Factors associated with time to diagnosis in early rheumatoid arthritis

Early diagnosis and treatment yield optimal outcomes in rheumatoid arthritis (RA); thus, barriers to disease recognition must be identified and addressed. We determined the impact of sociodemographic factors, medical comorbidities, family history, and disease severity at onset on the time to diagnosis in early RA. The Canadian early ArThritis CoHort study data on 1,142 early RA patients were analyzed for predictors of time to diagnosis using regression analysis. Sociodemographic factors (age, sex, income strata, education, ethnicity), measures of disease activity (joint counts, DAS28 score, acute-phase reactants, patient global evaluation, function), family history, serology, chronic musculoskeletal and mental health conditions, and obesity at diagnosis were considered. In multivariate linear regression analysis, more swollen joints (β = ?0.047 per joint, 95 % CI ?0.085, ?0.010, p = 0.014), higher erythrocyte sedimentation rate (ESR) (β = ?0.012 per 1 mm/h, 95 % CI ?0.022, ?0.002, p = 0.0018), and worse patient global scores (β = ?0.082 per 1 unit on a visual analogue scale, 95 % CI ?0.158, ?0.006, p = 0.034) at baseline predicted a shorter time to diagnosis. Anti-cyclic citrullinated peptide (anti-CCP) antibody positivity (β = 0.688, 95 % CI 0.261, 1.115, p = 0.002) and low income (annual <$20,000 β = 1.185, 95 % CI 0.227, 2.143, p = 0.015; annual $20,000–50,000 β = 0.933, 95 % CI 0.069, 1.798, p = 0.034) increased time to diagnosis. In the logistic regression models, the odds of being diagnosed within 6 months of symptom onset were increased for each swollen joint present [odds ratio (OR) 1.04, 95 % CI 1.02–1.06 per joint], each 1 mm/h elevation in the ESR (OR 1.01, 95 % CI 1.00–1.02), and decreased for patients who were either rheumatoid factor or anti-CCP positive compared to both factors being negative (OR 0.68, 95 % CI 0.51–0.91). Higher disease activity results in a more rapid diagnosis for Canadian patients with early RA, but those with lower income have delays in diagnosis. Strategies to identify patients with a less severe disease presentation and in lower socioeconomic strata are needed to ensure equal opportunity for optimal management.     

Badger responses to small-scale culling may compromise targeted control of bovine tuberculosis

Where wildlife disease requires management, culling is frequently considered but not always effective. In the British Isles, control of cattle tuberculosis (TB) is hindered by infection in wild badger (Meles meles) populations. Large-scale badger culling can reduce the incidence of confirmed cattle TB, but these benefits are undermined by culling-induced changes in badger behavior (termed perturbation), which can increase transmission among badgers and from badgers to cattle. Test–vaccinate/remove (TVR) is a novel approach that entails testing individual badgers for infection, vaccinating test-negative animals, and killing test-positive animals. Imperfect capture success, diagnostic sensitivity, and vaccine effectiveness mean that TVR would be expected to leave some infected and some susceptible badgers in the population. Existing simulation models predict that TVR could reduce cattle TB if such small-scale culling causes no perturbation, but could increase cattle TB if considerable perturbation occurs. Using data from a long-term study, we show that past small-scale culling was significantly associated with four metrics of perturbation in badgers: expanded ranging, more frequent immigration, lower genetic relatedness, and elevated prevalence of Mycobacterium bovis, the causative agent of TB. Though we could not reject the hypothesis that culling up to three badgers per social group might avoid perturbation, we also could not reject the hypothesis that killing a single badger prompted detectable perturbation. When considered alongside existing model predictions, our findings suggest that implementation of TVR, scheduled for 2014, risks exacerbating the TB problem rather than controlling it. Ongoing illegal badger culling is likewise expected to increase cattle TB risks.Infectious diseases are often difficult to control where wildlife hosts contribute to pathogen persistence. Wildlife culling is a frequently considered control option, which is sometimes effective (1, 2), but often ineffective (3–6).In the United Kingdom, the cattle farming industry is seriously affected by bovine tuberculosis (TB) caused by Mycobacterium bovis (7). Selective culling of test-positive cattle has helped to eradicate TB across much of the developed world, but eradication from the United Kingdom is impeded by M. bovis infection in European badgers (Meles meles) (8), as well as by continued transmission among cattle (9–11). Transmission has also been documented among badgers (12), from cattle to badgers (13), and from badgers to cattle (14, 15). Because badgers are clearly a contributing factor to the UK’s TB problem, successive TB control policies have included culling of badgers (7, 8). To date, cattle controls have emphasized selective slaughter of test-positive animals, whereas badger culls have typically been nonselective, with no testing of live animals before culling (but see ref. 16).The impacts of nonselective badger culling on M. bovis transmission are well established. Such culling reduces badger density (17), but also promotes dispersal into the culled area (18) as well as expanding badger ranging in and around the areas where culls occurred (19). In Britain these behavioral changes—termed social perturbation—have been linked to increases in the proportion of badgers infected with M. bovis (13, 20), and reductions in the spatial clustering of infection (21). In cattle, the incidence of confirmed TB was reduced inside large culling areas where badger numbers were substantially suppressed by annual “proactive” culling. However, on adjoining unculled lands, and in areas receiving localized “reactive” culling, reductions in badger numbers were smaller, the incidence of confirmed cattle TB was elevated (14, 15, 22–24), and spatial clustering of cattle infection was reduced (21).This propensity of nonselective badger culling to prompt social perturbation and hence increase disease transmission is a major constraint on its utility as a tool for controlling cattle TB. An alternative approach, first proposed in the 1980s, would be to target culling at test-positive badgers, just as current controls target test-positive cattle (16, 25). A further elaboration, termed test–vaccinate/remove (TVR), involves killing test-positive badgers while vaccinating test-negative badgers. A pilot TVR program is scheduled to take place across 100 sq km in Northern Ireland in 2014 (26).Selective culling approaches (such as TVR) are likely to remove relatively small numbers of badgers. First, constraints on capture success limit testing to 56–85% of the badger population (27, 28). Second, not all captured badgers will be infected with M. bovis: in the 10 initial proactive culls of the Randomized Badger Culling Trial (RBCT), 2–38% of badgers had infection detectable by bacterial culture at standard necropsy (29). Third, not all infected badgers are detectable by available live tests: the only available trap-side test detected 49% of badgers that were culture-positive at necropsy (30), and standard necropsy itself detected only 55% of infected badgers (31). This combination of imperfect capture success, low average infection prevalence, and imperfect test sensitivity means that the numbers of badgers to be killed by selective culling would probably be low, usually just one or two badgers within a social group (32). The same factors, combined with incomplete vaccine efficacy (33), mean that some infected and some susceptible badgers would be expected to remain despite implementation of TVR.Simulations indicate that the likely consequences of TVR for cattle TB control are highly sensitive to assumptions about whether culling small numbers of badgers prompts social perturbation (34, 35). Neither cage trapping for testing nor vaccination has been found to cause behavioral change. If the culling component of TVR likewise causes no perturbation, then TVR is predicted to reduce the prevalence of M. bovis infection in badgers and hence the incidence of cattle TB (34, 35). However, if TVR causes perturbation similar to that associated with past large- and small-scale culling, then it is projected to prompt sustained (34) or transient (35) increases in cattle TB. Unfortunately, it is not known which of these scenarios is more likely. Although the behavioral and epidemiological consequences of nonselective culling are relatively well understood, there have been no empirical studies of badgers’ behavioral responses to killing small numbers of animals per social group, as would occur under TVR and other forms of selective culling.In this paper, we use data from a large-scale study to assess whether killing small numbers of badgers would be expected to prompt social perturbation. We compare patterns of badger movement and M. bovis infection at the start of the RBCT (conducted 1998–2005) (14) with two indices of badger mortality. Our first measure, road density, provides an index of the numbers of badgers killed in road accidents (36), an important cause of badger mortality in Britain (37, 38). Our second measure is prior nonselective culling, conducted during the period 1986–1998 as small-scale badger removal operations (BROs), which typically targeted single farms (8). We hypothesized that high road densities and intense prior culling would each lead to expanded badger movement and elevated M. bovis prevalence. Further, we hypothesized that perturbation might be avoided if the number of badgers killed remained below a certain threshold, and sought to estimate this threshold.     

Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis

The objectives of this study were to develop a standard classification of digital ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic studies and to assess the reliability of these definitions as well as of the measurement of ulcer area. Ten North American rheumatologists with expertise in SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and came to a consensus on the definitions for digital, active, healed, and indeterminate ulcers. These ten raters then examined the right hand of ten SSc subjects twice and the left hand once to classify ulcers and to measure ulcer area. Weighted and Fleiss kappa were used to calculate intra- and interrater agreement on classification of ulcers, and intraclass correlation coefficient (ICC) was used to assess agreement on ulcer area. Because the traditional ICC calculations relied on a small number of ulcers, ICCs were recalculated using the results of linear mixed models to evaluate the variance components of observations on all the data. Intrarater kappa for classifying DU as not an ulcer/healed ulcer versus active/indeterminate ulcer was substantial (0.76), and interrater kappa was moderate (0.53). The ICC for ulcer area using the linear mixed models was moderate both for intrarater (0.57) and interrater (0.48) measurements. A consensus for the classification of DUs in SSc was developed, and after a training session, rheumatologists with expertise in SSc are able to reliably classify DUs and to measure ulcer area.     

Aneurysmal remodeling in the circle of Willis after carotid occlusion in an experimental model

Carotid occlusions are associated with de novo intracranial aneurysm formation in clinical case reports, but this phenomenon is not widely studied. We performed bilateral carotid ligation (n=9) in rabbits to simulate carotid occlusion, and sham surgery (n=3) for control. Upon euthanasia (n=3 at 5 days, n=6 at 6 months post ligation, and n=3 at 5 days after sham operation), vascular corrosion casts of the circle of Willis (CoW) were created. Using scanning electron microscopy, we quantified gross morphologic, macroscopic, and microscopic changes on the endocasts and compared findings with histologic data. At 5 days, CoW arteries of ligated animals increased caliber. The posterior communicating artery (PCom) increased length and tortuosity, and the ophthalmic artery (OA) origin presented preaneurysmal bulges. At 6 months, calibers were unchanged from 5 days, PComs further increased tortuosity while presenting segmental dilations, and the OA origin and basilar terminus presented preaneurysmal bulges. This exploratory study provides evidence that flow increase after carotid occlusion produces both compensatory arterial augmentation and pathologic remodeling such as tortuosity and saccular/fusiform aneurysm. Our findings may have considerable clinical implications, as these lesser-known consequences should be considered when managing patients with carotid artery disease or choosing carotid ligation as a therapeutic option.     

Improvement in psychosocial adjustment for psychiatric patients after a 16-week life skills education program

The Holden Psychological Screening Inventory, a 36-item screening inventory for psychosocial adjustment, was administered pre- and posttreatment to 31 psychiatric patients enrolled in a 16-week life skills education program. Statistically significant improvements in the Depression Symptomatology, Social Symptomatology, and Total scores were obtained, but the Psychiatric Symptomatology scale did not improve significantly. Size of effect was larger for Depression Symptomatology (.52) and Social Symptomatology (.30) than for Psychiatric Symptomatology (.23). On a 6-point scale all patients rated their overall satisfaction with the program on the two most favorable categories, excellent and very good. The results provide support for life skills education programming for psychiatric patients as part of the treatment and recovery process. © 1996 John Wiley & Sons, Inc.     

Persistent pulmonary consolidation treated with intrapulmonary percussive ventilation: A preliminary report

Intrapulmonary percussive ventilation (IPV) is a novel form of chest physiotherapy delivered by a percussive pneumatic device (IPV, Percussionaire, Sand Point, ID). There are few published reports about the use of IPV for diseases other than cystic fibrosis. We report our experience with three pediatric patients and one adult patient with persistent pulmonary consolidation refractory to conventional therapies. Three of the four patients had neuromuscular disease; one patient had segmental atelectasis due to aspiration. Three of the four patients showed clinical and radiographic improvement within 48 hours of starting IPV. The fourth patient experienced brief episodes of third-degree atrioventricular block, hypoxemia, and bradycardia during two IPV treatments. IPV was safely restarted and he slowly improved. We conclude that while IPV requires further clinical evaluation, it appears to be a safe and effective therapy for selected patients. However, close observation is essential during and after IPV treatments, especially in patients who have difficulty mobilizing or expectorating sputum. Pediatr Pulmonol. 1996; 21: 246–249. © 1996 Wiley-Liss, Inc.     

“Recovered memory” therapy for eating disorders: Implications of the Ramona verdict

“Recovered memory therapy” for eating disorders and other psychiatric conditions seeks to help the patient recover repressed memories of childhood sexual abuse and other traumatic experiences. Through this technique, it is hoped that the patient can work through these experiences to achieve relief from shame, body dissatisfaction, and symptoms of depression and eating disorders. However, this method was questioned in the recent Ramona case, where a father successfully sued two therapists and a hospital for allegedly implanting false memories of childhood sexual abuse in his bulimic daughter. The testimony and verdict in this case recall the principle of primum non nocere: Although it is clearly reasonable to consider an unproven therapeutic technique in an attempt to relieve human suffering, the potential risk of the technique—in this case the possible induction of false incest memories—must be weighed carefully against the technique's expected benefits. © 1996 by John Wiley & Sons, Inc.     

Association of HIV serostatus and metabolic syndrome with neurobehavioral disturbances

Journal of NeuroVirology - Metabolic syndrome (MetS), a constellation of related metabolic risk factors, is a common comorbidity associated with cognitive difficulty in people living with HIV...