Efficacy and safety of golimumab in patients with non-radiographic axial spondyloarthritis: a withdrawal and retreatment study (GO-BACK).

OBJECTIVES: The GO-BACK study was designed to evaluate the efficacy and safety of golimumab (GLM) treatment withdrawal in adults with non-radiographic axial spondyloarthritis (nr-axSpA) who demonstrate inactive disease during a 10-month open-label (OL) GLM run-in. METHODS: Eligible participants received OL GLM in period 1. In period 2, participants who achieved inactive disease were randomized 1:1:1 to receive double-blind (DB) treatment with monthly placebo (PBO, treatment withdrawal) or continued GLM treatment given monthly (GLM QMT) or every 2 months (GLM Q2MT). Participants who did not have a disease flare continued DB treatment for ∼12 months. Participants with a disease flare discontinued DB treatment and resumed monthly OL GLM. Primary endpoint compared the proportion of participants without a disease flare in the continued GLM treatment groups (QMT or Q2MT) vs PBO in a multiplicity-controlled, step-down fashion. Safety follow-up continued for ∼3 months after last treatment. RESULTS: A total of 188 patients, out of the 323 enrolled, were eligible for participation in period 2. Both GLM QMT and GLM Q2MT were superior to treatment withdrawal (PBO) in preventing disease flare (P < 0.001), with a treatment-difference vs PBO of 50.4% and 34.4% for the GLM QMT and GLM Q2MT groups, respectively. The time-to-first flare was significantly longer (log-rank P < 0.0001) with GLM treatment compared with PBO. Of 53 participants (in Q2MT or PBO) who had a confirmed disease flare, 51 (96.2%) attained a clinical response within 3 months of restarting OL GLM. Adverse events were consistent with the known GLM safety profile. CONCLUSION: Among participants with active nr-axSpA who attained inactive disease after 10 months of GLM treatment, continued GLM treatment is well tolerated and provides superior protection against disease flares compared with GLM withdrawal. (EudraCT: 2015-004020-65, registered on 30 March 2022; NCT: 03253796, registered on 18 August 2017.).

Infralingular Versus Supralingular Medial Osteotomy in Sagittal Split Osteotomy of the Mandible: A Randomized Control Study.

PURPOSE: A recently proposed modification of the sagittal split osteotomy (SSO) of the mandible places the horizontal medial cut 'low and short' of the lingula. The purpose of the study was to answer the following clinical question: Among patients undergoing mandibular setback procedures (≤ 8 mm) via SSO, does the placement of the medial horizontal osteotomy below the lingula (infralingular), when compared to placement above the lingula (supralingular), results in different neurosensory, bite force, and range of motion outcomes? MATERIALS AND METHODS: This was a single-center, double-blind, parallel-group study among patients undergoing mandibular setback by SSO (≤ 8 mm), between January 2021 and September 2022. Patients were randomly allocated in a ratio of 1:1 to the supralingular (control) and the infralingular (study) group. Primary outcome variables included neurosensory disturbance of the inferior alveolar nerve based on clinical neurosensory testing and severity graded using Zuniga and Essick's protocol, bite force, and maximum mouth opening evaluated postoperatively during the first week (T1), first month (T2), and third month (T3) of follow-up. Secondary outcome measures included the incidence of a bad split and distal segment interferences intraoperatively. Association between the variables was assessed using Pearson chi-squared test or Fisher's exact test based on the expected observations. A P value of ≤.05 was considered statistically significant. RESULTS: A total of 29 patients (58 osteotomies) were included in the study. Group 1 consisted of 15 patients (9 females and 6 males) with a mean age of 26.4 years. Group 2 consisted of 14 patients (8 females and 6 males) with a mean age of 25.9 years. Patients with severe neurosensory disturbance of the inferior alveolar nerve were more common in group 2 (n = 15, 53.6%) than group 1 (n = 4, 13.3%) at T1 (P value = .0001) and insignificant between the two groups at T2 (P value = .63) and T3 (P value = .99). Comparison of maximum mouth opening between the two groups at T1 (P value = .535), T2 (P value = .934), and T3 (P value = .703) and bite force at T1 (P = .324), T2 (P = .113), and T3 (P = .811) was not significant. CONCLUSION: Both SSO techniques have similar clinical outcomes among patients having mandibular setbacks (≤ 8 mm) for the variables studied.

Long-term tolerability and efficacy of golimumab in active non-radiographic axial spondyloarthritis: results from open-label extension.

OBJECTIVES: We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders' analyses were calculated using a non-responder imputation approach. RESULTS: Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%). CONCLUSIONS: Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA. TRIAL REGISTRATION: NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov.

What has changed in orthodontic patient care between the two surges of the COVID-19 pandemic? A thematic analysis.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) has brought new challenges to every specialty and orthodontics is no exception. Currently, there seems no way other than to mitigate the risk and proceed with routine orthodontic treatment. The aim of the present study was to conduct a qualitative inquiry into the coping strategies, perceptions and anticipations of orthodontic patients and the challenges faced by orthodontists. METHODS: An in-depth telephone interview of 30 patients and/or their parents and orthodontists belonging to an Academic-based Residency Program and Private Practice was conducted regarding the challenges, opportunities and futuristic ways of coping with COVID-19. Inputs were recorded, transcripts were prepared and anonymised, and a thematic analysis was performed. RESULTS: Six themes and several sub-themes emerged from the detailed interviews and their transcripts. The initial fearful situation due to COVID-19 has gradually transformed into a certain 'new normal' in the lives of patients and caregivers, explaining why patients started seeking orthodontic treatment as usual or even preferring to begin treatment during this period. Orthodontists in the midst of uncertainty are delivering quality care and expecting future innovations and changes to combat such pandemics. CONCLUSION: Humans can adapt to any crisis that runs over a period of time. The new insights obtained will help to plan treatment and set up practice to cope with pandemics and crises that can affect orthodontic treatment in the future.

The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis.

OBJECTIVE: Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA. DESIGN: A randomized controlled pilot study to test the efficacy of two dietary interventions. SUBJECTS: Adults 65-75 years of age with KOA. METHODS: Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. RESULTS: Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. CONCLUSIONS: We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.

Utilization of thromboelastography and a low molecular weight heparin anti-Xa assay for guidance in apixaban reversal: A case report.

Reversal of oral factor Xa (FXa) inhibitors, such as apixaban, remains a controversial topic. However, the controversy goes beyond what reversal agent to utilize. Often times these patients present with an acute major bleed and are difficult to assess whether reversal is warranted or not. Furthermore, it is difficult to assess whether reversal was successful in a timely manner. A paucity of literature exists regarding the utilization of low molecular weight heparin (LMWH) anti-Xa assays and thromboelastography for identifying coagulopathies associated with oral FXa inhibitors. We report a case of apixaban induced coagulopathy utilizing thromboelastography and a LMWH anti-Xa assay as a guide for reversal.

Total flucloxacillin plasma concentrations poorly reflect unbound concentrations in hospitalized patients with Staphylococcus aureus bacteraemia.

AIMS: Flucloxacillin dosing may be guided by measurement of its total plasma concentrations. Flucloxacillin is highly protein bound with fraction unbound in plasma (fu ) of around 0.04 in healthy individuals. The utility of measuring unbound flucloxacillin concentrations for patients outside the intensive care unit (ICU) is not established. We aimed to compare flucloxacillin fu in non-ICU hospitalised patients against healthy volunteers, and to examine the performance of a published model for predicting unbound concentrations, using total flucloxacillin and plasma albumin concentrations. METHODS: Data from 12 healthy volunteers (248 samples) and 47 hospitalized patients (61 samples) were examined. Plasma flucloxacillin concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. Flucloxacillin fu for the two groups was compared using a generalized estimating equation model to account for clustered observations. The performance of the single protein binding site prediction model in hospitalized patients was compared with measured unbound concentrations using Bland-Altman plots. RESULTS: The median (range) flucloxacillin fu for healthy (median albumin 45 g l-1 ) and hospitalized individuals (median albumin 30 g l-1 ) were 0.04 (0.02-0.07) and 0.10 (0.05-0.37), respectively (P < 0.0001). The prediction model underpredicted unbound flucloxacillin concentrations with a mean bias (95% limits of agreement) of -54% (-137%, +30%). CONCLUSIONS: The flucloxacillin fu values observed in our cohort of hospitalized patients had a wide range and were greater than those of healthy individuals. Unbound flucloxacillin plasma concentrations were predicted poorly by the model. Instead, unbound concentrations should be measured to guide dosing.

Effect of montelukast for treatment of asthma in cigarette smokers.

OBJECTIVE: Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma. METHODS: Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated. RESULTS: There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P < .05 vs placebo), 49% (fluticasone, P < .001 vs placebo), and 39% (placebo); the difference between montelukast and fluticasone was not significant (P = .14). Patients with a smoking history of ≤11 pack years (the median value) tended to show more benefit with fluticasone, whereas those with a smoking history of >11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups. CONCLUSIONS: In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.

Teaching Before, During, and After a Surgical Resuscitation.

Teaching during a surgical resuscitation can be difficult due to the infrequency of these events. Furthermore, when these events do occur, the trainee can experience cognitive overload and an overwhelming amount of stress, thereby impairing the learning process. The emergent nature of these scenarios can make it difficult for the surgical educator to adequately teach. Repeated exposure through simulation, role play, and "war games" are great adjuncts to teaching and preparation before crisis. However, surgical educators can further enhance the knowledge of their trainees during these scenarios by using tactics such as talking out loud, targeted teaching, and debriefing.

Gowers' Queen Square case notes on chorea: a 21st century re-appraisal.

OBJECTIVE: To analyze the case notes of 127 patients with chorea admitted to the National Hospital at Queen Square, London, under the care of William Richard Gowers and review his contribution to the study of choreas. METHODS: We consulted the case books available at the Queen Square Library, from 1878 to 1911, comprising 42 volumes. RESULTS: 97 patients (76.3%) were female and the age of presentation ranged from 4 to 60 years (mean 14.3). 43 patients (33.8%) experienced recurrent attacks of chorea. 29 patients (22.8%) had a family history of chorea. Past history of rheumatic fever was observed in 46 patients (36.2%). 54 patients (42.5%) had speech impairment while a similar number had a cardiac murmur. Generalized chorea occurred in 87.4% and hemichorea in 11.8%. Gowers diagnosed different forms of chorea: Huntington's disease, paralytic, persistent, recurrent, tetanoid, functional, maniacal, hemichorea and chorea gravidarum. CONCLUSIONS: Gowers was one of the pioneers in recognizing chorea as a physical sign found in a myriad of etiologies. He also provided a comprehensive description of the clinical features and natural history of Sydenham's chorea in his work.

Low-Molecular-Weight Heparin Anti-Xa Guided Reversal of Apixaban With Prothrombin Complex Concentrate in a Patient on Hemodialysis.

The growing use of oral factor Xa (FXa) inhibitors in patients with chronic kidney disease (CKD), particularly the recent increased use of apixaban in patients with end-stage renal disease (ESRD), has created a new dilemma in the already controversial topic of oral FXa inhibitor reversal. With the limited availability of anti-Xa levels specific to oral FXa inhibitors and even scarcer availability of reversal data for patients on these agents with ESRD, ensuring adequate reversal is currently often solely guided by repeat imaging and changes in clinical status. Low molecular weight heparin (LMWH) anti-Xa levels have been used as a more commonly accessible test to guide the need for and efficacy of reversal of oral FXa inhibitors in patients with normal renal function. However, evidence supporting this technique is again lacking in patients with renal dysfunction. This case report focuses on the use of LMWH anti-Xa levels to guide reversal of apixaban in a patient with ESRD on hemodialysis and correlation of those levels to the patient's clinical status.

Approach to the Patient With Short Stature: Genetic Testing.

The first step in the evaluation of the short child is to decide whether growth parameters in the context of the history are abnormal or a variant of normal. If growth is considered abnormal, system and hormonal tests are likely to be required, followed by more directed testing, such as skeletal survey and/or genetic screening with karyotype or microarray. In a small percentage of short children in whom a diagnosis has not been reached, this will need to be followed by detailed genetic analysis; currently, exome sequencing using targeted panels relevant to the phenotype is the commonly used test. Clinical scenarios are presented that illustrate how such genetic testing can be used to establish a molecular diagnosis, and how that diagnosis contributes to the management of the short child. New genetic causes for short stature are being recognized on a frequent basis, while the clinical spectrum for known genes is being extended. We recommend that an international repository for short stature conditions is established for new findings to aid dissemination of knowledge, but also to help in the definition of the clinical spectrum both for new and established conditions.

The Effects of COVID-19 on General Surgery Residency Programs in the United States.

Introduction: The COVID-19 pandemic impacted multiple aspects of surgical education. This survey delineates steps taken by general surgery residency programs to meet changing patient-care needs while continuing to provide adequate education. Methods: A survey was administered to program directors and coordinators of all United States general surgery residency programs to assess the early effects of the pandemic on residents from March 1 through May 31, 2020. Results: Of 303 programs contacted, 132 (43.6%) completed the survey. Residents were asked to work in areas outside of their specialty at 27.3% of programs. Residency curriculum was changed in 35.6% of programs, and 76.5% of programs changed their academic conferences. Resident schedules were altered at a majority of programs to limit resident-patient exposure, increase ICU coverage, or improve resident utilization. Surgical caseloads decreased at 93.8% of programs; 31.8% of those programs reported concerns regarding residents' achieving the minimum case numbers required to graduate. Conclusions: These results provided insight into the restructuring of general surgery residency programs during a pandemic and may be used to establish future pandemic response plans.

Diagnosis of childhood and adolescent growth hormone deficiency using transcriptomic data.

Background: Gene expression (GE) data have shown promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD) when comparing GHD children to normal children. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group. Methods: GE data was obtained from patients undergoing growth hormone stimulation testing. Data were taken for the 271 genes whose expression was utilized in our previous study. The synthetic minority oversampling technique was used to balance the dataset and a random forest algorithm applied to predict GHD status. Results: 24 patients were recruited to the study and eight subsequently diagnosed with GHD. There were no significant differences in gender, age, auxology (height SDS, weight SDS, BMI SDS) or biochemistry (IGF-I SDS, IGFBP-3 SDS) between the GHD and non-GHD subjects. A random forest algorithm gave an AUC of 0.97 (95% CI 0.93 - 1.0) for the diagnosis of GHD. Conclusion: This study demonstrates highly accurate diagnosis of childhood GHD using a combination of GE data and random forest analysis.

The clinical features of pathologically confirmed vascular parkinsonism.

OBJECTIVE: To evaluate in detail the clinical features in a large series of pathologically confirmed cases of vascular Parkinsonism (VP). BACKGROUND: In the absence of widely accepted diagnostic criteria for VP pathological confirmation of diagnosis is necessary to ensure diagnostic reliability, and has only been reported in a few small series. DESIGN/METHODS: The archival records of the Queen Square Brain Bank (QSBB) have been used to identify cases of Parkinsonism where cerebrovascular disease was the only pathological finding. Clinical notes were scrutinised and milestones of disease progression were compared with other atypical Parkinsonian syndromes from previous QSBB studies. RESULTS: Twenty-eight cases were included. Mean age of onset and disease duration were 70.6 (SD± 6.42) and 10.5 (SD± 66.1) years respectively. Bradykinesia was present in all cases, rigidity in 96%, falls in 76%, pyramidal signs in 54%, urinary incontinence in 50% and dementia in 39%.Visual hallucinations in 0%. Two-thirds had an insidious onset and a relentless rather than stepwise progression of disability. When compared with other Parkinsonian syndromes, VP had an older age of onset. CONCLUSIONS: In comparison with other Parkinsonian syndromes the patients were older and had an extremely low frequency of visual hallucinations compared with Parkinson's disease.