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This randomized trial compares the effects of half-dose conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) vs stable-dose csDMARDs on the risk of flares in patients with rheumatoid arthritis in sustained remission.Importance Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear. Objective To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. Design, Setting, and Participants ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. Interventions Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). Main Outcomes and Measures The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. Results Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred. Conclusions and Relevance Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy.Question In patients with rheumatoid arthritis in remission taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), is reducing the csDMARDs to half dose noninferior to stable csDMARD dosage for the outcome of rheumatoid arthritis flares? Findings In this randomized clinical trial that included 160 patients with rheumatoid arthritis in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs resulted in disease flares in 25% vs 6% over 12 months; this did not meet the noninferiority criterion of a 20% difference. There were significantly fewer patients with flares in the stable-dose group. Meaning These findings do not support the use of half-dose treatment in patients with rheumatoid arthritis in remission taking csDMARDs.

The aim of this study is to evaluate a surgical protocol for vertical ridge augmentation in the maxilla and mandible using autogenous onlay bone graft associated with a titanium mesh. A group of 18 partially edentulous patients, presenting the need for vertical bone augmentation of at least 4 mm, were treated before implant placement. During the first surgery, an autogenous bone graft was harvested from either the mandibular ramus or the mental symphysis and secured by means of titanium screws. Particulate bone was added and a titanium micro-mesh was used to stabilize and protect the graft. After a mean interval of 4.6 months, meshes and screws were removed and 37 endosseous implants were successfully placed. The desired bone gain was reached in all patients. Mean vertical bone augmentation obtained was 4.8 mm (range 4-7 mm). No major complications were recorded at recipient or donor sites. Abutment connection was carried out 2-3 months after implant placement. No implant was lost. Clinical parameters and probing depth, after prosthetic reconstruction, demonstrated the presence of a healthy peri-implant mucosa. The preliminary results suggest that, by using the presented technique, patients can be successfully rehabilitated by means of implant-supported prosthesis 6-7 months after the first surgery, even in case of severely atrophied maxilla.

Objective: To evaluate the mean overall effects over a 1-year period of a multidisciplinary in-patient rehabilitation programme for patients with ankylosing spondylitis. Design: Observer-blinded, randomized controlled trial, with assessments made after 4 and 12 months. Patients: Forty-six patients received a 3-week in-patient rehabilitation programme and 49 patients received treatment as usual. Methods: Primary outcomes were disease activity measured with the Bath Ankylosing Spondylitis Disease Activity Scale (BASDAI), and function measured with the Bath Ankylosing Spondylitis Functional Index (BASFI). Secondary outcomes included well-being, spinal and hip mobility, and healthrelated quality of life measured with the Medical Outcome Study Short Form-36. Overall treatment effects were estimated with Mixed models repeated measures analyses. Results: Significant overall treatment effects in favour of the rehabilitation group were found in the BASDAI score (mean difference over the 1-year period –10.0, 95% confidence interval: –3.7 to –16.3), in well-being (–7.3, 95% confidence interval: –1.0 to –14.7), and in the Medical Outcome Study Short Form-36 variables social functioning, role physical, role mental and bodily pain (mean differences ranging from 5.8 (pain) to 10.7 (role physical)). Conclusion: A 3-week in-patient rehabilitation programme had positive overall effects on disease activity, pain, function and well-being, and should be considered an important complement to medical disease management in persons with ankylosing spondylitis.

This article discusses the development of the first regional computerized database for the epidemiological evaluation of maxillofacial trauma and tests its usefulness by evaluating the appropriateness and completeness of the resulting information.The database was developed using Microsoft Access, implemented using Visual Basic. Data were entered in the database by 4 different maxillofacial specialists, one from each of the 4 main regional hospitals where maxillofacial trauma is treated. Clinical information was taken from 100 complete records of patients hospitalized for maxillofacial fractures at the Maxillofacial Division of San Giovanni Battista Hospital in Turin from January to June 2009.Thirteen database fields were used: general information, cause and mechanism of injury, fracture site, Facial Injury Severity Scale, head and neck examination, associated injuries, timing and type of surgery, and days of hospitalization.Overall, the data entered were 99.45% complete and 99.5% accurate. Thus, our regional maxillofacial database can be considered complete and accurate. Some of the errors, mainly in the fields "fracture site" and "Facial Injury Severity Scale," were attributable to an incorrect interpretation of facial fracture diagnoses, based on the medical records that were provided. Language: en

Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.

Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.

Purpose The authors report the 2-year experience of use of the PATATRAC telemedicine system in managing maxillofacial trauma. Materials and Methods Thirty-five regional hospitals on-line with PATATRAC in the period from January 2002–January 2004 have sent 18 consultations (11 men and 7 women) to the Maxillofacial Surgery Division of San Giovanni Battista Hospital in Turin for telemedicine evaluation of patients with maxillofacial trauma. Results Only 50% of the consultations (9 patients) sent via PATATRAC indicated maxillofacial treatment, and only one case resulted in immediate transfer. Of the remaining 8 transfers, 2 patients were transferred after treatment of associated lesions in the receiving hospital, and the other 6 patients were transferred as scheduled based on the availability of beds in the specialist center. Conclusions The results obtained, despite the poor number of telemedicine maxillofacial consultations, have mainly proved the usefulness of PATATRAC in drastically reducing expensive and unnecessary transfers of maxillofacial patients, without indications for either immediate or deferred treatment, thus also avoiding discomfort to the patient with other injuries.

Objectives: This study investigates expression of the neural growth-associated protein 43 (GAP-43) in the oral mucosa of (A) normal dentate subjects, (B) edentulous patients rehabilitated with conventional denture and (C) those rehabilitated with mandibular implant-retained overdentures (MIR-OVD), in the long term. This study evaluates morphological changes in the distribution and representation of sensory terminations and corpuscles in the alveolar mucosa under the action of different masticatory or prosthetic loads, in the three clinical groups. Material and methods: GAP-43 immunoreactivity (-ir) was compared with the distribution of nerves fibres in the mucosa, as visualised using anti-protein gene product 9.5 (PGP 9.5), a general marker for peripheral nerves and terminals. Results: GAP-43-ir was found to be highly expressed in the corium and submucosa in specimens from edentulous subjects wearing conventional denture and presenting a reduced number of PGP 9.5-ir nerves in the mucosa, but not in specimens from control subjects or patients wearing MIR-OVD, which on the contrary show a higher number of PGP 9.5-ir mucosal sensory fibres. Conclusion: As the mucosa under traditional denture has been shown to possess reduced innervation and the histological aspect of chronic overloading, these results may be considered indicative of a tentative induction to nerve re-growth in the under-innervated epithelium, or as a response to chronic inflammation. The detection of GAP-43-ir suggests that human oral mucosa presents signs of potential nerve plasticity also in the elderly, and that the type of rehabilitation and the condition of masticatory load transfer to the mucosa have important effects on the nerves underneath.