Inhaled analgesics for the treatment of prehospital acute pain-A systematic review.

BACKGROUND: Many prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents. METHODS: As part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs. RESULTS: We included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs. CONCLUSION: We found low-quality evidence suggesting that both MF and N2O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N2O.

Direct Synthesis of Methyl Chlorosilanes from Pd-Mg-SiO2 Substrates Using Mechanochemistry.

The direct reaction of methyl chloride with magnesium and palladium infused silica substrates to synthesize methyl chlorosilanes is reported. First, high energy ball milling on solid Mg-SiO2 mixtures produces elemental silicon and MgO. When PdCl2 is infused into the mixture, after additional ball milling and high-temperature reduction under H2 , dipalladium silicide (Pd2 Si) is produced. The silicon of the Pd2 Si readily reacts with MeCl under Müller-Rochow reaction conditions, to produce methyl chlorosilanes at yield ratios analogous to those of the traditional process. The dominant product is Me2 SiCl2 (selectivity > 30%), followed by MeSiCl3 and Me3 SiCl, with minor amounts of the remaining chlorosilanes. Silicon conversion exceeds 20% for most of the substrates. The elemental palladium, which remains within the Pd-Mg-SiO2 contact mass is re-converted to Pd2 Si at the next H2 /high-temperature treatment and reacts again with MeCl to repeat the methyl chlorosilane production. In principle, the resulting cycle of the mechanochemically induced formation of Pd2 Si followed by the reaction with MeCl can be repeated until the starting SiO2 converts completely to methyl chlorosilanes.

Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis.

BACKGROUND: Pain management is one of the most important interventions in the emergency medical services. The femoral nerve block (FNB) is, among other things, indicated for pre- and post-operative pain management for patients with femoral fractures but its role in the pre-hospital setting has not been determined. The aim of this review was to assess the effect and safety of the FNB in comparison to other forms of analgesia (or no treatment) for managing acute lower extremity pain in adult patients in the pre-hospital setting. METHODS: A systematic review (PROSPERO registration (CRD42018114399)) was conducted. The Cochrane and GRADE methods were used to assess outcomes. Two authors independently reviewed each study for eligibility, extracted the data and performed risk of bias assessments. RESULTS: Four studies with a total of 252 patients were included. Two RCTs (114 patients) showed that FNB may reduce pain more effectively than metamizole (mean difference 32 mm on a 100 mm VAS (95% CI 24 to 40)). One RCT (48 patients) compared the FNB with lidocaine and magnesium sulphate to FNB with lidocaine alone and was only included here for information regarding adverse effects. One case series included 90 patients. Few adverse events were reported in the included studies. The certainty of evidence was very low. We found no studies comparing FNB to inhaled analgesics, opioids or ketamine. CONCLUSIONS: Evidence regarding the effectiveness and adverse effects of pre-hospital FNB is limited. Studies comparing pre-hospital FNB to inhaled analgesics, opioids or ketamine are lacking.

Reactions: Antibacterial and bioactive dental restorative materials: Do they really work?

PURPOSE: The study and development of antibacterial materials for use in dental applications is growing with the development of novel materials and procedures. Examination of the effects of such antibacterial materials on oral pathogens as well as on stability and longevity of dental restorations is of paramount importance to the field. RESULTS: This review addressed the range of topics covered by the manuscripts presented at the Seoul symposium on antibacterial dental materials. CLINICAL SIGNIFICANCE: Based on the presented works, it seems that the emerging antibacterial and bioactive mate-rials can potentially benefit restorative dentistry; however, like many other subjects in clinical dentistry, good quality evidence on their effectiveness under clinical situations is yet to be accumulated.

Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: identification of the local environmental source as arboreal.

Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four distinct molecular types: VGI, VGII, VGIII, and VGIV, with no evidence of nuclear genetic exchange, indicating these represent distinct species. C. gattii VGII isolates are causing the Pacific Northwest outbreak, whereas VGIII isolates frequently infect HIV/AIDS patients in Southern California. VGI, VGII, and VGIII have been isolated from patients and animals in the Western US, suggesting these molecular types occur in the environment. However, only two environmental isolates of C. gattii have ever been reported from California: CBS7750 (VGII) and WM161 (VGIII). The incongruence of frequent clinical presence and uncommon environmental isolation suggests an unknown C. gattii reservoir in California. Here we report frequent isolation of C. gattii VGIII MATα and MATa isolates and infrequent isolation of VGI MATα from environmental sources in Southern California. VGIII isolates were obtained from soil debris associated with tree species not previously reported as hosts from sites near residences of infected patients. These isolates are fertile under laboratory conditions, produce abundant spores, and are part of both locally and more distantly recombining populations. MLST and whole genome sequence analysis provide compelling evidence that these environmental isolates are the source of human infections. Isolates displayed wide-ranging virulence in macrophage and animal models. When clinical and environmental isolates with indistinguishable MLST profiles were compared, environmental isolates were less virulent. Taken together, our studies reveal an environmental source and risk of C. gattii to HIV/AIDS patients with implications for the >1,000,000 cryptococcal infections occurring annually for which the causative isolate is rarely assigned species status. Thus, the C. gattii global health burden could be more substantial than currently appreciated.

Reproducibility of CSF quantitative culture methods for estimating rate of clearance in cryptococcal meningitis.

Quantitative cerebrospinal fluid (CSF) cultures provide a measure of disease severity in cryptococcal meningitis. The fungal clearance rate by quantitative cultures has become a primary endpoint for phase II clinical trials. This study determined the inter-assay accuracy of three different quantitative culture methodologies. Among 91 participants with meningitis symptoms in Kampala, Uganda, during August-November 2013, 305 CSF samples were prospectively collected from patients at multiple time points during treatment. Samples were simultaneously cultured by three methods: (1) St. George's 100 mcl input volume of CSF with five 1:10 serial dilutions, (2) AIDS Clinical Trials Group (ACTG) method using 1000, 100, 10 mcl input volumes, and two 1:100 dilutions with 100 and 10 mcl input volume per dilution on seven agar plates; and (3) 10 mcl calibrated loop of undiluted and 1:100 diluted CSF (loop). Quantitative culture values did not statistically differ between St. George-ACTG methods (P= .09) but did for St. George-10 mcl loop (P< .001). Repeated measures pairwise correlation between any of the methods was high (r≥0.88). For detecting sterility, the ACTG-method had the highest negative predictive value of 97% (91% St. George, 60% loop), but the ACTG-method had occasional (∼10%) difficulties in quantification due to colony clumping. For CSF clearance rate, St. George-ACTG methods did not differ overall (mean -0.05 ± 0.07 log10CFU/ml/day;P= .14) on a group level; however, individual-level clearance varied. The St. George and ACTG quantitative CSF culture methods produced comparable but not identical results. Quantitative cultures can inform treatment management strategies.

Notes from the field: identification of a Taenia tapeworm carrier - Los Angeles County, 2014.

Carriers of the pork tapeworm, Taenia solium, are the sole source of cysticercosis, a parasitic tissue infection. When tapeworm eggs excreted by the carrier are ingested, tapeworm larvae can form cysts. When cysts form in the brain, the condition is called neurocysticercosis and can be especially severe. In Los Angeles County an average of 136 county residents are hospitalized with neurocysticercosis each year. The prevalence of Taenia solium carriage is largely unknown because carriage is asymptomatic, making detection difficult. The identification and treatment of tapeworm carriers is an important public health measure that can prevent additional neurocysticercosis cases.

Development of a novel fibre optic beam profile and dose monitor for very high energy electron radiotherapy at ultrahigh dose rates.

Objective. Very high energy electrons (VHEE) in the range of 50-250 MeV are of interest for treating deep-seated tumours with FLASH radiotherapy (RT). This approach offers favourable dose distributions and the ability to deliver ultra-high dose rates (UHDR) efficiently. To make VHEE-based FLASH treatment clinically viable, a novel beam monitoring technology is explored as an alternative to transmission ionisation monitor chambers, which have non-linear responses at UHDR. This study introduces the fibre optic flash monitor (FOFM), which consists of an array of silica optical fibre-based Cherenkov sensors with a photodetector for signal readout.Approach. Experiments were conducted at the CLEAR facility at CERN using 200 MeV and 160 MeV electrons to assess the FOFM's response linearity to UHDR (characterised with radiochromic films) required for FLASH radiotherapy. Beam profile measurements made on the FOFM were compared to those using radiochromic film and scintillating yttrium aluminium garnet (YAG) screens.Main results. A range of photodetectors were evaluated, with a complementary-metal-oxide-semiconductor (CMOS) camera being the most suitable choice for this monitor. The FOFM demonstrated excellent response linearity from 0.9 Gy/pulse to 57.4 Gy/pulse (R2= 0.999). Furthermore, it did not exhibit any significant dependence on the energy between 160 MeV and 200 MeV nor the instantaneous dose rate. Gaussian fits applied to vertical beam profile measurements indicated that the FOFM could accurately provide pulse-by-pulse beam size measurements, agreeing within the error range of radiochromic film and YAG screen measurements, respectively.Significance. The FOFM proves to be a promising solution for real-time beam profile and dose monitoring for UHDR VHEE beams, with a linear response in the UHDR regime. Additionally it can perform pulse-by-pulse beam size measurements, a feature currently lacking in transmission ionisation monitor chambers, which may become crucial for implementing FLASH radiotherapy and its associated quality assurance requirements.

A comparative analysis of movement and physical activity in early childhood teacher education policy in five Nordic countries.

Introduction: The aim of this study is to investigate the integration of movement and physical activity (MoPA) within Early Childhood Teacher Education (ECTE) policies across Denmark, Finland, Iceland, Norway, and Sweden. This knowledge can inform the development of ECTE policies and practices that promote MoPA in Early Childhood Education and Care (ECEC) in Nordic countries and other countries worldwide. Methods: In this study, a Nordic cross-national network of researchers collaborated in investigating policy documents at the national and university levels, which govern the education of ECEC teachers. This study was inspired by the Non-affirmative Theory of Education, which provides a framework for understanding the various influences on curricular development in higher education. Based on this, a four-step comparative analytical process of national and university documents across the Nordic countries was conducted. It included keyword search for MoPA related courses and a qualitative description of MoPA in ECTE. Thus, a combination of investigations of policy documents at the national and university level and expert knowledge set a solid foundation for international comparison. Results: The comparative analysis of MoPA in ECTE reveals diverse approaches influenced by national and university policies. A central theme is the variability in MoPA integration across these nations. Finland and Norway prioritize MoPA with independent mandatory courses. In Iceland, compulsory MoPA courses exist at one of two universities, and in Sweden at three out of 19. All university colleges in Denmark offer an elective course. Furthermore, learning objectives related to MoPA are, to varying degrees, part of the internships in the countries, with Sweden being an exception. In the participating countries, the teachers decide the content of the MoPA courses with little guidance, support, and agreement on essential MoPA content within and across the ECTE's. Norway has established guidelines, and in Finland, there is a network of ECTE Physical Education (PE) educators, which, to some degree, increases the consistency and quality of MoPA in education. Discussion: The Nordic countries present diverse MoPA integration approaches rooted in national policies and educational traditions. The findings emphasize the necessity of independent and mandatory MoPA courses, integration of MoPA into internships and promoting networks across the educational and academic sectors to equip future early childhood educators with competencies for fostering physical activity, motor development and children's well-being.

Urinary incontinence.

Around 500,000 Danes are suffering from urinary incontinence, and stress urinary incontinence and urgency urinary incontinence, alone or mixed, are the most common types. Diagnostic workup is similar for all types of urinary incontinence (men and women) and can be done by the GP. Most conservative interventions can be commenced by the GP. In complicated or treatment-resistant cases and when surgery is needed, referral to a urologic or gynaecological department can be necessary, as argued in this review.

Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group.

BACKGROUND: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken. METHODS: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant predetermined safety or efficacy concerns. In Stage-2, the 1200mg dose was excluded per protocol because of increased mortality, and participants were randomised to 1600mg, 2000mg FCZ or AMB in a 1:1:1 ratio. FINDINGS: One hundred and sixty eight participants were enrolled with 48, 50, and 48 in the AMB, 1600mg and 2000mg cohorts. The Kaplan Meier proportion for mortality (90% CI) at 10 and 24 weeks for AMB was 17% (10, 29) and 24% (15, 37), compared to 20% (12, 32) and 30% (20, 43) for 1600mg, and 33% (23, 46) and 38% (27, 51) for 2000mg/day FCZ. With the exception of a higher incidence of gastrointestinal side effects in the 2000mg cohort, both induction doses of FCZ were safe and well tolerated. There were no life-threatening changes in electrocardiogram QTc which were similar across all doses of FCZ and AMB. The median (IQR) change in log10 cryptoccal colony forming units (CFU) from week 0 to week 2 was -8(-4.1,-1.9) for AMB; -2.5(-4.0, -1.4) for 1600mg FCZ and -8 (-3.2, -1.0) for 2000mg FCZ. The proportion (90% CI) CSF CM negative at 10 weeks was 81%(71,90) for AMB; 56%(45,69) for 1600mg FCZ and 60%(49,73) for 2000mg FCZ. INTERPRETATION: Induction phase weight and renal-adjusted doses of 1600mg and 2000mg/day FCZ for CM were safe and well tolerated except for increased GI side effects in the 2000mg/day dose, and had similar times to achieve CSF sterilization, but took significantly longer than AMB. The WHO recommended 1200mg FCZ was associated with a high mortality. While not statistically significant, mortality was numerically lower in the AMB compared to 1600mg and 2000mg FCZ These data make a case for a phase 3 study of higher doses of FZC.

Cryptococcus neoformans: the model organism for yeast antifungal drug susceptibility testing.

We describe an approach to antifungal susceptibility testing of the yeast Cryptococcus neoformans that shows promise for predicting the mycological response in patients to treatment. Quantitative cultures of the cerebrospinal fluid provide a direct measure of the patient's mycological response to treatment and have been used in multiple studies to identify the most promising antifungal drugs for subsequent testing in larger clinical studies. Using these quantitative measures of response, a modified macrobroth dilution assay system shows the potential for predicting the response of an individual patient to treatment with amphotericin B, fluconazole, or the combination of amphotericin B plus flucytosine. We describe this modified macrobroth dilution assay method, the statistical approach for assessing susceptibility, and the clinical decisions that can be guided by this in vitro antifungal drug susceptibility testing.

Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review.

INTRODUCTION: Acute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies. METHODS: The PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method. RESULTS: A total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine. CONCLUSIONS: Available evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.

Training to Promote Empathic Communication in Graduate Medical Education: A Shared Learning Intervention in Internal Medicine and General Surgery.

Background: Empathic communication skills have a growing presence in graduate medical education to empower trainees in serious illness communication. Objective: Evaluate the impact, feasibility, and acceptability of a shared communication training intervention for residents of different specialties. Design: A randomized controlled study of standard education v. our empathic communication skills-building intervention: VitalTalk-powered workshop and formative bedside feedback using a validated observable behavioral checklist. Setting/Subjects: During the 2018-2019 academic year, our intervention was implemented at a large single-academic medical center in the United States involving 149 internal medicine and general surgery residents. Measurements: Impact outcomes included observable communication skills measured in standardized patient encounters (SPEs), and self-reported communication confidence and burnout collected by surveys. Analyses included descriptive and inferential statistics, including independent and paired t tests and multiple regression model to predict post-SPE performance. Results: Of residents randomized to the intervention, 96% (n = 71/74) completed the VitalTalk-powered workshop and 42% (n = 30/71) of those residents completed the formative bedside feedback. The intervention demonstrated a 33% increase of observable behaviors (p < 0.001) with improvement in all eight skill categories, compared with the control who only showed improvement in five. Intervention residents demonstrated improved confidence in performing all elicited communication skills such as express empathy, elicit values, and manage uncertainty (p < 0.001). Conclusions: Our educational intervention increased residents' confidence and use of essential communication skills. Facilitating a VitalTalk-powered workshop for medical and surgical specialties was feasible and offered a shared learning experience for trainees to benefit from expert palliative care learning outside their field.

Posaconazole for chronic refractory coccidioidal meningitis.

Coccidioidal meningitis is a potentially lethal infection. Disease progression while taking fluconazole is a common complication and safe, effective, alternative treatments are limited. Posaconazole therapy resulted in symptomatic and laboratory improvement in 2 patients and clinical improvement in a third patient with chronic, previously unresponsive coccidioidal meningitis.

Iodide-catalyzed reductions: development of a synthesis of phenylacetic acids.

A new convenient and scalable synthesis of phenylacetic acids has been developed via the iodide catalyzed reduction of mandelic acids. The procedure relies on in situ generation of hydroiodic acid from catalytic sodium iodide, employing phosphorus acid as the stoichiometric reductant.

Impact of hospital type on risk-adjusted, traffic-related 30-day mortality: a population-based registry study.

BACKGROUND: Traffic incidents are still a major contributor to hospital admissions and trauma-related mortality. The aim of this nationwide study was to examine risk-adjusted traffic injury mortality to determine whether hospital type was an independent survival factor. METHODS: Data on all patients admitted to Swedish hospitals with traffic-related injuries, based on International Classification of Diseases codes, between 2001 and 2011 were extracted from the Swedish inpatient and cause of death registries. Using the binary outcome measure of death or survival, data were analysed using logistic regression, adjusting for age, sex, comorbidity, severity of injury and hospital type. The severity of injury was established using the International Classification of Diseases Injury Severity Score (ICISS). RESULTS: The final study population consisted of 152,693 hospital admissions. Young individuals (0-25 years of age) were overrepresented, accounting for 41% of traffic-related injuries. Men were overrepresented in all age categories. Fatalities at university hospitals had the lowest mean (SD) ICISS 0.68 (0.19). Regional and county hospitals had mean ICISS 0.75 (0.15) and 0.77 (0.15), respectively, for fatal traffic incidents. The crude overall mortality in the study population was 1193, with a mean ICISS 0.72 (0.17). Fatalities at university hospitals had the lowest mean ICISS 0.68 (0.19). Regional and county hospitals had mean ICISS 0.75 (0.15) and 0.77 (0.15), respectively, for fatal traffic incidents.When regional and county hospitals were merged into one group and its risk-adjusted mortality compared with university hospitals, no significant difference was found. A comparison between hospital groups with the most severely injured patients (ICISS ≤0.85) also did not show a significant difference (odds ratio, 1.13; 95% confidence interval, 0.97-1.32). CONCLUSIONS: This study shows that, in Sweden, the type of hospital does not influence risk adjusted traffic related mortality, where the most severely injured patients are transported to the university hospitals and centralization of treatment is common.

Movement and Physical Activity in Early Childhood Education and Care Policies of Five Nordic Countries.

The purpose of this study was to examine the values of movement and physical activity (MoPA) using government policy documents (e.g., laws and curricula) on early childhood education and care (ECEC) from Denmark, Finland, Iceland, Norway, and Sweden. This descriptive, comparative study was designed based on curriculum theory and used word count and content analyses to identify similarities and differences in the occurrence of MoPA in the ECEC policies of Nordic countries. Seven terms were identified as MoPA-related in Nordic policy documents. These terms occurred in various content contexts: development, environment, expression, health and well-being, learning and play, albeit sparsely. MoPA was referred to as both a goal in and of itself and as a means of achieving other goals (e.g., learning or development in another area). Formulations specifically dedicated to MoPA as a goal were present in the Danish and Finnish curricula and, to some extent, also in the Norwegian curriculum, while the Icelandic and Swedish curricula mentioned MoPA mostly as a means. Findings indicated that MoPA, which is important for children's development, health, and well-being, is a low-priority value, to varying degrees, in the ECEC policies enacted by Nordic countries and the guidance provided to educators and stakeholders therein is inexplicit.

Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.

A highly efficient palladium/copper cocatalytic system for direct arylation of heteroarenes: an unexpected effect of Cu(Xantphos)I.

Heteroarenes are important structural moieties in many chemical industry fields. A highly efficient Pd/Cu-catalyzed C-H arylation method for a range of heterocycles has been discovered. It was found that the key to the success of this transformation is a combination of a palladium catalyst and a well-defined copper cocatalyst. The efficiency and low loadings of catalyst (0.25 mol %) and cocatalyst (1 mol %) together with the mild reaction conditions demonstrate this method to be practically useful and mechanistically interesting.