of which 252 (84.0%) reported a prognosis1 year when their physician estimated1 year. Only 107 (26.3%) had PPPC with prognosis of ≤ 1 year (n=20 patients) or1 year (n=87 patients); (Κ = -0.20, p = 1.0). Of those with physician estimated prognosis of1 year, non-PPPC was more likely among patients with lower symptom burden- number and severity (both p ≤.001), without completed advance directive (p=.001). Among those with physician prognosis estimate1 year, no patient characteristic was associated with PPPC or non-PPPC.Non-PPPC between HF patients and their physicians is high. HF patients are more optimistic than clinicians in estimating life expectancy. These data demonstrate there are opportunities to improve the quality of prognosis disclosure between patients with advanced HF and their physicians. Interventions to improve PPPC might include serious illness communication training.

BACKGROUND: Improving adherence to anti-TB treatment is a public health priority in high-income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.METHODS: Key terms related to TB, treatment and adherence were used to search MEDLINE, EMBASE, Web of Science, PsycINFO and CINAHL in June 2019. Quantitative studies examining determinants (demographic, clinical, health systems or psychosocial) of non-adherence to anti-TB treatment in HILI settings were included.RESULTS: From 10,801 results, we identified 24 relevant studies from 10 countries. Definitions and methods of assessing adherence were highly variable, as were documented levels of non-adherence (0.9–89%). Demographic factors were assessed in all studies and clinical factors were frequently assessed (23/24). Determinants commonly associated with non-adherence were homelessness, incarceration, and alcohol or drug misuse. Health system (8/24) and psychosocial factors (6/24) were less commonly evaluated.CONCLUSION: Our review identified some key factors associated with non-adherence to anti-TB treatment in HILI settings. Modifiable determinants such as psychosocial factors are under-evidenced and should be further explored, as these may be better targeted by adherence support. There is an urgent need to standardise definitions and measurement of adherence to more accurately identify the strongest determinants.

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.

Conventional sampling for pharmacokinetic clinical studies requires removal of large blood volumes from patients. This can result in a physiological/emotional burden for children. Microsampling to support pharmacokinetic clinical studies in pediatrics may reduce this burden. Parents/guardians and bedside nurses completed a questionnaire describing their perception of the use of microsampling compared to conventional sampling to collect blood samples, based on their child's participation or their own role within a paired-sample pharmacokinetic clinical study. Responses were based on a seven-point Likert scale and were analyzed using frequency distributions. Fifty-one parents/guardians and seven bedside nurses completed a questionnaire. Parents/guardians (96%) and bedside nurses (100%) indicated that microsampling was highly acceptable and recommended as a method for collecting blood samples for pediatric patients. Responding to a question about the child indicating pain during the blood sampling procedure, 61% of parent/guardians reported no pain in their children, 14% remained neutral, and 26% reported that their child indicated pain; 71% of the bedside nurses slightly agreed that the children indicated pain. This study strongly suggests that parents/guardians and bedside nurses prefer microsampling to conventional sampling to conduct pediatric pharmacokinetic clinical studies. Employing microsampling may support increased participation by children in these studies. Pharmacokinetic clinical studies require the withdrawal of blood samples at multiple times during a dosing interval. This can result in a physiological or emotional burden, particularly for neonates or pediatric patients. Microsampling offers an important opportunity for pharmacokinetic clinical studies in vulnerable patient populations, where smaller sample volumes can be collected. However, microsampling is not commonly used in clinical studies. Understanding the perceptions of parents/guardians and bedside nurses about microsampling may ascertain if this technique offers an improvement to conventional blood sample collection to perform pharmacokinetic clinical studies for pediatric patients.

This exploratory study described the distribution of mental health service costs in youth with mental disorder and determined if costs differed for youth with comorbid internalizing and externalizing disorder compared to those with comorbid internalizing disorders. Data come from youth (8–17 years; n=75) receiving mental health services at a children’s hospital in Canada. Billing amounts specified in the Health Insurance Act of Ontario were used to estimate costs. Overall, past-year service use costs were $7436.63. Hospitalizations represented the largest cost. Youth with comorbid internalizing and externalizing disorders had higher total (β=0.81 [0.17, 1.45]), hospital (β=0.93 [0.03, 1.84]), and professional (β=0.87 [0.04, 1.69]) costs. These preliminary findings suggest that comorbidity type is associated with the costs of past-year mental health services used by youth. Research is needed to understand the reasons for elevated costs and whether the increased services used by youth with comorbid internalizing and externalizing disorders are effective.

Future Internet of Things (IoT) devices are expected to be fully ubiquitous. To achieve this vision, a new generation of IoT devices needs to be developed, which can operate autonomously. To achieve autonomy, IoT devices must be completely wireless, both in terms of transmission and power. Further, accurate sensing is another crucial parameter of autonomy. Several wireless standards have been developed for improving the efficiency of IoT applications. However, the powering of IoT devices, sensor accuracy, and efficiency of electronic devices are open research problems in literature. With the advent of metamaterial perfect absorbers (MPAs), electromagnetic waves can be used as a source of energy, to enable sensing of the phenomenon and as a carrier for exchanging data. In this article, an extensive application-based investigation has been conducted on design principles and various methods of enhancing MPA characteristics. Moreover, the current applications that benefit from MPA, such as absorption of undesired frequencies, optical switching, energy harvesting, and sensing, are investigated. Finally, some implemented examples of MPA in industrial applications are provided along with possible directions for future work and open research areas.

Augmented renal clearance (ARC, creatinine clearance > 130 mL/minute) makes difficult achievement of effective concentrations of renally cleared antibiotics in critically ill patients. This study examined the synergistic killing and resistance suppression for meropenem-ciprofloxacin combination dosage regimens against Pseudomonas aeruginosa isolates within the context of ARC. Clinically relevant meropenem and ciprofloxacin concentrations, alone and in combinations, were studied against three clinical isolates with a range of susceptibilities to each of the antibiotics. Isolate Pa1280 was susceptible to both meropenem and ciprofloxacin, Pa1284 had intermediate susceptibility to meropenem and was susceptible to ciprofloxacin, and CR380 was resistant to meropenem and had intermediate susceptibility to ciprofloxacin. Initially, isolates were studied in 72-hour static-concentration time-kill (SCTK) studies. Subsequently, the pharmacokinetic profiles expected in patients with ARC receiving dosage regimens, including at the highest approved daily doses (meropenem 6 g daily divided and administered as 0.5-hour infusions every 8 hours, or as a continuous infusion; ciprofloxacin 0.4 g as 1-hour infusions every 8 hours), were examined in a dynamic hollow-fiber infection model (HFIM) over 7-10 days. In both SCTK and HFIM, combination regimens were generally synergistic and suppressed growth of less-susceptible subpopulations, these effects being smaller for isolate CR380. The time-courses of total and less-susceptible bacterial populations in the HFIM were well-described by mechanism-based models, which enabled conduct of Monte Carlo simulations to predict likely effectiveness of approved dosage regimens at different creatinine clearances. Optimized meropenem-ciprofloxacin combination dosage regimens may be a viable consideration for P. aeruginosa infections in critically ill patients with ARC.

Background: Nosocomial pneumonia in the critical care setting is associated with increased morbidity, significant crude mortality rates and high health care costs. Ventilator-associated pneumonia represents about 80% of nosocomial pneumonia cases in intensive care units (ICUs). Wide variance in incidence of nosocomial pneumonia and diagnostic techniques used has been reported, while successful treatment remains complex and a matter of debate. Objective: To describe the epidemiology, diagnostic strategies and treatment modalities for nosocomial pneumonia in contemporary ICU settings across multiple countries around the world. Design, setting and patients: PneumoINSPIRE is a large, multinational, prospective cohort study of adult ICU patients diagnosed with nosocomial pneumonia. Participating ICUs from at least 20 countries will collect data on 10 or more consecutive ICU patients with nosocomial pneumonia. Site-specific information, including hospital policies on antibiotic therapy, will be recorded along with patient-specific data. Variables that will be explored include: aetiology and antimicrobial resistance patterns, treatment-related parameters (including time to initiation of antibiotic therapy, and empirical antibiotic choice, dose and escalation or de-escalation), pneumonia resolution, ICU and hospital mortality, and risk factors for unfavourable outcomes. The concordance of ventilator-associated pneumonia diagnosis with accepted definitions will also be assessed. Results and conclusions: PneumoINSPIRE will provide valuable information on current diagnostic and management practices relating to ICU nosocomial pneumonia, and identify research priorities in the field. Trial registration: ClinicalTrials.gov identifier NCT02793141.

Background While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock. Results We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38–65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1–3) days, the number of doses was 2 (1–2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5–43.5) h. TDM of Cmax and Cmin was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a Cmax/MIC > 8 and 353 (71%) having concentrations above Cmin recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes. Conclusion Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov

Introduction: Sepsis from bacterial infection remains a significant cause of morbidity and mortality. Antibiotic use continues to increase in the community and secondary care. This is driven by the potential benefits to the individual patient of a course of antibiotics. Far less attention is given to the potential adverse effects of antibiotic use in our view. These costs may be significant to both the individual and society.\ud \ud Areas covered: We review the evidence underpinning the costs and benefits of antibiotic use. We also discuss strategies to personalize medicine in this area that maximize the benefit to cost ratio for patients and society.\ud \ud Expert opinion: The body’s innate immune response to infection is similar to that of other inflammatory insults. Our view is as clinicians we need to differentiate these responses and hence require an accurate method to determine a diagnosis of a bacterial infection and monitor illness severity. Without this, clinicians will continue to prescribe significant volumes of unnecessary antibiotics in cases of non-bacterial inflammatory states.

Purpose of review Antibiotics are an essential treatment for septic shock. This review provides an overview of the key issues in antimicrobial therapy for septic shock. We include a summary of available evidence with an emphasis on data published in the last few years. Recent findings We examine apparently contradictory data supporting the importance of minimizing time to antimicrobial therapy in sepsis, discuss approaches to choosing appropriate antibiotics, and review the importance and challenges presented by antimicrobial dosing. Lastly, we evaluate the evolving concepts of de-escalation, and optimization of the duration of antimicrobials. Summary The topics discussed in this review provide background to key clinical decisions in antimicrobial therapy for septic shock: timing, antibiotic choice, dosage, de-escalation, and duration. Although acknowledging some controversy, antimicrobial therapy in septic shock should be delivered early, be of the adequate spectrum, appropriately and individually dosed, rationalized when possible, and of minimal effective duration.

Patients with severe trauma exhibit augmented renal clearance, which can alter the dosing requirement of renally eliminated drugs. This study aimed to develop a population pharmacokinetic model for levetiracetam in patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage, and use it to describe optimal dosing regimens. This was a prospective open-label observational study. Critically ill adult patients with severe traumatic brain injury or aneurysmal subarachnoid hemorrhage without renal dysfunction and receiving levetiracetam were eligible. Serial levetiracetam plasma concentrations were analyzed to develop a population pharmacokinetic model and perform dosing simulations. A two-compartment model best described the concentration–time data from 30 patients. The mean ± standard deviation parameter estimates were bioavailability (F) of 0.8 ± 0.2, absorption rate constant of 2.4 ± 2 h−1, clearance 2.5 ± 1.1 L/h, central volume of distribution 8.9 ± 3.0 L/h, and transfer rate constraints of 1.8 ± 1.1 h−1 from central to peripheral compartments and 0.7 ± 0.3 h−1 from peripheral to central compartments. For the simulated intermittent dosing regimens, on average, the median trough concentration reduced by 50% for every 40-mL/min/1.73 m2 increase in urinary creatinine clearance. Simulated doses of at least 6 g/day were required for some levels of augmented renal clearance. Patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage with augmented renal clearance are at risk of not achieving target levetiracetam plasma concentrations. We suggest dose titration guided by measured creatinine clearance, and/or, therapeutic drug monitoring if available, to minimize the risk of seizures.

Background Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. Methods An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid (‘intervention’) or a daily combination of rifampicin/isoniazid (‘standard’), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. Results Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7–91.4), compared with 19 of 25 (76.0%, CI 54.9–90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. Conclusion In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. Trial registration The trial was funded by the NIHR, UK and registered with ISRCTN (26/02/2013-No.04379941).

Applications and technologies of the Internet of Things are in high demand with the increase of network devices. With the development of technologies such as 5G, machine learning, edge computing, and Industry 4.0, the Internet of Things has evolved. This survey article discusses the evolution of the Internet of Things and presents the vision for Internet of Things 2.0. The Internet of Things 2.0 development is discussed across seven major fields. These fields are machine learning intelligence, mission critical communication, scalability, energy harvesting-based energy sustainability, interoperability, user friendly IoT, and security. Other than these major fields, the architectural development of the Internet of Things and major types of applications are also reviewed. Finally, this article ends with the vision and current limitations of the Internet of Things in future network environments.

Author(s): Leroux, Eric J.; Kaufman, Elizabeth A.; Kontaxis, Christian N.; Lipman, Grant S. | Abstract: Introduction: Pain control is an essential component of musculoskeletal injury treatment in the emergency department (ED). We evaluated the most effective type of cryotherapy for analgesia of acute musculoskeletal injury and the impact on opioid utilization.Methods: This was a prospective, randomized, single-blind controlled trial of adult ED patients who presented with acute musculoskeletal pain. Patients were randomized to either intensive targeted cryotherapy (crushed wetted ice in a plastic bag) or agitated chemical cold pack applied to the injury site for 20 minutes. All other diagnostic and therapeutic orders were at the discretion of the treating physician. Visual analog pain scores were measured at the time of cryotherapy application, at 20 minutes (time of cryotherapy removal), and at 60 minutes (40 minutes after removal).Results: We enrolled 38 patients, 17 randomized to intensive targeted cryotherapy and 21 to chemical cold packs, with well-matched demographics. The intensive targeted cryotherapy group achieved significantly greater pain relief at 20 minutes (2.1 [95% confidence interval (CI), 1.3 – 2.9] vs 0.9 [95% CI, 0.3 – 1.5], P l 0.05) and at 60 minutes (2.7 [95% CI, 1.6 – 3.7] vs 1.2 [95% CI, 0.6 – 1.7], P l 0.05), number need to trial (NNT) = 3.2. Opioid administration in the ED was significantly lower in the intensive targeted cryotherapy group (1 [6%] vs 7 [33%], P l 0.05), NNT = 3.6. Those who received a discharge opiate prescription had significantly higher 60-minute pain scores (7.3 ± 2.2 vs 4.1 ± 2.7, P l 0.05).Conclusion: Intensive targeted cryotherapy provided more effective analgesia than chemical cold packs for acute musculoskeletal injuries in the ED and may contribute to lower opioid usage.

The risk of tuberculosis (TB) is variable among individuals with latentMycobacterium tuberculosisinfection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0-29.2%) among child contacts, 4.8% (95% CI, 3.0-7.7%) among adult contacts, 5.0% (95% CI, 1.6-14.5%) among migrants and 4.8% (95% CI, 1.5-14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal-external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82-0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide. The risk of developing active tuberculosis (TB) in individuals with latent TB infection is highly variable within and among different risk groups. A personalized risk predictor was developed to better target preventative treatment to individuals at greatest risk, supporting evidence-based clinical decision-making for latent TB.

Background: Implantable cardioverter-defibrillators (ICDs) reduce the incidence of sudden cardiac death for high-risk patients with heart failure (HF), but shocks from these devices can also cause pain and anxiety at the end of life. Although professional society recommendations encourage proactive discussions about ICD deactivation, clinicians lack training in conducting these conversations, and they occur infrequently. Methods: As part of a six-center randomized controlled trial, we evaluated the educational component of a multicomponent intervention shown to increase conversations about ICD deactivation by clinicians who care for a subset of patients with advanced HF. This consisted of a 90-minute training workshop designed to improve the quality and frequency of conversations about ICD management. To characterize its utility as an isolated intervention, we compared HF clinicians' pre- and postworkshop scores (on a 5-point Likert scale) assessing self-reported confidence and skills in specific practices of advance care planning, ICD deactivation discussions, and empathic communication. Results: Forty intervention-group HF clinicians completed both pre- and postworkshop surveys. Preworkshop scores showed high baseline levels of confidence (4.36, standard deviation [SD] = 0.70) and skill (4.08, SD = 0.72), whereas comparisons of pre- and postworkshop scores showed nonsignificant decreases in confidence (−1.16, p = 0.252) and skill (−0.20, p = 0.843) after the training session. Conclusions: Our findings showed no significant changes in self-assessment ratings immediately after the educational intervention. However, our data did demonstrate that HF clinicians had high baseline self-perceptions of their skills in advance care planning conversations and appear to be well-primed for further professional development to improve communication in the setting of advanced HF.

Pardo-Oviedo, Juan Mauricio/0000-0003-0084-3449; Lopez-Delgado, Juan Carlos/0000-0003-3324-1129; Corradi, Francesco/0000-0002-5588-2608; De Backer, Daniel/0000-0001-9841-5762; POTA, VINCENZO/0000-0001-9999-3388; Tomescu, Dana/0000-0001-9673-5754; Sabetian, Golnar/0000-0001-8764-2150; Girardis, Massimo/0000-0002-2453-0829; Brazzi, Luca/0000-0001-7059-0622; Leone, Marc/0000-0002-3097-758X; Zabolotskikh, Igor Borisovich/0000-0002-3623-2546; De Lange, Dylan/0000-0002-0191-7270; ALMEKHLAFI, GHALEB A./0000-0002-0323-7025; Elke, Gunnar/0000-0002-4948-1605; Grigoras, Ioana/0000-0001-9412-9574; Czuczwar, Miroslaw/0000-0002-9025-6717; Nora, David/0000-0002-1133-7368; Masjedi, Mansoor/0000-0001-6175-9289; Gunst, Jan/0000-0003-2470-6393; Vidal-Cortes, Pablo/0000-0003-0225-9975; Szakmany, Tamas/0000-0003-3632-8844; Dimopoulos, George/0000-0002-3784-3103; Rello, Jordi/0000-0003-0676-6210; U nal, Necmettin/0000-0002-9440-7893; Tiberio, Iolanda FLC/0000-0002-5662-7895; Cortegiani, Andrea/0000-0003-1416-9993; Morton, Ben/0000-0002-6164-2854; Labeau, Sonia/0000-0003-3863-612X; Velickovic, Dejan/0000-0002-7312-2880; Paul, John/0000-0002-9307-3465; Pereira, Rui/0000-0002-3010-8384; Silversides, Jon/0000-0002-9562-5462; Paiva, Jose-Artur/0000-0003-4323-0220; Smuszkiewicz, Piotr/0000-0003-3067-8229; Paul, Cherish/0000-0001-6133-0036; Santos, Lurdes/0000-0002-0622-6823; PANTAZOPOULOS, IOANNIS/0000-0002-8846-519X; Ostermann, Marlies/0000-0001-9500-9080; Blot, Stijn/0000-0003-2145-0345; Naylor, Amanda/0000-0002-6431-0230; Shyamsundar, Murali/0000-0003-3797-8080; Aldecoa, Cesar/0000-0001-8789-5959; Summers, Charlotte/0000-0002-7269-2873; biskup, ewelina/0000-0002-9871-927X; Cornet, Alexander/0000-0002-9917-5251; Trenado Alvarez, Jose/0000-0002-2930-0766; Volta, Carlo/0000-0003-3533-6121; Gritsan, Alexey/0000-0002-0500-2887; Urkmez, Seval/0000-0002-3412-4226 WOS:000493268200001 PubMed ID: 31664501 PurposeTo describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).MethodsWe performed a multicenter (n=309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.ResultsThe cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.ConclusionThis multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. Pfizer investigator-initiated research grant AbSeS is a Trials Group Study of the European Society of Intensive Care Medicine. The study was supported by a Pfizer investigator-initiated research grant.

Objectives: Vancomycin is a commonly prescribed antibiotic in the intensive care unit (ICU). However, there is limited data describing its distribution into the interstitial space fluid (ISF) of tissues. The aim of this study was to describe the plasma and tissue ISF population pharmacokinetics of vancomycin in critically ill patients with sepsis. Methods: Serial vancomycin blood and ISF samples were collected at pre-specified time intervals in critically ill patients with sepsis. ISF sampling occurred using a subcutaneously inserted microdialysis catheter. Bioanalysis was undertaken using a validated spectrometric assay method. Population pharmacokinetic analysis was performed using Pmetrics® Results: Seven patients were recruited and pharmacokinetic data was available for six. The median (IQR) age, weight, Acute Physiological and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score and measured creatinine clearance (CrCL) were 55 (44-67) years, 85 (81-102) kg, 20 (16-29), 5 (4-8), and 90 (83-98) mL/min respectively. Vancomycin pharmacokinetics were best described by a three-compartment linear model. Measured CrCL (on vancomycin clearance) and weight (on volume of distribution of the central compartment, Vc) were the only patient covariates that improved the model fit. The coefficients of variation for the vancomycin rate constants into and out of the peripheral and tissue ISF compartments were also high, ranging from 47% to 134%. Conclusions: There is significant variability of vancomycin distribution into tissue ISF which we were not able to explain with patient characteristics. Refereed/Peer-reviewed

Non-designated preliminary (NDP) general surgery residents face the daunting challenge of obtaining a categorical residency position while undertaking the rigors of a general surgery residency. This additional application cycle represents a stressful time for these trainees and limited data exists to help guide applicants and program directors regarding the factors predictive of application success. While previous studies have focused solely on applicant related factors, no study to date has evaluated the effect of the residency program structure, institutional resources, or administrative support on these outcomes.A multicenter retrospective review of 10 general surgery residency programs over a 5-year period from 2014 to 2019 was performed. Applicant related information was compiled from NDP general surgery residents and the results of their attempted second application into a categorical position. Applicant factors including age, gender, standardized test scores (USMLE/ABSITE), and professional training were examined. Program and administrative structure including residency class size, number of NDP PGY-2 positions, number of assistant program directors and program director (PD) background were also examined. Primary success was defined as a NDP resident successfully obtaining a categorical position within general surgery or a surgical subspecialty. Secondary success was obtaining a categorical residency position in any field of medical practice other than surgery or a surgical subspecialty in the United States.A total of 260 NDP trainees were evaluated with an average age of 29.1. Almost seventy percent of applicants were male, 40% graduated from a non-U.S. medical school and 24.2% required a visa to work in the United States. Thirty 4 percent of NDPs successfully obtained a categorical surgery position and an additional 35% obtained a categorical residency position in a nonsurgical field for an overall match success rate of 68.9%. Factors associated with primary success included ABSITE score (p 0.001), US medical school graduation (p = 0.02), visa status (p = 0.03), presence of preliminary PGY-2 positions (p = 0.02), and PD professional development time (p = 0.004). Overall success was associated USMLE Step 1 scores (p = 0.02), number of approved chiefs (p = 0.03), presence of dedicated faculty researchers (p = 0.001), and PD professional development time (p 0.001).Applicant, program-related, and administrative factors all have a significant impact on the success of NDP general surgery residents in obtaining a categorical surgical position. Trainees should consider all of these factors when applying to NDP residencies and in approaching their second application cycle to maximize their likelihood of a successful match.

BackgroundNeighborhood poverty may increase childhood obesity risk. However, evidence for the neighborhood poverty-obesity relationship is limited. The purpose of this study was to examine how moving to a higher or lower poverty neighborhood impacts body mass index (BMI) z-score trajectories among youth, with the goal of informing policy change, interventions, and clinical practices to reduce childhood obesity.MethodsMethods entailed secondary analysis of existing longitudinal data. The sample included youth attending New York City public schools in grades kindergarten through twelfth from school years 2006/2007 through 2016/2017. Eligibility criteria included moving to a higher or lower poverty neighborhood during the data midpoint [school years 2010/2011 through 2013/2014] of the 12-year data-period; New York City-specific metrics were used to define both neighborhood (Neighborhood Tabulation Area) and relevant neighborhood poverty levels (ResultsOf 532,513 youth with home address data, 18,370 youth moved to a higher poverty neighborhood and 19,174 moved to a lower poverty neighborhood (n = 37,544). Females and males who moved to a higher poverty neighborhood experienced less favorable BMI z-score trajectories for obesity risk, though effects were small. Exploratory subgroup analyses demonstrated that negative effects of neighborhood poverty were most pronounced among young and adolescent females and young males, whereas effects were mixed for other subgroups.ConclusionsYouth who moved to higher poverty neighborhoods experienced less favorable BMI z-score trajectories for obesity risk, though effects were small and most consistent for females and younger youth. Additional research is needed to illuminate neighborhood poverty’s impact on obesity, in order to inform policy, intervention, clinical, and research efforts to reduce obesity and improve child well-being.

OBJECTIVE The aim of this study was to assess racial disparities in treatments and outcomes between Non-Hispanic black (NHB), Hispanic and Non-Hispanic white (NHW) children with type 1 diabetes (T1D). METHODS We reviewed electronic health records of children (

Summarization: Reliable, non-intrusive, short-term (of up to 12 h ahead) prediction of a building's energy demand is a critical component of intelligent energy management applications. A number of such approaches have been proposed over time, utilizing various statistical and, more recently, machine learning techniques, such as decision trees, neural networks and support vector machines. Importantly, all of these works barely outperform simple seasonal auto-regressive integrated moving average models, while their complexity is significantly higher. In this work, we propose a novel low-complexity non-intrusive approach that improves the predictive accuracy of the state-of-the-art by up to ∼10%. The backbone of our approach is a K-nearest neighbours search method, that exploits the demand pattern of the most similar historical days, and incorporates appropriate time-series pre-processing and easing. In the context of this work, we evaluate our approach against state-of-the-art methods and provide insights on their performance. Presented on: Advances in Building Energy Research

Purpose Deep phenotyping is an emerging trend in precision medicine for genetic disease. The shape of the face is affected in 30–40% of known genetic syndromes. Here, we determine whether syndromes can be diagnosed from 3D images of human faces. Methods We analyzed variation in three-dimensional (3D) facial images of 7057 subjects: 3327 with 396 different syndromes, 727 of their relatives, and 3003 unrelated, unaffected subjects. We developed and tested machine learning and parametric approaches to automated syndrome diagnosis using 3D facial images. Results Unrelated, unaffected subjects were correctly classified with 96% accuracy. Considering both syndromic and unrelated, unaffected subjects together, balanced accuracy was 73% and mean sensitivity 49%. Excluding unrelated, unaffected subjects substantially improved both balanced accuracy (78.1%) and sensitivity (56.9%) of syndrome diagnosis. The best predictors of classification accuracy were phenotypic severity and facial distinctiveness of syndromes. Surprisingly, unaffected relatives of syndromic subjects were frequently classified as syndromic, often to the syndrome of their affected relative. Conclusion Deep phenotyping by quantitative 3D facial imaging has considerable potential to facilitate syndrome diagnosis. Furthermore, 3D facial imaging of “unaffected” relatives may identify unrecognized cases or may reveal novel examples of semidominant inheritance.

Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy.The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens.Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation.Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.