Tele‐Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial

Objective

To test the effect of patient‐reported outcome (PRO)–based tele‐health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele‐health followup performed by rheumatologists or rheumatology nurses.

Methods

A total of 294 patients were randomized (1:1:1) to either PRO‐based tele‐health followup carried out by a nurse (PRO‐TN) or a rheumatologist (PRO‐TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self‐efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent‐to‐treat (ITT), and multivariate imputation analysis.

Results

Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO‐TR versus control were ?0.10 (90% confidence interval [90% CI] ?0.30, 0.13) and ?0.19 (90% CI ?0.41, 0.02) between PRO‐TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO‐TN had mean ± SD 1.72 ± 1.03 visits/year, PRO‐TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare.

Conclusion

Among RA patients with low disease activity or remission, a PRO‐based tele‐health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.

     

Diagnosis of autoimmune pancreatitis by core needle biopsy: application of six microscopic criteria

Autoimmune pancreatitis (AIP) has been established as a special entity of chronic pancreatitis (CP). However, its clinical distinction from pancreatic cancer and other types of CP is still difficult. The aim of this study was to evaluate the efficacy of pancreatic core needle biopsy for the diagnosis of AIP. In 44 core needle biopsy specimens, we assessed the following microscopic features: granulocytic epithelial lesions (GELs), more than ten IgG4-positive plasma cells/HPF, more than ten eosinophilic granulocytes/HPF, cellular fibrosis with inflammation, lymphoplasmacytic infiltration, and venulitis. All biopsies that showed four or more of the six features (22 of 44) were obtained from 21 of 26 patients whose clinical diagnosis and follow-up were consistent with AIP. All non-AIP CP patients (n = 14) showed three or less than three of the features in their biopsies. GELs were only observed in biopsy specimens from AIP patients. In conclusion, our data indicate that the six criteria we applied were able to recognize AIP in 76% of biopsy specimens using a cut-off level of four. When the specimens that revealed only three features but showed GELs were added, the sensitivity rose to 86%. Pancreatic core needle biopsy can therefore make a significant contribution to the diagnosis of AIP.     

High cortisol awakening response is associated with an impairment of the effect of bright light therapy

Objective: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non‐seasonal major depression. Method: Patients were treated with sertraline in combination with bright or dim light therapy for a 5‐week period. Saliva cortisol levels were measured in 63 patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time‐points: awakening and 20 and 60 min after awakening. Results: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas patients with a high CAR had no effect of bright light therapy compared with dim light therapy. Conclusion: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from that of antidepressants.     

Antimicrobial effects of an NO-releasing poly(ethylene vinylacetate) coating on soft-tissue implants in vitro and in a murine model

Infection of surgical meshes used in abdominal wall reconstructions often leads to removal of the implant and increases patient morbidity due to repetitive operations and hospital administrations. Treatment with antibiotics is ineffective due to the biofilm mode of growth of the infecting bacteria and bears the risk of inducing antibiotic resistance. Hence there is a need for alternative methods to prevent and treat mesh infection. Nitric oxide (NO)-releasing coatings have been demonstrated to possess bactericidal properties in vitro. It is the aim of this study to assess possible benefits of a low concentration NO-releasing carbon-based coating on monofilament polypropylene meshes with respect to infection control in vitro and in vivo. When applied on surgical meshes, NO-releasing coatings showed significant bactericidal effect on in vitro biofilms of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and CNS. However, using bioluminescent in vivo imaging, no beneficial effects of this NO-releasing coating on subcutaneously implanted surgical meshes in mice could be observed.     

Fracture risk in diabetic elderly men: the MrOS study

Aims/hypothesis

Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.

Methods

The MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.

Results

In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).

Conclusions/interpretation

Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.     

The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance. MEASUREMENTS: The effect of the genotype on the traits (mean +/- SD) was established; associations between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted for 0.91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0.001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68.2% to 67.8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels. CONCLUSIONS: The TSHR-727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid-related measures.     

Urinary disease in 2 Dogon populations with different exposure to Schistosoma haematobium infection: progression of bladder and kidney diseases in children and adults

BACKGROUND: Schistosoma haematobium infection causes severe urinary disease and considerable mortality. The factors that determine disease progression from mild to severe stages are not fully understood. METHODS: Here we describe a cross-sectional epidemiological study of kidney and bladder diseases in 2 Dogon populations with different exposure to S. haematobium infection. RESULTS: Early and high exposure resulted in more-severe disease, especially among young subjects, without clear evidence of a more-rapid development of immunity. Nevertheless, 50%-60% of subjects of all age classes in both villages showed no evidence of disease. Kidney and bladder disease peaked biphasically among young subjects and adults >25 years old. The first peak corresponded with infections of maximum intensity, whereas the second peak occurred among adults with infections of very low intensity. Kidney disease was correlated with circulating anodic antigen concentration in serum, whereas bladder disease was correlated with egg count and eosinophil cationic protein concentration in urine. Kidney and bladder disease did not correlate. Severe kidney disease was more frequent in certain families. CONCLUSIONS: The frequency of urinary disease is increased by infections acquired early during life, is regulated by strong clinical immunity in certain subjects, and may be dependent on hereditary factors. Kidney and bladder disease may involve different mechanisms of pathogenesis, which may differ between children and adults.     

Transplacental transfer of schistosomal circulating anodic antigens in cows

The present work investigated the transplacental passage of circulating anodic schistosome antigens (CAA) and the production of foetal antibodies in response to antigenic stimulation in Schistosoma mattheei infected cows. Three groups were available: six calves born to non-infected cows received colostrum from a pool from non-infected cows (group 1), six calves born to non-infected cows (group 2) and six calves born to infected cows (group 3) received colostrum from a pool from infected cows. Schistosoma-specific IgG1 antibody and CAA levels were measured in the colostrum pools, the sera collected from the cows, and the sera collected from the calves at birth, after intake of colostrum and at day 30. The specific IgG1 antibody levels were significantly higher in the sera from cows of group 3. In four cows of group 3 high CAA levels were detected. The specific IgG1 antibody levels were 0.646 and 0.176 OD for the infected and non-infected colostrum pool, respectively, and the CAA levels were 5667 and 2557 pg CAA/mL, respectively. At birth high levels of specific IgG1 antibody and CAA were detected in 4 calves of group 3; levels in the other two calves were negligible. After intake of colostrum, specific IgG1 antibody levels of group 1 increased slightly at day 1 to become again insignificant at day 30. In group 2 specific IgG1 antibody levels increased significantly between days 0 and 1, to decrease, although not significantly, at day 30. Finally, in group 3 the delta OD values increased at day 1 and remained high until day 30. After intake of colostrum the CAA level increased very slightly for groups 1 and 2 to become again undetectable at day 30. In group 3 a nonsignificant decrease in CAA levels was observed at day 1 followed by a further significant decrease to reach low levels at day 30. The suggested intrauterine antigenic stimulation may be important not only for generating immune responses to natural early infections, but also for enhancing the immunogenicity and efficacy of vaccines administered to newborns.