Efficacy and safety of multiple intra-articular corticosteroid injections for osteoarthritis-a systematic review and meta-analysis of randomized controlled trials and observational studies.

OBJECTIVES: To investigate the efficacy and safety of multiple intra-articular corticosteroid (IACS) injections for the treatment of OA. METHODS: We conducted electronic searches of several databases for randomized controlled trials (RCTs) and observational studies. Standard mean difference was calculated for efficacy, whereas hazard ratio (HR) was used for adverse effects. Results were combined using the random effects model. Heterogeneity was measured using I2 statistics. RESULTS: Six RCTs were included for efficacy assessment. The use of multiple IACS appeared to be better than comparator (standard mean difference for pain -0.47, 95% CI -0.62, 0.31). However, there was considerable heterogeneity (I2 92.6%) and subgroup analysis by comparator showed no separation of regular IACS from placebo, though timing of pain assessments was questionable. Fourteen RCTs and two observational studies were assessed for the safety of multiple IACS. Minor local adverse events were similar in both groups. One RCT found that regular IACS every 3 months for 2 years caused greater cartilage loss compared with saline injection (-0.21 vs 0.10 mm). One cohort study found that multiple IACS injections associated with worsening of joint space narrowing (HR 3.02, 95% CI 2.25, 4.05) and increased risk of joint replacement (HR 2.54, 95% CI 1.81, 3.57). CONCLUSION: Multiple IACS injections are no better than placebo for OA pain according to current evidence. The preliminary finding of a detrimental effect on structural OA progression warrants further investigation. Efficacy and safety of multiple IACS reflecting recommended best practice has yet to be assessed.

Defensive Confidence and Certainty in Unchanged Attitudes: The Role of Affect-Cognition Matching.

Despite much prior research on matching appeals to the affective-cognitive orientation of attitudes, little attention has focused on the consequences of affect-cognition (mis)matching when individuals resist persuasion. We propose that unlike a matched attack, an attack that is mismatched to the affective-cognitive orientation of attitudes would result in low defensive confidence individuals holding onto their unchanged attitudes with less certainty than high defensive confidence individuals. As hypothesized, low defensive confidence participants were less certain after an affective than a cognitive attack for a cognitive issue (Study 1), and the opposite was true for an affective issue (Study 2). Both patterns occurred again when the affective-cognitive orientation of attitudes was manipulated (Study 3) or measured as an individual difference (Study 4). Moreover, perceived knowledge mediated the effects on attitude certainty (Study 4). We end by discussing implications for our understanding of affect-cognition matching and attitude certainty.

When Objective Ambivalence Predicts Subjective Ambivalence: An Affect-Cognition Matching Perspective.

Understanding when people are likely to feel ambivalent is important, as ambivalence is associated with key attitude outcomes, such as attitude-behavior consistency. Interestingly, the presence of conflicting positive and negative reactions (objective ambivalence) is weakly related to feeling conflicted (subjective ambivalence). We tested a novel situation that can influence the correspondence between objective and subjective ambivalence: whether a message and a recipient's topic match in affective versus cognitive orientation. When a person encounters a message with an affective or cognitive match to the topic, conflicting reactions may be more accessible, increasing feelings of ambivalence. Across five studies, greater objective-subjective ambivalence correspondence occurred with an affective-cognitive match between message and topic orientation. Studies 4 and 5 also demonstrated that this primarily occurred when the message was counterattitudinal. This work contributes to the literature explaining the gap between measures of objective and subjective ambivalence as well as how messages can influence attitude strength properties.

Clinical characteristics and outcomes in Asian patients with heart failure with mildly reduced ejection fraction.

Introduction: Data on heart failure (HF) with mildly reduced ejection fraction (HFmrEF) is still emerging, especially in Asian populations. This study aims to compare the clinical characteristics and outcomes of Asian HFmrEF patients with those of HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods: Patients admitted nationally for HF between 2008 and 2014 were included in the study. They were categorised according to ejection fraction (EF). Patients with EF <40%, EF 40%-49% and EF ≥50% were categorised into the following groups: HFrEF, HFmrEF and HFpEF, respectively. All patients were followed up till December 2016. Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular death and/or HF rehospitalisations. Results: A total of 16,493 patients were included in the study - HFrEF, n = 7,341 (44.5%); HFmrEF, n = 2,272 (13.8%); and HFpEF n = 6,880 (41.7%). HFmrEF patients were more likely to be gender neutral, of mid-range age and have concomitant diabetes mellitus, hyperlipidaemia, peripheral vascular disease and coronary artery disease (P < 0.001). The two-year overall mortality rates for HFrEF, HFmrEF and HFpEF were 32.9%, 31.8% and 29.1%, respectively. HFmrEF patients had a significantly lower overall mortality rate compared to HFrEF patients (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.83-0.95; P < 0.001) and a significantly higher overall mortality rate (adjusted HR 1.25, 95% CI 1.17-1.33; P < 0.001) compared to HFpEF patients. This was similarly seen with cardiovascular mortality and HF hospitalisations, with the exception of similar HF hospitalisations between HFmrEF and HFpEF patients. Conclusion: HFmrEF patients account for a significant burden of patients with HF. HFmrEF represents a distinct HF phenotype with high atherosclerotic burden and clinical outcomes saddled in between those of HFrEF and HFpEF. Further therapeutic studies to guide management of this challenging group of patients are warranted.

Does smoking protect against osteoarthritis? Meta-analysis of observational studies.

OBJECTIVES: To determine whether smoking is protective against the development of osteoarthritis (OA). METHODS: Observational studies for the association between smoking and OA were systematically searched through Medline (1950-), Embase (1980-), Web of Science (1960-), PubMed, Google and relevant references. ORs and 95% CIs were directly retrieved or calculated. Current standards for reporting using MOOSE were followed. Quality-related aspects such as study design, setting, sample selection and confounding bias were recorded. Stratified and meta-regression analyses were undertaken to examine the covariates. RESULTS: Of 48 studies (537 730 participants) identified from the systematic literature search, 8 were cohort, 21 cross-sectional and 19 case-control. There was an overall negative association between smoking and OA (OR=0.87; 95% CI 0.80 to 0.94) and subgroup analysis confirmed this in case-control studies (OR=0.82; 95% CI 0.70 to 0.95), but not in cohort (OR=0.92; 95% CI 0.81 to 1.06) or cross-sectional studies (OR=0.89; 95% CI 0.78 to 1.01). Within case-control studies a negative association occurred only in hospital settings (OR=0.65; 95% CI 0.52 to 0.81), not in community settings (OR=0.90; 95% CI 0.75 to 1.08). The association was also seen in knee OA, radiographic OA and smoking as a secondary exposure (covariate or confounding factor). Meta-regression analysis demonstrated that a hospital setting and smoking as a secondary exposure were the major source of the negative association. CONCLUSIONS: The protective effect of smoking in OA observed in some epidemiological studies is likely to be false. It may be caused by selection bias, often in a hospital setting where control subjects have smoking-related conditions and studies that are not primarily designed to investigate smoking. Critical appraisal of such studies is needed.

A cascade of irx1a and irx2a controls shh expression during retinogenesis.

In animal retina, hedgehog expression drives waves of neurogenesis, but genetic programs that control its expression during retinal neurogenesis are poorly elucidated. We have previously reported that irx1a is required for propagation of the sonic hedgehog (shh) expression waves in developing zebrafish retina. Here, we found that irx2a is expressed in the developing retina and that knockdown of irx2a results in a retinal phenotype strikingly similar to that of irx1a morphants. The expression of irx2a in retina ganglion cells was shown to be irx1a- and ath5-dependent suggesting that irx1a and ath5 are transcriptional regulators of irx2a. Furthermore, irx2a expression could rescue impaired propagation of shh waves in irx1a morphants. Together, these observations suggest that Irx2 functions downstream of irx1a to control shh expression in the retina. We proposed a novel transcriptional cascade of ath5-irx1a-irx2a in the regulation of hedgehog waves during vertebrate retinal development.

Meta-analysis on continuous nerve monitoring in thyroidectomies.

In the last decade, the introduction of continuous intraoperative recurrent laryngeal nerve (RLN) monitoring (C-IONM) has enabled the operator to verify the functional integrity of the vagus nerve-recurrent laryngeal nerve (VN-RLN) axis in real-time. We aim to present the current evidence on C-IONM utility for thyroid surgery by conducting the first meta-analysis on this technique. A systematic review of literature was conducted by two independent reviewers via Ovid in the Medline, EMBASE, and Cochrane reviews databases. The search was limited to human subject research in peer-reviewed articles of all languages published between Jan 1946 and April 2020. Medical subject headings (MeSH) terms utilized were thyroid surgery, thyroidectomies, recurrent laryngeal nerve, vagal nerve, monitor, and stimulation. Thirty-eight papers were identified from Ovid, another six papers were identified by hand-search. A random effect meta-analysis was performed with assessment of heterogeneity using the I2 value. A total of 23 papers that investigated the use of continuous vagal nerve monitoring during thyroid surgery were identified. The proportion of nerves at risk (NAR) with temporary RLN paralysis postoperation was 2.26% (95% CI: 1.6-2.9, I2  = 37). The proportion of NAR with permanent RLN palsy postoperation was 0.05% (95% CI: 0.08-0.2, I2  = 0). In this meta-analysis, there is one case of temporary vagal nerve paralysis secondary to VN electrode dislodgement, and a case of hemodynamic instability manifested in bradycardia and hypotension in the initial phase of surgery shortly after calibration. C-IONM is a safe and effective means by which RLN paralyses in thyroid surgery can be reduced.

Comparison of early versus late laser goniopuncture following deep sclerectomy for the management of open-angle glaucoma.

PURPOSE: To compare the outcome of early versus late Nd:YAG laser goniopuncture (LGP) after deep sclerectomy with mitomycin C (DSMMC) for open-angle glaucoma (OAG). METHODS: A retrospective study of consecutive OAG eyes that underwent a LGP following DSMMC was recruited between June 2012 and November 2015. Success was defined as intraocular pressure (IOP) less than 21, 18 or 15 mm Hg with a reduction of more than 20% IOP from baseline without (complete success) or with medications (qualified success). RESULTS: 99 eyes with OAG that underwent DSMMC were recruited into the study. Of these, 49 eyes (49.49%) had undergone LGP post-DSMMC. IOP was significantly reduced following LGP from 28.4 to 11.8 mm Hg. Comparison of Kaplan-Meier survival curves out to 60 months after LGP showed a trend towards better outcomes in the late LGP group with the only statistically significant difference noted for qualified success with IOP target <15 mm Hg. Complications were few with no difference noted between early and late LGP groups. CONCLUSION: There appears to be a trend towards late LGP being more effective after DSMMC when compared with early LGP; this however was not significant. This study corroborates previous published data confirming LGP is an effective and safe procedure for lowering IOP post-DSMMC procedure.

POPPER MACULOPATHY: LONG-TERM FOLLOW-UP AND CASE SERIES.

PURPOSE: To report a case series of popper maculopathy. METHODS: Clinical history, examination findings, retinal imaging, and progress of the disease are described. RESULTS: Four male patients with a mean age of 37 years (range 25-48) and different duration of popper use (ranging from first time user to chronic user) presented with central scotomata, phosphenes, or photophobia. Optical coherence tomography in all cases demonstrated subfoveal disruption of the ellipsoid zone. Three cases also showed hyperreflectivity of the ellipsoid zone, and one case had a foveal detachment. Chronic user of poppers was associated with more severe macular changes. One patient had a 3-year follow-up and demonstrated complete resolution of signs on retinal imaging after ceasing popper use. CONCLUSION: Popper maculopathy may show complete resolution of signs on long-term follow-up, even after chronic popper ingestion.

Cadmium affects retinogenesis during zebrafish embryonic development.

Ocular malformations are commonly observed in embryos of aquatic species after exposure to toxicants. Using zebrafish embryos as the model organism, we showed that cadmium exposure from sphere stage (4 hpf) to end of segmentation stage (24 hpf) induced microphthalmia in cadmium-treated embryos. Embryos with eye defects were then assessed for visual abilities. Cadmium-exposed embryos were behaviorally blind, showing hyperpigmentation and loss of camouflage response to light. We investigated the cellular basis of the formation of the small eyes phenotype and the induction of blindness by studying retina development and retinotectal projections. Retinal progenitors were found in cadmium-treated embryos albeit in smaller numbers. The number of retinal ganglion cells (RGC), the first class of retinal cells to differentiate during retinogenesis, was reduced, while photoreceptor cells, the last batch of retinal neurons to differentiate, were absent. Cadmium also affected the propagation of neurons in neurogenic waves. The neurons remained in the ventronasal area and failed to spread across the retina. Drastically reduced RGC axons and disrupted optic stalk showed that the optic nerves did not extend from the retina beyond the chiasm into the tectum. Our data suggested that impairment in neuronal differentiation of the retina, disruption in RGC axon formation and absence of cone photoreceptors were the causes of microphthalmia and visual impairment in cadmium-treated embryos.

Presumed choroidal metastasis from soft tissue myoepithelial carcinoma.

PURPOSE: To report a case of presumed choroidal metastasis from soft tissue myoepithelial carcinoma and highlight challenges in its diagnosis. OBSERVATIONS: A 52-year-old man was referred with a two-week history of photopsia in his left eye. His background medical history included known soft tissue myoepithelial carcinoma metastatic to his bone, lung, liver and chest wall. A large, raised, yellow choroidal lesion was identified nasal to and abutting the optic disc. This lesion demonstrated growth 1 month after presentation. The patient died with widespread metastatic disease 5 months after initial presentation. CONCLUSION AND IMPORTANCE: Soft tissue myoepithelial carcinoma can rarely metastasise to the choroid and present as a rapidly-growing, yellow, echodense tumour with serous retinal detachment. MRI brain can assist in tumour evaluation and monitoring progression, while immunoperoxidase stains and molecular testing can assist with diagnosis. The condition has an aggressive natural history and poor prognosis.

Light-induced Amaurosis: A Rare Manifestation of Internal Carotid Artery Stenosis.

Light-induced amaurosis (LIA) is a rare presentation of internal carotid artery (ICA) stenosis. This report documents a 74-year-old Caucasian male who presented with profound right monocular vision loss, occurring on every occasion upon entering brightly lit environments. This was managed successfully with a right carotid endarterectomy. This case is presented to highlight the recognition and understanding of LIA and its importance for preservation of vision and prevention of ICA-related stroke.

Data mining for chinese materia medica and pharmacological research.

Chinese materia medica (CMM) is becoming increasingly important in modern health care, with the potential for new or improved clinical protocols and reduction in treatment costs. Conventional approaches to drug discovery are based on knowledge of biological systems and screen phenotypes in the context of a whole organism. It will be valuable to identify the CMM that would induce certain biological responses (such as angiogenesis). The authors have developed a database that they plan to commercialize that contains traditional knowledge of Chinese medicine and pharmacology along with their own experimental data from controlled scientific observations by using the zebrafish as a model of CMM-induced pathology. The database is visualized and functions via the World Wide Web by subscription or license. The authors have also written software for personal digital assistant (PDA) devices that supports multiple users performing screening experiments worldwide. This provides a platform for the study of CMM, and data mining of this resource will help evaluate CMM in the context of experimental observations of biological aberrations.

Affective and cognitive meta-bases of attitudes: Unique effects on information interest and persuasion.

The authors investigated the predictive utility of people's subjective assessments of whether their evaluations are affect- or cognition driven (i.e., meta-cognitive bases) as separate from whether people's attitudes are actually affect- or cognition based (i.e., structural bases). Study 1 demonstrated that meta-bases uniquely predict interest in affective versus cognitive information above and beyond structural bases and other related variables (i.e., need for cognition and need for affect). In Study 2, meta-bases were shown to account for unique variance in attitude change as a function of appeal type. Finally, Study 3 showed that as people became more deliberative in their judgments, meta-bases increased in predictive utility, and structural bases decreased in predictive utility. These findings support the existence of meta-bases of attitudes and demonstrate that meta-bases are distinguishable from structural bases in their predictive utility.

Cadmium inhibits neurogenesis in zebrafish embryonic brain development.

Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis.

Evaluation of the Early to Mid-term Efficacy and Safety of Deep Sclerectomy without an Intrascleral Spacer for Open-angle Glaucoma in an Australian Population.

PURPOSE: This study aims to evaluate the early to the midterm efficacy of deep sclerectomy (DS) without an intra-scleral spacer for open-angle glaucoma (OAG) patients. MATERIALS AND METHODS: Retrospective study of 99 eyes (88 patients) with open-angle glaucoma who underwent DS were recruited in a consecutive order following informed consent. Intraocular pressure (IOP) was collected up to 60 months post operation (mean 19.87 ± 15.13 months). Criteria of success were defined as the qualified success (QS) or complete success (CS) with IOP level less than 21, 18 and 15 mm Hg and a reduction of more than 20% IOP from baseline. QS includes additional medication post-DS, while CS requires no other medications or surgery post-DS. Further analysis includes comparing the criteria of success based on several factors. The data were analyzed using statistical package for social sciences (SPSS version 21) statistical software. RESULTS: The QS at 60 months for IOP less than 21, 18 and 15 mm Hg is 71.3% (45.12 ± 2.46), 63.9% (40.41 ± 2.75) and 48.7% (35.62 ± 2.85), respectively. The CS at 60 months for IOP less than 21, 18 and 15 mm Hg are 69.3% (47.51 ± 2.77), 57.9% (40.41 ± 2.75) and 45.2% (35.62 ± 2.85), respectively. There was no significant difference between QS and DS post-DS based on the level of experience of the surgeons; intraoperation complication; age and gender. There was a significant reduction in IOP post operation (p < 0.001). CONCLUSION: DS is observed to be an effective surgical method with a favorable safety profile to manage patients with open-angle glaucoma. It has a better safety profile compared to trabeculectomy (TE) and can be performed by surgeons of different experience safely and successfully. CLINICAL SIGNIFICANCE: To our knowledge, this is the first report of DS in an Australian population with up to 60 months of follow-up. It is an effective procedure for IOP control in patients with OAG and has fewer complications compared to TE. DS is less popular than TE primarily due to a perceived steep learning curve, but most of the literature on DS describe single surgeon results. Our study compared the outcome of five surgeons with a variety of experience and found no significant differences in the rate of success for all levels of IOP. HOW TO CITE THIS ARTICLE: Hui MM, Clement CI. Evaluation of the Early to Mid-term Efficacy and Safety of Deep Sclerectomy without an Intrascleral Spacer for Open-angle Glaucoma in an Australian Population. J Curr Glaucoma Pract 2018;12(3):107-112.