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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.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.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.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.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 ( Plt; .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.Public health training centers' strengths in workforce development can complement and extend existing efforts to support the CHW workforce.

Background: Groin hernia management has a significant worldwide diversity with multiple surgical techniques and variable outcomes. The International guidelines for groin hernia management serve to help in groin hernia management, but the acceptance among general surgeons remains unknown. The aim of our study was to gauge the degree of agreement with the guidelines among health care professionals worldwide. Methods: Forty-six key statements and recommendations of the International guidelines for groin hernia management were selected and presented at plenary consensus conferences at four international congresses in Europe, the America’s and Asia. Participants could cast their votes through live voting. Additionally, a web survey was sent out to all society members allowing online voting after each congress. Consensus was defined as > 70% agreement among all participants. Results: In total 822 surgeons cast their vote on the key statements and recommendations during the four plenary consensus meetings or via the web survey. Consensus was reached on 34 out of 39 (87%) recommendations, and on six out of seven (86%) statements. No consensus was reached on the use of light versus heavy-weight meshes (69%), superior cost-effectiveness of day-case laparo-endoscopic repair (69%), omitting prophylactic antibiotics in hernia repair, general or local versus regional anesthesia in elderly patients (55%) and re-operation in case of immediate postoperative pain (59%). Conclusion: Globally, there is 87% consensus regarding the diagnosis and management of groin hernias. This provides a solid basis for standardizing the care path of patients with groin hernias.

BackgroundVancomycin has been used in clinical practice for over 50 years; however, validated, pharmacokinetic (PK) data relating clinical outcomes to different dosing regimens in neonates are lacking. Coagulase negative staphylococci (CoNS) are the most commonly isolated organisms in neonatal, late-onset sepsis (LOS). Optimised use to maximise efficacy while minimising toxicity and resistance selection is imperative to ensure vancomycin’s continued efficacy.MethodsNeoVanc is a European, open-label, Phase IIb, randomised, controlled, non-inferiority trial comparing an optimised vancomycin regimen to a standard vancomycin regimen when treating LOS known/suspected to be caused by Gram-positive organisms (excludingStaphylococcus aureus) in infants aged ≤ 90 days. Three hundred infants will be recruited and randomised in a 1:1 ratio. Infants can be recruited if they have culture confirmed (a positive culture from a normally sterile site and at least one clinical/laboratory criterion) or clinical sepsis (presence of any ≥ 3 clinical/laboratory criteria) in the 24 h before randomisation.The optimised regimen consists of a vancomycin loading dose (25 mg/kg) followed by 5 ± 1 days of 15 mg/kg q12h or q8h, dependent on postmenstrual age (PMA). The standard regimen is a 10 ± 2 day vancomycin course at 15 mg/kg q24h, q12h or q8h, dependent on PMA.The primary endpoint is a successful outcome at the test of cure visit (10 ± 1 days after the end of vancomycin therapy). A successful outcome consists of the patient being alive, having successfully completed study vancomycin therapy and having not had a clinical/microbiological relapse/new infection requiring treatment with vancomycin or other anti-staphylococcal antibiotic for > 24 h.Secondary endpoints include clinical/microbiological relapse/new infection at the short-term follow-up visit (30 ± 5 days after the initiation of vancomycin), evaluation of safety (renal/hearing), vancomycin PK and assessment of a host biomarker panel over the course of vancomycin therapy.DiscussionBased on previous pre-clinical data and a large meta-analysis of neonatal, PK/pharmacodynamic data, NeoVanc was set up to provide evidence on whether a loading dose followed by a short vancomycin course is non-inferior, regarding efficacy, when compared to a standard, longer course. If non-inferiority is demonstrated, this would support adoption of the optimised regimen as a way of safely reducing vancomycin exposure when treating neonatal, Gram-positive LOS.Trial registrationClinicalTrials.gov,NCT02790996. Registered on 7 April 2016.EudraCT, 2015–000203-89. Entered on 18 July 2016.

Item does not contain fulltext Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.

The European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST) has determined breakpoints for amphotericin B, itraconazole and posaconazole for Aspergillus species. This Technical Note is based on the EUCAST amphotericin B, itraconazole and posaconazole rationale documents (available on the EUCAST website: http://www.eucast.org/antifungal_susceptibility_testing_afst/rationale_documents_for_antifungals/). The amphotericin B and itraconazole breakpoints are based on epidemiological cut-off values and clinical experience. The posaconazole breakpoints are also based on pharmacokinetic and pharmacodynamic data. Breakpoints will be reviewed regularly or when new data emerge.

Three-dimensional (3D) magnetization-prepared rapid gradient-echo imaging has been proposed as a method for improving signal-to-noise ratio (S/N) and contrast-to-noise ratio (C/N) in rapid abdominal imaging. Originally, a standard sequential phase-encoding order was proposed. In the present study, two approaches to a 3D centric phase-encoding order are presented: (a) application of the two-dimensional (2D) centric order to one of the 3D encoding directions, and (b) an interleaved square spiral order, which is the segmented 3D analog of the 2D centric order. With use of simulation, phantom, and volunteer results, the proposed 3D centric methods are compared in terms of S/N, C/N, and artifacts to the 3D sequential method and 2D magnetization-prepared methods. The second centric approach was found to be superior to the first; however, in general, the 3D technique was found to be inferior to the 2D technique for abdominal imaging because of motion artifact in the 3D image set caused by misregistration among the multiple breath holds required.

It has been shown that magnetic resonance image data can be corrected for the effects of motion by using retrospective adaptive techniques which employ navigator (NAV) echoes. We demonstrate the accuracy with which NAV echoes can measure motion, as well as the independent nature of the respective view-to-view and intraview corrections. © 1991 Academic Press. Inc.

The authors describe an adaptive motion correction method for three-dimensional magnetic resonance (MR) imaging. Three-dimensional imaging offers many advantages over two-dimensional multisection imaging but is susceptible to image corruption due to motion. Thus, it has been of limited use in the imaging of mobile structures, and the relatively long imaging times required have hindered its use in patients who tend to move during imaging. The authors' technique uses interleaved "navigator" echoes to provide a measure of displacement for each image echo in the acquisition and then uses this information to allow correction of the image data. The theory for signal corruption due to motion and the correction scheme that follows from it are presented. This method can produce excellent results when the motion is correctly modeled.

The European Committee on Antimicrobial Susceptibility Testing-Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST) has revised the EDef 7.1 document on the method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for fermentative yeasts. Changes are: dimethylsulphoxide is now the recommended solvent for caspofungin, micafungin and fluconazole; the shelf-life of plates containing the echinocandins prepared from stock solutions in dimethylsulphoxide is extended to 6 months at −80°C; testing of amphotericin and Cryptococcus has been incorporated; and minimum inhibitory concentration ranges for quality control strains and anidulafungin are included.

Mantle cell lymphoma (MCL) has a worse prognosis than MALT lymphoma (MALTL). Distinction between MCL and MALTL on purely morphologic grounds can be difficult. Cyclin D1 (PRAD1/bcl1) is overexpressed in MCL as a result of a t(11:14) gene rearrangement, which leads to overexpression of cyclin D1 mRNA and protein. The immunohistochemical detection of cyclin D1 in MCL has been reported by several authors to be highly specific with sensitivity ranging from 70%-100%, but diagnostic laboratories have reported difficulty in finding a reliable method for cyclin D1 immunostaining. The aim of this study was to evaluate and optimize a method for detection of cyclin D1 by paraffin section immunoperoxidase staining. Sections of routinely processed tissue from five MCL and one splenic marginal zone lymphoma (MZL) were immunostained using a mixture of two primary monoclonal antibodies and a standard avidin-streptavidin method. Antigen retrieval was performed using 1) steam heat in citrate buffer, 2) as in "1" followed by sonication for one minute, and 3) as in "2" followed by enzymatic digestion. All the above were repeated, with the additional use of catalyzed signal amplification (CSA). Later, sections of the same cases, plus three MALTL were immunostained as in "2". Steam heat antigen retrieval alone produced the best results. All MCL showed positive nuclear staining while the MZL and all MALTL were negative. Sonication did not enhance staining noticeably, whereas enzymatic digestion produced cytoplasmic staining. CSA increased background staining with no significant gain in nuclear stain intensity. We conclude that cyclin D1 immunostaining of formalin-fixed, paraffin-embedded tissue can be reliably achieved by heat induces antigen retrieval and a cocktail of two monoclonal antibodies.

A common type of motion present in clinical magnetic resonance imaging examinations is rotational motion, such as that due to voluntary motion during head examinations. The correction scheme presented in this work offers a method for eliminating the effects of rotations within the imaging plane. Integral to the implementation of this technique is the concept and design of spatial-frequency-tuned markers, which are used to track the rotational motion. These studies showed that it is possible to accurately track the motion, measuring both axis and angle of rotation, and use this information to retrospectively correct the acquired images. These markers can also provide information about any translational motion present. The resulting images show a marked decrease in artifacts and improved clarity.

A method of reordering phase and slab encoding that can be used to address some of the inherent problems due to motion in three dimensional imaging is described and implemented. The method is shown to be more robust with respect to reducing artifacts resulting from several fundamental types of motion. It can be readily implemented on a standard magnetic resonance imager with essentially no increase in total imaging time. Results of simulations and phantom and in vivo experiments are presented.

Despite the fact that respiratory motion is a major factor limiting the image quality of MR examinations in the upper abdomen, little quantitative information is available about the kinematics of visceral motion during respiration. The objective of this study was to obtain a measure of the relative longitudinal and transverse displacements of the upper abdominal organs during breathing using an MR line scan technique.

Retrospective correction of magnetic resonance (MR) image data to eliminate the effects of patient motion is possible with use of adaptive correction techniques. These methods require an accurate record of the motion that occurs during imaging. The authors evaluated whether motion information suitable for adaptive correction could be obtained from phase-encoded image data alone rather than from separate navigator echoes. Once such displacements were estimated from the image data, motion correction proceeded with use of the same algorithm used for the navigator echoes. The results show that image data alone can be used to effectively measure view-to-view displacements in phantoms, but external markers are required for accurate measurement during axial head imaging of patients.

Various compensation methods for different types of motion during MR image acquisition have been proposed. Presented here is a postprocessing scheme for eliminating artifacts due to linear, intra-slice motion of known velocity. The data for each phase encoding or "view" acquired from a moving object are shown to differ from those which would be measured from the stationary object by a phase factor which depends on the object's displacement from a reference point. This derivation is then used to propose a correction scheme for linear motion in which all phase encodings measured at different positions of the moving object are collapsed onto the same reference position. After subsequent reconstruction, the object appears perfectly "focused." By selection of different reference positions, the method permits positioning of the compensated object as desired within the field of view of the image. This property allows the method to be extended to create sequences of corrected images with smooth object motion between frames of the sequence. The basic correction scheme and its variations were tested experimentally in phantom studies with velocities as large as 8 cm/s.

Three boys had chloromas arising in the head. Their cases show the different stages of disease that can be present when such a diagnosis is made. Any tumor of the face can be a manifestation of an underlying hematologic disorder. Thorough examination of the peripheral blood and bone marrow should be made before any extensive surgical procedure is undertaken. The interdisciplinary conference is particularly important in the management of childhood cancer and leukemia since major advances have been made employing multimodal 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.

Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC 50 ) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC 50 )/15.4 predicted terminal galactomannan ( P = 0.003), and a ratio of >6 suggested a lower terminal galactomannan level ( P = 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival.

Objectives: The study aims to assess the population pharmacokinetics of fluconazole and the adequacy of current dosages and breakpoints against Candida albicans and non-albicans spp. in liver transplant (LT) patients. Patients and methods: Patients initiated i.v. fluconazole within 1month from liver transplantation (LTx) for prevention or treatment of Candida spp. infections. Multiple assessments of trough and peak plasma concentrations of fluconazole were undertaken in each patient by means of therapeutic drug monitoring. Monte Carlo simulations were performed to define the probability of target attainment (PTA) with a loading dose (LD) of 400, 600, and 800mg at day 1, 7, 14, and 28 from LTx, followed by a maintenance dose (MD) of 100, 200, and 300mg daily of the pharmacokinetic/pharmacodynamic target of AUC24h/MIC ratio ≥ 55.2. Results: Nineteen patients were recruited. A two-compartment model with first-order intravenous input and first-order elimination was developed. Patient’s age and time elapsed from LTx were the covariates included in the final model. At an MIC of 2mg/L, a LD of 600mg was required for optimal PTAs between days 1 and 20 from LTx, while 400mg was sufficient from days 21 on. A MD of 200mg was required for patients aged 40–49years old, while a dose of 100mg was sufficient for patients aged ≥ 50years. Conclusions: Fluconazole dosages of 100–200mg daily may ensure optimal PTA against C. albicans, C. parapsilosis, and C. tropicalis. Higher dosages are required against C. glabrata. Estimated creatinine clearance is not a reliable predictor of fluconazole clearance in LT patients.

Aims: The aim of this study was to determine clinical variables associated with posaconazole exposure among adult patients with haematological malignancies who received posaconazole tablets for prophylaxis of invasive fungal infections (IFIs). Methods: The study population included adult patients with haematological malignancies who received posaconazole delayed-release tablets for prophylaxis of IFIs after induction chemotherapy for acute leukaemia or graft-versus-host-disease (GVHD) complicating hematopoietic stem cell transplantation (HSCT) in the period January 2016–December 2017. Results: Sixty-six consecutive patients with 176 posaconazole Cmin were included for evaluation in the study. Subtherapeutic posaconazole concentrations (< 0.7mgl−1) were observed at least once in 33.3% of patients (22/66), and overall in 17.0% of therapeutic drug monitoring (TDM) episodes (30/176). At multilevel linear regression, use of PPIs (P=0.008), use of intermediate or high dose steroids (>0.7mgkg−1 daily) (P=0.022) and male gender (P=0.025) were significantly associated with decreased Cmin, whereas time from starting therapy (P=0.032) was associated with increased Cmin in our patient population. Conclusion: Posaconazole exposure during treatment with delayed-released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.

A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The aim was to assess the population pharmacokinetics (popPK) and pharmacodynamics of levofloxacin among older patients. PopPK and Monte Carlo simulation were performed to define the permissible doses in older patients according to various degrees of renal function. Classification and regression tree (CART) analysis was used to detect the cutoff 24-hour area under the concentration-time curve (AUC 24 )/MIC ratio that best correlated with the clinical outcome. The probability of target attainment (PTA) of this value was calculated against different pathogens. A total of 168 patients were included, and 330 trough and 239 peak concentrations were used for the popPK analysis. Creatinine clearance (CrCL) was the only covariate that improved the model fit (levofloxacin CL = 0.399 + 0.051 × CrCL CKD-EPI [creatinine clearance estimated by means of the chronic kidney disease epidemiology]). Drug doses ranged between 500 mg every 48 h and 500 mg every 12 h in relation to different renal functions. The identified cutoff AUC 24 /MIC ratio (≥95.7) was the only covariate that correlated with a favorable clinical outcome in multivariate regression analysis (odds ratio [OR], 20.85; 95% confidence interval [CI], 1.56 to 186.73). PTAs were optimal (>80%) against Escherichia coli and Haemophilus influenzae , borderline against Staphylococcus aureus , and suboptimal against Pseudomonas aeruginosa . The levofloxacin doses defined in our study may be effective for the treatment of infections due to bacterial pathogens, with an MIC of ≤0.5 mg/liter in older patients with various degrees of renal function, while minimizing the toxicity risk. Conversely, the addition of another active antimicrobial should be considered whenever treating infections caused by less susceptible pathogens.

Objectives To assess the population pharmacokinetics (popPK) of daptomycin at the conventional dose of 6 mg/kg/day in a cohort of oncohaematological patients. Methods Patients underwent serial blood sampling on day 3 of therapy (before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9 and 12 h after dosing) to assess the pharmacokinetic profile of daptomycin. PopPK and Monte Carlo simulation were performed to define the probability of target attainment (PTA) with 6, 8, 10 and 12 mg/kg/day of the pharmacokinetic/pharmacodynamic target of AUC 24 /MIC >1081. Results Thirty patients were recruited. A two-compartment open model with first-order intravenous input and first-order elimination was developed. Estimated creatinine clearance (CL CR ), serum albumin concentration (Alb) and presence of AML were covariates included in the final model. Monte Carlo simulation showed that the conventional 6 mg/kg/day dose resulted in optimal PTAs (≥80%) in the presence of pathogens with an MIC up to 0.5 mg/L only in patients with CL CR 50-100 mL/min/1.73 m 2 , Alb 26-45 g/L and a haematological diagnosis other than AML. Conversely, higher dosages, up to 12 mg/kg/day, were needed to achieve this goal in the presence of pathogens with an MIC of 0.25-0.5 mg/L in all of the other tested scenarios. In patients with CL CR 101-150 mL/min/1.73 m 2 and Alb 15-25 g/L, suboptimal PTAs (

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