Does the publication of NICE guidelines for venous thromboembolism chemical prophylaxis influence the prescribing patterns of UK hip and knee surgeons?

IntroductionWe assessed the practice of surgeons regarding venous thromboembolism (VTE) chemical prophylaxis for total hip replacement (THR) and total knee replacement (TKR), before and after issuing of updated National Institute for Health and Care Excellence (NICE) guidance in 2018.MethodsA survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients was assessed after publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored.ResultsFollowing the new guidance, 34% (n=87) used low-molecular-weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH) and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip surgeons and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs after=73%; p<0.001), and aspirin for TKR (before=18% vs after=84%; p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs after=92.6%; p=0.011) and TKR (before=87.0% vs after=98.8%; p<0.001).ConclusionOver one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis.     

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease

Purpose

Because of the evolutionary loss of the uricolytic pathway, humans accumulate poorly soluble urate as the final product of purine catabolism. Restoration of uricolysis through enzyme therapy is a promising treatment for severe hyperuricemia caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG conjugation on the activity and stability of the enzymatic complement required for conversion of urate into the more soluble (S)-allantoin.

Methods

We produced in recombinant form three zebrafish enzymes required in the uricolytic pathway. We carried out a systematic study of the effect of PEGylation on the function and stability of the three enzymes by varying PEG length, chemistry and degree of conjugation. We assayed in vitro the uricolytic activity of the PEGylated enzymatic triad.

Results

We defined conditions that allow PEGylated enzymes to retain native-like enzymatic activity even after lyophilization or prolonged storage. A combination of the three enzymes in an appropriate ratio allowed efficient conversion of urate to (S)-allantoin with no accumulation of intermediate metabolites.

Conclusions

Pharmaceutical restoration of the uricolytic pathway is a viable approach for the treatment of severe hyperuricemia.

     

Detection of Chlamydia pneumoniae in atherosclerotic coronary arteries

Chlamydia pneumoniae has recently been associated with the development of coronary heart diseases by sero-epidemiological studies and by direct detection of the organism in atherosclerotic tissues. The aim of our study was to employ a semi-nested PCR approach to investigate the presence of C. pneumoniae in both normal and atherosclerotic coronary arteries of humans obtained at autopsy. Moreover, we have evaluated the role of infection with C. pneumoniae in relation to the extent of coronary atherosclerosis. One hundred and eighty coronary artery specimens were collected at autopsy from 60 consecutive subjects (three arterial segments from each subject). Atherosclerosis in each arterial segment was graded histologically by the Stary classification. Thirty normal coronary arteries were also taken at autopsy as control. PCR results evidenced the presence of C. pneumoniae DNA in atherosclerotic coronary arteries in 19 (31.7%) of 60 subjects examined, while none of the 30 subjects with non-atherosclerotic tissues was positive (p=0.001). Moreover, of the 180 atherosclerotic specimens examined, C. pneumoniae DNA was detected in 3.4% (2/59) of mild atherosclerotic lesions, and in 14.0% (17/121) of advanced atherosclerotic lesions (p=0.05). Our results demonstrate that the presence of C. pneumoniae DNA may be associated with the severity of coronary atherosclerosis.     

Molecular Epidemiology of Cryptosporidiosis in Iranian Children,Tehran, Iran

Background

Cryptosporidium is a worldwide protozoan parasite and one of the most common causes of infection and diarrhea in humans and cattle. The aim of the present study was determination of subtypes of Cryptosporidium among children with diarrhea in Tehran by sequence analysis of the highly polymorphic 60-kDa glycoprotein (GP60) gene.

Methods

Fecal samples were collected from 794 diarrheic children. Initial identification of Cryptosporidium was carried out on stool samples by Ziehl-Neelsen acid-fast staining method. DNA was extracted from positive microscopically samples and Cryptosporidium genotypes and subtypes were determined, accordingly.

Results

Out of 794 collected samples, 19 (2.40%) were positive for Cryptosporidium oocysts. Sequences analysis of GP60 gene showed that 17 (89.47%) of the positive isolates were Cryptosporidium parvum and 2 (10.52%) were C. hominis. All subtypes of C. parvum isolates belonged to allele families IIa (6/17) and IId (11/17). The most common allele in all 17 isolates belonged to IId A20G1a (41.18%). A22G1 (IF) subtype was detected in two C. hominis isolates of the children.

Conclusion

The predominancy of C. parvum species (specially, IId A20G1a subtype) in current study underlines the importance of zoonotic Cryptosporidium transmission in Iran.     

Eating disorders in adolescents: correlations between symptoms and central control of eating behavior

The aim of this study was to verify the relationship between eating disorders (binge eating and bulimia nervosa) and body image dissatisfaction with BMI, anorexigenic and orexigenic factors in adolescents. Thirty-two adolescents, (13 obese [BMI=36.65±5.68] and 19 non-obese [BMI=22.18±3.11]), aged between 14 and 19y, were recruited. Symptoms of eating disorders were measured by self-report questionnaires (BSQ, BITE and BES). Hormones, cytokines and neuropeptides were determined by Elisa kits (Phoenix peptide). A positive correlation was found between: leptin and BES (r=.724), BSQ (r=.705) and BITE (r=.696); BMI and BES (r=.663), BSQ (r=.525) and BITE (r=.732); the same pattern was observed to insulin and TNF-α. A negative correlation was found in α-MSH and AgRP with BES, BSQ and BITE. Blood levels of hormones and neuropeptides could be the link between obesity and eating disorders in adolescents. However, it is not clear which is the cause and which is the consequence.     

Monarch-1 Activation in Murine Macrophage Cell Line (J774 A.1) Infected with Iranian Strain of Leishmania major

Background

Leishmania major is an intracellular parasite transmitted through the bite of the female phlebotomine sand flies. Leishmania major is able to escape the host immune defense and survive within macrophages. Modulation of the NF-κB (Nuclear Factor-Kappa B) activation and suppression of the pro-inflammatory cytokines by L. major are the main evasion mechanisms that remain to be explored. This study aims to examine the expression level of the Monarch-1 in L. major-infected macrophages, as a negative regulator of the NF-κB activation.

Methods

Murine macrophage cell line (J774 A.1) was infected by metacyclic form of Leishmania promastigotes at macrophage/parasite ratio of 1:10. After harvesting infected cells at different times, total RNA was extracted and converted to cDNA. Semi-quantitative RT-PCR was performed for Monarch-1 by specific primers. Hypoxanthine Phospho-Ribosyl Transferase (HPRT) was used as an internal control to adjust the amount of mRNA in each sample.

Results

Semiquantitive analysis of Monarch-1 mRNA expression level showed a significant expression increase within 6 to 30 hours after L. major infection of macrophages when compared to the control macrophages.

Conclusion

Monarch-1 expression level reveals a significant increase in the early phase of macrophage infection with L. major, which in turn may suppress IL-12 production in Leishmania infected macrophages and deeply influence the relationship between host and parasite.     

Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

间硝苯地平对DOCA-satl 高血压大鼠心肌膜碎片二氢吡啶结合位点的影响

用 DOCA-salt 高血压大鼠心肌肥厚模型，观察间硝苯地平（m-Nif）对肥厚心肌膜碎片二氢吡啶（DHP）结合位点的影响。结果显示：预防或治疗性给予m-Nif（20 mg·kg^-1·d^-1）12 或 9 周，血压降低，心室重和心肌线粒体钙含量减少，且肥厚心肌DHP结合位点密度显著降低（450±25, 462±36 fmol·mg^-1 vs 836±47 fmol·mg^-1 protein, P<0.001）。提示：m-Nif预防和逆转DOCA-salt 高血压大鼠心肌肥厚的作用可能与其减少肥厚心肌DHP 结合位点密度和血压降低有关。     

口服Carvedilol治疗心力衰竭多中心研究(MOCHA)

标题　Ｃａｒｖｅｄｉｌｏｌ对慢性心力衰竭患者左心室功能的改善和存活的提高呈剂量相关性作者　ＢｒｉｓｔｏｗＭＲ，ＧｉｌｂｅｒｔＥＭ，ＡｂｒａｈａｍＷＴ，等　　Ｃｉｒｃｕｌａｔｉｏｎ１９９６，９４：２８０７～２８１６　　研究疾病：充血性心力衰竭。目的：对Ｃａｒｖｅｄｉｌｏｌ治疗慢性心力衰竭患者剂量－疗效特征进行评价。　　设计：随机、双盲、安慰剂对照的多中心研究，剂量效应关系研究。病人资料：共３４５名心力衰竭患者，年龄１８～８５岁，左室射血分数≤０－３５，心力衰竭症状时间≥３月，研究前所有患者必须用利…