Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

Formate Additive for Efficient and Stable Methylammonium-Free Perovskite Solar Cells by Gas-Quenching.

In order to promote the commercialization of perovskite solar cells, gas-quenching is considered to be a promising technique for perovskite film fabrication. However, when handling with methylammonium-free (MA-free) perovskites, it is often difficult to obtain high-quality perovskite films by gas-quenching. Herein, formate additives are employed to regulate the crystallization of MA-free perovskite, and improve the quality of perovskite films. Different additives of formamidine formate (FAFO) and potassium formate (KFO) is compared to investigate the role of formate groups in the crystallization of perovskite films prepared by gas-quenching. The FAFO additive facilitates the perovskite crystallization in (001) orientation whereas KFO favors for (111) orientation. The MA-free device with addition of FAFO demonstrate a champion power conversion efficiency of 20.94 %, compared to that of 20.14 % for KFO devices. In addition, FAFO device also exhibits improved thermal stability in ambient condition without encapsulation, extending the T80 lifetime by 18 times compared to the pristine device.

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

PURPOSE OF THE REVIEW: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. RECENT FINDINGS: Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I2 = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

Association between knee symptoms, change in knee symptoms over 6-9 years, and SF-6D health state utility among middle-aged Australians.

OBJECTIVES: Health state utilities (HSUs) are an input metric for estimating quality-adjusted life-years (QALY) in cost-utility analyses. Currently, there is a paucity of data on association of knee symptoms with HSUs for middle-aged populations. We aimed to describe the association of knee symptoms and change in knee symptoms with SF-6D HSUs and described the distribution of HSUs against knee symptoms' severity. METHODS: Participants (36-49-years) were selected from the third follow-up (completed 2019) of Australian Childhood Determinants of Adult Health study. SF-6D HSUs were generated from the participant-reported SF-12. Association between participant-reported WOMAC knee symptoms' severity, change in knee symptoms over 6-9 years, and HSUs were evaluated using linear regression models. RESULTS: For the cross-sectional analysis, 1,567 participants were included; mean age 43.5 years, female 54%, BMI ± SD 27.18 ± 5.31 kg/m2. Mean ± SD HSUs for normal, moderate, and severe WOMAC scores were 0.820 ± 0.120, 0.800 ± 0.120, and 0.740 ± 0.130, respectively. A significant association was observed between worsening knee symptoms and HSUs in univariable and multivariable analyses after adjustment (age and sex). HSU decrement for normal-to-severe total-WOMAC and WOMAC-pain was - 0.080 (95% CI - 0.100 to - 0.060, p < 0.01) and - 0.067 (- 0.085 to - 0.048, p < 0.01), exceeding the mean minimal clinically important difference (0.04). Increase in knee pain over 6-9 years was associated with a significant reduction in HSU. CONCLUSION: In a middle-aged population-based sample, there was an independent negative association between worse knee symptoms and SF-6D HSUs. Our findings may be used by decision-makers to define more realistic and conservative baseline and ongoing HSU values when assessing QALY changes associated with osteoarthritis interventions.

Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

BACKGROUND: Current pharmacologic therapies for patients with osteoarthritis are suboptimal. OBJECTIVE: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. DESIGN: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). SETTING: Single-center study with patients from southern Tasmania, Australia. PARTICIPANTS: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. INTERVENTION: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. MEASUREMENTS: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. RESULTS: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. LIMITATION: Modest sample size and short duration. CONCLUSION: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. PRIMARY FUNDING SOURCE: University of Tasmania and Natural Remedies Private Limited.

Efficacy and safety of tocilizumab in treatment of Takayasu arteritis: A systematic review of randomized controlled trials.

BACKGROUND: Takayasu arteritis (TAK) is a chronic immune vasculitis in which Interleukin-6 (IL-6) receptors play a key role in pathogenesis. Tocilizumab (TCZ), an IL-6 receptor antagonist with a favorable safety and efficacy profile, has been tried as an option for patients with TAK. This systematic review analyzed the evidence from randomized control trials (RCT) assessing the safety and efficacy of TCZ in patients with TAK. METHODS: MEDLINE, Embase, the Cochrane Library, and clinical trial registries were searched from inception to July 2018. We included RCT assessing the efficacy and safety of TCZ versus placebo/other comparators for the treatment of patients with TAK. The risk of bias (RoB) was assessed using Cochrane RoB tool. RESULTS: 2799 identified articles were screened as per abstract and title; 42 selected full-texts articles were assessed for the potential inclusion. One trial, reported in two publications, comparing subcutaneous TCZ (162 mg/week) versus matching placebo in 36 patients with TAK was included. The relapse-free rate at 24 weeks was 50.6% and 22.9% in TCZ and placebo arm, respectively. The hazard ratio (HR) for time to first relapse was statistically significant in the per-protocol population (HR 0.34 [95.41% CI, 0.11-1.00]; p = .0345), while non-significant in the intention-to-treat population (HR 0.41 [95.41% CI, 0.15-1.10]; p = .0596). The serious adverse events were higher in the placebo arm. CONCLUSIONS: This systematic review finds the existing evidence from RCT on efficacy and safety profile of TCZ in TAK to be promising but limited. Additional evidence is required to draw a stronger conclusion.

No association between proton pump inhibitor use and risk of dementia: Evidence from a meta-analysis.

BACKGROUND AND AIM: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. METHODS: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case-control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle-Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non-PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. RESULTS: Twelve studies (eight cohort and four case-control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96-1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case-control: P = 0.14), sex (RR 1.25 [95% CI: 0.97-1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91-1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. CONCLUSION: We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

Thiazolidinedione use is associated with reduced risk of Parkinson's disease in patients with diabetes: a meta-analysis of real-world evidence.

BACKGROUND: The thiazolidinedione (TZD) class of oral antidiabetic agents are used to treat type 2 diabetes mellitus (DM). This meta-analysis aimed to understand the protective effect of TZD on Parkinson's disease (PD) in people with diabetes. METHOD: A literature search was performed in PubMed, Embase, and Cochrane central from inception to until 30 September 2019. We included all real-world evidence studies assessing the use of TZD class of drugs and the risk of PD in people with diabetes. Quality of the studies was evaluated using the Newcastle-Ottawa scale. The primary outcome was the pooled hazard ratio (HR) of PD among type 2 DM TZD users as compared with TZD non-users in people with diabetes. The secondary outcome was the HR of PD among type 2 DM TZD users as compared with non-users (include both diabetic and nondiabetic population). Meta-analysis was performed using RevMan software. RESULTS: Out of five studies selected for inclusion, four studies fulfilled the criteria for primary outcomes. The participants' mean age and follow-up duration were 66.23 ± 9.59 years and 5.25 years (2.97-7.9 years), respectively. There was a significant reduction in the risk of PD (pooled adjusted HR of 0.81 [95% CI 0.70-0.93, p = 0.004]) in TZD users compared with non-TZD users in people with diabetes. A significant protective effect of TZD was observed in Caucasian population (3 studies) (HR 0.78 (95% CI 0.66-0.92), p = 0.003). CONCLUSION: This meta-analysis demonstrates a potential neuroprotective effect of TZD for PD risk in the population with DM.

Effects of walnut intake on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

The impact of walnuts on blood pressure (BP) is not a well-established fact. Although several studies have assessed the effects of walnut consumption on BP, results are conflicting. Thus, we examined the effects of walnut doses and length of supplementation on BP. Biomedical databases were searched for published trials that compared walnut-enhanced diet to control diet. Eighteen trials met eligibility criteria (n = 1,799). Overall, walnut consumption neither did alter SBP (weighted mean difference [WMD]: 0.08 mmHg; 95% CI: -0.69, 0.85) nor DBP (WMD: 0.08 CI: -0.26, 0.42). In subgroup analyses, walnut ingestion ≤40 g was statistically correlated with reduction in SBP (WMD: -0.53 mmHg, 95% CI: -0.79, -0.26) and DBP (WMD: -0.191 mmHg, 95% CI: -0.384, -0.034). Moreover, the length of intervention ≥8 weeks was linked to a significant reduction in SBP (WMD: -1.18 mmHg, 95% CI: -1.30, -1.06). Following dose-response evaluation, walnut intake significantly changed SBP (p = .015) and DBP (p = .026) through a nonlinear fashion at walnut dose up to 40 g/d. Nevertheless, these statistical results cannot be translated into clinical practice, once the changes expressed as WMD are slight taking into consideration the absolute values of BP categories. In conclusion, this meta-analysis does not support walnut consumption as a BP-lowering strategy.

Vitamin D supplementation for the management of knee osteoarthritis: a systematic review of randomized controlled trials.

Conflicting evidence exists concerning the supplementation of vitamin D in knee osteoarthritis condition. This systematic literature review was done to explore the effects of vitamin D supplementation in the management of knee osteoarthritis. Electronic literature search was done in databases like PubMed®, Embase®, and Cochrane CENTRAL from inception to 6th July 2016. The quality of included Randomized Controlled Trials (RCTs) was assessed using Cochrane risk of bias tool. We considered change in Western Ontario and McMaster Universities (WOMAC) index, Visual Analog Scale (VAS) and Functional Pain Score (FPS) as the primary outcome measure. Change in tibial cartilage thickness, joint space width and safety profile was considered as secondary outcomes. Participants were randomized either to treatment or placebo group. Participants received cholecalciferol as an intervention through oral route in the dose range of 800-60,000 IU except in the one study where participants received ergocalciferol. All included RCTs showed a significant increase in serum vitamin D level in the treatment group compared to the placebo group at the end point. No significant reduction in pain and function was reported on WOMAC scale except in one study. No significant difference was reported for WOMAC stiffness in any study. VAS was assessed in three studies in which two showed statistically significant improvement in knee pain. Three of the RCTs reported safety data with one incidence of calculus ureteric and hip fracture found to be related to the drug. The study found evidence from RCTs to be insufficient to support the use of vitamin D supplementation for patients with knee osteoarthritis.

Porphyrins as Corrosion Inhibitors for N80 Steel in 3.5% NaCl Solution: Electrochemical, Quantum Chemical, QSAR and Monte Carlo Simulations Studies.

The inhibition of the corrosion of N80 steel in 3.5 wt. % NaCl solution saturated with CO2 by four porphyrins, namely 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin (HPTB), 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphyrin (T4PP), 4,4',4″,4‴-(porphyrin-5,10,15,20-tetrayl)tetrakis(benzoic acid) (THP) and 5,10,15,20-tetraphenyl-21H,23H-porphyrin (TPP) was studied using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization, scanning electrochemical microscopy (SECM) and scanning electron microscopy (SEM) techniques. The results showed that the inhibition efficiency, η% increases with increasing concentration of the inhibitors. The EIS results revealed that the N80 steel surface with adsorbed porphyrins exhibited non-ideal capacitive behaviour with reduced charge transfer activity. Potentiodynamic polarization measurements indicated that the studied porphyrins acted as mixed type inhibitors. The SECM results confirmed the adsorption of the porphyrins on N80 steel thereby forming a relatively insulated surface. The SEM also confirmed the formation of protective films of the porphyrins on N80 steel surface thereby protecting the surface from direct acid attack. Quantum chemical calculations, quantitative structure activity relationship (QSAR) were also carried out on the studied porphyrins and the results showed that the corrosion inhibition performances of the porphyrins could be related to their EHOMO, ELUMO, ω, and µ values. Monte Carlo simulation studies showed that THP has the highest adsorption energy, while T4PP has the least adsorption energy in agreement with the values of σ from quantum chemical calculations.

Impact of Pain on Activities of Daily Living in Older Adults: A Cross-Sectional Analysis of Korean Longitudinal Study of Aging (KLoSA).

Pain, particularly musculoskeletal (MSK) and multi-site pain, significantly impacts activities of daily living (ADL) in the elderly, leading to a decline in overall quality of life (QoL). This study, comprising 7490 participants, (mean age: 69 ± 10; females: 57%) from the sixth wave of the Korean Longitudinal Study of Aging (KLoSA), aimed to assess the association between self-reported pain and ADL impairment among the elderly population. Notably, 62% of participants reported experiencing pain, with back pain being the most prevalent (36%) and stomachache the least (0.39%). A majority (61%) of individuals reported MSK-related pain. Additionally, 20% reported pain at one site and 0.03% experienced pain at 12 sites. ADL impairment was observed in 376 (5.0%) participants. Compared to those without pain, participants reporting moderate and severe pain had higher odds of ADL impairment [2.31 (95% CI, 1.66-3.21) and 2.98 (95% CI, 1.95-4.53), respectively]. Pain experienced in the shoulder, arm, wrist, back, hip, leg, and ankle had a significant association with ADL impairment, with ORs ranging from 2.66 (95% CI, 1.80-3.93; hip pain) to 1.36 (95% CI 1.07-1.72; back pain). Furthermore, multi-site pain was associated with higher ADL impairment [1-6 sites: OR: 1.49 (95% CI, 1.11-2.01); 7-12 sites: OR: 7.16 (95% CI, 3.60-14.26)]. These findings underscore the importance of addressing MSK and multi-site pain through targeted interventions, potentially enhancing ADL and contributing to an improved QoL among the elderly population.

Trajectory of metabolic syndrome and its association with knee pain in middle-aged adults.

OBJECTIVE: Metabolic syndrome (MetS) is characterised by the clustering of central obesity with metabolic abnormalities. We aimed to describe the association of MetS and trajectories of MetS over 10-13 years with knee symptoms in general population-based middle-aged adults. METHODS: Fasting blood biochemistry, waist circumference and blood pressure measures were collected during Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-6; n = 2447; mean age:31.48 ± 2.60) and after 10-13 year at CDAH-3 (year:2014-2019; n = 1549; mean age:44 ± 2.90). Participants were defined as having MetS as per International Diabetes Federation (IDF) definition. Knee symptoms were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale at CDAH-3 (mid-adulthood). RESULTS: The prevalence of MetS increased from 8 % at young adulthood (female:52.06 %) to 13 % in mid-adulthood (female:53.78 %) over 10-13 years. Presence of MetS at mid-adulthood was associated with knee symptoms at mid-adulthood [ratio of means (RoM): 1.33; 95%CI:1.27,1.39]. Four MetS trajectories were identified-'No MetS' (85.01 %); 'Improved MetS' (2.14 %), 'Incident MetS' (8.81 %), and 'Persistent MetS, (4.04 %). Compared to 'No MetS', 'Persistent MetS' [RoM:1.15; 95%CI:1.06,1.25], 'Incident MetS' [RoM:1.56; 95%CI:1.48,1.65], and 'Improved MetS' [RoM:1.22; 95%CI:1.05,1.41] was associated with higher knee symptoms. Notably, 'Incident MetS' was strongly associated with knee symptoms [RoM: 1.56; 95%CI:1.48,1.65] and pain [RoM:1.52; 95%CI:1.37,1.70] at mid-adulthood. CONCLUSION: In this sample of middle-aged adults, there was a significant positive association between MetS and knee symptoms. Relative to those without MetS at either life stage, the elevation in mean knee pain scores was more pronounced for those who developed MetS after young adulthood than for those who had MetS in young adulthood.

Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials.

OBJECTIVE: Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. METHODS: PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. RESULT: Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], - 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, - 0.37; 95% CI, - 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. CONCLUSION: Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine.

Experimental and computational approach on the development of a new Green corrosion inhibitor formulation for N80 steel in 20% formic acid.

Organic acids are employed as scale dissolvers in the oil & gas industry during production to stimulate oil recovery by pumping in the formations. Corrosion of metallic surfaces in organic acid solutions poses a significant issue in the oil and gas sector. In recent years, considering the stringent environmental regulations, there has been a growing research interest in environmentally safe inhibitors. This paper explores the synthesis of 2-(3-(carboxymethyl)-1H-imidazol-3-ium-1-yl) acetate (IZ) and its first-time application for corrosion mitigation of N80 steel in 20% formic acid. A detailed experimental study involving gravimetric, electrochemical, and surface analytical techniques is reported herein. The electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) analyses suggest a rise of impedance with IZ and a mixed-type inhibition behavior, respectively. The inhibition efficiency (IE) is 99.54% at 200 mg/L at 308 K, reaching 99.4% at 363 K with the introduction of KI as a synergistic agent. Computational studies revealed that the inhibitor IZ gets protonated in the experimental environment. The protonated form shows a tendency to receive electrons from the metal surface and shows a greater energy of adsorption compared to that of the neutral form.

Effect of Curcuma longa extract on serum inflammatory markers and MRI-based synovitis in knee osteoarthritis: secondary analyses from the CurKOA randomised trial.

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

Efficacy and safety of hydroxychloroquine in osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/AIMS: Conventional disease-modifying anti-rheumatic drugs have been trialed in osteoarthritis (OA). Hydroxychloroquine (HCQ), which has shown its effectiveness in rheumatoid arthritis, has been trialed for the treatment of OA; however, its efficacy and safety remain unclear. This systematic review and meta-analysis evaluate efficacy and safety of HCQ for the treatment of OA. METHODS: MEDLINE, EMBASE, and Cochrane Central were searched from inception through June 2020. Two reviewers independently screened for randomized controlled trials (RCTs) comparing HCQ with placebo or other active-comparators for the treatment of knee, hand, or hip OA, extracted data, and performed Cochrane risk of bias assessments. RESULTS: Six RCTs, four in hand OA, two in knee OA, consisting of 842 patients (436 in HCQ arm, 406 in control arm) were included. RCTs were conducted between 2012 and 2020, one each at UK, Netherlands, Germany, Italy, Iran, and Egypt; follow-up period ranged 24 to 52 weeks. High-quality evidence showed no clinically important pain reduction with HCQ compared to placebo/active-control in hand OA (standardized mean difference [SMD], 0.14; 95% confidence interval [CI], -0.20 to 0.48). Effect on pain reduction in knee and hand OA was small and non-significant (SMD, -0.09; 95% CI, -0.44 to 0.25). High-quality evidence showed no improvement in dysfunction with HCQ compared to placebo in hand OA patients (SMD, 0.08; 95% CI, -0.23 to 0.40). Effect on dysfunction improvement in knee and hand OA was modest and statistically non-significant (SMD, -0.20; 95% CI,-0.57 to 0.18). No improvement in quality of life was observed in hand OA. CONCLUSION: HCQ has no benefit in reducing pain and improving physical function in hand or knee OA patients.

A systematic review of cost-effectiveness analyses of continuous versus intermittent renal replacement therapy in acute kidney injury.

INTRODUCTION: Though cost-effectiveness analyses (CEAs) have evaluated continuous renal replacement therapy (RRTs) and intermittent RRTs in acute kidney injury (AKI) patients; it is yet to establish which RRT technique is most cost-effective. We systematically reviewed the current evidence from CEAs of CRRT versus IRRT in patients with AKI. AREAS COVERED: PubMed, EMBASE, and Cochrane databases searched for CEAs comparing two RRTs. Overall, seven CEAs, two from Brazil and one from US, Canada, Colombia, Belgium, and Argentina were included. Five CEAs used Markov model, three reported following CHEERS, none accounted indirect costs. Time horizon varied from 1-year-lifetime. Marginal QALY gain with CRRT compared to IRRT was reported across CEAs. Older CEAs found CRRT to be costlier and not cost-effective than IRRT (ICER 2019 US$: 152,671$/QALY); latest CEAs (industry-sponsored) reported CRRT to be cost-saving versus IRRT (-117,614$/QALY). Risk of mortality, dialysis dependence, and incidence of renal recovery were the key drivers of cost-effectiveness. EXPERT OPINION: CEAs of RRTs for AKI show conflicting findings with secular trends. Latest CEAs suggested CRRT to be cost-effective versus IRRT with dialysis dependence rate as major driver of cost-effectiveness. Future CEAs, preferably non-industry sponsored, may account for indirect costs to improve the generalizability of CEAs.

How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials.

Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA.

A Randomised Controlled Trial of YOGa and Strengthening Exercise for Knee OsteoArthritis: Protocol for a Comparative Effectiveness Trial (YOGA Trial).

Osteoarthritis (OA) is a common joint disorder for which there is no cure. Current treatments are suboptimal. Exercise is a core treatment for knee OA, with muscle strengthening exercise commonly recommended. Yoga is a mind-body exercise intervention that can improve flexibility, muscle strength, balance, and fitness and potentially reduce symptoms of OA. However, there is a scarcity of robust, high-quality conclusive evidence on the efficacy of yoga in knee OA. We are currently conducting the first randomised comparative effectiveness and cost-effectiveness trial of a yoga program compared with a strengthening exercise program in patients with symptomatic knee OA. This study protocol describes the design and conduct of this trial. The YOGA study is a phase III, single-centre, parallel, superiority, randomised, active-controlled trial which will be conducted in Hobart, Australia. One hundred and twenty-six participants (63 in each arm) aged over 40 years with symptomatic knee OA will be recruited from the community and randomly allocated to receive either a 24-week yoga program (3×/week) or a strengthening exercise program (3×/week). The primary outcome will be change in knee pain over 12 weeks, assessed using a 100 mm visual analogue scale (VAS). The secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life, gait speed, biomarkers, and others over 12 and 24 weeks. We will also assess whether the presence of neuropathic pain moderates the effects of yoga compared to strengthening exercise. Additional data, such as cost and resource utilization, will be collected for the cost-effectiveness analysis. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored throughout the study. Once completed, this trial will contribute to the knowledge of whether yoga can be used as a simple, effective, low-cost option for the management of knee OA, thus saving economic costs in the healthcare system.