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BACKGROUND: Observational studies suggest vitamin D and marine ω-3 fatty acid (n-3 FA) supplements are associated with lower systemic inflammation. However, past trials have been inconsistent. METHODS: The randomized, double-blind, placebo-controlled VITamin D and OmegA-3 TriaL (VITAL) tested vitamin D (2000 IU/day) and/or n-3 FA (1 g/day) supplementation in a 2 × 2 factorial design among women ≥55 and men ≥50 years of age. We assessed changes in interleukin (IL)-6, tumor necrosis factor receptor 2 (TNFR2), and high-sensitivity C-reactive protein (hsCRP) concentrations from baseline to 1 year among participants randomized to vitamin D + n-3 FA (392), vitamin D (392), n-3 FA (392), or placebo only (385). Geometric means and percent changes were compared, adjusting for baseline factors. RESULTS: Baseline characteristics were well balanced. In the active arms, 25-OH vitamin D rose 39% and n-3 FA rose 55% vs minimal change in placebo arms. Neither supplement reduced biomarkers at 1 year. Vitamin D resulted in 8.2% higher IL-6 (95% CI, 1.5%-15.3%; adjusted P = 0.02), but TNFR2 and hsCRP did not. Among 784 receiving vitamin D, hsCRP increased 35.7% (7.8%-70.9%) in those with low (<20 ng/mL) but not with higher baseline serum 25(OH) vitamin D [0.45% (-8.9% to 10.8%); P interaction = 0.02]. Among 777 randomized to n-3 FA, hsCRP declined [-10.5% (-20.4% to 0.8%)] in those with baseline low (<1.5 servings/week), but not with higher fish intake [6.4% (95% CI, -7.11% to 21.8%); P interaction = 0.06]. CONCLUSIONS: In this large sample from a population-based randomized controlled trial, neither vitamin D nor n-3 FA supplementation over 1 year decreased these biomarkers of inflammation. CLINICALTRIALSGOV IDENTIFIER: NCT01169259; NCT01351805.
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Ácidos Graxos Ômega-6/farmacologia , Inflamação/tratamento farmacológico , Vitamina D/farmacologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos Ômega-6/sangue , Ácidos Graxos Ômega-6/metabolismo , Feminino , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Receptores Tipo II do Fator de Necrose Tumoral/análise , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Estados Unidos , Vitamina D/sangue , Vitamina D/metabolismoRESUMO
OBJECTIVE: Racial variation in total knee replacement (TKR) utilization in the United States has been reported in administrative database studies. We investigated racial variation in TKR procedures in a diverse cohort with severe knee pain followed in an ongoing clinical trial. METHODS: VITAL (VITamin D and OmegA-3 TriaL) is a nationwide, randomized controlled trial of 25,874 adults, 20% of whom are black. We identified a subgroup highly likely to have knee osteoarthritis based on severity of knee pain, physician-diagnosed knee osteoarthritis, and inability to walk 2 to 3 blocks without pain. Participants completed a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and self-reported incident TKR annually in follow-up. Using Cox regression, we analyzed the association of black versus white race with TKR, adjusting for demographic and socioeconomic characteristics, comorbidities, and WOMAC pain and function. RESULTS: Among 1070 participants who met the inclusion criteria, black participants reported worse baseline WOMAC pain (45 vs. 32, P < 0.001) and worse function (45 vs. 32, P < 0.001). During a median of 3.6 years (interquartile range, 3.2, 3.8 years) of follow-up, TKRs were reported by 180 participants. Black participants were less likely to undergo TKR (11% vs. 19%). After adjustment, the hazard ratio for TKR for black versus white participants was 0.51 (95% confidence interval, 0.32-0.81). Lower use of TKR among black participants was observed across all levels of income and education. CONCLUSIONS: Despite worse baseline knee pain and function, black participants had much lower adjusted risk of having TKR than white participants, demonstrating persistent racial disparity in TKR utilization.
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Artralgia , Artroplastia do Joelho , População Negra/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/etnologia , População Branca/estatística & dados numéricos , Adulto , Idoso , Artralgia/diagnóstico , Artralgia/etiologia , Artroplastia do Joelho/métodos , Artroplastia do Joelho/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/cirurgia , Medição da Dor/métodos , Medição da Dor/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de DoençaRESUMO
PURPOSE: Gout is a common inflammatory arthritis characterized by repeated acute flares. The ability to accurately identify gout flares is critical for comparative effectiveness studies of gout treatments. We developed and examined the accuracy of a claims-based algorithm to identify gout flares. METHODS: Patients receiving care at an academic medical center between 2006 and 2010 with a diagnosis of gout or hyperuricemia were selected using an electronic medical record-Medicare claims linked dataset. Gout flares were identified by several claims-based algorithms using a diagnosis of gout combined with gout-related medication claims and/or procedure codes for arthrocentesis or joint injection. We calculated positive predictive value of these algorithms based on physician documentation of gout flare in medical record as the gold standard. Negative predictive value of the gout flare algorithm was calculated in a randomly selected subgroup of 200 patients with gout. RESULTS: Among 3952 subjects with gout or hyperuricemia, 503 flares were identified using the medication-based algorithm, and 290 were identified using the procedure-based algorithm. The positive predictive value for gout flares ranged from 50-54% for the medication-based algorithms and 59-68% for the procedure-based algorithms. The negative predictive value of the algorithm combining both medication and procedure claims was high (85.2%). CONCLUSION: Use of gout diagnosis codes in combination with medication dispensing or procedure codes did not appear to accurately capture gout flares in patients with gout in a claims database. However, the claims-based flare algorithm could be useful in identifying a cohort of gout patients with no flares. Copyright © 2016 John Wiley & Sons, Ltd.
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Algoritmos , Bases de Dados Factuais/estatística & dados numéricos , Gota/epidemiologia , Hiperuricemia/epidemiologia , Centros Médicos Acadêmicos , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Gota/diagnóstico , Gota/fisiopatologia , Humanos , Hiperuricemia/diagnóstico , Masculino , Medicare , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estados UnidosRESUMO
Mast cells contribute importantly to allergic and innate immune responses by releasing various preformed and newly synthesized mediators. Previous studies have shown mast cell accumulation in human atherosclerotic lesions. This report establishes the direct participation of mast cells in atherogenesis in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Atheromata from compound mutant Ldlr(-/-) Kit(W-sh)(/W-sh) mice showed decreased lesion size, lipid deposition, T-cell and macrophage numbers, cell proliferation and apoptosis, but increased collagen content and fibrous cap development. In vivo, adoptive transfer of syngeneic wild-type or tumor necrosis factor (TNF)-alpha-deficient mast cells restored atherogenesis to Ldlr(-/-)Kit(W-sh/W-sh) mice. Notably, neither interleukin (IL)-6- nor interferon (IFN)-gamma-deficient mast cells did so, indicating that the inhibition of atherogenesis in Ldlr(-/-)Kit(W-sh/W-sh) mice resulted from the absence of mast cells and mast cell-derived IL-6 and IFN-gamma. Compared with wild-type or TNF-alpha-deficient mast cells, those lacking IL-6 or IFN-gamma did not induce expression of proatherogenic cysteine proteinase cathepsins from vascular cells in vitro or affect cathepsin and matrix metalloproteinase activities in atherosclerotic lesions, implying that mast cell-derived IL-6 and IFN-gamma promote atherogenesis by augmenting the expression of matrix-degrading proteases. These observations establish direct participation of mast cells and mast cell-derived IL-6 and IFN-gamma in mouse atherogenesis and provide new mechanistic insight into the pathogenesis of this common disease.
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Aterosclerose/imunologia , Aterosclerose/patologia , Citocinas/metabolismo , Mediadores da Inflamação/fisiologia , Mastócitos/imunologia , Mastócitos/metabolismo , Animais , Aterosclerose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos TransgênicosRESUMO
We report the case of an 80-year-old man with restrictive strabismus in lateral gaze following multiple oculoplastic procedures for idiopathic epiphora. Despite excellent initial response to nasal conjunctival recession with lysis of adhesions and a miminal recession of the medial rectus muscle, the patient suffered recurrence of diplopia associated with limitation of abduction due to aggressive, deep, subconjunctival scarring. Given the history of oral lichen planus (LP), the patient was diagnosed with ocular involvement of LP. He underwent a second conjunctival recession, this time accompanied by an intensive LP treatment regimen. Nine months after surgery, he remained diplopia free and orthophoric in primary gaze. Surgeons treating restrictive strabismus in patients with LP should consider implementing systemic and topical immunosuppressive treatment simultaneously with surgical management.
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Recidiva , Estrabismo , Humanos , Masculino , Idoso de 80 Anos ou mais , Estrabismo/cirurgia , Estrabismo/etiologia , Líquen Plano/diagnóstico , Líquen Plano/complicações , Líquen Plano/tratamento farmacológico , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Glucocorticoides/uso terapêutico , Diplopia/etiologia , Diplopia/diagnósticoRESUMO
OBJECTIVE: To investigate immunomodulator use, risk factors and management for rheumatoid arthritis (RA) flares, and mortality for patients with pre-existing RA initiating immune checkpoint inhibitors (ICI) for cancer. METHODS: We performed a retrospective cohort study of all patients with RA meeting 2010 ACR/EULAR criteria that initiated ICI for cancer at Mass General Brigham or Dana-Farber Cancer Institute in Boston, MA (2011-2022). We described immunomodulator use and changes at baseline of ICI initiation. We identified RA flares after baseline, categorized the severity, and described the management. Baseline factors were examined for RA flare risk using Fine and Gray competing risk models. We performed a landmark analysis to limit the potential for immortal time bias, where the analysis started 3 months after ICI initiation. Among those who survived at least 3 months, we examined whether RA flare within 3 months after ICI initiation was associated with mortality using Cox regression. RESULTS: Among 11,901 patients who initiated ICI for cancer treatment, we analyzed 100 pre-existing RA patients (mean age 70.3 years, 63 % female, 89 % on PD-1 monotherapy, 50 % lung cancer). At ICI initiation, 71 % were seropositive, 82 % had remission/low RA disease activity, 24 % were on glucocorticoids, 35 % were on conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and 10 % were on biologic or targeted synthetic DMARDs. None discontinued glucocorticoids and 3/35 (9 %) discontinued DMARDs in anticipation of starting ICI. RA flares occurred in 46 % (incidence rate 1.84 per 1000 person-months, 95 % CI 1.30, 2.37); 31/100 flared within 3 months of baseline. RA flares were grade 1 in 16/46 (35 %), grade 2 in 25/46 (54 %), and grade 3 in 5/46 (11 %); 2/46 (4 %) required hospitalization for RA flare. Concomitant immune-related adverse events occurred in 15/46 (33 %) that flared. A total of 72/100 died during follow-up; 21 died within 3 months of baseline. Seropositivity had an age-adjusted sdHR of 1.95 (95 % CI 1.02, 3.71) for RA flare compared to seronegativity, accounting for competing risk of death. Otherwise, no baseline factors were associated with RA flare, including cancer type, disease activity, RA duration, and deformities. 9/46 (20 %) patients had their ICI discontinued/paused due to RA flares. In the landmark analysis among 79 patients who survived at least 3 months, RA flare in the first 3 months was not associated with lower mortality (adjusted HR 1.24, 95 % CI 0.71, 2.16) compared to no RA flare. CONCLUSION: Among patients with pre-existing RA, few changed immunomodulator medications in anticipation of starting ICI, but RA flares occurred in nearly half. RA flares were mostly mild and treated with typical therapies. Seropositivity was associated with RA flare risk. A minority had severe RA flares requiring disruption of ICI, and RA flares were not associated with mortality.
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Antirreumáticos , Artrite Reumatoide , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Artrite Reumatoide/tratamento farmacológico , Fatores de Risco , Antirreumáticos/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Fatores Imunológicos/uso terapêuticoRESUMO
Objective: Inflammation, manifesting as effusion and synovitis, is thought to contribute to pain in knee osteoarthritis (OA). We conducted a pilot study to investigate recruitment feasibility and assess whether effusion on ultrasound of the knee was associated with greater reduction in knee pain after corticosteroid injection. Methods: A pilot study was conducted from 2020 to 2021 including patients ≥40 years with knee OA undergoing clinically indicated corticosteroid injections. At baseline, participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale and had an ultrasound of the injected knee(s) to assess for effusion, defined as anechoic material in the suprapatellar recess. KOOS Pain was re-assessed two weeks following injection. We used mixed linear models to evaluate the change in KOOS Pain scores for knees with and without effusion to determine estimates of the magnitude of association. Results: We recruited 10 participants who contributed 16 knees from 4 clinical sessions. The mean age was 68 years (standard deviation [SD] 13) and 90% were female. Six knees had effusion. At baseline, knees without effusion had greater pain (mean KOOS Pain 44, SD 19) compared to those with effusion (mean KOOS Pain 51, SD 15). Knees without effusion had a 6 point (95% CI -16, 28) greater improvement in KOOS Pain 2-weeks post injection compared to those with effusion. Conclusion: This pilot study demonstrated clinic-based recruitment was feasible. We did not observe clinically important or statistically significant differences in pain relief post corticosteroid injection between knee OA patients with or without effusion.
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OBJECTIVE: Inflammation is a potential pain generator and treatment target in knee osteoarthritis (OA). Inflammation can be detected on magnetic resonance imaging (MRI) and by synovial fluid white blood cell count (WBC). However, the performance characteristics of synovial fluid WBC for the detection of synovitis have not been established. This study was undertaken to determine the sensitivity and specificity of synovial fluid WBC in identifying inflammation in knee OA using MRI effusion-synovitis as the gold standard. METHODS: We identified records of patients seen at an academic center with a diagnosis code for knee OA, a procedural code for knee aspiration, and a laboratory order for synovial fluid WBC in the same encounter, as well as an MRI within 12 months of the aspiration. MRIs were read for effusion-synovitis using the MRI OA Knee Score (MOAKS). We dichotomized effusion-synovitis as 1) none or small, or 2) medium or large. We calculated the sensitivity and specificity of synovial fluid WBC using MRI effusion-synovitis (medium/large) as the gold standard. We used the Youden index to identify the best cut point. RESULTS: We included 75 patients. Mean ± SD age was 63 ± 12 years, and 69% were female. The synovial fluid WBC was higher in the medium/large effusion-synovitis group (median 335 [interquartile range (IQR) 312]) than in the none/small group (median 194 [IQR 272]). The optimal cut point was 242, yielding a sensitivity of 71% (95% confidence interval [95% CI] 56-83%) and specificity of 63% (95% CI 41-81%). CONCLUSION: The sensitivity and specificity of synovial fluid WBC in identifying effusion-synovitis on MRI were limited. Further research is needed to better understand the association between MRI and effusion-synovitis measured by synovial fluid and to determine which measure more strongly relates to synovial histopathology and patient outcomes.
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Osteoartrite do Joelho , Sinovite , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Líquido Sinovial/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Inflamação/patologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Contagem de LeucócitosRESUMO
OBJECTIVE: Middle-aged subjects with meniscal tear treated with arthroscopic partial meniscectomy (APM) experience greater progression of damage to joint structures on imaging than subjects treated nonoperatively. It is unclear whether these changes are clinically relevant. The goal of this study was to assess whether worsening in magnetic resonance imaging (MRI)-assessed tissue damage over 18 months leads to subsequent worsening in knee pain over the subsequent 3.5 years. METHODS: We used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of APM versus physical therapy for subjects ages ≥45 years with knee pain, cartilage damage, and meniscal tear. We assessed whether change in cartilage surface area damage score (and other structural measures) from baseline to 18 months, assessed on MRI with the MRI Osteoarthritis Knee Score (MOAKS) system, was associated with change in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (range 0-100; 100 = worst) from 18 to 60 months. RESULTS: The primary analysis included 168 subjects with complete MRI data at baseline and 18 months and KOOS data at 18 and 60 months. We did not observe clinically important associations between change in cartilage surface area score between baseline and 18 months and change in pain scores from 18 to 60 months. Pain scores in the worst tertile for cartilage surface area damage score progression worsened by 0.45 points more than in the best tertile (95% confidence interval -4.45, 5.35). Similarly, we did not observe clinically important associations between changes in bone marrow lesions, osteophytes, or synovitis and subsequent pain. CONCLUSION: We did not observe clinically important associations between early changes in cartilage damage and other structural measures and worsening in pain over the subsequent 3.5 years. Further follow-up is required to assess this association over a longer follow-up period.
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Doenças Ósseas , Traumatismos do Joelho , Osteoartrite do Joelho , Lesões do Menisco Tibial , Pessoa de Meia-Idade , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/complicações , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Dor/complicações , Imageamento por Ressonância Magnética/métodos , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/cirurgiaRESUMO
Background: Patients with pre-existing rheumatoid arthritis initiating immune checkpoint inhibitors for cancer might be at risk of increased mortality, rheumatoid arthritis flares, and other immune-related adverse events (AEs). We aimed to determine whether pre-existing rheumatoid arthritis was associated with higher mortality and immune-related AE risk in patients treated with immune checkpoint inhibitors. Methods: This retrospective, comparative cohort study was conducted at the Mass General Brigham Integrated Health Care System and the Dana-Farber Cancer Institute in Boston (MA, USA). We searched data repositories to identify all individuals who initiated immune checkpoint inhibitors from April 1, 2011, to April 21, 2021. Patients with pre-existing rheumatoid arthritis had to meet the 2010 American College of Rheumatology-European Alliance of Associations for Rheumatology (ACR-EULAR) criteria. For each pre-existing rheumatoid arthritis case, we matched up to three non-rheumatoid arthritis comparators at the index date of immune checkpoint inhibitor initiation by sex (recorded as male or female), calendar year, immune checkpoint inhibitor target, and cancer type and stage. The coprimary outcomes were time from index date to death and time to the first immune-related AE, measured using an adjusted Cox proportional hazards model. Deaths were identified by medical record and obituary review. Rheumatoid arthritis flares and immune-related AE presence, type, and severity were determined by medical record review. Findings: We identified 11 901 patients who initiated immune checkpoint inhibitors for cancer treatment between April 1, 2011, and April 21, 2021; of those, 101 met the 2010 ACR-EULAR criteria for rheumatoid arthritis. We successfully matched 87 patients with pre-existing rheumatoid arthritis to 203 non-rheumatoid arthritis comparators. The median age was 71·2 years (IQR 63·2-77·1). 178 (61%) of 290 participants were female, 112 (39%) were male and 268 (92%) participants were White. PD-1 was the most common immune checkpoint inhibitor target (80 [92%] of 87 patients with rheumatoid arthritis vs 188 [93%] of 203 comparators). Lung cancer was the most common cancer type (43 [49%] vs 114 [56%]), followed by melanoma (21 [24%] vs 50 [25%]). 60 (69%) patients with rheumatoid arthritis versus 127 (63%) comparators died (adjusted hazard ratio [HR] of 1·16 [95% CI 0·86-1·57]; p=0·34). 53 (61%) patients with rheumatoid arthritis versus 99 (49%) comparators had any all-grade immune-related AE (adjusted HR 1·72 [95% CI 1·20-2·47]; p=0·0032). There were two (1%) grade 5 immune-related AEs (deaths) due to myocarditis, both in the comparator group. Rheumatoid arthritis flares occurred in 42 (48%) patients with rheumatoid arthritis, and inflammatory arthritis occurred in 14 (7%) comparators (p<0·0001). Those with rheumatoid arthritis were less likely to have rash or dermatitis (five [6%] vs 28 [14%]; p=0·048), endocrinopathy (two [2%] vs 22 [11%]; p=0·0078), colitis or enteritis (six [7%] vs 28 [14%] comparators; p=0·094), and hepatitis (three [3%] vs 19 [9%]; p=0·043). Interpretation: Patients with pre-existing rheumatoid arthritis initiating immune checkpoint inhibitors had similar risk of mortality and severe immune-related AEs as matched comparators. Although patients with pre-existing rheumatoid arthritis were more likely to have immune-related AEs, this finding was mostly due to mild rheumatoid arthritis flares. These results suggest that this patient population can safely receive immune checkpoint inhibitors for cancer treatment. Funding: None.
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OBJECTIVE: Meniscal tear in persons aged ≥45 years is typically managed with physical therapy (PT), and arthroscopic partial meniscectomy (APM) is offered to those who do not respond. Prior studies suggest APM may be associated with greater progression of radiographic changes. METHODS: We assessed changes between baseline and 60 months in the Kellgren-Lawrence (KL) grade and OARSI radiographic score (including subscores for joint space narrowing and osteophytes) in subjects aged 45-85 years enrolled into a seven-center randomized trial comparing outcomes of APM with PT for meniscal tear, osteoarthritis changes, and knee pain. The primary analysis classified subjects according to treatment received. To balance APM and PT groups, we developed a propensity score and used inverse probability weighting (IPW). We imputed a 60-month change in the OARSI score for subjects who underwent total knee replacement (TKR). In a sensitivity analysis, we classified subjects by randomization group. RESULTS: We analyzed data from 142 subjects (100 APM, 42 PT). The mean ± SD weighted baseline OARSI radiographic score was 3.8 ± 3.5 in the APM group and 4.0 ± 4.9 in the PT group. OARSI scores increased by a mean of 4.1 (95% confidence interval [95% CI] 3.5-4.7) in the APM group and 2.4 (95% CI 1.7-3.2) in the PT group (P < 0.001) due to changes in the osteophyte component. We did not observe statistically significant differences in the KL grade. Sensitivity analyses yielded similar findings to the primary analysis. CONCLUSION: Subjects treated with APM had greater progression in the OARSI score because of osteophyte progression but not in the KL grade. The clinical implications of these findings require investigation.
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OBJECTIVE: Several current and many emerging osteoarthritis (OA) treatments are intraarticular (IA) injections; however, little is known about physicians' perceptions and beliefs regarding IA injections or their considerations when deciding whether to recommend them to patients. We aimed to investigate physician-perceived benefits and drawbacks of offering IA injections. METHODS: We conducted individual interviews with orthopedic surgeons, rheumatologists, and physiatrists who treat patients with knee OA. We conducted a thematic analysis to identify factors that physicians weigh when making IA injection recommendations. RESULTS: We interviewed 18 physicians from academic and community practices. We identified the following 4 categories of themes that influenced providers' recommendations to their patients regarding injections: 1) the physician's knowledge, beliefs, and concerns, including their propensity to rely on guidelines versus clinical experience, and understanding of the efficacy and risks associated with injectables, such as possible cartilage damage; 2) the characteristics of the injectable product, such as ease or number of administrations needed; 3) the individual patient-specific factors, including OA severity, comorbidities, and patient preference for and expectations of specific IA injections; and 4) the financial and administrative factors, including insurance coverage and out-of-pocket costs. CONCLUSION: Physicians factor the uncertain efficacy of injectable treatments and the need to manage patient expectations into their decision to offer IA therapies. Some providers relied on evidence and guidelines while others were swayed more by clinical experience. High out-of-pocket costs were seen as a barrier to use. These findings may help in the delivery of IA injections for OA and in the development of injectable products.
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Osteoartrite do Joelho , Médicos , Humanos , Injeções Intra-Articulares , Osteoartrite do Joelho/tratamento farmacológico , Preferência do Paciente , Pesquisa QualitativaRESUMO
Objective: Knee osteoarthritis (OA) can substantially limit function, which can be assessed both objectively and subjectively. We examined whether objective performance tests are associated with self-reported function. Methods: We analyzed baseline data from the Osteoarthritis Registry of Biomarker and Imaging Trajectories (ORBIT) of participants ≥40 years old with symptomatic and radiographic knee OA. Subjects completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Activities of Daily Living (ADL) scales and other assessments of pain and comorbidity. Subjects performed the timed single leg balance test (SLB), 30-s sit-to-stand (30s STS), Timed-Up-and-Go (TUG), and 40-m fast paced walk (40 âm Walk). We used Pearson correlation coefficients to examine associations between performance and KOOS subscales. We adjusted for potential confounders using partial correlations. Results: We enrolled 101 subjects (mean age 63.7 (standard deviation (SD) 10.1), mean BMI 30.0 (SD 5.6), and 63% female). The mean (SD) values for the performance tests were: SLB 20.1 (18.9) seconds, 30s STS 11.7 (4.6) stands, TUG 9.4 (2.3) seconds, and 40 âm Walk 27.6 (6.5) seconds. Correlations between performance tests and self-report measures did not exceed 0.39, with the absolute value of correlations between KOOS ADL and performance measures ranging from 0.24 to 0.39. Adjusted partial correlations were largely similar to the crude correlations. Conclusions: Self-reported function in persons with knee OA had weak to modest correlations with objective function. Objective performance tests capture elements of physical function that self-report data do not and point to the potential value of including objective measures of functional status in OA trials.
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OBJECTIVE: Intraarticular (IA) injections are used frequently for knee osteoarthritis (OA), but little is known about patients' attitudes toward these therapies. We aimed to better understand patients' perceptions of the facilitators of and barriers to IA injections for knee OA. METHODS: We conducted a qualitative, descriptive, exploratory study and held focus groups and individual interviews with participants with knee OA, including some who had and some who had not received IA injections. We conducted a thematic analysis to identify themes describing the factors that participants found influential when deciding whether to try an IA injection. RESULTS: We held 3 focus groups with 12 participants and conducted 3 individual interviews (15 participants total). We identified the following 4 themes that shaped participants' decisions to receive a specific injection: 1) the impact of OA on participants' lives; 2) participants' attitudes and concerns, including desire to avoid surgery, willingness to accept uncertain outcomes, and concerns about side effects and dependence; 3) the way participants gathered and processed information from physicians, peers, and the internet; and 4) the availability of injectable products. Participants weighed the desire to regain function and delay surgery with concerns about side effects, uncertain efficacy, and costs. CONCLUSION: Participants were concerned about the effectiveness, toxicity, availability, and cost of injectable products. They balanced disparate sources of information, uncertain outcomes, limited product availability, and other injection-related concerns with a desire to decrease pain. These findings can provide clinicians, investigators, and public health professionals with insights into challenges that patients face when making injection decisions.
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Conhecimentos, Atitudes e Prática em Saúde , Injeções Intra-Articulares/psicologia , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/psicologia , Manejo da Dor/métodos , Preferência do Paciente , Pesquisa QualitativaRESUMO
OBJECTIVE: To identify predictors of rheumatic immune-related adverse events (irAEs) following immune checkpoint inhibitor (ICI) treatment for cancer. METHODS: We performed a case-control study to predict the occurrence of rheumatic irAEs in cancer patients who initiated ICI treatment at Mass General Brigham and the Dana-Farber Cancer Institute between 2011 and 2020. We screened for the presence of rheumatic irAEs by reviewing the medical records of patients evaluated by rheumatologists or those prescribed nonglucocorticoid immunomodulatory drugs after the time of ICI initiation (baseline). Review of medical records confirmed the presence of rheumatic irAEs and the indications necessitating immunomodulatory drug treatment. Controls were defined as patients who did not experience rheumatic irAEs, did not have preexisting rheumatic disease, did not have a clinical evaluation by a rheumatologist after ICI treatment, did not receive an immunomodulatory drug after ICI, did not receive systemic glucocorticoids after ICI, and survived at least 6 months after the initial ICI treatment. We used logistic regression to estimate the odds ratios (ORs) (with 95% confidence intervals [95% CIs]) for the risk of a rheumatic irAE in the presence of various baseline predictors. RESULTS: A total of 8,028 ICI recipients were identified (mean age 65.5 years, 43.1% female, 31.8% with lung cancer). After ICI initiation, 404 patients (5.0%) were evaluated by rheumatologists, and 475 patients (5.9%) received an immunomodulatory drug to treat any irAEs. There were 226 confirmed rheumatic irAE cases (2.8%) and 118 de novo inflammatory arthritis cases (1.5%). Rheumatic diseases (either preexisting rheumatic diseases or rheumatic irAEs) were a common indication for immunomodulatory drug use (27.9%). Baseline predictors of rheumatic irAEs included melanoma (multivariable OR 4.06 [95% CI 2.54-6.51]) and genitourinary (GU) cancer (OR 2.22 [95% CI 1.39-3.54]), both relative to patients with lung cancer; combination ICI treatment (OR 2.35 [95% CI 1.48-3.74]), relative to patients receiving programmed death 1 inhibitor monotherapy; autoimmune disease (OR 2.04 [95% CI 1.45-2.85]) and recent glucocorticoid use (OR 2.13 [95% CI 1.51-2.98]), relative to patients not receiving a glucocorticoid, compared to the 2,312 controls without rheumatic irAEs. Predictors of de novo inflammatory arthritis were similar to those of rheumatic irAEs. CONCLUSION: We identified novel predictors of rheumatic irAE development in cancer patients, including baseline presence of melanoma, baseline presence of GU tract cancer, preexisting autoimmune disease, receiving or having received combination ICI treatment, and receiving or having received glucocorticoids. The proportion of cancer patients experiencing rheumatic irAEs may be even higher than was reported in the present study, since we used stringent criteria to identify cases of rheumatic irAEs. Our findings could be used to identify cancer patients at risk of developing rheumatic irAEs and de novo inflammatory arthritis and may help further elucidate the pathogenesis of rheumatic irAEs in patients with cancer who are receiving ICI treatment.
Assuntos
Artrite Reumatoide/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Patients with meniscal tears reporting meniscal symptoms such as catching or locking have traditionally undergone arthroscopy. The present study was undertaken to investigate whether patients with meniscal tears who report meniscal symptoms have greater improvement with arthroscopic partial meniscectomy (APM) than physical therapy (PT). METHODS: We used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial, which randomized participants with knee osteoarthritis (OA) and meniscal tear to APM or PT. The frequency of each meniscal symptom (clicking, catching, popping, intermittent locking, giving way, swelling) was measured at baseline and 6 months. We used linear regression models to determine whether the difference in improvement in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score at 6 months between patients treated with APM versus PT was modified by the presence of each meniscal symptom. We also determined the percentage of participants with resolution of meniscal symptoms by treatment group. RESULTS: We included 287 participants. The presence (versus absence) of any of the meniscal symptoms did not modify the improvement in KOOS pain score between APM versus PT by >0.5 SD (all P interaction >0.05). APM led to greater resolution of intermittent locking and clicking than PT (locking 70% versus 46%, clicking 41% versus 25%). No difference in resolution of the other meniscal symptoms was observed. CONCLUSION: Meniscal symptoms were not associated with improved pain relief. Although symptoms of clicking and intermittent locking had a greater reduction in the APM group, the presence of meniscal symptoms in isolation should not inform clinical decisions surrounding APM versus PT in patients with meniscal tear and knee OA.
Assuntos
Traumatismos do Joelho , Osteoartrite do Joelho , Lesões do Menisco Tibial , Artroscopia , Humanos , Traumatismos do Joelho/complicações , Meniscectomia/efeitos adversos , Meniscos Tibiais/cirurgia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/cirurgia , Dor/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Lesões do Menisco Tibial/cirurgiaRESUMO
Abdominal aortic aneurysm (AAA), an inflammatory disease, involves leukocyte recruitment, immune responses, inflammatory cytokine production, vascular remodeling, neovascularization, and vascular cell apoptosis, all of which contribute to aortic dilatation. This study demonstrates that mast cells, key participants in human allergic immunity, participate in AAA pathogenesis in mice. Mast cells were found to accumulate in murine AAA lesions. Mast cell-deficient KitW-sh/KitW-sh mice failed to develop AAA elicited by elastase perfusion or periaortic chemical injury. KitW-sh/KitW-sh mice had reduced aortic expansion and internal elastic lamina degradation; decreased numbers of macrophages, CD3+ T lymphocytes, SMCs, apoptotic cells, and CD31+ microvessels; and decreased levels of aortic tissue IL-6 and IFN-gamma. Activation of mast cells in WT mice via C48/80 injection resulted in enhanced AAA growth while mast cell stabilization with disodium cromoglycate diminished AAA formation. Mechanistic studies demonstrated that mast cells participated in angiogenesis, aortic SMC apoptosis, and matrix-degrading protease expression. Reconstitution of KitW-sh/KitW-sh mice with bone marrow-derived mast cells from WT or TNF-alpha-/- mice, but not from IL-6-/- or IFN-gamma-/- mice, caused susceptibility to AAA formation to be regained. These results demonstrate that mast cells participate in AAA pathogenesis in mice by releasing proinflammatory cytokines IL-6 and IFN-gamma, which may induce aortic SMC apoptosis, matrix-degrading protease expression, and vascular wall remodeling, important hallmarks of arterial aneurysms.
Assuntos
Aneurisma da Aorta Abdominal/induzido quimicamente , Mastócitos/imunologia , Elastase Pancreática/farmacologia , Animais , Aorta/anatomia & histologia , Aorta/metabolismo , Aorta/patologia , Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/patologia , Elastina/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Mastócitos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Elastase Pancreática/genética , Elastase Pancreática/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To determine the 5-year outcome of treatment for meniscal tear in osteoarthritis. METHODS: We examined 5-year follow-up data from the Meniscal Tear in Osteoarthritis Research trial (METEOR) of physical therapy versus arthroscopic partial meniscectomy. We performed primary intent-to-treat (ITT) and secondary as-treated analyses. The primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scale; total knee replacement (TKR) was a secondary outcome measure. We used piecewise linear mixed models to describe change in KOOS pain. We calculated 5-year cumulative TKR incidence and used a Cox model to estimate hazard ratios (HRs) for TKR, with 95% confidence intervals (95% CIs). RESULTS: Three hundred fifty-one participants were randomized. In the ITT analysis, the KOOS pain scores were ~46 (scale of 0 [no pain] to 100 [most pain]) at baseline in both groups. Pain scores improved substantially in both groups over the first 3 months, continued to improve through the next 24 months (to ~18 in each group), and were stable at 24-60 months. Results of the as-treated analyses of the KOOS pain score were similar. Twenty-five participants (7.1% [95% CI 4.4-9.8%]) underwent TKR over 5 years. In the ITT model, the HR for TKR was 2.0 (95% CI 0.8-4.9) for subjects randomized to the arthroscopic partial meniscectomy group, compared to those randomized to the physical therapy group. In the as-treated analysis, the HR for TKR was 4.9 (95% CI 1.1-20.9) for subjects ultimately treated with arthroscopic partial meniscectomy, compared to those treated nonoperatively. CONCLUSION: Pain improved considerably in both groups over 60 months. While ITT analysis revealed no statistically significant differences following TKR, greater frequency of TKR in those undergoing arthroscopic partial meniscectomy merits further study.
Assuntos
Lesões do Menisco Tibial/terapia , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Lesões do Menisco Tibial/etiologia , Lesões do Menisco Tibial/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Knee pain from osteoarthritis is frequent in the adult population. Prior trials have had conflicting results concerning the therapeutic effects of vitamin D on knee pain, and few trials have investigated marine Omega-3 fatty acids (n-3 FA). METHODS: In the double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), 25,871 US adults were randomized in a 2-by-2 factorial design to receive vitamin D or n-3 FA. We identified a subgroup with chronic knee pain prior to randomization and assessed knee pain at baseline and annually during follow-up using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (graded on a 0-100 scale, where 100 indicates worst symptoms). Repeated measures modeling was used to test the effect of randomized treatment on WOMAC pain scores over follow-up after adjustment for age and sex. Analyses were repeated for WOMAC function and stiffness. RESULTS: This study included 1,398 participants who returned at least one knee pain questionnaire. The mean age was 67.7 years, 66% were women, and the mean ± SD WOMAC pain score was 37 ± 19. The mean ± SD follow-up time was 5.3 ± 0.7 years. WOMAC pain did not differ between the active vitamin D group and the vitamin D placebo group or between the active n-3 FA group and the n-3 FA placebo group at any time point during follow-up. Linear time-by-treatment interactions were not significant for either treatment (vitamin D, P = 0.41; n-3 FA, P = 0.77). Vitamin D and n-3 FA supplementation did not significantly affect WOMAC function or stiffness scores over time. CONCLUSION: Our findings indicate that vitamin D and n-3 FA supplementation for a mean of 5.3 years does not reduce knee pain or improve function or stiffness in a large sample of US adults with chronic knee pain.
Assuntos
Dor Crônica/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Articulação do Joelho/efeitos dos fármacos , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Dor Crônica/fisiopatologia , Método Duplo-Cego , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Resultado do Tratamento , Vitamina D/administração & dosagem , Vitaminas/administração & dosagemRESUMO
OBJECTIVE: Synovitis is a prevalent feature in patients with knee osteoarthritis (OA) and meniscal tear and is associated with pain and cartilage damage. Patient-reported swelling is also prevalent in this population. The aim of this study was to investigate the cross-sectional association between patient-reported swelling and effusion-synovitis detected by magnetic resonance imaging (MRI) in patients with OA and meniscal tear. METHODS: We used baseline data from a multicenter, randomized controlled trial, Meniscal Tear in Osteoarthritis Research (METEOR). MRI-identified effusion-synovitis, a proxy for effusion and synovitis on noncontrast MRIs, was graded as none/small versus medium/large. Using MRI-identified effusion-synovitis as the gold standard, we assessed the sensitivity, specificity, and positive predictive value of patient self-reported swelling in the previous week (none, intermittent, constant) to detect effusion and synovitis. RESULTS: We analyzed data from 276 patients. Twenty-five percent of patients reported no swelling, 40% had intermittent swelling, and 36% had constant swelling. Fifty-two percent had MRI-identified medium/large-grade effusion-synovitis. As compared with MRI-identified effusion-synovitis, any patient-reported swelling (versus none) had a sensitivity of 84% (95% confidence interval [95% CI] 77-89), a specificity of 34% (95% CI 26-43), and a positive predictive value of 57% (95% CI 54-61). A history of constant swelling (versus none or intermittent) showed a sensitivity of 46% (95% CI 37-54), a specificity of 75% (95% CI 67-82), and a positive predictive value of 66% (95% CI 58-74). CONCLUSION: We found that the sensitivity and specificity of patient-reported swelling were modest when compared with effusion-synovitis detected by MRI. These data urge caution against using patient-reported swelling as a proxy of inflammation manifesting as effusion-synovitis.