A prospective observational study

Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T>MIC, 50%T>4×MIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non- attainment. Results: Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T>MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T>4×MIC. A hyperbolic relationship between CLCRCG (25–255 ml/ minute) and meropenem serum concentrations at the end of the dosing interval (C8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non- attainment (for MIC 8 mg/L, additionally, moderate renal impairment). Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed

Unilateral Hearing Loss Caused by Bilateral Otosclerosis in the Context of Prior Viral Infection - Case Report

This is a case report of a patient who presented with left sided hearing loss. The patient was found to have mixed conductive and sensorineural hearing loss of the left ear and restrictive hearing of the right ear. Subsequent imaging demonstrated evidence of bilateral otosclerosis. Otosclerosis is characterized by progressive pathological bone remodeling in the otic capsule, resulting in hearing loss. Given the disease burden of otosclerosis and the corresponding effects on quality of life, providers must have knowledge of the disease to incorporate it into working differential diagnoses for patients presenting with hearing loss. With increasing recognition of otosclerosis cases, there is greater hope for patients to explore and obtain treatment for the disease. Surgical treatment of otosclerosis can consist of surgical exploration of the middle ear with possible stapedectomy or stapedotomy, which have shown promising results. Alternatively, patients who are poor surgical candidates or who do not wish to pursue surgery, can pursue hearing aids for symptomatic management of their hearing loss

Quality assurance guidelines for superficial hyperthermia clinical trials: II. Technical requirements for heating devices

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle

The Karlsruhe temperature time series since 1779

This paper presents the long-term Karlsruhe temperature series re-digitized and reconstructed from handwritten manuscripts from 1779 to 1875 archived in various libraries. Despite great efforts, data from some periods remained missing in the manuscript departments so that the main Karlsruhe series remained partially fragmented. Combined with historic climate records available in the archive of German Weather Service (DWD), the entire series until 2008, when the official Karlsruhe station was relocated to Rheinstetten, is one of the longest climate series available for Germany. The series includes various observational parameters on a daily or even sub-daily basis converted into SI units or contemporary units. The focus of this paper is on the temperature series and presents some first statistical analyses to demonstrate the additional benefit of possessing unique long-term instrumental climate data on a sub-daily basis. The entire temperature series was homogenized with respect to consistent observation times and to an urban boundary site. It is shown that the width of the distribution function quantified from constructed daily maximum and minimum temperature has substantially broadened in the summer months, but not during winter or the entire year. The number of summer and hot days has substantially increased in the last 30–50 years, while the number of frost and ice days has decreased. Summer or hot days as well as heat waves were very rare before 1920, being unrepresentative of a period mainly unaffected by climate change. Singularities of the climate system, such as the (cold) Schafskälte in June or the (warm) Hundstage in July/August, are clearly shown in most periods. The (cold) Ice Saints in May, however, have a high frequency only in the coldest period between 1870 and 1960; they are hardly detectable in most of the preceding years. Temperature statistics show that the severity of late spring frosts has gradually increased during the entire record mainly as a result of later frost occurrences

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives.

Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4-18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water which yielded estimates in excess of 3 days. To investigate this disparity we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n=4) and deuterium-labeled glucose (n=9), a compound with more rapid labeling kinetics. To interpret results we developed a novel mechanistic model. We applied this model to both previously-published (n=5) and newly-generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (R=0.26, from published values). Analysis of heavy water datasets yielded turnover rates consistent with a short blood half-life, but parameters, particularly marrow transit-time, were poorly-defined. Analysis of glucose-labeling data yielded more precise estimates of half-life, 0.79 ± 0.25 days (19 hours), and marrow transit-time, 5.80 ± 0.42 days. Substitution of this marrow transit-time in the heavy water analysis gave a better-defined blood half-life, 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing R to vary yielded a best-fit value, R=0.19. Reanalysis of the previously-published model and data also revealed the origin of their long estimates for neutrophil half-life, an implicit assumption that R is very large, which is physiologically untenable. We conclude that stable isotope labeling in healthy humans is consistent with a blood neutrophil half-life of less than one day

Evaluating the ergonomics of cardiac arrest: Quantitative

An estimated 300,000 patients suffer out-of-hospital cardiac arrest annually; around 8% o these patients survive. For these patients, there is mounting data that demonstrates high-quality cardiopulmonary resuscitation(CPR) increases the likelihood of return of spontaneous circulation and neurologically intact survival [1-4]. Despite the importance of high quality CPR, performance of CPR is inconsistent as the delivery requires coordinated teams and a built space to support quality care [5]. In 2015-16, we implemented an iterative, multidisciplinary simulation-based approach to determine the optimal physical layout of the ED resuscitation rooms to improve the resuscitation team\u27s ability to: 1) obtain continuous, real-time feedback on the quality of delivered CPR; 2) quickly identify cardiac rhythm on pulse checks; and 3) identify the team leader. After consensus via survey, we evaluated CPR quality during cardiac resuscitation and determined the influence of the physical layout on CPR quality

Longitudinal cosmetic outcome after planned IORT boost with low kV X-rays: monocentric results from the TARGIT BQR registry

Background: Intraoperative radiotherapy can serve as an anticipated boost (IORT boost) in combination with a subsequent external whole breast irradiation in high-risk breast cancer patients and is part of many guidelines. Nevertheless, there are only few prospective data available regarding cosmetic outcome after IORT boost using kV X-rays. The aim of this study was to evaluate the cosmetic outcome of patients treated within the prospective phase IV TARGeted Intraoperative radioTherapy (TARGIT) Boost Quality Registry (BQR) study (NCT01440010) in one center.Methods: In the context of the TARGIT BQR study standardized photos in three positions (arms down, arms up, from the side) were available for different time points. For this analysis a layperson, a radiation oncologist and a gynecologist evaluated available photos at different time points during follow-up with up to 4 years using the Harvard scale (comparison of treated and the untreated breast; rating: excellent, good, fair, poor). Longitudinal results were compared to preoperative results (baseline).Results: Seventy-three patients were available for the analysis. Baseline cosmetic assessment was excellent/good in 98.8% (mean value for all three positions). Postoperative cosmetic outcome (median) was good for all positions and remained constant for 4 years. Around 30% of the patients showed a constant or even improved cosmetic outcome compared to baseline. Only few patients showed a poor result at 4 years. The majority of patients showed an excellent or good cosmetic outcome at all time points.Conclusions: Patients from the prospective TARGIT BQR study treated with IORT boost and additional whole breast irradiation showed good or excellent cosmetic outcomes in most cases during 4 years of follow-up. These results add important information for shared decision making in breast cancer patients

Evaluating the ergonomics of cardiac arrest care

Purpose: To identify the ideal physical setup that maximizes vital equipment visibility for the resuscitation team to allow rapid assessment of cardiac rhythms during pulse checks, real-time feedback on CPR quality, and better identification of the team leader. Design: Quality Improvement (QI) project. Setting: Adult Emergency Department in an urban, academic, level I trauma and tertiary referral center treating over 70,000 patients per year. Participants/Subjects: Key stakeholders involved in cardiac arrest care were identified and invited to participate in a simulation exercise during the 2014-15 and 2015-16 academic year. Participants in these simulation evaluations were Johns Hopkins Adult Emergency Department and ancillary staff including, but not limited to: Attending physicians, resident physicians, registered nurses, clinical technicians, support associates, pharmacy, human factors engineers, and health science informaticians. Methods: A simulated cardiac arrest case, utilizing a medium-fidelity mannequin, was performed with participants playing usual resuscitation team roles in various ergonomic layouts utilizing an iterative approach to improve the 2015-16 academic year design. A multidisciplinary quality improvement team created a new design proposal based on feedback and results from the prior year\u27s simulation sessions and this layout (attached) was evaluated. Qualitative feedback was collected via immediate post-simulation surveys to assess: Zoll cardiac resuscitation device visibility, team leader identification, other team member identification, communication, and equipment access. CPR quality was measured and recorded during the simulation. Results/Outcomes: Data from survey results identified significant improvement. Zoll visibility, 4.7-5 on a 5-point scale, improved 62% from the standard layout (2.9-5). The team leader rated 5 from all participants and communication increased to 4.7 compared to 4.5 rating in standard layout. Implications: There is limited published literature addressing the impact of ergonomics on CPR quality during Emergency Department resuscitations. We used an iterative, multi-disciplinary, simulation-based approach to generate an optimal physical layout that would improve the resuscitation team\u27s ability to 1) obtain continuous, real-time feedback on the quality of delivered CPR; 2) quickly identify cardiac rhythm on pulse checks; and 3) identify the team leader. We quantified the impact of these layout changes using team surveys. The next steps are to measure how performance standards, as defined by the American Heart Association, are affected by the change in CPR ergonomics

Consensus care recommendations for alfapump® in cirrhotic patients with refractory or recurrent ascites.

BACKGROUND The alfapump® is an implantable class III medical device that pumps ascitic fluid from the peritoneal space to the urinary bladder from where it is excreted. The pump reduces or abrogates the need for repeated paracentesis in patients with recurrent or refractory ascites. AIMS To improve outcomes for alfapump® implantation and pre- and post-implant patient management in both clinical trial and real-world settings by development of consensus recommendations. METHODS The alfapump® working group consisting of hepatologists and surgeons with extensive experience in implantation of the alfapump® and patient management met on two occasions: (1) to determine the key areas where recommendations should be made; and (2) to discuss the experiences of the working group within those areas and formulate draft statements. Developed statements were submitted to the group and consensus sought on relevance and wording through a collaborative iterative approach in order to consolidate the recommendations into consensus statements. Only recommendations agreed upon unanimously were included. RESULTS Twenty-three consensus recommendations were developed in the areas of pre-implantation procedure, (three statements), surgical implant procedure (11 statements), immediate post-implant care (three statements) and long-term management (six statements). CONCLUSIONS The consensus statements are a valuable reference resource for physicians managing patients with the alfapump® and for those considering management strategies for patients with refractory ascites