Osteoarthritis today: Lost in translation?

Osteoarthritis (OA) is a highly prevalent joint disease that is associated with pain, loss of function, and high direct and indirect economic costs. The current therapeutic options are inadequate, providing only a moderate symptom relief without the possibility of disease modification. While treatment options and personalized medicines are increasing for many complex diseases, OA drug development has been impeded by the advanced state of disease at the time of diagnosis and intervention, heterogeneity in both symptoms and rates of progression, and a lack of validated biomarkers and relevant outcome measures. This review article summarizes the OA landscape, including therapies in development as potential OA treatments, potential biomarkers undergoing evaluation by the US Food and Drug Administration, and a summary of current OA treatment guidelines, with a particular focus on the knee OA.     

Recent advances in construction of small molecule-based fluorophore-drug conjugates

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.     

Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

ABSTRACT

Purpose

New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates.     

Anxiety sensitivity as a mediator of the association between asthma and smoking

Objective: Despite its negative effects, smoking is more common among individuals with asthma compared to those without. Anxiety sensitivity (fear of arousal-related sensations) is associated with both smoking and asthma; however, no research, to date, has examined the interplay between these three factors. Thus, the purpose of the current study was to evaluate the mediating role of anxiety sensitivity in the association between asthma diagnosis and smoking status. Methods: The current study was a secondary analysis of data from three existing datasets of non-smokers and smokers with and without asthma (n?=?433; 56.3% female, M_age?=?34.01 years, SD?=?13.9). Participants provided information on their asthma diagnosis status and smoking status and completed self-report measures. Results: As hypothesized, after controlling for gender, race and age, there was a significant indirect effect of asthma diagnosis on smoking status through anxiety sensitivity (95% CI?=?0.07–0.48). Conclusions: These results indicate that the association between asthma diagnosis and smoking status appears to be driven, in part, by anxiety sensitivity and suggest that anxiety sensitivity may serve as an important target for prevention and intervention efforts for smokers with asthma.     

Does the video head impulse test replace caloric testing in the assessment of patients with chronic dizziness? A systematic review and meta-analysis

IntroductionCaloric testing is the most frequently used test to assess peripheral vestibular function since the beginning of the 20th century. However, the video head impulse test, vHIT, has gained prominence in the field of neurotology, as it is a faster examination, easier to perform and less uncomfortable for the patient.ObjectiveTo compare, through systematic review and meta-analysis, the proportion of altered cases between vHIT tests and caloric testing in patients with chronic dizziness, in addition to assessing the sensitivity and specificity of vHIT, with caloric testing as the gold standard.MethodsThe literature search was carried out in the PubMed, Scopus, BVS-Bireme, Web of Science, Embase, Cochrane and ProQuest indexed databases, with no restrictions regarding the publication period. All articles that contained the results of the two tests were included in the evaluation of patients with dizziness. Two researchers independently conducted data selection and extraction from the studies, strictly following the inclusion and exclusion criteria defined in the research protocol. In case of disagreement during the selection, a discussion was carried out with a third evaluator.ResultsEleven of the 1293 initial articles met the eligibility criteria and were analyzed. 2670 patients were evaluated, of which 1112 (41.6%) were males and 1558 (58.4%) females, with a mean age of 51.6 years. The proportion of altered results in the vHIT was 21% (95%CI 9% –33%), and 55% in the caloric testing (95%CI 43% –67%).ConclusionThe vHIT does not substitute for caloric testing. The tests are complementary in assessing the patient with dizziness, as they describe the tonotopy of the ampullary crest at different frequency ranges of stimulation. In chronic cases, the vHIT has a low sensitivity and high diagnostic specificity in comparison to caloric testing.     

高效液相色谱串联质谱法测定氯沙坦钾中的遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸

目的建立了一种高效液相色谱-三重四极杆串联质谱法,对氯沙坦钾原料药中遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)进行测定。方法色谱柱为岛津Shim-pack XR-ODSⅡ色谱柱(2.0 mm×150 mm,2.2μm),流动相为0.1%甲酸水溶液(A)和甲醇(B),进行梯度洗脱,流速0.3 mL·min^-1,柱温为40℃,采用ESI离子化-三重四极杆质谱多反应监测(MRM)正离子模式检测,碰撞电压分别为-11,-13和-13 V,碰撞气氩气270 kPa,NMBA的离子对分别为m/z 147.15→117.10,147.15→87.10和147.15→44.10。结果该方法中NMBA在1~100 ng·mL^-1内线性关系良好,日内和日间的保留时间和峰面积的重复性良好(RSD均小于1.10%,n=6和n=18),低、中、高3个浓度的平均回收率在94.40%~98.04%之间。结论本方法简单方便,可快速有效的对氯沙坦钾原料药中NMBA进行限度检查并实现定量分析。     

The role of cardiopulmonary exercise testing in evaluating children with exercise induced dyspnoea

Exercise induced dyspnoea (EID) is a common manifestation in children and adolescents. Although EID is commonly attributed to exercise induced bronchoconstriction, several conditions other than asthma can cause EID in otherwise healthy children and adolescents. Cardiopulmonary exercise testing (CPET) offers a non-invasive comprehensive assessment of the cardiovascular, ventilatory and metabolic responses to exercise and is a powerful diagnostic and prognostic tool. CPET is a reproducible, non-invasive form of testing that allows for comparison against age- and gender-specific norms. CPET can assess the child’s exercise capacity, determine the limiting factors associated with this, and be used to prescribe individualised interventions. EID can occur due to asthma, exercise induced laryngeal obstruction, breathing pattern disorders, chest wall restriction and cardiovascular pathology among other causes. Differentiating between these varied causes is important if effective therapy is to be initiated and quality of life improved in subjects with EID.     

Prospective comparative study of intraoperative “Towel clip test” and “Vertical patella test” assessing lateral retinaculum tightness in patients undergoing TKA

BackgroundProper patellar tracking is one of the most important aspect of TKA to ensure good functional outcome. A patellar tracking problem noted intraoperatively serves as a warning sign and should prompt the surgeon to reassess position of each component. Various tests are there to assess lateral retinaculum tightness viz. "No thumb test", "Towel clip test". A new test "Vertical patella test" is described to assess lateral retinaculum tightness. A study was conducted to assess the effectiveness, correlation and validity of two techniques.Materials & MethodsPatients >50 years of age and with diagnosis of Osteoarthritis knee having less than 30 varus and flexion deformity going in for primary TKA were selected with a sample size of 100 knees in a tertiary care centre. Revision cases or patients with flexion contracture more than 30, complex knee surgery; with pre existing patellar tilt were excluded from study.ResultsResults of both tests were found to correlate in 75% of case with sensitivity of 96.65% and specificity of 75.00%. Kappa came out to be 0.634 which shows good agreement of vertical patella test and towel clip test. Result was computed using excel and SPSS and was found to be significant with p value< 0.05. Lateral retinaculum release was done in 8 knees.ConclusionsVertical patella test correlates with towel clip test, is easy to perform and saves time. The limitation of our study was small sample size.