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OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE). METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred. RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day. CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.
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Glucocorticoides , Lúpus Eritematoso Sistêmico , Prednisolona , Exacerbação dos Sintomas , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Feminino , Masculino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Adulto , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Redução da Medicação/métodos , Estudos Longitudinais , Progressão da Doença , Estudos de Coortes , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.
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Anticorpos Antinucleares , Lúpus Eritematoso Sistêmico , Humanos , DNA , Coleta de Dados , Testes HematológicosRESUMO
OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).
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Lúpus Eritematoso Sistêmico , Índice de Gravidade de Doença , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Longitudinais , Progressão da Doença , Glucocorticoides/uso terapêutico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Documentation of intraoperative details is critical for understanding and advancing hernia care, but is inconsistent in practice. Therefore, to improve data capture on a statewide level, we implemented a financial incentive targeting documentation of hernia defect size and mesh use. METHODS: The Abdominal Hernia Care Pathway (AHCP), a voluntary pay for performance (P4P) initiative, was introduced in 2021 within the statewide Michigan Surgical Quality Collaborative (MSQC). This consisted of an organizational-level financial incentive for achieving 80% performance on eight specific process measures for ventral hernia surgery, including complete documentation of hernia defect size and location, as well as mesh characteristics and fixation technique. Comparisons were made between AHCP and non-AHCP sites in 2021. RESULTS: Of 69 eligible sites, 47 participated in the AHCP in 2021. There were N = 5362 operations (4169 at AHCP sites; 1193 at non-AHCP sites). At AHCP sites, 69.8% of operations had complete hernia documentation, compared to 50.5% at non-AHCP sites (p < 0.0001). At AHCP sites, 91.4% of operations had complete mesh documentation, compared to 86.5% at non-AHCP sites (p < 0.0001). The site-level hernia documentation goal of 80% was reached by 14 of 47 sites (range 14-100%). The mesh documentation goal was reached by 41 of 47 sites (range 4-100%). CONCLUSIONS: Addition of an organizational-level financial incentive produced marked gains in documentation of intra-operative details across a statewide surgical collaborative. The relatively large effect size-19.3% for hernia-is remarkable among P4P initiatives. This result may have been facilitated by surgeons' direct role in documenting hernia size and mesh use. These improvements in data capture will foster understanding of current hernia practices on a large scale and may serve as a model for improvement in collaboratives nationally.
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Hérnia Ventral , Humanos , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Reembolso de Incentivo , Telas CirúrgicasRESUMO
OBJECTIVE: Compare adverse outcomes up to 5 years after sleeve gastrectomy and gastric bypass in patients with Medicaid. BACKGROUND: Sleeve gastrectomy is the most common bariatric operation among patients with Medicaid; however, its long-term safety in this population is unknown. METHODS: Using Medicaid claims, we performed a retrospective cohort study of adult patients who underwent sleeve gastrectomy or gastric bypass from January 1, 2012, to December 31, 2018. Instrumental variables survival analysis was used to estimate the cumulative incidence and heterogeneity of outcomes up to 5 years after surgery. RESULTS: Among 132,788 patients with Medicaid, 84,717 (63.8%) underwent sleeve gastrectomy and 48,071 (36.2%) underwent gastric bypass. A total of 69,225 (52.1%) patients were White, 33,833 (25.5%) were Black, and 29,730 (22.4%) were Hispanic. Compared with gastric bypass, sleeve gastrectomy was associated with a lower 5-year cumulative incidence of mortality (1.29% vs 2.15%), complications (11.5% vs 16.2%), hospitalization (43.7% vs 53.7%), emergency department (ED) use (61.6% vs 68.2%), and reoperation (18.5% vs 22.8%), but a higher cumulative incidence of revision (3.3% vs 2.0%). Compared with White patients, the magnitude of the difference between sleeve and bypass was smaller among Black patients for ED use [5-y adjusted hazard ratios: 1.01; 95% confidence interval (CI), 0.94-1.08 vs 0.94 (95% CI, 0.88-1.00), P <0.001] and Hispanic patients for reoperation [5-y adjusted hazard ratios: 0.95 (95% CI, 0.86-1.05) vs 0.76 (95% CI, 0.69-0.83), P <0.001]. CONCLUSIONS: Among patients with Medicaid undergoing bariatric surgery, sleeve gastrectomy was associated with a lower risk of mortality, complications, hospitalization, ED use, and reoperations, but a higher risk of revision compared with gastric bypass. Although the difference between sleeve and bypass was generally similar among White, Black, and Hispanic patients, the magnitude of this difference was smaller among Black patients for ED use and Hispanic patients for reoperation.
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Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Adulto , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/complicações , Medicaid , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: To explore the feasibility and effectiveness of telehealth-supervised exercise for adults with Systemic lupus erythematosus (SLE). METHODS: This was a non-randomised controlled pilot trial comparing telehealth-supervised exercise (8 weeks, 2 days/week, 45 min, moderate intensity) plus usual care with usual care alone. Mixed methods were used to assess change in fatigue (FACIT-fatigue), quality of life (SF36), resting fatigue and pain (11-point scale), lower body strength (five-time sit-to-stand) and endurance (30 s sit-to-stand), upper body endurance (30 s arm curl), aerobic capacity (2 min step test), and experience (survey and interviews). Group comparison was performed statistically using a two-sample T-test or Mann-Whitney U-test. Where known, we used MCID or MCII, or assumed a change of 10%, to determine clinically meaningful change within groups over time. Interviews were analysed using reflexive thematic analysis. RESULTS: Fifteen female adults with SLE were included (control group n = 7, exercise group n = 8). Statistically significant differences between groups, in favour of the exercise intervention, were noted for SF36 domain emotional well-being (p = 0.048) and resting fatigue (p = 0.012). There were clinically meaningful improvements over time for FACIT-fatigue (+6.3 ± 8.3, MCID >5.9), SF36 domains physical role functioning (+30%), emotional role functioning (+55%), energy/fatigue (+26%), emotional well-being (+19%), social functioning (+30%), resting pain (-32%), and upper body endurance (+23%) within the exercise group. Exercise attendance was high (98%, 110/112 sessions); participants strongly agreed (n = 5/7, 71%) or agreed (n = 2/7, 29%) they would do telehealth-supervised exercise again and were satisfied with the experience. Four themes emerged: (1) ease and efficiency of exercising from home, (2) value of live exercise instruction, (3) challenges of exercising at home, and (4) continuation of telehealth-supervised exercise sessions. CONCLUSION: Key findings from this mixed-method investigation suggest that telehealth-supervised exercise was feasible for, and well-accepted by, adults with SLE and resulted in some modest health improvements. We recommend a follow-up RCT with more SLE participants.
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Lúpus Eritematoso Sistêmico , Telemedicina , Adulto , Humanos , Feminino , Projetos Piloto , Qualidade de Vida , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/psicologia , Terapia por Exercício/métodos , Fadiga/etiologia , Fadiga/psicologia , DorRESUMO
INTRODUCTION: Sufficient overlap of mesh beyond the borders of a ventral hernia helps prevent hernia recurrence. Guidelines from the European Hernia Society and American Hernia Society recommend ≥ 2 cm overlap for open repair of < 1-cm hernias, ≥ 3-cm overlap for open repair of 1-4-cm hernias, ≥ 5-cm overlap for open repair of > 4-cm hernias, and ≥ 5-cm overlap for all laparoscopic ventral hernia repairs. We evaluated whether current practice reflects this guidance. METHODS: We used the Michigan Surgical Quality Collaborative Hernia Registry to evaluate patients who underwent elective ventral and umbilical hernia repair between 2020 and 2022. Mesh overlap was calculated as [(width of mesh - width of hernia)/2]. The main outcome was "sufficient overlap," defined based on published EHS and AHS guidelines. Explanatory variables included patient, operative, and hernia characteristics. The main analysis was a multivariable logistic regression to evaluate the association between explanatory variables and sufficient mesh overlap. RESULTS: 4178 patients underwent ventral hernia repair with a mean age of 55.2 (13.9) years, 1739 (41.6%) females, mean body mass index (BMI) of 33.1 (7.2) kg/m2, and mean hernia width of 3.7 (3.4) cm. Mean mesh overlap was 3.7 (2.5) cm and ranged from - 5.5 to 21.4 cm. Only 1074 (25.7%) ventral hernia repairs had sufficient mesh overlap according to published guidelines. Operative factors associated with increased odds of sufficient overlap included myofascial release (adjusted odds ratio [aOR] 5.35 [95% CI 4.07-7.03]), minimally invasive approach (aOR 1.86 [95% CI 1.60-2.17]), and onlay mesh location (aOR 1.31 [95% CI 1.07-1.59]). Patient factors associated with increased odds of sufficient overlap included prior hernia repair (aOR 1.59 [95% CI 1.32-1.92]). CONCLUSION: Although sufficient mesh overlap is recommended to prevent ventral hernia recurrence, only a quarter of ventral hernia repairs in a state-wide cohort of patients had sufficient overlap according to evidence-based guidelines. Factors strongly associated with sufficient overlap included myofascial release, mesh type, and laparoscopic repair.
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Hérnia Ventral , Laparoscopia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hérnia Ventral/cirurgia , Herniorrafia , Recidiva , Sistema de Registros , Telas Cirúrgicas , AdultoRESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune inflammatory disease with a prevalence varying from 4.3 to 150 people in 100,000, or approximately five million people worldwide. Systemic manifestations frequently include internal organ involvement, a characteristic malar rash on the face, pain in joints and muscles, and profound fatigue. Exercise is purported to be beneficial for people with SLE. For this review, we focused on studies that examined all types of structured exercise as an adjunctive therapy in the management of SLE. OBJECTIVES: To evaluate the benefits and harms of structured exercise as adjunctive therapy for adults with SLE compared with usual pharmacological care, usual pharmacological care plus placebo and usual pharmacological care plus non-pharmacological care. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of exercise as an adjunct to usual pharmacological treatment in SLE compared with placebo, usual pharmacological care alone and another non-pharmacological treatment. Major outcomes were fatigue, functional capacity, disease activity, quality of life, pain, serious adverse events, and withdrawals due to any reason, including any adverse events. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our major outcomes were 1. fatigue, 2. functional capacity, 3. disease activity, 4. quality of life, 5. pain, 6. serious adverse events, and 7. withdrawals due to any reason. Our minor outcomes were 8. responder rate, 9. aerobic fitness, 10. depression, and 11. anxiety. We used GRADE to assess certainty of evidence. The primary comparison was exercise compared with placebo. MAIN RESULTS: We included 13 studies (540 participants) in this review. Studies compared exercise as an adjunct to usual pharmacological care (antimalarials, immunosuppressants, and oral glucocorticoids) with usual pharmacological care plus placebo (one study); usual pharmacological care (six studies); and another non-pharmacological treatment such as relaxation therapy (seven studies). Most studies had selection bias, and all studies had performance and detection bias. We downgraded the evidence for all comparisons because of a high risk of bias and imprecision. Exercise plus usual pharmacological care versus placebo plus usual pharmacological care Evidence from a single small study (17 participants) that compared whole body vibration exercise to whole body placebo vibration exercise (vibrations switched off) indicated that exercise may have little to no effect on fatigue, functional capacity, and pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). The study did not report disease activity, quality of life, and serious adverse events. The study measured fatigue using the self-reported Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue), scale 0 to 52; lower score means less fatigue. People who did not exercise rated their fatigue at 38 points and those who did exercise rated their fatigue at 33 points (mean difference (MD) 5 points lower, 95% confidence interval (CI) 13.29 lower to 3.29 higher). The study measured functional capacity using the self-reported 36-item Short Form health questionnaire (SF-36) Physical Function domain, scale 0 to 100; higher score means better function. People who did not exercise rated their functional capacity at 70 points and those who did exercise rated their functional capacity at 67.5 points (MD 2.5 points lower, 95% CI 23.78 lower to 18.78 higher). The study measured pain using the SF-36 Pain domain, scale 0 to 100; lower scores mean less pain. People who did not exercise rated their pain at 43 points and those who did exercise rated their pain at 34 points (MD 9 points lower, 95% CI 28.88 lower to 10.88 higher). More participants from the exercise group (3/11, 27%) withdrew from the study than the placebo group (1/10, 10%) (risk ratio (RR) 2.73, 95% CI 0.34 to 22.16). Exercise plus usual pharmacological care versus usual pharmacological care alone The addition of exercise to usual pharmacological care may have little to no effect on fatigue, functional capacity, and disease activity (low-certainty evidence). We are uncertain whether the addition of exercise improves pain (very low-certainty evidence), or results in fewer or more withdrawals (very low-certainty evidence). Serious adverse events and quality of life were not reported. Exercise plus usual care versus another non-pharmacological intervention such as receiving information about the disease or relaxation therapy Compared with education or relaxation therapy, exercise may reduce fatigue slightly (low-certainty evidence), may improve functional capacity (low-certainty evidence), probably results in little to no difference in disease activity (moderate-certainty evidence), and may result in little to no difference in pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). Quality of life and serious adverse events were not reported. AUTHORS' CONCLUSIONS: Due to low- to very low-certainty evidence, we are not confident on the benefits of exercise on fatigue, functional capacity, disease activity, and pain, compared with placebo, usual care, or advice and relaxation therapy. Harms data were not well reported.
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Exercício Físico , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Fadiga/etiologia , Fadiga/terapia , Terapia por Exercício/métodos , Dor , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/complicações , Qualidade de VidaRESUMO
Disease-modifying anti-rheumatic drugs (DMARDs) are effective treatments for inflammatory arthritis but carry an increased risk of infection. For patients undergoing surgery, there is a need to consider the trade-off between a theoretical increased risk of infection with continuation of DMARDs perioperatively versus an increased risk of disease flare if they are temporarily withheld. We used the Grading of Recommendations Assessment, Development and Evaluation methodology to develop recommendations for perioperative use of DMARDs for people with inflammatory arthritis undergoing elective surgery. The recommendations form part of the National Health and Medical Research Council-endorsed Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis. Conditional recommendations were made against routinely discontinuing conventional synthetic and biologic (b) DMARDs in the perioperative period but to consider temporary discontinuation of bDMARDs in individuals with a high risk of infection or where the impact of infection would be severe. A conditional recommendation was made in favour of temporary discontinuation of targeted synthetic DMARDs in the perioperative period.
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Antirreumáticos , Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/cirurgia , Austrália/epidemiologia , Antirreumáticos/uso terapêutico , Procedimentos Cirúrgicos EletivosRESUMO
Infrared active colloidal semiconducting nanocrystals (NCs) are important for applications including photodetectors and photovoltaics. While much research has been conducted on nanocrystalline materials such as the Pb and Hg chalcogenides, less toxic alternatives such as SnTe have been far less explored. Previous synthetic work on SnTe NCs have characterized photophysical properties of the nanoparticles. This study focuses on understanding the fundamental chemical mechanisms involved in SnTe NC formation, with the aim to improve synthetic outcomes. The solvent oleylamine, common to all SnTe syntheses, is found to form a highly reactive, heteroleptic Sn-oleylamine precursor that is the primary molecular Sn species initiating NC formation and growth. Further, the capping ligand oleic acid (OA) reacts with this amine to produce tin oxide (SnOx), facilitating the formation of an NC SnOx shell. Therefore, the use of OA during synthesis is counterproductive to the formation of stoichiometric SnTe nanoparticles. The knowledge of chemical reaction mechanisms creates a foundation for the production of high-quality, unoxidized, and stoichiometric SnTe NCs.
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Mercúrio , Nanopartículas , Ligantes , Nanopartículas/químicaRESUMO
INTRODUCTION: Clinician time and resources may be underutilised if the treatment they offer does not match patient expectations and attitudes. We developed a questionnaire (AxEL-Q) to guide clinicians toward elements of first-line care that are pertinent to their patients with low back pain. METHODS: We used guidance from the COSMIN consortium to develop the questionnaire and evaluated it in a sample of people with low back pain of any duration. Participants were recruited from the community, were over 18 years and fluent in English. Statements that represented first-line care were identified. Semantic scales were used to measure attitude towards these statements. These items were combined to develop the questionnaire draft. Construct validity was evaluated with exploratory factor analysis and hypotheses testing, comparing to the Back Beliefs Questionnaire and modified Pain Self-Efficacy Questionnaire. Reliability was evaluated and floor and ceiling effects calculated. RESULTS: We recruited 345 participants, and had complete data for analysis for 313 participants. The questionnaire draft was reduced to a 3-Factor questionnaire through exploratory factor analysis. Factor 1 comprised 9 items and evaluated Attitude toward staying active, Factor 2 comprised 4 items and evaluated Attitude toward low back pain being rarely caused by a serious health problem, Factor 3 comprised 4 items and evaluated Attitude toward not needing to know the cause of back pain to manage it effectively. There was a strong inverse association between each factor and the Back Beliefs Questionnaire and a moderate positive association with the modified Pain Self-Efficacy Questionnaire. Each independent factor demonstrated acceptable internal consistency; Cronbach α Factor 1 = 0.92, Factor 2 = 0.91, Factor 3 = 0.90 and adequate interclass correlation coefficients; Factor 1 = 0.71, Factor 2 = 0.73, Factor 3 = 0.79. CONCLUSION: This study demonstrates acceptable construct validity and reliability of the AxEL-Q, providing clinicians with an insight into the likelihood of patients following first-line care at the outset.
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Dor Lombar , Atitude , Comparação Transcultural , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Laparoscopic magnetic sphincter augmentation (MSA) has emerged as an alternative to laparoscopic Nissen fundoplication (LNF) for the management of symptomatic gastroesophageal reflux disease (GERD). While short-term outcomes of MSA compare favorably to those of LNF, direct comparisons of long-term outcomes are lacking. We hypothesized that the long-term patient-reported outcomes of MSA would be similar to those achieved with LNF. METHODS: We tested this hypothesis in a retrospective cohort undergoing primary LNF or MSA between March 2013 and July 2015. The primary outcome was GERD-Health Related Quality of Life (GERD-HRQL) score at long-term follow-up relative to baseline. Secondary outcomes included dysphagia and bloating scores, proton-pump inhibitor (PPI) cessation, reoperations, and overall satisfaction with surgery. RESULTS: 70 patients (25 MSA, 45 LNF) met criteria for study inclusion. MSA patients had lower baseline BMI (median: 27.1 [IQR: 22.7-29.9] versus 30.4 [26.4-32.8], p = 0.02), lower total GERD-HRQL (26 [19-32] versus 34 [25-40], p = 0.02), and dysphagia (2 [0-3] versus 3 [1-4], p = 0.02) scores. Median follow-up interval exceeded 5 years (MSA: 68 [65-74]; LNF: 65 months [62-69]). Total GERD-HRQL improved from 26 to 9 after MSA (p < 0.001) and from 34 to 7.5 after LNF (p < 0.01); these scores did not differ between groups (p = 0.68). Dysphagia (MSA: 1 [0-2]; LNF: 0 [0-2], p = 0.96) and bloating (MSA: 1.5 [0.5-3.0]; LNF: 3.0 [1.0-4.0], p = 0.08) scores did not show any statistically significant differences. Device removal was performed in 4 (16%) MSA patients and reoperation in 3 (7%) LNF patients. Eighty-nine percent of LNF patients reported satisfaction with the procedure, compared to 70% of MSA patients (p = 0.09). CONCLUSIONS: MSA appears to offer similar long-term improvement in disease-specific quality of life as LNF. For MSA, there was a trend toward reduced long-term bloating compared to LNF, but need for reoperation and device removal may be associated with patient dissatisfaction.
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Transtornos de Deglutição , Refluxo Gastroesofágico , Laparoscopia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Esfíncter Esofágico Inferior/cirurgia , Seguimentos , Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Humanos , Laparoscopia/métodos , Fenômenos Magnéticos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: The incidence of failed endovascular (EVAR) and open repair (OR) is increasing. Redo aortic repair is required in 10% of patients. Extension of the proximal sealing zone above the visceral arteries to adequate, healthier thoracic aorta using a fenestrated graft (FEVAR) can rescue a failing repair. A custom-made device can treat proximal type 1a endoleaks or proximal dilatation post endovascular or open repair, respectively. The aim of this investigation was to present a single-centre experience with FEVAR for patients with a failing aortic repair. METHODS: A prospectively maintained database of FEVAR patients treated with a Zenithâ Fenestrated endovascular (ZFEN) device (Cook Medical LLC, Bloomington, Indiana, USA) was interrogated for individuals who had the device implanted as a rescue therapy after prior endovascular (EVAR) or open repair (OR). Statistical analysis was performed with SPSS v 25 software. RESULTS: Between January 1, 2011 and March 31, 2019, 17 ZFEN devices were implanted. 10 patients had a type 1a endoleak from a prior EVAR and 7 patients had proximal disease progression after prior OR. There were 12 males and 5 females, median age of 75 (interquartile range, IQR 7). 76.4% (n = 13) of patients had an American Society of Anaesthesiologists (ASA) grade of 3. Primary technical success was 70.5% (n = 12). Of the remainder, 4 cases (24%) had a type III endoleak at completion angiogram; of which, 2 patients (12%) required re-intervention within 30 days. One further case (6%) had primary assisted technical success as stenting of a flow limiting dissection flap in an iliac vessel was required. Peri-operative rate of deployment related complications and systemic complications were 5.8% (n = 1) and 35% (n = 6), respectively. Median length of hospital stay was 11 days (IQR 11). There was no mortality within the study follow up. Overall 30-day re-intervention rate was 23.5%. Overall survival was 92% at one year. CONCLUSION: FEVAR is a safe but technically challenging option for rescue of failing aortic repairs. These are a high-risk group of patients and this is reflected in the high post-operative morbidity rate. Technical success was high and 30-day mortality was low.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular/efeitos adversos , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/cirurgia , Feminino , Humanos , Masculino , Desenho de Prótese , Reoperação/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) have been an important advance in the management of inflammatory arthritis, but are expensive medications, carry a risk of infection and other adverse effects, and are often perceived as a burden by patients. We used GRADE methodology to develop recommendations for dose reduction and discontinuation of b/tsDMARD in people with rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) who have achieved a low disease activity state or remission. The recommendations form part of the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis, an NHMRC-endorsed 'living' guideline, in which recommendations are updated in near real-time as new evidence emerges. Conditional recommendations were made in favour of dose reduction in RA and AxSpA but not in PsA. Abrupt discontinuation of b/tsDMARD is not recommended in any of the three diseases.
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Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Produtos Biológicos , Humanos , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Austrália , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamenteRESUMO
BACKGROUND: Despite being rare, pancreaticoduodenal artery aneurysms (PDAAs) carry a risk of rupture of up to 50% and are frequently associated with coeliac artery occlusion. METHODS: PubMed and Embase databases were searched using appropriate terms. The systematic review was conducted according to PRISMA guidelines. RESULTS: We present the case of a 2 cm pancreaticoduodenal artery aneurysm pre-operative angiography demonstrated that the coeliac artery was occluded and the pancreaticoduodenal artery was providing collateral blood supply to the liver. Treatment was a staged hybrid intervention inclusive of an aorto-hepatic bypass using a 6 mm graft, followed by coil embolisation of the aneurysm. We also present a systematic review of the management of PDAAs. Two hundred and ninety-two publications were identified initially with 81 publications included in the final review. Of the 258 peripancreatic aneurysms included, 175 (61%) were associated with coeliac artery disease either occlusion or stenosis. Abdominal pain was the main presentation in 158 cases. Rupture occurred in 111 (40%) of patients with only ten (3.8%) cases being unstable on presentation. Fifty (18%) cases were detected incidentally while investigating another pathology. Over half the cases (n=141/54.6%) were treated by trans arterial embolisation (TAE) alone, while 37 cases had open surgery only. Twenty-one cases needed TAE and a coeliac stent. Seventeen cases underwent hybrid treatment (open and endovascular). Sixteen cases were treated conservatively and in 26 cases, treatment was not specified. CONCLUSION: PDAAs are commonly associated with coeliac artery disease. The most common presentation is pain followed by rupture. The scarcity of literature about true peripancreatic artery aneurysms associated with CA occlusive disease makes it difficult to assess the natural history or the appropriate treatment. Revascularisation of hepatic artery is better done with bypass in setting of median arcuate ligament compression and occluded celiac trunk.
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OBJECTIVE: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort. METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses. RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia. CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.
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Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/imunologia , Linfopenia/induzido quimicamente , Neutropenia/induzido quimicamente , Adulto , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Fibromyalgia (FM) is prevalent but often under-recognized in patients with systemic lupus erythematosus (SLE). Patient-reported outcomes (PROs) from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) can identify co-morbid FM in patients with rheumatic diseases. The present study examined the utility of the MDHAQ in recognizing FM in patients with SLE during routine consultations. METHODS: Patients with SLE completed an MDHAQ. FM status was determined by the validated 2016 revision of the ACR 2010/2011 preliminary FM criteria. Individual PROs from the MDHAQ and composite Fibromyalgia Assessment Tool (FAST) indices of the discriminatory PROs were compared between patients with and without FM using Student's unpaired t-test and receiver operating characteristic curve analysis to determine the area under the curve (AUC). The physician's clinical impression of FM was recorded, and the SLE Disease Activity Index was used to assess disease activity. RESULTS: Of 88 patients with SLE, 23 (26%) satisfied the 2016 FM criteria. The FAST3 composite measure of two out of three of pain (≥6/10), joint count (≥16/48) and symptom checklist (≥16/60) correctly classified 89% of patients (AUC=0.90, kappa=0.71). Physician diagnosis demonstrated moderate agreement with the 2016 FM criteria (kappa=0.43) but missed 43% of patients with FM. In the presence of active disease, the FAST3 correctly classified 91% of patients. CONCLUSIONS: Co-morbid FM is prevalent in SLE yet often underdiagnosed by physicians. The simple FAST3 index of the MDHAQ provides an easy-to-use self-reported tool to improve identification of FM in patients with SLE.
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Fibromialgia/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Adolescente , Adulto , Idoso , Comorbidade , Feminino , Fibromialgia/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
Thermoresponsive hydrogels are used for an array of biomedical applications. Lower critical solution temperature-type hydrogels have been observed in nature and extensively studied in comparison to upper critical solution temperature (UCST)-type hydrogels. Of the limited protein-based UCST-type hydrogels reported, none have been composed of a single coiled-coil domain. Here, we describe a biosynthesized homopentameric coiled-coil protein capable of demonstrating a UCST. Microscopy and structural analysis reveal that the hydrogel is stabilized by molecular entanglement of protein nanofibers, creating a porous matrix capable of binding the small hydrophobic molecule, curcumin. Curcumin binding increases the α-helical structure, fiber entanglement, mechanical integrity, and thermostability, resulting in sustained drug release at physiological temperature. This work provides the first example of a thermoresponsive hydrogel comprised of a single coiled-coil protein domain that can be used as a vehicle for sustained release and, by demonstrating UCST-type behavior, shows promise in forging a relationship between coiled-coil protein-phase behavior and that of synthetic polymer systems.
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Portadores de Fármacos/química , Hidrogéis/química , Polímeros/química , Proteínas/química , Preparações de Ação Retardada/química , Portadores de Fármacos/síntese química , Hidrogéis/síntese química , Interações Hidrofóbicas e Hidrofílicas , Domínios Proteicos/genética , Engenharia de Proteínas , TemperaturaRESUMO
OBJECTIVES: Fatigue remains a debilitating feature of systemic lupus erythematosus (SLE). Although in some cases this may be the result of intercurrent fibromyalgia, mood disorder or untreated metabolic syndrome, in many cases the cause is unclear. The aim of this study was to investigate the relationship between fatigue and red cell distribution width (RDW), a measure of variability in erythrocyte size and volume. METHODS: A total of 225 patients were recruited from three clinics in England and Australia. Patients completed the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score or 12-item Short Form survey (SF-12) to measure fatigue, which was compared with RDW and haemoglobin. In a subgroup of 72 patients, markers of disease activity were also assessed for correlation with fatigue using univariate and multivariate analysis with fatigue as the dependent variable. RESULTS: In all three groups, significant correlations between fatigue and RDW were observed (p<0.001; p=0.02; p<0.001 respectively) and this was preserved in multivariate analysis. There was no correlation between fatigue and haemoglobin in two groups (with the correlation between RDW and fatigue remaining significant in non-anaemic patients in the third group). In subgroup analysis, fatigue was not associated with any measures of disease activity. CONCLUSIONS: We report a reproducible, statistically significant association between RDW and fatigue levels in a diverse population of patients with SLE. The findings of this study raise the possibility of a potential novel biological basis for fatigue in those in whom there is a lack of an alternate explanation.
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Anemia , Índices de Eritrócitos , Lúpus Eritematoso Sistêmico , Anemia/sangue , Austrália , Inglaterra , Fadiga , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/terapia , Índice de Gravidade de DoençaRESUMO
Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by sonic hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth and increases DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (also known as p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma.