Number and type of guideline implementation tools varies by guideline,clinical condition,country of origin,and type of developer organization: content analysis of guidelines

Background

Guideline implementation tools (GI tools) can improve clinician behavior and patient outcomes. Analyses of guidelines published before 2010 found that many did not offer GI tools. Since 2010 standards, frameworks and instructions for GI tools have emerged. This study analyzed the number and types of GI tools offered by guidelines published in 2010 or later.

Methods

Content analysis and a published GI tool framework were used to categorize GI tools by condition, country, and type of organization. English-language guidelines on arthritis, asthma, colorectal cancer, depression, diabetes, heart failure, and stroke management were identified in the National Guideline Clearinghouse. Screening and data extraction were in triplicate. Findings were reported with summary statistics.

Results

Eighty-five (67.5%) of 126 eligible guidelines published between 2010 and 2017 offered one or more of a total of 464 GI tools. The mean number of GI tools per guideline was 5.5 (median 4.0, range 1 to 28) and increased over time. The majority of GI tools were for clinicians (239, 51.5%), few were for patients (113, 24.4%), and fewer still were to support implementation (66, 14.3%) or evaluation (46, 9.9%). Most clinician GI tools were guideline summaries (116, 48.5%), and most patient GI tools were condition-specific information (92, 81.4%). Government agencies (patient 23.5%, clinician 28.9%, implementation 24.1%, evaluation 23.5%) and developers in the UK (patient 18.5%, clinician 25.2%, implementation 27.2%, evaluation 29.1%) were more likely to generate guidelines that offered all four types of GI tools. Professional societies were more likely to generate guidelines that included clinician GI tools.

Conclusions

Many guidelines do not include any GI tools, or a variety of GI tools for different stakeholders that may be more likely to prompt guideline uptake (point-of-care forms or checklists for clinicians, decision-making or self-management tools for patients, implementation and evaluation tools for managers and policy-makers). While this may vary by country and type of organization, and suggests that developers could improve the range of GI tools they develop, further research is needed to identify determinants and potential solutions. Research is also needed to examine the cost-effectiveness of various types of GI tools so that developers know where to direct their efforts and scarce resources.

     

Expression of an Acid Urease with Urethanase Activity in <Emphasis Type="Italic">E. coli</Emphasis> and Analysis of Urease Gene

Urea in alcoholic beverage is a precursor of ethyl carbamate (EC), which is carcinogenic. Enzymatic elimination of urea has attracted much research interest. Acid urease with good tolerance toward ethanol and acid is ideal enzyme for such applications. In the present work, the structural genes of urease from Providencia rettgeri JN-B815, ureABC were efficiently expressed in E. coli BL21(DE3) in an active form (apourease) exhibiting both urease and urethanase (hydrolyze EC) activities. The specific activities of the purified apourease were comparatively low, which were 2.1 U/mg for urease and 0.6 U/mg for urethanase, respectively. However, apourease exhibited good resistance toward ethanol and acidic conditions. The relative activities of urease and urethanase remained over 80% in the buffers within pH 4–7. And the recoveries of both urease and urethanase activities were more than 50% in 5–25% ethanol solution. Apourease was utilized to eliminate urea in wine, and the residual urea in model wine was less than 50% after treatment with apourease for 30 h. Then 3D structure of UreC was predicted, and it was docked with urea and EC, respectively. The docking result revealed that three hydrogen bonds were formed between urea and amino acid residues in the active site of urease, whereas only one hydrogen bond can be formed between EC and the active center. Moreover, EC exhibited greater steric hindrance than urea when combined with the active site. Due to the low specific activities of apourease, both structural genes and accessory genes of urease were co-expressed in E. coli BL21(DE3). The holoenzyme was expressed as inclusion body. After renaturation and purification, the specific activities of urease and urethanase reached 10.7 and 3.8 U/mg, which were 5.62-fold and 6.33-fold of those of apourease, respectively. Therefore, accessory subunits of urease play an important role in enhancing urease and urethanase activities.     

Neuroprotective Effects of Simvastatin and Cilostazol in <Emphasis Type="SmallCaps">l</Emphasis>-Methionine-Induced Vascular Dementia in Rats

Vascular dementia (VaD) is a degenerative cerebrovascular disorder that leads to progressive decline in cognitive abilities and memory. Several reports demonstrated that oxidative stress and endothelial dysfunction are principal pathogenic factors in VaD. The present study was constructed to determine the possible neuroprotective effects of simvastatin in comparison with cilostazol in VaD induced by l-methionine in rats. Male Wistar rats were divided into four groups. Group I (control group), group II received l-methionine (1.7 g/kg, p.o.) for 32 days. The remaining two groups received simvastatin (50 mg/kg, p.o.) and cilostazol (100 mg/kg, p.o.), respectively, for 32 days after induction of VaD by l-methionine. Subsequently, rats were tested for cognitive performance using Morris water maze test then sacrificed for biochemical and histopathological assays. l-methionine induced VaD reflected by alterations in rats’ behavior as well as the estimated neurotransmitters, acetylcholinesterase activity as well as increased brain oxidative stress and inflammation parallel to histopathological changes in brain tissue. Treatment of rats with simvastatin ameliorated l-methionine-induced behavioral, neurochemical, and histological changes in a manner comparable to cilostazol. Simvastatin may be regarded as a potential therapeutic strategy for the treatment of VaD. To the best of our knowledge, this is the first study to reveal the neuroprotective effects of simvastatin or cilostazol in l-methionine-induced VaD.

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KU0063794, a Dual mTORC1 and mTORC2 Inhibitor,Reduces Neural Tissue Damage and Locomotor Impairment After Spinal Cord Injury in Mice

Autophagy is an intracellular catabolic mechanism for the degradation of cytoplasmic constituents in the autophagosomal–lysosomal pathway. This mechanism plays an important role in homeostasis and it is defective in certain diseases. Preceding studies have revealed that autophagy is developing as an important moderator of pathological responses associated to spinal cord injury (SCI) and plays a crucial role in secondary injury initiating a progressive degeneration of the spinal cord. Thus, based on this evidence in this study, we used two different selective inhibitors of mTOR activity to explore the functional role of autophagy in an in vivo model of SCI as well as to determine whether the autophagic process is involved in spinal cord tissue damage. We treated animals with a novel synthetic inhibitor temsirolimus and with a dual mTORC1 and mTORC2 inhibitor KU0063794 matched all with the well-known inhibitor of mTOR the rapamycin. Our results demonstrated that mTOR inhibitors could regulate the neuroinflammation associated to SCI and the results that we obtained evidently demonstrated that rapamycin and temsirolimus significantly diminished the expression of iNOS, COX2, GFAP, and re-established nNOS levels, but the administration of KU0063794 is able to blunt the neuroinflammation better than rapamycin and temsirolimus. In addition, neuronal loss and cell mortality in the spinal cord after injury were considerably reduced in the KU0063794-treated mice. Accordingly, taken together our results denote that the administration of KU0063794 produced a neuroprotective function at the lesion site following SCI, representing a novel therapeutic approach after SCI.     

CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy

In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K ^trans) as a biomarker for blood–brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K ^trans (K ^trans-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K ^trans-PIV, and smaller FIV (P?<?0.001). K ^trans-PIV showed good correlation with FIV (P?<?00.001, R ²?=?0.6997). In the regression analyses, K ^trans-PIV was the best predictor of clinical outcomes (P?=?0.009, odds ratio (OR)?=?1.960) and also the best predictor for FIV (F?=?75.590, P?<?0.0001). In conclusion, combining PCT and K ^trans maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.     

Questionable papers in citation databases as an issue for literature review

In recent years, the academic world has been faced with much academic misconduct. Examples involve plagiarizing papers, manipulating data, and launching predatory or hijacked journals. The literature exposing these activities is growing exponentially, and so is the presentation of criteria or guidelines for counteracting the problem. Most of the research is focused on predatory or hijacked journal detection and providing suitable warnings. Overlooked in all this is the fact that papers published in these journals are questionable, but nevertheless show up in standard citation databases. We need some way to flag them so future researchers will be aware of their questionable nature and prevent their use in literature review.