Clinical Efficacy of Biosimilar Switch of Adalimumab for Management of Uveitis.

BACKGROUND: Adalimumab has demonstrated efficacy in non-infectious uveitis. With the introduction of biosimilar agents such as Amgevita, we aimed to quantify efficacy and tolerability compared to Humira in a multi-centre UK cohort. METHODS: Patients identified from tertiary uveitis clinics in 3 centres, after institution-mandated switching was implemented. RESULTS: Data collected for 102 patients, aged 2-75 years, with 185 active eyes. Following switch, rates of uveitis flare were not significantly different (13 events before, 21 after, p = .132). Rates of elevated intraocular pressure were decreased (32 before, 25 afterwards, p = .006) and dosing of oral and intra-ocular steroids was stable. Twenty-four patients (24%) requested to return to Humira, commonly due to pain from injection or technical difficulty with the device. CONCLUSION: Amgevita is safe and effective for inflammatory uveitis with non-inferiority to Humira. Significant numbers of patients requested to switch back due to side effects including injection site reactions.

Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups.

BACKGROUND: Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15-20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. METHODS: Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years) and adolescent (14-18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. RESULTS: A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4-20] vs. 7(3-13] vs. 7(3-14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. CONCLUSIONS: Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and "classic" autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Outcomes following mycophenolate mofetil versus cyclophosphamide induction treatment for proliferative juvenile-onset lupus nephritis.

BACKGROUND: Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC). METHODS: UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann-Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis. RESULTS: Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4-8 and 10-14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141-390) days after MMF treatment, and 151 (117-305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157-1266) days for MMF, and 343 (198-635) days for IVCYC ( p = 0.47). CONCLUSION: This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.

Correction to "Automatic Quality Assessment of Echocardiograms Using Convolutional Neural Networks: Feasibility on the Apical Four-Chamber View".

In the above paper [1], the first footnote should have indicated the following information: A. H. Abdi and C. Luong are joint first authors.

Attenuated Phenotype of a Recent House Finch-Associated Mycoplasma gallisepticum Isolate in Domestic Poultry.

Mycoplasma gallisepticum, known primarily as a respiratory pathogen of domestic poultry, has emerged since 1994 as a significant pathogen of the house finch (Haemorhousmexicanus) causing severe conjunctivitis and mortality. House finch-associated M. gallisepticum (HFMG) spread rapidly and increased in virulence for the finch host in the eastern United States. In the current study, we assessed virulence in domestic poultry with two temporally distant, and yet geographically consistent, HFMG isolates which differ in virulence for house finches-Virginia 1994 (VA1994), the index isolate of the epidemic, and Virginia 2013 (VA2013), a recent isolate of increased house finch virulence. Here we report a significant difference between VA1994 and VA2013 in their levels of virulence for chickens; notably, this difference correlated inversely to the difference in their levels of virulence for house finches. VA1994, while moderately virulent in house finches, displayed significant virulence in the chicken respiratory tract. VA2013, while highly virulent in the house finch, was significantly attenuated in chickens relative to VA1994, displaying less-severe pathological lesions in, and reduced bacterial recovery from, the respiratory tract. Overall, these data indicate that a recent isolate of HFMG is greatly attenuated in the chicken host relative to the index isolate, notably demonstrating a virulence phenotype in chickens inversely related to that in the finch host.

Evidence of trade-offs shaping virulence evolution in an emerging wildlife pathogen.

In the mid-1990s, the common poultry pathogen Mycoplasma gallisepticum (MG) made a successful species jump to the eastern North American house finch Haemorhous mexicanus (HM). Subsequent strain diversification allows us to directly quantify, in an experimental setting, the transmission dynamics of three sequentially emergent geographic isolates of MG, which differ in the levels of pathogen load they induce. We find significant among-strain variation in rates of transmission as well as recovery. Pathogen strains also differ in their induction of host morbidity, measured as the severity of eye lesions due to infection. Relationships between pathogen traits are also investigated, with transmission and recovery rates being significantly negatively correlated, whereas transmission and virulence, measured as average eye lesion score over the course of infection, are positively correlated. By quantifying these disease-relevant parameters and their relationships, we provide the first analysis of the trade-offs that shape the evolution of this important emerging pathogen.

Common garden experiment reveals pathogen isolate but no host genetic diversity effect on the dynamics of an emerging wildlife disease.

Host genetic diversity can mediate pathogen resistance within and among populations. Here we test whether the lower prevalence of Mycoplasmal conjunctivitis in native North American house finch populations results from greater resistance to the causative agent, Mycoplasma gallisepticum (MG), than introduced, recently-bottlenecked populations that lack genetic diversity. In a common garden experiment, we challenged wild-caught western (native) and eastern (introduced) North American finches with a representative eastern or western MG isolate. Although introduced finches in our study had lower neutral genetic diversity than native finches, we found no support for a population-level genetic diversity effect on host resistance. Instead we detected strong support for isolate differences: the MG isolate circulating in western house finch populations produced lower virulence, but higher pathogen loads, in both native and introduced hosts. Our results indicate that contemporary differences in host genetic diversity likely do not explain the lower conjunctivitis prevalence in native house finches, but isolate-level differences in virulence may play an important role.

A 30 year perspective of the quality of evidence published in 25 clinical journals: signs of change?

METHODS: The quality of clinical studies published in five different specialties, over three decades was evaluated. Computerised search of the Medline database was undertaken to evaluate the articles published in 25 clinical journals in 1983, 1993, and 2003 from five different specialties (medicine, surgery, paediatrics, anaesthesia, and psychiatry). The number of randomised controlled trials (RCTs), meta-analyses, and other clinical trials (non-RCT) were noted. RESULTS: From the 27,030 articles evaluated, there were 2283 (8.4%) RCTs, 166 (0.6%) meta-analyses, and 4153 (15.4%) other clinical trials. For the proportion of RCTs, the rank order of the specialties was; anaesthesia (503; 18%), psychiatry (294; 9.6%), medicine (899; 8.1%), paediatrics (326; 6.4%), and surgery (261; 5.3%) (p<0.001). For the proportion of meta-analysis, the rank order of the specialties was; psychiatry (36; 1.2%), medicine (105; 0.9%), paediatrics (15; 0.3%), anaesthesia (6; 0.2%), and surgery (4; 0.1%) (p<0.001). Overall, from 1983 to 2003, there were increases in the proportion of RCTs (449, 5.9% to 1027, 9.6%), meta-analysis (0, 0% to 127, 1.2%), and other clinical trials (897, 12% to 1983, 19%) (p<0.001). This trend was apparent in each clinical specialty (p<0.001). CONCLUSIONS: Over the three decades evaluated, clinical trials, notably RCTs and meta-analysis form only a small proportion of articles published in prominent journals from five clinical specialties. This is notwithstanding the modest increases in the proportions of RCTs and meta-analysis over the same period.

A review of 300 attempted strangulation cases. Part I: criminal legal issues.

Three hundred strangulation cases, submitted for misdemeanor prosecution to the San Diego City Attorney's Office, were evaluated to determine the signs and symptoms of attempted strangulation that could be used to corroborate the victim's allegation of being "choked" for purposes of prosecution. The study reveals that a lack of training may have caused police and prosecutors to overlook symptoms of strangulation or to rely too heavily on the visible signs of strangulation. Because most victims of strangulation had no visible injuries or their injuries were too minor to photograph, opportunities for higher level criminal prosecution were missed.

A review of 300 attempted strangulation cases Part II: clinical evaluation of the surviving victim.

Medical literature describing victims who survive strangulation is scant. The majority of articles on strangulation are found in the forensic literature, describing the post-mortem findings on autopsy. This article presents a suggested protocol for the evaluation and treatment of the surviving victim of strangulation, based upon a review of the available literature. It also corroborates the findings of Strack et al., in the study by the San Diego City Attorney's Office, described in Part I of this series.

A review of 300 attempted strangulation cases Part III: injuries in fatal cases.

A review of 300 cases of alleged strangulation assault, submitted for misdemeanor prosecution by the San Diego City Attorney's Office, led to a search for medical evidence that would be useful to prosecute these cases (see Strack et al. in this issue of the Journal). The injuries identified in these non-fatal cases are similar to injuries found in fatal domestic violence strangulation assaults. This article reviews the injuries recognizable at autopsy in cases of strangulation in domestic violence victims.

Seasonal symptom severity in patients with rheumatic diseases: a study of 1,424 patients.

OBJECTIVE: To examine the nature of seasonal symptoms, their prevalence, and differences among rheumatic disorders by examining longitudinal data over a period of up to 24 years. METHODS: We used a questionnaire assessment of seasonal symptoms using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 1,424 patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Clinical status was evaluated with standard assessment measures, and reported symptoms were compared with actual seasonal differences measured for periods of up to 24 years. RESULTS: About 50% of patients with rheumatic disease reported exacerbation of rheumatic symptoms (pain, global severity, and fatigue) by seasonal changes. The presence of seasonal symptoms was not related to diagnosis or to seasonal affective disorder (SAD) symptoms, and symptoms were less common in older patients and in men. The number of symptoms and the severity of allied factors (depression, anxiety, pain, global severity, number of months with seasonal symptoms) were increased in persons with FM and/or complete SAD symptoms. Using circular statistics, the modal months for worse symptoms were December and January, and for best symptoms was July. Bimodal patterns of seasonality were identified for global severity, joint pain, fatigue, and socialization. Seasonal symptoms differed as to the degree at which they were dispersed around the 12 month circle. When pain and global severity measurements obtained over a 24 year period were analyzed, pain was slightly increased in the summer and global severity was not related to season at all. Even when patients who specifically reported worse symptoms in winter and best symptoms in summer were examined, no effect of season could be found. CONCLUSION: Seasonal rheumatic symptoms are commonly reported across all rheumatic diseases, but appear to reflect perception rather than reality since reported symptoms do not agree with measured clinical scores. In addition, regardless of seasonal complaints, measured pain and global severity scores are not worse in winter. Although patients with FM and Season (+) patients report more severe symptoms, their pattern of reporting and their actual scores do not differ according to season compared to persons without FM or positive seasonality.

The assessment of functional impairment in fibromyalgia (FM): Rasch analyses of 5 functional scales and the development of the FM Health Assessment Questionnaire.

OBJECTIVE: Functional assessment by self-report questionnaire plays an important role in most rheumatic conditions, but psychometric properties of questionnaires have not been studied in fibromyalgia (FM), particularly by Rasch analysis, which allows for examining adequacy of the questionnaire scale. To assess currently used instruments, we examined the Fibromyalgia Impact Scale (FIQ), 4 versions of the Health Assessment Questionnaire (HAQ), and the Medical Outcome Survey Short Form (SF-36). METHODS: More than 2,500 patients from 4 sites (3 US, 1 Israel) completed the FIQ. The HAQ questionnaires were completed by 1438 patients participating in the US National Data Bank for Rheumatic Diseases. Seven hundred sixty patients from Wichita, Kansas, completed the SF-36. Rasch analysis was applied separately to each of these data sets. RESULTS: The FIQ systematically underestimated functional impairment by its handling of activities not usually performed. All questionnaires had problems with non-unidimensionality and ambiguous items when applied to patients with FM. In addition, scales were found to be non-linear. Because of these findings we used the 20 item HAQ questionnaire as an item bank to develop a new questionnaire more suitable for use in FM, the fibromyalgia HAQ (FHAQ). This questionnaire fits the Rasch model well, is relevant, is linear, and has a long, well spaced scale. CONCLUSION: No available functional assessment questionnaire works well in FM. A new questionnaire, the FHAQ, was developed. It has appropriate metric properties and should function well in this condition. Since the FHAQ is a subset of the larger HAQ questionnaire, a new questionnaire is not required; only a different method of scoring is needed. Additional studies regarding sensitivity to change are required to fully validate the FHAQ.

The comparative risk and predictors of adverse gastrointestinal events in rheumatoid arthritis and osteoarthritis: a prospective 13 year study of 2131 patients.

OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) itself may be a risk factor for adverse gastrointestinal (GI) events, but this hypothesis has not been studied in a large sample, nor has the effect of time on risk factors been studied. We investigated rates and risk factors for GI events in RA and osteoarthritis (OA) and assessed the additional risks conveyed by having RA. METHODS: A prospective study of patients with OA and RA from a single center was undertaken using questionnaires mailed at 6 month intervals. The relationship between drug therapy and GI events was assessed in the same 6 month time frame. Over 13 years of biannual assessments, 2,131 patients were studied for serious GI events and adverse GI symptoms during 9,621 patient-years of observation. RESULTS: The incidence rate (IR) for GI hospitalization was 1.56 and 1.28 per 100 patient-years, and for GI bleeding or perforation was 0.50 and 0.58 for RA and OA, respectively. After controlling for age, sex, nonsteroidal antiinflammatory drug (NSAID) and steroid use, the incidence rate ratio (IRR) for RA versus OA did not differ for hospitalization [IRR 1.07 (95% CI 0.66, 1.74)] or for bleeding or perforation [IRR 0.63 (95% CI 0.29, 1.35)]. In multivariate analyses for both groups combined, the IRR was 2.95 (2.05, 4.24) for prednisone use, 1.41 (1.08, 1.85) for NSAID use, and 1.46 (1.22, 1.74) for every 10 year increase in age. In additional multivariate models, Health Assessment Questionnaire disability was also a significant risk factor. During the study period, the odds of NSAID use decreased 2.94 times per 10 year period, while the odds of prednisone use increased by 1.49. Dysphagia [IRR 1.11 (1.00, 1.24)], anorexia [IRR 1.13 (1.03, 1.23)], nausea [IRR 1.13 (1.04, 1.25)], heartburn [IRR 1.12 (1.05, 1.19)], vomiting [IRR 1.20 (1.02, 1.42)], peptic ulcer symptoms [IRR 1.20 (1.11, 1.29)], and abdominal pain [IRR 1.11 (1.01, 1.22)] were associated with NSAID use, but not with steroids. CONCLUSION: Patients with RA and OA do not differ in the rates and risk factors for GI hospitalizations and symptoms after controlling for age, steroid use, NSAID use, or (for OA) body mass index. Prednisone is a more important risk factor among patients with RA than NSAID.

Relationship of temperament and perceptions of nonshared environment in bulimia nervosa.

OBJECTIVE: Examine the relationship between temperament variables and perceptions of nonshared environment as they relate to bulimia nervosa. METHOD: Fifty-seven adult women completed the Tridimensional Personality Questionnaire and the Sibling Inventory of Differential Experience. These measures provided assessments of frequently studied temperament traits as well as nonshared environmental factors believed to be associated with psychopathology and temperament. RESULTS: Bulimic subjects showed higher levels of harm avoidance than did control subjects. Also, bulimic subjects perceived their fathers as less affectionate and more controlling than control subjects. Among bulimics, high levels of harm avoidance were associated with high levels of maternal affection and low levels of maternal control. Similarly, among bulimics, high levels of novelty seeking were more likely to be associated with decreased paternal control than was true for control subjects. DISCUSSION: These findings highlight the possible relationship between particular temperamental variables and associated family responses in bulimia nervosa.

A content analysis of research in family therapy journals.

In order to assess trends in family therapy research, empirical articles (N = 195) from three family therapy journals over a 5-year period were coded for several variables: authorship, external funding, methodology, sample, purpose, cost effectiveness, use of therapeutic model, and topic. Results indicated that a large pecentage of research in these journals focused on nonclinical issues and used nonclinical samples. Authors were affiliated with a wide variety of disciplines and reported low levels of external funding for their research. While a majority of the studies used quantitative methods, there appeared to be a growing number of studies using qualitative methods. Implications of these findngs are discussed in light of research reviews over the past two decades.

The use of theory in family therapy research: a content analysis of family therapy journals.

Ninety-five studies from Family Process and Journal of Marital and Family Therapy were evaluated with regard to their use of theory. While a majority of the articles were judged to use theory in either an explicit or an implicit manner, 42% did not appear to draw on theory in either the introductory or discussion sections. Studies that used qualitative methods appeared to use theory more frequently and explicitly than those using quantitative methods alone. Systems theory was found to be the most common conceptual framework, followed by feminism. We conclude that the link between theory and research in family therapy needs strengthening and suggest that the role of theory in family therapy be reexamined.

Use of combination therapy in the routine care of patients with rheumatoid arthritis: physician and patient surveys.

AIMS: To describe the utilization of combination therapy in the treatment of rheumatoid arthritis (RA). METHODS: Review of published articles and abstracts, and patient/physician questionnaire data. RESULTS: Combination therapy was rarely used in the early 1980s and is now (1999) used for about 25% of RA patients in the US. Physician and patient surveys indicate that methotrexate plus hydroxychloroquine is the most commonly used combination in North America, and physician surveys indicate that methotrexate plus sulfasalazine is the most commonly used combination in Europe. Patient questionnaire data indicate that 13.4% of patients in the US take methotrexate and hydroxychloroquine, and between 11% and 15% of patients with recent onset of RA receive treatment with disease-modifying antirheumatic drug (DMARD) combinations. CONCLUSIONS: Combination therapy with agents such as hydroxychloroquine and methotrexate is used in up to 25% of RA patients in the US, but the use of "aggressive combination therapy" is unusual. Whether combination therapy as currently practiced is beneficial remains to be determined.

Evidence of disordered symptom appraisal in fibromyalgia: increased rates of reported comorbidity and comorbidity severity.

OBJECTIVE: Using a large series of unselected consecutive patients, to investigate whether patients with fibromyalgia differ from those with rheumatoid arthritis (RA) or osteoarthritis (OA) in the number of reported comorbid conditions and in their perceived importance, and thereby to investigate differences in symptom appraisal and somatization. METHOD: In a clinical care setting, 1,298 patients with fibromyalgia and 2,396 with RA or OA participating in longitudinal data bank research as part of their routine medical care completed questionnaires concerning the presence or absence of 23 comorbid conditions, and then rated the current importance of each condition to them. Additional information concerning psychological factors and disease severity was also obtained. RESULTS: In analyses adjusted for age and sex, patients with fibromyalgia reported more conditions (4.5 vs. 3.1) than those with RA or OA. In 17 of 23 conditions, the condition was more commonly reported in fibromyalgia than in RA or OA. In 20 of the 23 conditions, the importance attached to the conditions by fibromyalgia patients exceeded that of the importance attributed by RA/OA patients. After adjustment for anxiety, statistical differences between the groups for importance was lost for 6 conditions. CONCLUSIONS: Fibromyalgia patients report more medical conditions and report that they are more important to them than do patients with RA or OA. These differences extend to conditions that might be expected to cause symptoms, as well as to those that are usually symptom free. These data suggest that, on average, patients with fibromyalgia appraise medical symptoms and their importance differently from patients with other rheumatic conditions.