A randomised comparison of two intranasal dexmedetomidine doses for premedication in children

We compared sedation levels in children following administration of intranasal dexmedetomidine. One hundred and sixteen children aged between 1 and 8 years were enrolled in this prospective, randomised trial. Children were assigned to receive either intranasal dexmedetomidine 1 μg.kg^?1 (Group 1) or 2 μg.kg^?1 (Group 2). Thirty‐one (53%) patients from Group 1 and 38 (66%) patients from Group 2 were satisfactorily sedated at the time of anaesthetic induction. Logistic regression showed a significant interaction effect (p = 0.049), with the odds ratio between Group 2 over Group 1 estimated as 1.1 (95% CI 0.5–2.7) for the 1–4 year age group, and 10.5 (95% CI 1.4–80.2) for the 5–8 year age group. Both doses produced a similar level of satisfactory sedation in children aged 1–4 years, whereas 2 μg.kg^?1 resulted in a higher proportion of satisfactory sedation in children aged 5–8 years. There were no adverse haemodynamic effects. We conclude that intranasal dexmedetomidine in a premedication dose of 2 μg.kg^?1 resulted in excellent sedation in children.     

CpG Oligodeoxynucleotides as TLR9 Agonists

Toll-like receptors (TLRs) are part of the innate immune system, and they belong to the pattern recognition receptors (PRR) family. The PRR family is designed to recognize and bind conserved pathogen-associated molecular patterns, which are not generated by the host and are restricted and essential to microorganisms. TLR9, which recognizes unmethylated CpG (cytosine guanosine dinucleotide), is a very promising target for therapeutic activation. Stimulation of TLR9 activates human plasmacytoid dendritic cells and B cells, and results in potent T helper-1 (T_h1)-type immune responses and antitumor responses in mouse tumor models and in patients. Several pharmaceutical companies, such as Pfizer, Idera, and Dynavax, are developing CpG oligodeoxynucleotides (ODNs) for the treatment of cancer, along with other conditions, such as infections and allergy. CpG ODNs have shown promising results as vaccine adjuvants and in combination with cancer immunotherapy. Several TLR9 agonists are being developed and have entered clinical trials to evaluate their safety and efficacy for the treatment of several hematopoietic and solid tumors. In this review, we discuss the use of CpG ODNs in several phase I and II clinical trials for the treatment of NHL, renal cell carcinoma, melanoma, and non-small cell lung cancer, either alone or in combination with other agents.     

Coenzyme Q10 exogenous administration attenuates cold stress cardiac injury

The influence of coenzyme Q10 (CoQ10) in cold stress test (-15 degrees C for 4 hours) cardiac functional impairment was studied in isolated isovolumic heart of control rats (C; n=12) and of placebo (P; n=11) and treated rats (CoQ10; n=10). In addition, electron microscopic evaluation of left ventricular (LV) slices (n=3 in each group) allowed us to analyze the myocardial ultrastructure. Maximal values of developed pressure (DPmax) were similarly decreased in cold stressed animals (C=129+/-3.9 mmHg; P=106+/-6.7 mmHg; CoQ10=91+/-3.9 mmHg); however, volume-induced enhancement of pressure generation (slope of DP volume relations: C=0.248+/-0.0203 mmHg / microl; P=0.2831+/-0.0187 mmHg / microl; CoQ10=0.2387 ( 0.0225 mmHg / microl; p > 0.05), and the duration of systole (C=80+/-1.6 ms; P=78+/-1.3 ms; CoQ10=80+/-2.7 ms) were not altered. Myocardial relaxation, evaluated by the relaxation constant (C=39+/-1.9 ms; P=42+/-3.4 ms; CoQ10=51+/-6.0 ms), as well as resting stress / strain relations were unaffected by cold stress. Myocardial samples showed that pretreatment with CoQ10 attenuates myofibrillar and mitochondrial lesions, and prevents mitochondrial fractional area increase (P: 53.11%>CoQ10: 38.78%=C: 33.87%; p< 0.005) indicating that the exogenous administration of CoQ10 can reduce cold stress myocardial injury.     

Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth muscle

Bradykinin (10^–8-10^–5M) caused a concentration-dependent increase in cyclic GMP (cGMP) production in bovine tracheal smooth muscle in the absence of epithelium. The effect was calcium-dependent and was inhibited by pyrogallol (10 M) and methylene blue (10 M). The inhibition of pyrogallol was reversed by superoxide dismutase (100 Usnowml). Nitric oxide (NO) synthase inhibitors, N ^G-methyl-l-arginine (10–100 M) and N ^G-nitro-l-arginine (10–100 M) reduced cGMP accumulation induced by bradykinin in a concentration-dependent fashion, and the inhibition was reversed by l-arginine. Immunohistochemistry with a specific antibody against neuronal NO synthase from rat cerebellum showed positive staining localized in some nerve fibers. Bradykinin-induced cGMP accumulation appears to be related to the release of NO, part of which is probably synthesized in nonadrenergic noncholinergic nerve in bovine trachea.Offprint requests to: Dr. Hong Sheng     

The utility of cervical elastosonography in prediction of cervical insufficiency: cervical elastosonography and cervical insufficiency

Objective: To evaluate the utility of cervical elastosonography (ES) in prediction of cervical insufficiency (CI).

Methods: A total of 40 women, of which 20 who had previously received the diagnosis of CI and 20 healty women were included in the study. None of the women were pregnant. All subjects underwent sonographic evaluation including cervical length measurement and ES of uterine cervix. Adjacent muscular tissue was the reference point for elastosonography evaluation. Tissue strain ratio values were obtained from all the patients.

Results: The area around the internal cervical os of the group with CI was found to be significantly softer as compared to the control group (higher SR rate, p?<?0.05). Furthermore, the outer parts of the cervix (sites A and D) were also found harder in the group that had CI (lower SR rate, p?<?0.05).

Conclusions: According to our knowledge, this is preliminary study to evaluate the predictive value of cervical ES in CI and we concluded that ES can be used as reliable method to determine CI but it is necessary to be studied in different cohort groups.     

Pathways to Colonoscopy in the South: Seeds of Health Disparities

Objectives. We aimed to highlight sociodemographic differences in how patients access colonoscopy.Methods. We invited all eligible patients (n = 2500) from 2 academy-affiliated colonoscopy centers in Alachua County, Florida (1 free standing, 1 hospital based), to participate in a precolonoscopy survey (September 2011–October 2013); patients agreeing to participate (n = 1841, response rate = 73.6%) received a $5.00 gift card.Results. We found sociodemographic differences in referral pathway, costs, and reasons associated with obtaining the procedure. Patients with the ideal pathway (referred by their regular doctor for age-appropriate screening) were more likely to be Black (compared with other minorities), male, high income, employed, and older. Having the colonoscopy because of symptoms was associated with being female, younger, and having lower income. We found significant differences for 1 previously underestimated barrier, having a spouse to accompany the patient to the procedure.Conclusions. Patients’ facilitators and barriers to colonoscopy differed by sociodemographics in our study, which implies that interventions based on a single facilitator will not be effective for all subgroups of a population.Colorectal cancer (CRC), the second leading cause of US cancer deaths in 2013 (50 830),1 is not distributed equally. Nationally, it is estimated that incidence is 25% higher, and mortality from CRC 50% higher, in Black Americans than in Whites.2,3 Most CRC diagnoses follow evaluation by colonoscopy. Although consumers have a range of CRC screening tests, from least invasive (fecal occult blood test, fecal immunochemical test) to most invasive (sigmoidoscopy, colonoscopy),4 if polyps are indicated, a colonoscopy is required as follow-up. Thus, colonoscopy is both an entry point and a pivotal event in the process of preventing, detecting, and treating CRC. CRC can be prevented through the removal of precancerous polyps or detected at an early, easily treatable stage5; findings indicate6 that colonoscopy with polypectomy reduces mortality from CRC by 53%. Although rates of CRC screening have increased,3 there is need for improvement. More than one third of Americans are not in compliance with screening guidelines,7 with rates being lower in the southern United States.8In 2008, Etzioni et al.9 presented a model of patient and provider-level factors that influence decision-making in colon cancer and that can lead to health disparities in disease recurrence and survival. The Etzioni model identifies key points of vulnerability in the treatment process where the potential to achieve high-quality, guideline-recommended care can be lost. The model captures patients after surgery, beginning with the decision to refer patients to a medical oncologist for adjuvant treatment; it is relevant because there is considerable evidence of inequities in who receives adjuvant treatment based on older age,10,11 comorbidities,12,13 low income,7 coverage with Medicaid rather than Medicare,13 Black race,14 female gender,15,16 and being unmarried.9We propose that this model starts too late in the process; health disparities originate prior to colonoscopy and can increase at each decision point along a continuum. In an elaborated model (Figure 1), we suggest that CRC health disparities research should begin with an investigation of entry into the health care system and the subsequent pathways to colonoscopy. Referral patterns, costs, and patient demographics influence patient access to care, colonoscopy compliance, and postcolonoscopy decision-making.Open in a separate windowFIGURE 1—Pathways to colonoscopy, treatment, and outcomes.     

A theory-based intervention to promote medication adherence in patients with rheumatoid arthritis: A randomized controlled trial

Clinical Rheumatology - Adherence to prescribed medication regimens is fundamental to the improvement and maintenance of the health of patients with rheumatoid arthritis. It is therefore important...     

Empirical Comparison of Publication Bias Tests in Meta-Analysis

Background

Decision makers rely on meta-analytic estimates to trade off benefits and harms. Publication bias impairs the validity and generalizability of such estimates. The performance of various statistical tests for publication bias has been largely compared using simulation studies and has not been systematically evaluated in empirical data.

Methods

This study compares seven commonly used publication bias tests (i.e., Begg’s rank test, trim-and-fill, Egger’s, Tang’s, Macaskill’s, Deeks’, and Peters’ regression tests) based on 28,655 meta-analyses available in the Cochrane Library.

Results

Egger’s regression test detected publication bias more frequently than other tests (15.7% in meta-analyses of binary outcomes and 13.5% in meta-analyses of non-binary outcomes). The proportion of statistically significant publication bias tests was greater for larger meta-analyses, especially for Begg’s rank test and the trim-and-fill method. The agreement among Tang’s, Macaskill’s, Deeks’, and Peters’ regression tests for binary outcomes was moderately strong (most κ’s were around 0.6). Tang’s and Deeks’ tests had fairly similar performance (κ?>?0.9). The agreement among Begg’s rank test, the trim-and-fill method, and Egger’s regression test was weak or moderate (κ <?0.5).

Conclusions

Given the relatively low agreement between many publication bias tests, meta-analysts should not rely on a single test and may apply multiple tests with various assumptions. Non-statistical approaches to evaluating publication bias (e.g., searching clinical trials registries, records of drug approving agencies, and scientific conference proceedings) remain essential.