New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the ...management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations.
The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach.
Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended.
These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.
Aims
To analyse blood glucose control according to continuous glucose monitoring use in data from the CareLink™ database, and to identify factors associated with continuation of sensor use during ...sensor‐augmented pump therapy.
Methods
The analysis used data from 10 501 people with Type 1 and 2 diabetes mellitus, of whom 7916 (61.7%) had used glucose sensors for ≥ 15 days during any 6‐month period over a 2‐year observation period. Data were analysed according to the extent of sensor use ( < 25%, 25–49%, 50–74% and ≥ 75% of the time). Time to discontinuation of sensor use was also analysed in new users of glucose sensors.
Results
Compared with patients in the lowest sensor usage group and non‐users, the highest glucose sensor usage group had significantly (P < 0.0001) lower mean blood glucose and blood glucose sd, were more likely to achieve a mean blood glucose concentration < 8.6 mmol/l, (odds ratio 1.5, 95% CI 1.3–1.7; P < 0.0001), and had 50% fewer hypoglycaemic (blood glucose concentration < 2.8 mmol/l) episodes. Among new users, sensor use during the first month of therapy was an important predictor of subsequent discontinuation. Lack of full reimbursement was also significantly associated with early discontinuation, whereas measures of glycaemic control were predictive of discontinuation during long‐term treatment.
Conclusions
The use of continuous glucose monitoring was significantly associated with reductions in hypoglycaemia and improved metabolic control during insulin pump therapy. Sensor use during the first month was strongly associated with long‐term adherence; patient education and training may be helpful in achieving this.
What's new?
The generalizability to routine clinical use of results obtained on continuous glucose monitoring under the controlled conditions pertaining in clinical trials remains to be established.
This study, which involved data from > 10 000 people with diabetes, is the largest study to have analysed objective data derived from a self‐uploaded patient electronic database.
The analysis showed that the routine home use of continuous glucose monitoring was significantly associated with a reduction in hypoglycaemia and improved metabolic control in people with diabetes receiving insulin pump therapy.
Our study empirically examined how Davis's Technology Acceptance Model (TAM) helped managers predict a user's intention to revisit a website and how this changed over time as a user gained experience ...of the Internet and the website. The user's experience of the website played a moderating role. For less experienced users,
perceived ease of use was found to be a more important factor in deciding to revisit the website, whereas
perceived usefulness had more effect on more experienced users. Thus, web designers can identify and remove web factors that hinder user acceptance and address underlying obstacles to post-adoption usage.
The novelty of the study consisted in applying TAM to a free-content website while considering the moderating effects of Internet and website experience. Significant practical implications can be derived from the results.
Aims
To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues.
Methods
After a 2‐month dose‐optimization ...period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months randomization phase (RP). The MDI group was subsequently switched to pump therapy during a 6‐month continuation phase (CP). The primary endpoint was the between‐group difference in change in mean HbA1c from baseline to the end of the RP.
Results
The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (−1.1 ± 1.2% vs −0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI–pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia.
Conclusions
Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes.
Given their safety and efficiency in protecting protein integrity, polysorbates (PSs) have been the most widely used excipients for the stabilization of protein therapeutics for years. In recent ...decades, however, there have been numerous reports about visible or sub-visible particles in PS-containing biotherapeutic products, which is a major quality concern for parenteral drugs. Alternative excipients that are safe for parenteral administration, efficient in protecting different protein drugs against various stress conditions, effective in protein stabilization in high-concentrated liquid formulations, stable under the storage conditions for the duration of the product's shelf-life, and compatible with other formulation components and the primary packaging are highly sought after. The aim of this paper is to review potential alternative excipients from different families, including surfactants, carbohydrate- and amino acid-based excipients, synthetic amphiphilic polymers, and ionic liquids that enable protein stabilization. For each category, important characteristics such as the ability to stabilize proteins against thermal and mechanical stresses, current knowledge related to the safety profile for parenteral administration, potential interactions with other formulation components, and primary packaging are debated. Based on the provided information and the detailed discussion thereof, this paper may pave the way for the identification or development of efficient excipients for biotherapeutic protein stabilization.
•Starch laurate was prepared by esterification of hydrolyzed rice starch with lauroyl chloride.•Lauroylation decreased the SDS and RS contents of hydrolyzed rice starch.•O/W emulsions were prepared ...using hydrolyzed rice starch and rice starch laurate as stabilizers.•An emulsion with higher stability may be prepared with rice starch laurate.
The effect of esterification on hydrolyzed rice starch was analyzed, for this aim rice starch was hydrolyzed and subsequently esterified with lauroyl chloride at three modification levels. Starch derivatives were characterized regarding their degree of substitution (DS), water solubility index, z-potential, gelatinization, and digestibility properties. DS of derivatives of rice starch laurate ranged from 0.042 to 1.86. It was determined that after esterification the water solubility index increased from 3.44 to 53.61%, the z-potential decreased from −3.18 to −11.27, and the content of slowly digestible starch (SDS) decreased from 26.22 to 5.13%. Different emulsions with starch concentrations ranging from 6 to 30 wt% were evaluated. The most stable emulsions were those having 20 and 30 wt% of rice starch laurate.
Aims
To assess the efficacy of insulin pumps with automated insulin suspension systems in a real‐world setting.
Methods
We analysed anonymized data uploaded to CareLink™ by people (n=920) with Type 1 ...diabetes using the MiniMed Paradigm Veo system and the MiniMed 640G system (Medtronic International Trading Sàrl, Tolochanez, Switzerland) with SmartGuard technology, with or without automated insulin suspension enabled, between February 2016 and June 2018. Users with ≥15 days of sensor data and ≥70% sensor‐wear time were classified as sensor‐augmented pump alone, sensor‐integrated pump with low glucose suspend enabled or sensor‐integrated pump with predictive low glucose management enabled.
Results
The median (25th–75th percentile) system use was 161 (58–348) days. The median time spent with sensor glucose values ≤3 mmol/l was 0.8 (0.3–1.7)% in the sensor‐augmented pump group, 0.3 (0.1–0.7)% in the sensor‐integrated pump with low glucose suspend group, and 0.3 (0.1–0.5)% in the sensor‐integrated pump with predictive low glucose management group. In individuals switching from sensor‐augmented pump to sensor‐integrated pump with low glucose suspend (n=31), there were significant reductions in the monthly rate of hypoglycaemic events <3 mmol/l (rate ratio 0.63, 95% CI 0.45–0.89; P=0.009) and in the percentage of time with glucose values ≤3 mmol/l sensor‐augmented pump: 0.63% (95% CI 0.34–1.29), sensor‐integrated pump with low glucose suspend: 0.33% (95% CI 0.16–0.64); P=0.001. The monthly rate of hypoglycaemic events decreased further in individuals (n=139) switching from sensor‐integrated pump with low glucose suspend to sensor‐integrated pump with predictive low glucose management rate ratio 0.82 (95% CI 0.69–0.98); P<0.0274. Similar results were seen for events <3.9 mmol/l. There was no difference in median time spent in target glucose range.
Conclusion
Real‐world UK data show that increasing automation of insulin suspension reduces hypoglycaemia exposure in people with Type 1 diabetes.
What's new?
Insulin pumps that automatically suspend insulin delivery based on actual or predicted low glucose levels reduce nocturnal and overall hypoglycaemia in randomized controlled trials, but even with these devices some people continue to struggle with nocturnal hypoglycaemia.
This is one of the first real‐world studies to assess the effectiveness of automated insulin suspension systems.
Both daytime and nocturnal hypoglycaemia were reduced to low levels.
Automated insulin suspension in response to hypoglycaemia can reduce the burden of hypoglycaemia in real‐world clinical practice.
These reductions in hypoglycaemia are achieved with no loss of mean glucose control.
Predictive suspension of insulin adds incremental value to threshold suspend systems.
A new genus, Tryposoma gen. nov., is introduced to accommodate two African anostostomatid species formerly classified under the genus Libanasa Walker (Tryposoma kilomeni (Hemp & Johns) comb. nov. and ...Tryposoma brachyurum (Karny) comb. nov.). This taxonomic revision includes a key of the species. Detailed discussions on the genital structure of the newly described genus are also provided.
Gaia Early Data Release 3 Torra, F.; Castañeda, J.; Fabricius, C. ...
Astronomy and astrophysics (Berlin),
05/2021, Letnik:
649
Journal Article
Recenzirano
Odprti dostop
Context.
The
Gaia
Early Data Release 3 (
Gaia
EDR3) contains results derived from 78 billion individual field-of-view transits of 2.5 billion sources collected by the European Space Agency’s
Gaia
...mission during its first 34 months of continuous scanning of the sky.
Aims.
We describe the input data, which have the form of onboard detections, and the modeling and processing that is involved in cross-matching these detections to sources. For the cross-match, we formed clusters of detections that were all linked to the same physical light source on the sky.
Methods.
As a first step, onboard detections that were deemed spurious were discarded. The remaining detections were then preliminarily associated with one or more sources in the existing source list in an observation-to-source match. All candidate matches that directly or indirectly were associated with the same source form a match candidate group. The detections from the same group were then subject to a cluster analysis. Each cluster was assigned a source identifier that normally was the same as the identifiers from
Gaia
DR2. Because the number of individual detections is very high, we also describe the efficient organising of the processing.
Results.
We present results and statistics for the final cross-match with particular emphasis on the more complicated cases that are relevant for the users of the
Gaia
catalogue. We describe the improvements over the earlier
Gaia
data releases, in particular for stars of high proper motion, for the brightest sources, for variable sources, and for close source pairs.
Strain superinfection occurs when a second strain infects a host already infected with and having mounted an immune response to a primary strain. The incidence of superinfection with Anaplasma ...marginale, a tick-borne rickettsial pathogen of domestic and wild ruminants, has been shown to be higher in tropical versus temperate regions. This has been attributed to the higher prevalence of infection, with consequent immunity against primary strains and thus greater selective pressure for superinfection with antigenically distinct strains. However an alternative explanation would be the differences in the transmitting vector, Dermacentor andersoni in the studied temperate regions and Rhipicephalus microplus in the studied tropical regions. To address this question, we examined two tropical populations sharing the same vector, R. microplus, but with significantly different infection prevalence. Using two separate markers, msp1α (one allele per genome) and msp2 (multiple alleles per genome), there were higher levels of multiple strain infections in the high infection prevalence as compared to the low prevalence population. The association of higher strain diversity with infection prevalence supports the hypothesis that high levels of infection prevalence and consequent population immunity is the predominant driver of strain superinfection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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