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Invasive aspergillosis occurs in a wide range of clinical scenarios, is protean in its manifestations, and is still associated with an unacceptably high mortality rate. Early diagnosis is critical to a favourable outcome, but is difficult to achieve with current methods. Deep tissue diagnostic specimens are often difficult to obtain from critically ill patients. Newer antifungal agents exhibit differential mould activity, thus increasing the importance of establishing a specific diagnosis of invasive aspergillosis. For these reasons, a range of alternate diagnostic strategies have been investigated. Most investigative efforts have focused on molecular and serological diagnostic techniques. The detection of metabolites produced by Aspergillus spp and a range of aspergillus-specific antibodies represent additional, but relatively underused, diagnostic avenues. The detection of galactomannan has been incorporated into diagnostic criteria for invasive aspergillosis, reflecting an increased understanding of the performance, utility, and limitations of this technique. Measurement of (1,3)-β-D glucan in blood may be useful as a preliminary screening tool for invasive aspergillosis, despite the fact that this antigen can be detected in a number of other fungi. There have been extensive efforts directed toward the detection of Aspergillus spp DNA, but a lack of technical standardisation and relatively poor understanding of DNA release and kinetics continues to hamper the broad applicability of this technique. This review considers the application, utility, and limitations of the currently available and investigational diagnostic modalities for invasive aspergillosis.

Climate change will be the greatest threat to humanity and global ecosystems in the coming years, and there is a pressing need to understand and communicate the impacts of warming, across the perspectives of the natural and social sciences. Hoegh-Guldberg et al. review the climate change–impact literature, expanding on the recent report of the Intergovernmental Panel on Climate Change. They provide evidence of the impacts of warming at 1°, 1.5°, and 2°C—and higher—for the physical system, ecosystems, agriculture, and human livelihoods. The benefits of limiting climate change to no more than 1.5°C above preindustrial levels would outweigh the costs. Science , this issue p. eaaw6974 Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.

Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.

Purpose Wide variation in care and costs exists regarding the management of abdominal wall hernias, with unproven benefit for many therapies. This work establishes a specialty society-based solution to improve the quality and value of care delivered to hernia patients during routine clinical management on a national scale. Methods The Americas Hernia Society Quality Task Force was charged by the Americas Hernia Society leadership to develop an initiative that utilizes the concepts of continuous quality improvement (CQI). A disease-based registry was created to collect information for CQI incorporating real-time outcome reporting, patient reported outcomes, stakeholder engagement, and collaborative learning methods to form a comprehensive quality improvement effort. Results The Americas Hernia Society Quality Collaborative (AHSQC) was formed with the mission to provide health care professionals real-time information for maximizing value in hernia care. The initial disease areas selected for CQI were incisional and parastomal hernias with ten priorities encompassing the spectrum of care. A prospective registry was created with real-time analytic feedback to surgeons. A data assurance process was implemented to ensure maximal data quality and completeness. Four collaborative meetings per year were established to meet the goals of the AHSQC. As of the fourth quarter 2014, the AHSQC includes nearly 2377 patients at 38 institutions with 82 participating surgeons. Conclusions The AHSQC has been established as a quality improvement initiative utilizing concepts of CQI. This ongoing effort will continually refine its scope and goals based on stakeholder input to improve care delivered to hernia patients.

Background. Chronic pulmonary aspergillosis (CPA) is a severe, progressive respiratory infection characterized by multiple pulmonary cavities and increased levels of antibodies to Aspergillus species. We report the first use of posaconazole in patients with CPA. Methods. A retrospective study was performed. A composite clinical and radiological evaluation was used to assess response to posaconazole therapy. The rates of clinical response and failure after 6 and 12 months of therapy were determined. Kaplan-Meier survival models were developed to describe the time to clinical response and failure. The underlying diagnosis, the type of therapy (primary or salvage), Aspergillus antibody titer, and posaconazole serum concentrations were assessed as covariates. Aspergillus species were identified and minimum inhibitory concentrations (MICs) of triazoles were determined using standard techniques. Results. There were 79 patients that initially received posaconazole 400 mg twice per day. The median age of patients was 61 years, and 57% were male. Response to posaconazole was observed in 61% of patients at 6 months and in 46% at 12 months. Kaplan-Meier plots showed that the first response to posaconazole was observed in some patients only after approximately 1 year of therapy. Covariates were not significant. Adverse reactions were observed in 12 patients (15%) (nausea in 5, rash in 5, headache in 1, and lethargy in 1), leading to withdrawal of treatment for 9 patients. Aspergillus species were recovered from 22 patients. A posaconazole MIC of >8 mg/L was found in 4 isolates; in 1 of these isolates, this emerged during therapy. Treatment failed in all 4 patients from whom these 4 isolates had been recovered. Conclusion. Posaconazole is a safe and partially effective treatment for CPA. Prospective comparative studies are now required.

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. This guideline addresses the treatment of umbilical and epigastric hernias in clinically challenging situations (cirrhosis, dialysis, subsequent pregnancy, rectus diastasis), as well as the treatment of Spigelian and primary lumbar hernias. Emphasises the need for better evidence

We explored concentration-toxicity relationships for itraconazole among 216 patients. Logistic regression revealed a progressive increase in the probability of toxicity with increasing concentrations of itraconazole. Classification and regression tree analysis suggested that 17.1 mg/L of itraconazole (measured using a bioassay) was the concentration level at which the population of patients was separated into 2 groups, each with a high and a low probability of toxicity.

PurposeThe penetration of hernia prevention techniques into surgical practice remains unknown.MethodsA survey about knowledge/attitudes on hernia prevention was sent to the members of hernia societies.ResultsThe 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%).ConclusionsThere appears to be some application of hernia prevention principles related to fascial closure; however, the use of prophylactic mesh still appears to be controversial.

In the face of increasing antimicrobial tolerance and resistance there is a global obligation to optimise oral antimicrobial dosing strategies including narrow spectrum penicillins, such as penicillin-V. We conducted a randomised, crossover study in healthy volunteers to characterise the influence of probenecid on penicillin-V pharmacokinetics and estimate the pharmacodynamics against Streptococcus pneumoniae . Twenty participants took six doses of penicillin-V (250 mg, 500 mg or 750 mg four times daily) with and without probenecid. Total and free concentrations of penicillin-V and probenecid were measured at two timepoints. A pharmacokinetic model was developed, and the probability of target attainment (PTA) calculated. The mean difference (95% CI) between penicillin-V alone and in combination with probenecid for serum total and free penicillin-V concentrations was significantly different at both timepoints (total: 45 min 4.32 (3.20–5.32) mg/L p  <  0.001 , 180 min 2.2 (1.58–3.25) mg/L p  <  0.001 ; free: 45 min 1.15 (0.88–1.42) mg/L p  <  0.001 , 180 min 0.5 (0.35–0.76) mg/L p  <  0.001 ). There was no difference between the timepoints in probenecid concentrations. PTA analysis shows probenecid allows a fourfold increase in MIC cover. Addition of probenecid was safe and well tolerated. The data support further research into improved dosing structures for complex outpatient therapy and might also be used to address penicillin supply shortages.