The Need for Responsive Workforce Development During the Pandemic and Beyond: A Case Study of the Regional Public Health Training Centers.

CONTEXT: The COVID-19 pandemic underscored the importance of a strong public health infrastructure for protecting and supporting the health of communities. This includes ensuring an adaptive workforce capable of leading through rapidly changing circumstances, communicating effectively, and applying systems thinking to leverage cross-sector partnerships that help promote health equity. The 10 Regional Public Health Training Centers (PHTCs) advance the capacity of the current and future public health workforce through skill development and technical assistance in these and other strategic areas. PROGRAM: This study examines activities through which the Regional PHTCs and their partners supported the public health workforce during the pandemic. Representatives of the 10 Regional PHTCs completed a survey in the spring of 2022. The survey included (1) pulling trends in training usage from 2018-2021 annual performance reports and (2) questions assessing the type, content, and reach of training needs assessments, training and technical assistance, student placements, and PHTC Network collaborative activities that occurred from January 1, 2020, to December 31, 2021. Respondents also reflected on trends in use, challenges, lessons learned, stories of impact, and future PHTC practice. EVALUATION: During the pandemic, the Regional PHTCs engaged in numerous efforts to assess needs, provide training and technical assistance to the practice community, facilitate projects that built student competency to support public health agency efforts, and collaborate as the PHTC Network on national-level initiatives. Across these activities, the Regional PHTCs adjusted their approaches and learned from each other in order to meet regional needs. DISCUSSION: The Regional PHTCs provided student and professional development in foundational public health knowledge and skills within their regions and nationally while being flexible and responsive to the changing needs of the field during the pandemic. Our study highlights opportunities for collaboration and adaptive approaches to public health workforce development in a postpandemic environment.

Public Health Training Centers' Support for Community Health Workers: Case Studies of Needs Assessment, Training, and Student Field Placement Initiatives.

CONTEXT: Community health workers (CHWs) are vital frontline public health workers. Given their trusted roles and connection to and understanding of the communities they serve, CHWs are able to link underserved communities to resources and public health agencies. With CHWs' increased prominence in the public health workforce, calls have been made for expanding and supporting CHW training and career development opportunities. PROGRAM: Public health training centers (PHTCs) are mandated to assess public health workforce needs, provide evidence-based professional development trainings, and increase students' aptitude for working with underserved and underresourced communities through applied practice experiences. Public health training centers can support CHWs in each of these areas. DESIGN: Case studies from 3 PHTCs are provided to exemplify how PHTCs are well positioned to support the critical CHW workforce via assessment, training, and student field placements. IMPLEMENTATION: A regional needs assessment survey with a designated section for CHWs, the provision of accessible and relevant CHW training, and CHW-focused student field placements were implemented in PHTC Regions 6/South Central, 1/New England, and 5/Great Lakes, respectively. EVALUATION: The Region 6 needs assessment found that CHWs in Oklahoma had multiple core roles and training interests. A crosswalk of needs and available training in the region guided the creation of tailored CHW trainings. Across 35 CHW-targeted trainings in Region 1, 88.5% of trainees were satisfied with the trainings and identified actions they could take to apply information they learned to their work. Significant improvements ( P < .001) in knowledge occurred across the 13 trainings that had pre-/posttests. In Region 5, students engaged with CHW-based organizations in Wisconsin to inform statewide CHW priority action items and deliverables and found the field placements meaningful for their academic experience. DISCUSSION: Public health training centers' strengths in workforce development can complement and extend existing efforts to support the CHW workforce.

Guidelines for Treatment of Umbilical and Epigastric Hernias From the European and Americas Hernia Societies-A Web-Based Survey on Surgeons' Opinion.

Background and aims: The European and Americas Hernia Society's (EHS and AHS) Guidelines on the treatment of primary midline ventral hernias were launched to guide surgeons. As a part of a dissemination plan of the guideline, this study aimed to evaluate the level of consensus between recommendations and the current surgical practices of EHS and AHS members before implementation. Material and methods: A questionnaire was constructed including questions on the current practice of the members and nine selected key recommendations from the guidelines. An on-stage consensus voting was performed at the EHS Congress in Hamburg 2019 followed by a SurveyMonkey sent to all EHS and AHS members. Consensus with a recommendation was defined as an agreement of ≥70%. Results: A total of 178 votes were collected in Hamburg. A further 499/1,754 (28.4%) of EHS and 150/1,100 (13.6%) of AHS members participated in the SurveyMonkey. A consensus was reached for 7/9 (78%) of the recommendations. The two recommendations that did not reach consensus were on indication and the technique used for laparoscopic repair. In current practice, more AHS participants used a preformed patch; 50.7% (76/150) compared with EHS participants 32.1% (160/499), p < 0.001. Conclusion: A consensus was achieved for most recommendations given by the new guideline for the treatment of umbilical and epigastric hernias. Recommendations that did not reach consensus were on indication and technique for laparoscopic repair, which may reflect the lack of evidence on these topics.

Dosage Individualization of Linezolid: Precision Dosing of Linezolid To Optimize Efficacy and Minimize Toxicity.

The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing. A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients (65.4% male, 65.5 [±14.6] years) who underwent routine therapeutic drug monitoring for linezolid. Linezolid concentrations were analyzed by using high-performance liquid chromatography. Population pharmacokinetic modeling was performed using a nonparametric methodology with Pmetrics, and Monte Carlo simulations were employed to calculate the 100% time >MIC after the administration of a fixed regimen of 600 mg administered every 12 h (q12h) intravenously (i.v.). The dose of linezolid needed to achieve a PTA ≥ 90% for all susceptible isolates classified according to EUCAST was estimated to be as high as 2,400 mg q12h, which is 4 times higher than the maximum licensed linezolid dose. The final PK model was then used to construct software for dosage individualization, and the performance of the software was assessed using 10 new patients not used to construct the original population PK model. A three-compartment model with an absorptive compartment with zero-order i.v. input and first-order clearance from the central compartment best described the data. The dose optimization software tracked patients with a high degree of accuracy. The software may be a clinically useful tool to adjust linezolid dosages in real time to achieve prespecified drug exposure targets. A further prospective study is needed to examine the potential clinical utility of individualized therapy.

Comparing the outcomes of external oblique and transversus abdominus release using the AHSQC database.

PURPOSE: Myofascial release techniques at the time of complex hernia repair allow for tension-free closure of the midline fascia. Two common techniques are the open external oblique release (EOR) and the transversus abdominis release (TAR). Each technique has its reported advantages and disadvantages, but there have been few comparative studies. The purpose of this project was to compare the outcomes of these two myofascial release techniques. METHODS: The Americas Hernia Society Quality Collaborative (AHSQC) database was queried and produced a data set on 24 May 2018. All patients undergoing open incision hernia repair with an open EOR or TAR were evaluated, and outcomes were compared including hernia recurrence, quality of life, and 30-day wound-related complications. RESULTS: 3610 patients met the inclusion criteria of undergoing open incisional hernia repair (501 undergoing EOR and 3109 undergoing TAR). Seventy surgeons from 50 institutions contributed EOR patients, and 124 surgeons from 89 institutions contributed TAR patients with no differences between the two groups in surgeons' affiliation. Comparing open EOR and TAR showed no significant differences in hernia recurrence, quality of life, or 30-day surgical site infection rate. EOR had a significantly higher rate of surgical site occurrences compared with TAR (p < 0.05); however, this did not result in an increase in surgical site occurrences requiring procedural interventions. CONCLUSIONS: Equivalent outcomes were achieved using the EOR or TAR techniques in the open repair of incisional hernias. Both techniques offer consistently good outcomes and are important adjuncts in the repair of complex incisional hernias.

Evolving concepts in ventral hernia repair and physical therapy: prehabilitation, rehabilitation, and analogies to tendon reconstruction.

PURPOSE: The abdominal wall and musculoskeletal tendons share many anatomic, physiologic, and functional characteristics. This review aims to highlight these similar characteristics and to present a rationale why the treatment principles of successful musculoskeletal tendon reconstruction, including principles of surgical technique and physical therapy, can be used in the treatment of complex abdominal wall reconstruction or ventral hernia repair. METHODS: The MEDLINE/PubMed database was used to identify published literature relevant to the purpose of this review. CONCLUSIONS: There are several anatomical and functional similarities between the linea alba and musculoskeletal tendons. Because of this reason, many of the surgical principles for musculoskeletal tendon repair and ventral hernia repair overlap. Distribution of tension is the main driving principle for both procedures. Suture material and configuration are chosen to maximize tension distribution among the tissue edges, as seen in the standard of care multistrand repairs for musculoskeletal tendons, as well as in the small bites for laparotomy technique described in the STITCH trial. Physical therapy is also one of the mainstays of tendon repair, but surprisingly, is not routine in ventral hernia repair. The evidence surrounding physical therapy prehabilitation and rehabilitation protocols in other disciplines is significant. This review challenges the fact that these protocols are not routinely implemented for ventral hernia repair, and presents the rationale and feasibility for the routine practice of physical therapy in ventral hernia repair.

Hemipelvectomy hernia: case series and literature review.

PURPOSE: Hemipelvectomy is a major operation in which significant portions of the pelvic girdle and lower extremity are resected. The development of hernia following hemipelvectomy is a complex surgical challenge with limited published guidelines for management. We present our experience with three cases of hernia repair following internal hemipelvectomy and review the previously described ten cases of similar patients. METHODS: A systematic review of the current literature regarding hernias in the setting of hemipelvectomy was performed. A comprehensive search strategy on MEDLINE/PUBMED database searching for the key words of hemipelvectomy and hernia was used. RESULTS: There were 13 reported cases of incisional hernia after hemipelvectomy. The indication for hemipelvectomy was sarcoma in 77% of cases. The median time to presentation for hernia repair was 3 years following initial resection. Mesh repair was used in 77%. Identified risk factors for the development of incisional hernia included chemoradiation, wound infection, multiple operations, and weight gain. There was one event of hernia recurrence with a mean follow-up of 16 months. CONCLUSION: Hernia in the setting of hemipelvectomy is an infrequently reported problem. General principles in management are similar to all hernia repairs and include local approximation of tissues, avoidance of contamination or wound infection, and use of prosthetic mesh when local tissue is inadequate for a tension-free repair.

EHS and AHS guidelines for treatment of primary ventral hernias in rare locations or special circumstances.

BACKGROUND: Rare locations of hernias, as well as primary ventral hernias under certain circumstances (cirrhosis, dialysis, rectus diastasis, subsequent pregnancy), might be technically challenging. The aim was to identify situations where the treatment strategy might deviate from routine management. METHODS: The guideline group consisted of surgeons from the European and Americas Hernia Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in formulating the recommendations. The Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists were used to evaluate the quality of full-text papers. A systematic literature search was performed on 1 May 2018 and updated 1 February 2019. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was followed. RESULTS: Literature was limited in quantity and quality. A majority of the recommendations were graded as weak, based on low quality of evidence. In patients with cirrhosis or on dialysis, a preperitoneal mesh repair is suggested. Subsequent pregnancy is a risk factor for recurrence. Repair should be postponed until after the last pregnancy. For patients with a concomitant rectus diastasis or those with a Spigelian or lumbar hernia, no recommendation could be made for treatment strategy owing to lack of evidence. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias in patients with special conditions, including Spigelian and lumbar hernias. All recommendations were weak owing to a lack of evidence. Further studies are needed on patients with rectus diastasis, Spigelian and lumbar hernias.

ANTECEDENTES: Las hernias de localización rara, así como las hernias ventrales primarias en determinadas circunstancias (cirrosis, diálisis, diástasis de recto, tras un embarazo) pueden ser complejas desde el punto de vista técnico. El objetivo fue identificar situaciones en las que la estrategia de tratamiento pudiera ser diferente del tratamiento habitual. MÉTODOS: Esta guía fue elaborada por cirujanos de las sociedades europeas y americana de hernia (European Hernia Society, EHS y American Hernia Society, AHS). La búsqueda sistemática de la literatura se efectuó el 1 de mayo de 2018 y se actualizó el 1 de febrero de 2019. Para evaluar la calidad de los artículos completos seleccionados se utilizó la normativa SIGN (Scottish Intercollegiate Guidelines Network). Las recomendaciones formuladas siguieron la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) y la redacción de la guía siguió las normas AGREE (Appraisal of Guidelines for Research & Evaluation). RESULTADOS: La literatura es limitada en cantidad y calidad. La mayoría de las recomendaciones se calificaron como débiles en función de la baja calidad de la evidencia. En pacientes con cirrosis o en diálisis, se sugiere una reparación con malla preperitoneal. Un embarazo tras la reparación de una hernia es un factor de riesgo de recidiva. La reparación debería posponerse hasta después del último embarazo. Debido a la falta de evidencia no se pudo hacer ninguna recomendación para la reparación de hernias en pacientes con diástasis de recto concomitante o con hernias de Spigel o lumbares. CONCLUSIÓN: Esta es la primera guía europea y americana del tratamiento de hernias umbilicales y epigástricas en pacientes con patologías especiales, incluyendo las hernias de Spigel y lumbares. Todas las recomendaciones fueron débiles debido a la falta de evidencia. Se necesitan más estudios en pacientes con diástasis de recto, hernias de Spigel y lumbares.

How to design a study to evaluate therapeutic drug monitoring in infectious diseases?

BACKGROUND: Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. OBJECTIVES: We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. SOURCES: The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. CONTENT: This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. IMPLICATIONS: This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies.

Guidelines for treatment of umbilical and epigastric hernias from the European Hernia Society and Americas Hernia Society.

BACKGROUND: Umbilical and epigastric hernia repairs are frequently performed surgical procedures with an expected low complication rate. Nevertheless, the optimal method of repair with best short- and long-term outcomes remains debatable. The aim was to develop guidelines for the treatment of umbilical and epigastric hernias. METHODS: The guideline group consisted of surgeons from Europe and North America including members from the European Hernia Society and the Americas Hernia Society. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done on 1 May 2018, and updated on 1 February 2019. RESULTS: Literature reporting specifically on umbilical and epigastric hernias was limited in quantity and quality, resulting in a majority of the recommendations being graded as weak, based on low-quality evidence. The main recommendation was to use mesh for repair of umbilical and epigastric hernias to reduce the recurrence rate. Most umbilical and epigastric hernias may be repaired by an open approach with a preperitoneal flat mesh. A laparoscopic approach may be considered if the hernia defect is large, or if the patient has an increased risk of wound morbidity. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias. It is recommended that symptomatic umbilical and epigastric hernias are repaired by an open approach with a preperitoneal flat mesh.

ANTECEDENTES: La reparación de las hernias umbilicales y epigástricas es un procedimiento quirúrgico frecuente con una tasa esperada de complicaciones baja. Sin embargo, sigue en discusión cuál es el mejor método de reparación óptimo para obtener los mejores resultados a corto y a largo plazo. El objetivo del estudio fue desarrollar una guía para el tratamiento de las hernias umbilicales y epigástricas. MÉTODOS: El grupo para la elaboración de la guía estuvo formado por cirujanos europeos y norteamericanos junto con miembros de la European Hernia Society (EHS) y de la America's Hernia Society (AHS). Para elaborar la guía, se siguieron las recomendaciones GRADE (Grading of Recommendations Assessment, Development and Evaluation), SIGN (Scottish Intercollegiate Guidelines Network) y AGREE (Appraisal of Guidelines for Research & Evaluation). Se realizó una búsqueda sistemática de la literatura el 1 de mayo de 2018, que luego se actualizó el 1 de febrero de 2019. RESULTADOS: Los trabajos dedicados de forma específica a las hernias umbilicales y epigástricas eran muy limitados en cantidad y calidad, por lo que la mayoría de las recomendaciones que se extrajeron fueron calificadas como débiles y basadas en una baja calidad de la evidencia. La recomendación principal era utilizar una malla en la reparación de las hernias umbilicales y epigástricas para reducir la tasa de recidiva. La mayoría de las hernias umbilicales y epigástricas pueden repararse mediante un abordaje abierto con una malla plana preperitoneal. Se puede considerar el abordaje laparoscópico si el defecto de la hernia es grande o si el paciente tiene un riesgo aumentado de morbilidad de la herida. CONCLUSIÓN: Esta es la primera guía europea y americana del tratamiento de las hernias umbilicales y epigástricas. Se sugiere reparar las hernias sintomáticas umbilicales y epigástricas mediante un abordaje abierto con una malla plana preperitoneal.

Primary non-complicated midline ventral hernia: overview of approaches and controversies.

Umbilical hernias and epigastric hernias are some of the most common hernias in the world. Umbilical and epigastric hernia defects can range from small (<1 cm) to very large/complex hernias, and treatment options should be tailored to the clinical situation. Repair techniques include open, laparoscopic, and robotics options, each with advantages and disadvantages. A mesh-based repair is indicated in most cases due to having fewer associated recurrences. Overall outcomes are favorable following umbilical and epigastric hernia repairs; however, some patients have chronic complaints mostly related to recurrences. This report is an overview of available techniques for repair of umbilical and epigastric hernias. It also discusses ongoing controversies related to umbilical and epigastric hernia repairs, the limitations of available literature, and the need for future research.

Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

Hernia prevention: practice patterns and surgeons' attitudes about abdominal wall closure and the use of prophylactic mesh.

PURPOSE: The penetration of hernia prevention techniques into surgical practice remains unknown. METHODS: A survey about knowledge/attitudes on hernia prevention was sent to the members of hernia societies. RESULTS: The 497 respondents were mostly from the US (47%) or Europe (40%). Most reported practicing, but not measuring their suture-to-wound length closure of > 4:1 (63%) and practicing but not measuring the number of stitches (58%). Reasons for not using short stitch closure were: does not apply to patient population (19%), not familiar enough with methods to correctly execute (25%), takes too long (13%), not reimbursed (4%), concerned about closure-related complications (27%), and other (22%). Regarding prophylactic mesh, respondents stated they were not familiar with literature (11%), familiar with literature but would not use (24%), familiar with literature and interested in use (45%), familiar with literature and using (15%), and other (5%). CONCLUSIONS: There appears to be some application of hernia prevention principles related to fascial closure; however, the use of prophylactic mesh still appears to be controversial.

Prophylactic mesh used in ileal conduit formation following radical cystectomy: a retrospective cohort.

PURPOSE: Given the difficulty of durable repairs, there is continued interest in hernia prevention. One emerging prevention technique for parastomal hernias is prophylactic mesh placement, whereby mesh is inserted during the index procedure as hernia prophylaxis. We evaluated our experience using prophylactic mesh when creating an ileal conduit. METHODS: We retrospectively reviewed patients undergoing robotic cystectomy with ileal conduit from 6/2010 to 8/2017. Patient demographics and operative/perioperative outcomes were documented. We evaluated hernia recurrence using postoperative computed tomography scanning or physical exam. Prophylactic mesh was inserted at the operating surgeon's discretion using a synthetic resorbable or biologic mesh. RESULTS: During the study period, 38 patients underwent robotic-assisted cystectomy with ileal conduit formation. Average patient age was 68 years, with 28 (74%) male and 35 (92%) Caucasian patients. Three patients (8%) required conversion to open, and one patient (3%) had a concomitant colorectal resection. Thirty-one (88%) patients had postoperative computed tomography scanning. Prophylactic mesh was used in 18 patients (47%) in a retrorectus position. Of these, 15 (83%) patients had synthetic resorbable mesh and 3 (17%) patients had biologic mesh. At average follow-up of 21 months, one hernia recurred (5%) in a patient without mesh placement at the time of ileal conduit. At an average follow-up of 11 months, there have been no recurrences and no mesh-related complications in the prophylactic mesh group. CONCLUSIONS: Using prophylactic mesh in ileal conduit, creation is feasible and may decrease the parastomal hernia formation rate. Further study of using synthetic resorbable and biologic meshes for hernia prophylaxis is warranted.

Population pharmacokinetics and pharmacodynamics of fosfomycin in non-critically ill patients with bacteremic urinary infection caused by multidrug-resistant Escherichia coli.

OBJECTIVES: To describe the population pharmacokinetics of fosfomycin for patients with bacteraemic urinary tract infection (BUTI). The analysis identified optimal regimens on the basis of pharmacodynamic targets and assessed the adequacy of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoints for Escherichia coli. METHODS: Data of 16 patients with BUTI caused by multidrug-resistant E. coli (FOREST clinical trial) received intravenous fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic analysis was performed, and Monte Carlo simulations were undertaken using 4 g every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target attainment was assessed using pharmacodynamic targets for E. coli for static effect, 1-log drop in bacterial burden and resistance suppression. RESULTS: Sixty-four plasma samples were collected over a single dosing interval (day 2 or 3 after starting fosfomycin treatment). Fosfomycin concentrations were highly variable. Pharmacodynamic target attainment analysis showed mild improvement by increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable to reach bacterial resistance suppression targets. CONCLUSIONS: Fosfomycin concentrations are highly variable-a fact partially explained by renal impairment. The present work supports the use of 4 g every 6 hours as an effective regimen for the treatment of non-critically ill patients with BUTI caused by multidrug-resistant E. coli, as higher dosages might increase toxicity but may not significantly increase efficacy. The current information may suggest that fosfomycin susceptibility breakpoints need to be reappraised.

Comparison of piperacillin exposure in the lungs of critically ill patients and healthy volunteers.

Background: Severe infections of the respiratory tracts of critically ill patients are common and associated with excess morbidity and mortality. Piperacillin is commonly used to treat pulmonary infections in critically ill patients. Adequate antibiotic concentration in the epithelial lining fluid (ELF) of the lung is essential for successful treatment of pulmonary infection. Objectives: To compare piperacillin pharmacokinetics/pharmacodynamics in the serum and ELF of healthy volunteers and critically ill patients. Methods: Piperacillin concentrations in the serum and ELF of healthy volunteers and critically ill patients were compared using population methodologies. Results: Median piperacillin exposure was significantly higher in the serum and the ELF of critically ill patients compared with healthy volunteers. The IQR for serum piperacillin exposure in critically ill patients was six times greater than for healthy volunteers. The IQR for piperacillin exposure in the ELF of critically ill patients was four times greater than for healthy volunteers. The median pulmonary piperacillin penetration ratio was 0.31 in healthy volunteers and 0.54 in critically ill patients. Conclusions: Greater variability in serum and ELF piperacillin concentrations is observed in critically ill patients compared with healthy adult subjects and must be considered in the development of dosage regimens. Pulmonary penetration of antimicrobial agents should be studied in critically ill patients, as well as healthy volunteers, during drug development to ensure appropriate dosing of patients with pneumonia.

Comparison of hernia registries: the CORE project.

INTRODUCTION: The aim of the international CORE project was to explore the databases of the existing hernia registries and compare them in content and outcome variables. METHODS: The CORE project was initiated with representatives from all established hernia registries (Danish Hernia Database, Swedish Hernia Registry, Herniamed, EuraHS, Club Hernie, EVEREG, AHSQC) in March 2015 in Berlin. The following categories were used to compare the registries: initiation and funding, data collection and use for certification of hernia centers, patient data and data protection, operative data, registration of complications and follow-up data. RESULTS: The Danish Hernia Database is the only one to qualify as a genuine national registry where participation is compulsory for entry of all procedures by all surgeons performing a hernia operation. All other registries have to be considered as voluntary and completeness of data depends upon the participating hospitals and surgeons. Only the Danish Hernia Database and the Swedish Hernia Registry are publicly funded. All other registries are reliant on financial support from the medical technology industry. As an incentive for voluntary participation in a hernia registry, hospitals or surgeons are issued a certificate confirming that they are taking part in a quality assurance study for hernia surgery. Due to data protection and privacy regulations, most registries are obliged or have chosen to enter their patient data anonymously or coded. The Danish Hernia Database and Swedish Hernia Registry utilize a national personal patient code. In the Herniamed Registry, patient data are saved in a coded and anonymous format after obtaining the patient's informed consent. CONCLUSION: Despite the differences in the way data are collected for each of the listed hernia registries, the data are indispensable in clinical research.

Suboptimal Exposure to Anti-TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy.

A placebo-controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV -ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure.

Delivering precision antimicrobial therapy through closed-loop control systems.

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.