This study had two aims: (i) to investigate outcomes of medication tapering in stable RA patients on biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) and conventional synthetic DMARDs (csDMARDs) in a real-world prospective cohort; and (ii) to evaluate possible predictors of flare with medication taper.
A prospective cohort of patients with RA in sustained remission or low disease activity while on stable bDMARD/tsDMARDs +/- csDMARDs for at least 6 months underwent medication tapering/stopping and was tracked for 2 years. Patients were evaluated for flares in four groups: no taper, only bDMARD/tsDMARD taper, only csDMARD taper and both csDMARD and bDMARD/tsDMARD taper.
The RHEUMTAP cohort included 131 patients that met eligibility criteria, of which 52 patients underwent a medication taper. Flare was experienced by 15 patients in the taper and two in the no-taper groups. Patients undergoing any taper/stop overall were 10 times more likely to experience a flare compared with those not tapered (HR 10.43, 95% CI 2.98-36.53, P = 0.0002). The group tapering bDMARD/tsDMARD had 31 times higher risk of flare (HR 31.43, 95% CI 6.35-155.55, P <0.0001) than the no-taper group. Patients tapering both csDMARDs and bDMARD/tsDMARDs had 18 times higher risk of flare than the no-taper group (HR 18.45, 95% CI 2.55-133.37, P = 0.0039). The only csDMARD taper group had a 91% lower risk of flare than the bDMARD/tsDMARD taper group (HR 0.09, 95% CI 0.01-0.69, P = 0.0213).
In our real-world prospective RHEUMTAP cohort study on the outcomes of different medication tapering groups in well-controlled RA, patients who tapered or stopped bDMARDs/tsDMARDs with or without background therapy were more likely to experience a flare than patients that did not taper any medications and those that tapered only csDMARDs.

The risks of concomitant benzodiazepine (BZ) and opioid use are significant. Despite the urgent need to reduce BZ use among patients taking opioids, no treatment intervention research to our knowledge has addressed treatment for this concurrent, high-risk use. The current study will evaluate the efficacy of augmenting BZ taper procedures with CBT for anxiety disorders that has been adapted specifically for patients with concomitant BZ and opioid use (either use as prescribed or misuse), a high-risk patient population. Research combining rapidly scalable behavioral interventions ancillary to pharmacological approaches delivered via telehealth in primary care settings is innovative and important given concerning trends in rising prevalence of BZ/opioid co-prescription, BZ-associated overdose deaths, and known barriers to implementation of behavioral health interventions in primary care. CBT delivery using telehealth has the potential to aid adherence and promote access and dissemination of procedures in primary care. Lastly, the current study will utilize an experimental therapeutics approach to preliminarily explore the mechanism of action for the proposed interventions. The overall aim of the present pilot randomized controlled trial is to examine the feasibility and preliminary efficacy of a BZ taper with CBT for anxiety disorders adapted for patients with concomitant BZ (BZT + CBT) and opioid use to a BZ taper with a control health education program (BZT + HE) in a sample of individuals (N = 54) who have been prescribed and are taking benzodiazepines and opioids for at least 3 months prior to baseline and experience anxious distress. Screening and outcome measures, methods, and implications are described. Trial Registration: ClinicalTrials.gov (NCT05573906).

UNASSIGNED: The aim of this study was to evaluate and compare the pericervical dentin preservation and fracture resistance of root canal-treated teeth with rotary endodontic file systems of different types of taper.
UNASSIGNED: Thirty-two single-rooted human-extracted premolars were used. They were mounted in wax, and preoperative cone-beam computed tomography (CBCT) scans were taken with 11 × 8 Field of view (FOV). The evaluation of the pericervical dentin thickness was done at the cementoenamel junction level. After pre-CBCT, the 32 samples were divided into four groups (n = 8) - Group A: fixed tapered hand files, Group B: variable regressive tapered TruNatomy, Group C: progressive tapered ProTaper Gold, and Group D: fixed tapered HyFlex EDM. Following instrumentation, postoperative CBCT scans were taken to evaluate pericervical dentin thickness. Obturation was done and access cavity was restored with composite. Fracture strength was checked for all the samples using \"universal testing machine\" until fracture, and calculated in newtons (N).
UNASSIGNED: Student\'s t-test and ANOVA test, along with Tukey\'s post hoc analysis, were used for comparing mean values between the groups, and P < 0.05 was considered statistically significant.
UNASSIGNED: The results of this study showed that there is no statistically significant difference in preserving pericervical dentin with file system of different types of taper and fracture resistance between the groups.
UNASSIGNED: Within the limitations of the study, it was concluded that different types of file taper systems used for root canal preparation have no significant effect on the preservation of pericervical dentin and fracture resistance of teeth.

Rituximab is used for the treatment of active rheumatoid arthritis. In the present study, we examined the long-term flare risk and safety of reduced doses of rituximab.
This was a prospective, observational, single-center study of patients starting rituximab on standard dose (SD). Patients were switched to low dose (LD) (1 g every 6 months), based on the treating rheumatologist\'s decision after having achieved sustained clinical responses, while the rest of the patients continued on standard dose (SD). During a 60-month period, we assessed (Kaplan-Meier survival analysis) the relapse rate (increase ≥ 1.2 in DAS28-ESR for ≥ 6 months) and discontinuations due to treatment failure in the low dose group, and we compared the incidence of serious adverse events (SAEs) between LD and SD groups.
Out of 361 patients [females 83.4%, mean age 61.9 (10.6) years, seropositive 50.3%, median total comorbidities count 4], 81 patients (22.4%) entered LD in a median time of 24 months (95% CI 18-30 months). Seropositivity (OR 1.823), more than 2 previous bDMARDs failures (OR 0.428), and DAS28 < 4.88 at 6 months (OR 2.329) predicted the odds of entering LD (p < 0.05 for all). During 60 months of follow-up, only 7.5% of patients on LD relapsed. Patients on LD had significantly less SAEs and all-cause hospitalizations as compared to the SD group (p < 0.05 for all). Linear regression analysis showed that previous hospitalization while on bDMARDs (p < 0.0001), use of prednisolone > 5 mg/day while on rituximab (p < 0.0001), and a history of ≥ 2 previous csDMARDs (p = 0.041) predicted the risk of SAEs.
In a cohort of patients with established RA and significant comorbidities who taper rituximab after substantial initial disease activity improvement, a low rate of relapses and lower risk of SAEs compared to SD were recorded. Seropositivity, a lower number of previous bDMARDs use, and lower DAS28 at 6 months predicted the probability of entering the LD regimen.

Corrosion at the modular taper junctions in total hip arthroplasty is clinically relevant because wear particles and ions generated at this interface can lead to adverse local tissue reactions or even implant failure. In vitro tribo-corrosion tests are usually accomplished in saline solutions or calf serum (CS), but the addition of H2O2 and FeCl3 have been suggested to mimic inflammatory conditions in the joint. Inflammatory conditions may aggravate corrosive processes and, therefore, should lead in vitro to a more severe and realistic tribo-corrosive material attack. Corrosion testing at 12/14 tapers comprising a CoCrMo head taper and a Ti6Al4V trunnion was accomplished in five electrolytes (Ringer\'s solution (RS), RS with 30 mM H2O2 and/or 0.7 mM FeCl3 and CS) under dynamical loading for five million cycles. Resulting material loss was determined gravimetrically and by ion analysis. The tribo-corrosive material degradation was investigated by light and electron microscopy. FeCl3 enhanced the material loss from taper connections while H2O2 did not lead to a significant alteration of total material loss. In comparison to pure RS, corrosion testing in CS decreased material loss at the head taper while it increased material loss at the trunnion. The combination of FeCl3 and H2O2 led to an enhanced occurrence of micro cracks at the trunnion surface. Adding FeCl3 and optionally also H2O2 aggravates material loss in in vitro corrosion testing of taper junctions and leads to harsher and probably more realistic testing conditions. STATEMENT OF SIGNIFICANCE: Tribo-corrosive processes at taper connections in hip implants are complex and can lead to major clinical implications. Joint inflammation is assumed to aggravate taper corrosion in vivo, why FeCl3 and H2O2 have been proposed as additives to electrolytes to simulate inflammatory conditions in vitro. Often used fretting test setups, however, do not involve real taper geometries. Besides, testing is often accomplished in saline solutions or calf serum, which do not induce a clinically significant amount of corrosive material degradation. This study presents an approach to increase tribo-corrosive processes at realistic taper connections by adding FeCl3 and/or H2O2. Unlike H2O2, FeCl3 increased material loss from taper connections. The combination of both additives enhanced micro crack formation at the trunnion surfaces.

BACKGROUND: The degree to which opioid-induced hyperalgesia contributes to the pain experience of patients with chronic pain remains relatively undescribed. The objective of this pilot study was to determine if experimental pain responses improve in patients with chronic pain as they undergo a planned opioid taper.
METHODS: This was a prospective observational study. Seven patients with chronic neuropathic pain on at least 120 mg morphine equivalents/day were enrolled. The participants were followed over the course of an individualized opioid taper to a lower dose. Measures of experimental pain sensitivity, including indicators of central pain modulation, were collected on a biweekly basis; in addition, measures of function and quality of life were collected monthly. The effect of opioid taper on pain responses and functional outcomes over time were examined using longitudinal mixed-effects regression modeling and general linear regression modeling with regularization as a function of baseline dose, end dose, and taper rate.
RESULTS: In this small sample of patients undergoing highly individualized and variable opioid taper, the opioid taper was significantly associated with improved pain responses to the cold-pressor test, with the pain threshold on average increasing by 1.14 s every 6 weeks (p = 0.0084, 95% confidence interval [CI] for 6-week change 0.3039-2.0178) and pain tolerance on average increasing by 2.87 s every 6 weeks (p = 0.0026, 95% CI for 6-week change 1.02-4.7277). Taper-related changes in central pain modulation were not observed, although conditioned modulation trended toward improvement by the completion of opioid taper. Similarly, no declines in function and quality of life were observed with the opioid taper, suggesting stability despite decreased opioid dose.
CONCLUSIONS: Opioid taper was associated with improvements in experimental pain responses without a decline in function and quality of life, suggestive of diminished opioid-induced hyperalgesia in this clinical sample.
BACKGROUND: ClinicalTrials.gov identifier, NCT03912298.

BACKGROUND: Single crowns or fixed partial dentures retainers usually get dislodged due to inadequate resistance form. Hence, it is prudent to evaluate features of a tooth preparation, which can prevent these failures.
OBJECTIVE: To evaluate the effect of auxiliary features, occlusal surface modifications, and total occlusal convergence (TOC) on the resistance of a full veneer crown.
METHODS: An ivorine mandibular molar tooth was prepared with features of inadequate resistance form, i.e., 2.5 mm axial wall height and TOC of 20°. Seven auxiliary preparation features were subsequently added one by one to it. They were mesiodistal grooves, buccolingual and mesiodistal grooves, buccolingual grooves, mesiodistal boxes, occlusal inclined planes, 8° reduced TOC in the cervical aspect, and mesiodistal grooves added to 8° reduced TOC in the cervical aspect. Ten dies with their respective crowns were prepared for each group. Resistance testing of all the samples was performed on the INSTRON testing machine.
RESULTS: Modification of the overtapered die preparation by reducing the TOC to 8° in the cervical 1.5 mm of the axial wall and then subsequently adding mesiodistal grooves to the reduced TOC cervically offered the greatest resistance to dislodgment statistically.
CONCLUSIONS: For an overtapered preparation, reducing the TOC to 8° in the cervical aspect and subsequently adding proximal grooves can provide maximum resistance form.

OBJECTIVE: To investigate the relationship between real life glucocorticoid (GC) dosing and relapse rates in patients with new onset giant cell arteritis (GCA) in a single center.
METHODS: Complete clinical data taken from the inpatient and outpatient records of consecutive GCA patients followed beyond stopping GC were retrospectively analyzed for GC doses, other immunomodulatory agents and relapses.
RESULTS: We included 54 patients with GCA confirmed by biopsy or imaging and followed over their complete GC course. In the 25% dose percentile, patients who needed no pulse therapy at onset reached a dose of 15 mg prednisolone or lower at day 40, of 7.5 mg prednisolone or lower on day 169 (after 24 weeks), and were off prednisolone on day 496 (70 weeks). They were below BSR-recommended doses between week 4 and week 12 and above these after week 14. The cumulative prednisolone dose reached in this 25% quartile was 3.74 g. Of the 54 patients, 24 (44%) relapsed, only 4 of whom had stopped GC clearly (17-58 weeks) earlier than the 25% dose quartile and one was distinctly (>10%) below the 25% GC percentile. Methotrexate treatment was not significantly associated with fewer relapses (p= 0.178).
CONCLUSIONS: Despite a long-term GC regimen with slow rates of reduction in the low dose range and high cumulative prednisolone doses, 44% of the patients relapsed. Only five (21%) of these relapses may have been prevented by adhering to the recommended GC regimen.

High-dose, long-term opioid therapy (LtOT) is associated with risk for serious harms. Rapid opioid discontinuation may lead to increased pain, psychological distress, and illicit opioid use, but gradual, supported opioid taper may reduce these risks. We previously demonstrated that an opioid taper support and pain coping skills training intervention reduced opioid dose more than usual care (43% vs 19% dose reduction from baseline), with no increase in pain intensity and a significant reduction in activity interference. We aim to adapt and test this intervention in the Kaiser Permanente Washington healthcare system with STRategies to Improve Pain and Enjoy life (STRIPE, NCT03743402), a pragmatic, randomized trial. Our goal was to randomize 215 participants on moderate-high dose (≥40 morphine milligram equivalent/day) LtOT to either cognitive-behavioral therapy-based pain coping skills training involving 18 telephone sessions over 52 weeks with optional opioid taper support or usual care. Data are collected from electronic health records, claims, and self-report. The primary outcomes are mean daily opioid dose and the pain intensity, interference with enjoyment of life, and interference with general activity (PEG) score at 12 months (primary time point) and 6 months (secondary time point). Secondary outcomes include having ≥30% opioid dose reduction from baseline, and patient-reported problem opioid use, opioid-related difficulties, pain self-efficacy, opioid craving, global impression of change, and anxiety and depressive symptoms at 6 and 12 months. If effective, this treatment could reduce opioid exposure and associated risks to patients, families, and communities while offering patients an alternative for managing pain.

OBJECTIVE: The aim of this ex vivo randomized study is to evaluate the efficiency of gutta-percha cones that match a nickel-titanium instrumentation system and nonmatching greater taper cones, when used with continuous warm vertical condensation technique.
METHODS: Thirty-six straight canals were prepared using ProTaper Next files, and the apical third was obturated using either ProTaperNext cones (group A), ISO uniform greater taper cones (group B), or nonstandardized cones (group C). Cone adaptation time was quantified by the number of required modifications. Micro-computed tomography was used to measure voids and sealer percentage.
RESULTS: There was no significant difference between the groups regarding void volume (p = 0.666), percentage (p = 0.379), and the number of modifications (p = 0.757). Sealer percentage, however, was significantly lower in group B when compared to group A (p = 0.0194).
CONCLUSIONS: In straight canals, matching gutta-percha cones were not associated with significantly better obturation or saving time to fit the cone.
CONCLUSIONS: Using gutta-percha cones that do not match a nickel-titanium instrumentation system to obturate the straight canals with continuous warm vertical condensation technique is as efficient as using matching cones in terms of obturation quality and ease of cone fit.