Interventions for tophi in gout.

BACKGROUND: Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014.  OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout. SEARCH METHODS: We updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020. SELECTION CRITERIA: We included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol. Two trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias. Moderate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16). More participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal. Moderate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded for indirectness and imprecision). Participants on lesinurad in the original study continued (CONT) on the same dose. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution; 43/65 in the lesinurad 400 mg CONT arm compared to 38/64 in the lesinurad 200 mg CONT arm had tophi resolution (RR 1.11, 95% CI 0.85 to 1.46). Lesinurad 400 mg plus febuxostat may result in no difference in adverse events; 57/65 in the lesinurad 400 mg CONT arm had an adverse event compared to 50/64 in lesinurad 200 mg CONT arm (RR 1.12, 95% CI 0.96 to 1.32). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events; 10/65 participants in the lesinurad 400 mg CONT arm withdrew due to an adverse event compared to 10/64 participants in the lesinurad 200 mg CONT arm (RR 0.98, 95% CI 0.44 to 2.20). Lesinurad 400 mg plus febuxostat may result in no difference in mean serum uric acid (sUA), which was 3 mg/dl in the lesinurad 400 mg CONT group compared to 3.9 mg/dl in the lesinurad 200 mg CONT group (mean difference -0.90, 95% CI -1.51 to -0.29). Participants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. Low-certainty evidence downgraded for indirectness and imprecision showed that lesinurad 400 mg (CROSS) may result in tophi resolution (17/34) compared to lesinurad 200 mg (CROSS) (14/33) (RR 1.18, 95% CI 0.70 to 1.98). Lesinurad 400 mg in combination with febuxostat may result in no difference in adverse events (33/34 in the lesinurad 400 mg CROSS arm compared to 27/33 in the lesinurad 200 mg (CROSS); RR 1.19, 95% CI 1.00 to 1.41). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events, 5/34 in the lesinurad 400 mg CROSS arm withdrew compared to 2/33 in the lesinurad 200 mg CROSS arm (RR 2.43, 95% CI 0.51 to 11.64). Lesinurad 400 mg plus febuxostat results in no difference in sUA (4.2 mg/dl in lesinurad 400 mg CROSS) compared to lesinurad 200 mg (3.8 mg/dl in lesinurad 200 mg CROSS), mean difference 0.40 mg/dl, 95% CI -0.75 to 1.55. AUTHORS' CONCLUSIONS: Moderate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.

The Effects of Dexamethasone on the Time to Pain Resolution in Dental Periapical Abscess.

BACKGROUND: Dental infections are frequently encountered in the emergency department (ED), with periapical abscesses being among the most painful. Traditional pain management strategies include local anesthetic injections, oral analgesics, and intravenous opioids. OBJECTIVES: We sought to identify an alternative pain management strategy with early use of dexamethasone as adjunct to conventional therapies for inflammation and pain at the site of infection. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled study comparing the analgesic effect of dexamethasone and placebo in ED patients with periapical abscess during a 2-year timeframe at two urban academic EDs. Adult patients presenting with physical examination findings consistent with a diagnosis of periapical abscess were randomized to receive oral dexamethasone or an identical placebo. Pain was assessed using the verbal numeric scale in person at discharge and via telephone at 12, 24, 48, and 72 h after discharge from the ED. RESULTS: Seventy-three patients were enrolled, with 37 receiving dexamethasone and 36 receiving placebo. Follow-up pain scores were obtained for 52 patients at 12, 24, 48, and 72 h. Ten patients from the dexamethasone group and 11 from placebo group were lost to follow-up. Patients who received dexamethasone reported a greater reduction in pain at 12 h compared with the placebo group (p = 0.029). Changes in pain scores from baseline and at 24, 48, and 72 h were not statistically significant. No adverse events were reported. CONCLUSIONS: Single-dose dexamethasone as adjunct to conventional medical management for pain caused by periapical abscess demonstrated a significant reduction in pain 12 h post treatment compared with placebo.

Interventions for tophi in gout.

BACKGROUND: Tophi develop in untreated or uncontrolled gout. Their presence can lead to severe and potentially fatal complications. To date there have been no systematic reviews focused on the management of tophi in gout. OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout. SEARCH METHODS: We searched three databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE. We handsearched American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts from 2010 to 2011, references from included studies and trial registries. We completed the most recent search on 20 May 2013. SELECTION CRITERIA: All published randomised controlled trials (RCTs) or controlled clinical trials with quasi-randomised methods of allocating participants to treatment examining interventions for tophi in gout in adults. Possible interventions included urate-lowering pharmacological treatment (e.g. benzbromarone, probenecid, allopurinol, febuxostat, pegloticase), surgical removal or other interventions such as haemodialysis. DATA COLLECTION AND ANALYSIS: Two review authors extracted data from titles, abstracts and selected studies for detailed review, and extracted data and risk of bias independently. Major outcomes were number of participants with complete resolution of tophi, number of study participant withdrawals due to adverse events, joint pain reduction, function, quality of life, serum urate normalisation and total adverse events. MAIN RESULTS: Only one study, at low risk of all biases, met the inclusion criteria. This was the pooled results from two RCTs (225 participants, 145 with tophi at baseline) randomised to one of three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Moderate-quality evidence from one study indicated that biweekly pegloticase 8 mg infusion reduced tophi in the subset of participants with tophi, but increased withdrawals due to adverse events in all participants, and monthly infusion appeared to result in less benefit.Biweekly pegloticase treatment resulted in resolution of tophi in 21/52 participants compared with 2/27 who received placebo (risk ratio (RR) 5.45, 95% confidence intervals (CI) 1.38 to 21.54; number needed to treat for an additional beneficial outcome (NNTB) 3 (95% CI 2 to 6).Eleven of 52 participants with monthly pegloticase treatment had complete resolution of one or more tophi compared with 2/27 who received placebo (RR 2.86, 95% CI 0.68 to 11.97).Participant-reported pain relief of 30% or greater, function, quality of life, serum urate normalisation, were reported for all participants but not separately for those with tophi; therefore, we did not include the results.Pegloticase administered biweekly resulted in more withdrawals due to adverse events compared with placebo (15/85 participants with pegloticase versus 1/43 participants with placebo; RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for an additional harmful outcome (NNTH) 7, 95% CI 4 to 17). Pegloticase administered monthly also resulted in more withdrawals due to adverse events than placebo (16/84 participants with pegloticase versus 1/43 participants with placebo; RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Most withdrawals were due to infusion reactions.Total adverse events were high in all treatment groups: 80/85 participants administered pegloticase biweekly reported an adverse event compared with 41/43 from the placebo group (RR 0.99, 95% CI 0.91 to 1.07); 84/84 participants administered pegloticase monthly reported an adverse event versus 41/43 in the placebo group (RR 1.05, 95% CI 0.98 to 1.14). As 80% of adverse events were due to flares of gout, probably unrelated to the drug treatment per se, this may explain the high rate of adverse events in the placebo group - who were essentially untreated. AUTHORS' CONCLUSIONS: This study showed pegloticase is probably beneficial in the management of tophi in gout, in terms of resolution of tophi, but with a high risk of adverse infusion reactions. However, there is a need for more RCT data considering other interventions, including surgical removal of tophi.

Molecular silicate and aluminate species in anhydrous and hydrated cements.

The compositions and molecular structures of anhydrous and hydrated cements are established by using advanced solid-state nuclear magnetic resonance (NMR) spectroscopy methods to distinguish among different molecular species and changes that occur as a result of cement hydration and setting. One- and two-dimensional (2D) solid-state (29)Si and (27)Al magic-angle spinning NMR methodologies, including T(1)-relaxation-time- and chemical-shift-anisotropy-filtered measurements and the use of very high magnetic fields (19 T), allow resonances from different silicate and aluminate moieties to be resolved and assigned in complicated spectra. Single-pulse (29)Si and (27)Al NMR spectra are correlated with X-ray fluorescence results to quantify the different crystalline and disordered silicate and aluminate species in anhydrous and hydrated cements. 2D (29)Si{(1)H} and (27)Al{(1)H} heteronuclear correlation NMR spectra of hydrated cements establish interactions between water and hydroxyl moieties with distinct (27)Al and (29)Si species. The use of a (29)Si T(1)-filter allows anhydrous and hydrated silicate species associated with iron-containing components in the cements to be distinguished, showing that they segregate from calcium silicate and aluminate components during hydration. The different compositions of white Portland and gray oilwell cements are shown to have distinct molecular characteristics that are correlated with their hydration behaviors.

Management of anastomotic leaks after Roux-en-Y bypass using self-expanding polyester stents.

BACKGROUND: To analyze the outcomes of a series of endoscopically placed polyester self-expanding polyflex stents (SEPSs) for the management of anastomotic leaks after Roux-en-Y bypass. Anastomotic leaks after gastric bypass cause significant morbidity and mortality. Covered polyester SEPSs might have a role in the treatment of these leaks. METHODS: A retrospective chart review was performed from January 2006 to November 2006 that included all acute and chronic leaks treated with SEPSs. RESULTS: A total of 6 patients were treated with stents, with a mean procedure time of 22 minutes. Of these 6 patients, 5 had acute postoperative leaks and 1 had a chronic fistula. Five patients started oral intake 1-6 days after their procedure. All acute leaks had complete healing at a median of 44 days. The patient with a chronic gastrocutaneous fistula required revisional surgery for fistula closure. In addition, 5 patients had stent migration, and 3 required stent replacement. CONCLUSION: An endoscopically placed SEPS provides a less-invasive alternative to treat acute anastomotic leaks after Roux-en-Y bypass while simultaneously allowing oral intake. The results of this case series have demonstrated this treatment to be safe and effective.

Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis.

Nanometric field-effect-transistor (FET) sensors are made on the tip of spear-shaped dual carbon nanoelectrodes derived from carbon deposition inside double-barrel nanopipettes. The easy fabrication route allows deposition of semiconductors or conducting polymers to comprise the transistor channel. A channel from electrodeposited poly pyrrole (PPy) exhibits high sensitivity toward pH changes. This property is exploited by immobilizing hexokinase on PPy nano-FETs to give rise to a selective ATP biosensor. Extracellular pH and ATP gradients are key biochemical constituents in the microenvironment of living cells; we monitor their real-time changes in relation to cancer cells and cardiomyocytes. The highly localized detection is possible because of the high aspect ratio and the spear-like design of the nano-FET probes. The accurately positioned nano-FET sensors can detect concentration gradients in three-dimensional space, identify biochemical properties of a single living cell, and after cell membrane penetration perform intracellular measurements.

The assessment of pain and discomfort in individuals with mental retardation.

This research was conducted to replicate and expanded the work of Bodfish et al. [Bodfish, J. W., Harper, V. N., Deacon, J. R., & Symons, F. J. (2001, May). Identifying and measuring pain in persons with developmental disabilities: A manual for the Pain and Discomfort Scale (PADS). Western Carolina Center Research Reports] by assessing the functional sensitivity of the Pain and Discomfort Scale (PADS) in patients with MR. We used the PADS to detect pain and discomfort during a dental scaling and polishing procedure. Subjects (N=28) with cognitive and communication deficits were assessed at multiple baselines, during and after the procedure. The results indicated that scores on the PADS were significantly higher during the scaling procedure than during all other observations quantified by the PADS. We conclude that the PADS is a functionally sensitive measure that may lack specificity, but that may also represent the state of the psychometric art of assessing pain in patients who have MR.

Mini-implant behavior to shear tensile forces in the porcine mandible.

AIM: To determine the tangential tensile force loading behavior of mini-implants relative to cortical bone thickness in the porcine mandible. METHODS: Eighteen mini-implants were placed both anteriorly and posteriorly perpendicular to the bone surface in porcine mandibles and subjected to shear tests using a Universal Testing Machine (Instron). Further, cone beam CT was used to measure cortical bone thickness at each mini-implant site. RESULTS: The shear strength differed significantly between the anterior (mean 89.05 ± 35.9 N) and posterior (mean 179.85 ± 29.01 N) sites. The same was true for the cortical bone thickness (anteriorly, mean 3.59 ± 0.49 mm; posteriorly, mean 4.24 ± 0.5 mm). CONCLUSION: The shear forces required to dislodge mini-implants were much higher than forces typically applied for orthodontic purposes. Therefore, mandibular cortical bone supporting monocortical orthodontic mini-implants would most likely withstand immediate loading with tangential shear forces. In addition, it seems that mini-implants loaded tangentially continue to exhibit adequate anchorage for orthodontic forces even after they are displaced.

Neighboring group-controlled hydrolysis: towards "designer" drug release biomaterials.

To give the first demonstration of neighboring group-controlled drug delivery rates, a series of novel, polymerizable ester drug conjugates was synthesized and fully characterized. The monomers are suitable for copolymerization in biomaterials where control of drug release rate is critical to prophylaxis or obviation of infection. The incorporation of neighboring group moieties differing in nucleophilicity, geometry, and steric bulk in the conjugates allowed the rate of ester hydrolysis, and hence drug liberation, to be rationally and widely controlled. Solutions (2.5 x 10-5 mol dm-3) of ester conjugates of nalidixic acid incorporating pyridyl, amino, and phenyl neighboring groups hydrolyzed according to first-order kinetics, with rate constants between 3.00 +/- 0.12 x 10-5 s -1 (fastest) and 4.50 +/- 0.31 x 10- 6 s-1 (slowest). The hydrolysis was characterized using UV-visible spectroscopy. When copolymerized with poly(methyl methacrylate), free drug was shown to elute from the resulting materials, with the rate of release being controlled by the nature of the conjugate, as in solution. The controlled molecular architecture demonstrated by this system offers an attractive class of drug conjugate for the delivery of drugs from polymeric biomaterials such as bone cements in terms of both sustained, prolonged drug release and minimization of mechanical compromise as a result of release. We consider these results to be the rationale for the development of "designer" drug release biomaterials, where the rate of required release can be controlled by predetermined molecular architecture.