Harnessing the wisdom of crowds can improve guideline compliance of antibiotic prescribers and support antimicrobial stewardship.

Antibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept of "wisdom of crowds", which states that a group's collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance.

Experimental Study of the Formation of Organosulfates from α-Pinene Oxidation. 2. Time Evolution and Effect of Particle Acidity.

The present work is an extensive laboratory study of organosulfate (OS) formation from the reaction of α-pinene oxidation products or proxies with acidified ammonium sulfate aerosols in three different acidity conditions ((NH4)2SO4 0.06 M; (NH4)2SO4/H2SO4 0.06 M/0.005 M; (NH4)2SO4/H2SO4 0.03 M/0.05 M). The kinetics of the reactions of α-pinene, α-pinene oxide, isopinocampheol, pinanediol, and myrtenal with ammonium sulfate particles were studied using a quasi-static reactor. The reaction of α-pinene oxide with the highly acidic ammonium sulfate particles was determined to be 7, 10, 21, and 24 times faster than for isopinocampheol, α-pinene, pinanedial, and myrtenal, respectively, for an OS precursor concentration of 1 ppm and after 1 h reaction time. The effective rate coefficients for OS formation from α-pinene oxide were determined to be 2 orders of magnitude higher in highly acidic conditions than for the two other acidity conditions. For α-pinene oxide reactions with highly acidic ammonium sulfate particles, OS formation was observed to increase linearly with (i) the time of reaction up to 400 min (r2 > 0.95) and (ii) α-pinene oxide gas-phase concentration. However, OS formation from α-pinene oxide reactions with slightly acidic or pure ammonium sulfate particles was limited, with a plateau ([OS]max = 0.62 ± 0.03 µg) reached after around 15-20 min. Organosulfate dimers (m/z 401 and m/z 481) were detected not only with highly acidic particles but also with slightly acidic and pure ammonium sulfate particles, indicating that oligomerization processes do not require strong acidity conditions. Dehydration products of organosulfates (m/z 231 and m/z 383) were observed only under highly acidic conditions, indicating the key role of H2SO4 on the dehydration of organosulfates and the formation of olefins in the atmosphere. Finally, this kinetic study was completed with simulation chamber experiments in which the mass concentration of organosulfates was shown to depend on the available sulfate amount present in the particle phase (r2 = 0.96). In conclusion, this relative comparison between five organosulfate precursors shows that epoxide was the most efficient reactant to form organosulfates via heterogeneous gas-particle reactions and illustrates how gas-particle reactions may play an important role in OS formation and hence in the atmospheric fate of organic carbon. The kinetic data presented in this work provide strong support to organosulfate formation mechanisms proposed in part 1 ( J. Phys. Chem. A 2016 , 120 , 7909 - 7923 ).

Comparative characteristics of older people with type 1 diabetes treated with continuous subcutaneous insulin infusion or insulin injection therapy: data from the German/Austrian DPV registry.

AIM: To compare clinical characteristics and outcomes in adults with type 1 diabetes aged ≥ 60 years using continuous subcutaneous insulin infusion (CSII) vs. insulin injection therapy. Further, to determine the percentage of older adults with type 1 diabetes using CSII. RESEARCH DESIGN AND METHODS: Retrospective study using data of the Diabetes Prospective Follow-up Registry (DPV). Including percentage CSII use from 2008 to 2018, and the characteristics of 9547 individuals extracted from the DPV in March 2019 (N = 1404 CSII; N = 8143 insulin injection therapy). Wilcoxon rank sum tests were used for continuous variables and chi-square tests for categorical variables to compare clinical characteristics of people using CSII vs. insulin injection therapy. Adjusted analyses used generalized linear models to compare diabetes-related outcomes. RESULTS: CSII usage has increased in older adults (from 12% in 2008 to 23% in 2018). After adjustment, CSII was associated with lower HbA1c [60.7 mmol/mol (7.7 ± 0.1%) vs. 62.8% (7.9 ± 0.1%)], lower daily insulin dose (0.49 ± 0.02 vs. 0.61 ± 0.01 IU/kg), fewer days in hospital (8.1 ± 0.12 vs. 11.2 ± 0.11 days/person-year), fewer severe hypoglycaemic events (0.16 ± 0.02 vs. 0.21 ± 0.03 events/person-year) and fewer diabetic ketoacidosis (0.06 ± 0.01 vs. 0.08 ± 0.01 events/person-year). Individuals on CSII showed lower rates of microalbuminuria and also have a diagnosis of depression and neuropathy. CONCLUSIONS: A growing number of older adults are using insulin pumps. Older age in itself should not be seen as a contraindication for CSII.

Pluto's Interaction With Energetic Heliospheric Ions.

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190R P distance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow-frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range.

Observation of nighttime new particle formation over the French Landes forest.

Improving the understanding of processes related to atmospheric particle sources is essential to better assess future climate. Especially, how biogenic volatile organic compounds (BVOCs) are involved in new particle formation (NPF) is still unclear, highlighting the need for field studies in sites that have not yet been explored. Weakly anthropised, mostly composed of maritime pines (known as strong monoterpene emitters), vast and under the influence of sea spray inputs, the Landes forest (located in the southwestern part of France) is a suitable ecosystem to explore these questions. The aim of the present work was to investigate for the first time NPF in the Landes forest, and to identify the conditions for NPF. During a field campaign conducted in July 2015, clear NPF was observed during nighttime, at a high frequency rate (37.5%), whereas only two daytime episodes were observed. Growth rates during NPF events were in the range 9.0-15.7nmh-1, and nucleation rates (J10) in the range 0.8-8 particles cm3s-1, typically in the range of reported values from rural sites. Nocturnal NPF started at sunset, lagging the reductions of temperature and ozone concentration as well as the increase of relative humidity, atmospheric stability and monoterpene concentration. We established that NPF occurred during more stratified atmosphere episodes, reflecting that NPF is more influenced by local processes at the Landes forest site (Bilos). Concentration of the sum of monoterpenes, here mainly α- and ß-pinene, was observed to be maximal during NPF episodes. On the contrary, ozone concentration was lower, which may indicate a larger consumption during nights where NPF episodes occur. Results strongly suggest the contribution of BVOC oxidation to nocturnal NPF, in both nucleation and the growth stages.

Efficacy and tolerability of bimatoprost versus travoprost in patients previously on latanoprost: a 3-month, randomised, masked-evaluator, multicentre study.

AIM: To evaluate the efficacy and safety of replacing latanoprost with another prostaglandin analogue (PGA) in patients with glaucoma or ocular hypertension requiring additional intraocular pressure (IOP) lowering while on latanoprost. METHODS: Prospective, randomised, investigator-masked, multicentre clinical trial. Patients on latanoprost 0.005% monotherapy requiring additional IOP lowering discontinued latanoprost and were randomised to bimatoprost 0.03% (n = 131) or travoprost 0.004% (n = 135). IOP was measured at latanoprost-treated baseline and after 1 month and 3 months of replacement therapy. RESULTS: Baseline mean diurnal IOP on latanoprost was similar between groups. The mean diurnal IOP was significantly lower with bimatoprost than with travoprost at 1 month (p = 0.009) and 3 months (p = 0.024). Overall, 22.0% of bimatoprost patients versus 12.1% of travoprost patients achieved a > or =15% reduction in diurnal IOP from latanoprost-treated baseline at both months 1 and 3 (p = 0.033). At month 3, the additional mean diurnal IOP reduction from latanoprost-treated baseline was 2.1 (95% CI 1.7 to 2.5) mm Hg (11.0%) with bimatoprost and 1.4 (95% CI 0.9 to 1.8) mm Hg (7.4%) with travoprost (p = 0.024). At 3 months, 11.5% of bimatoprost and 16.5% of travoprost patients demonstrated a > or =1-grade increase in physician-graded conjunctival hyperaemia (p = 0.288). Hyperaemia was reported as a treatment-related adverse event in 3.1% of bimatoprost and 1.5% of travoprost patients (p = 0.445). CONCLUSION: Patients on latanoprost requiring lower IOP achieved a greater additional short-term diurnal IOP reduction when latanoprost was replaced by bimatoprost compared with travoprost. Low rates of hyperaemia were observed in patients treated with bimatoprost or travoprost after switching from latanoprost.

New insights into adolescent acne.

Interest in sebaceous gland functioning and its diseases is increasing. This article provides a summarized update of the current knowledge of the pathophysiology of acne vulgaris and the new treatment concepts that have emerged in recent years. Recent literature is reviewed regarding teenage acne, focusing on pathogenesis, associations, controversies and considerations in therapy to further help practitioners stay current on the issues regarding this topic. Current research is expected to provide new and improved treatments in the near future.

Evaluation of the immunochromatographic CORIS Giardia-Strip test for rapid diagnosis of Giardia lamblia.

The aim of this study was to evaluate the performance of the CORIS Giardia-Strip test (CORIS Bioconcept, Gembloux, Belgium) as a rapid initial method for the routine diagnosis of giardiasis. Compared to a commercial ELISA-coproantigen test (ProSpect Giardia-ELISA-microplate assay; Remel, Lenexa, KS, USA), the commercial strip test had a sensitivity of 58%, a specificity of 99%, a positive predictive value of 93% and a negative predictive value of 93% (n=158). These results are comparable to those obtained using microscopy of direct wet-mounted stool. Since the CORIS Giardia-Strip test is simpler to perform, it can replace direct wet-mounted stool microscopy for the rapid diagnosis of giardiasis; however, its sensitivity is inferior to that of other immunochromatographic antigen detection tests and fresh stool samples are required for its use. Nevertheless, the results suggest that a positive CORIS Giardia-Strip test outcome does not need confirmation, while samples with negative results should be re-examined using another, more sensitive, test.

[Value of sonographic diagnosis in retroperitoneal teratoma in adults]. / Zum Stellenwert der sonographischen Diagnostik beim retroperitonalen Teratom des Erwachsenen.

A 56-year old man was admitted with a tumour-like lesion located in the retroperitoneal space with adherence to the left adrenal gland. An extensive diagnostic procedure could neither establish the diagnosis nor differentiate the lesion from the adrenal gland. After tumour biopsy by ultrasound surgery was recommended and performed and the final diagnosis--mature teratoma--was established. In this article we discuss the genesis and therapeutic possibilities of mature teratoma in adults.

Deficient type I protein kinase A isozyme activity in systemic lupus erythematosus T lymphocytes: II. Abnormal isozyme kinetics.

Systemic lupus erythematosus (SLE) T cells exhibit deficient type I protein kinase A (PKA-1) isozyme phosphotransferase activity, resulting in impaired phosphorylation of plasma membrane-associated proteins. To determine the mechanism of this isozyme deficiency, we studied 16 SLE subjects with a mean (+/-1 SD) SLE disease activity index of 16.7 +/- 8.8 and 16 normal controls. Immunoblotting of type I regulatory (RI) subunit protein in SLE and control T cells demonstrated no significant differences in the amount of protein. Analysis of isozyme kinetics in SLE T cells demonstrated a 2.2-fold increase in the Michaelis-Menten constant, a 2.5-fold increase in the apparent association constant for cAMP, a 3.8-fold decrease in the maximal velocity, and a reduction in the mean maximal binding of cAMP to the RI subunit compared with control T cells. Reduction of the Hill coefficient from 1.2 in normal T cells to 0.7 in SLE T cells indicated a loss of positive cooperativity between cAMP binding sites A and B. An increase in the apparent association constant for cAMP signifies relative resistance to cAMP, indicating that higher intracellular concentrations of cAMP are necessary to activate the isozyme. Because the R subunit of PKA is the only intracellular receptor for cAMP, the abnormal isozyme kinetics may account for the deficiency of PKA-I phosphotransferase activity and impaired PKA-I-catalyzed protein phosphorylation observed in SLE T cells. This disordered isozyme function may contribute to the altered signal transduction and observed cellular immune dysfunctions in SLE. Moreover, these altered isozyme kinetics raise the possibility of a structural defect(s) in the RI subunit.

Effect of graded dietary alpha-tocopherol supplementation on concentrations in plasma and selected tissues of pigs from weaning to slaughter.

Five groups of six purebred German Landrace barrows were fed from 7 to 100 kg live weight restricted amounts of a complete basal feed containing 5 IU vitamin E/kg and supplemented with 0, 20, 40, 80 or 160 IU all-rac-alpha-tocopheryl acetate/kg. The concentrations of alpha-tocopherol were analysed by HPLC in plasma collected throughout the experiment and in cardiac muscle, M. longissimus, liver and adipose tissue at slaughter after 24 h fasting. Body mass gain, feed intake and feed conversion rate were not affected by vitamin E. Plasma alpha-tocopherol was related to the logarithm of supplemental dietary vitamin E (r2 = 0.61). A spell of diarrhea was associated with a significant decrease of plasma levels. In tissues, a clear rank-order of vitamin E storage was found with adipose tissue containing the highest concentrations followed by, in order of decreasing concentrations, liver, cardiac muscle and M. longissimus. Tissue alpha-tocopherol concentrations were related to the logarithm of supplemental dietary vitamin E. Linear correlations were found between alpha-tocopherol concentrations in plasma and tissues allowing an assessment of tissue vitamin E status from plasma alpha-tocopherol analysis.

Determination of peripheral plasma prostanoid concentration: an unreliable index of 'in vivo' prostanoid activity.

Plasma concentrations of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TxB2 were determined in 4 healthy volunteers by gas chromatography-negative ion chemical ionization mass spectrometry. TxB2 concentrations in all volunteers increased with time during blood collection, increases occurred more sporadically in the case of PGE2, PGF2 alpha and 6-keto-PGF1 alpha. Rapid changes in plasma prostanoid concentrations within a sampling series were unpredictable and were inexplicable. The measured plasma prostanoid concentrations apparently depended on the sampling conditions, which could not be adequately standardized and controlled. However, very short term changes in plasma prostanoid levels cannot be excluded.