Objective Early diffuse scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early diffuse SSc. Methods Seventy‐one patients with diffuse SSc of <3 years' duration were enrolled in a multicenter, randomized, placebo‐controlled, double‐blind trial. Thirty‐five patients were treated with MTX and 36 with placebo. Treatment was administered for 12 months. The primary outcome measures were skin score (as determined with 2 different indices) and physician global assessment. Results At baseline, there were no statistically significant differences in skin scores, carbon monoxide diffusing capacity (DLCO), physician global assessment, or other secondary outcome measurements between the 2 treatment groups. At study completion, results slightly favored the MTX group (mean ± SEM modified Rodnan skin score 21.4 ± 2.8 in the MTX group versus 26.3 ± 2.1 in the placebo group [P < 0.17]; UCLA skin score 8.8 ± 1.2 in the MTX group versus 11.0 ± 0.9 in the placebo group [P < 0.15]; DLCO in the MTX group 75.7 ± 4.6 versus 61.8 ± 3.4 in the placebo group [P < 0.2]). In addition, physician global assessment results favored MTX (P < 0.035), whereas patient global assessment did not differ significantly between groups. When between‐group differences for changes in scores from baseline to 12 months were examined using intent‐to‐treat methodology, MTX appeared to have a favorable effect on skin scores (modified Rodnan score −4.3 in the MTX group versus 1.8 in the placebo group [P < 0.009]; UCLA score −1.2 in the MTX group versus 1.2 in the placebo group [P < 0.02]), but differences in the degree of change in the DLCO and physician global assessment were not significant. For the UCLA skin score, these differences in results were not statistically significant after adjustment for baseline differences in sex distribution and steroid use. Dropout rates were similar in the 2 groups. Conclusion Although results of this trial demonstrated a trend in favor of MTX versus placebo in the treatment of early diffuse SSc, the between‐group differences were small and the power to rule out false‐negative results was only 50%. Our findings do not provide evidence that MTX is significantly effective in the treatment of early diffuse SSc.

Umbilical cord blood (CB) transplantation is thought to be associated with a reduced risk of severe graft-versus-host-disease (GVHD) compared with bone marrow transplantation (BMT). The cytokine cascade is known to be important in the pathogenesis of GVHD; however, previous studies investigating the cytokine secretion pattern of CB cells have been contradictory because of variations in experimental techniques. In this study, the cytokine profile of cord and adult blood lymphocytes and lymphocyte subsets has been assessed at the single-cell level by flow cytometry, using CD4/CD8 and CD45RA/CD45RO markers. Cord and adult blood mononuclear cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in the presence of monensin. After 4 to 24 hours of incubation, interleukin-2 (IL-2), IL-4, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) production was measured by three-color flow cytometry. The results show that cord blood lymphocytes (CBL) produce less IL-2, IL-4, IFN-γ, and TNF-α than adult peripheral blood lymphocytes (ABL). Further subset analysis showed that in CBL the majority of cytokine producing cells were CD4+CD45RA+, whereas in ABL the cytokine-producing cells were both CD4+CD45RO+ and CD8+CD45RO+. These results suggest that the reduced incidence of GVHD in CB transplantation may partly due to the altered cytokine profile seen in CBL.

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Prevalence and incidence rates for rheumatic diseases were found to be minimal among the Inuit people in the Keewatin District of the Northwest Territories, Canada. Patient identification was achieved by a review of medical records. All identified patients were interviewed and examined by a participating rheumatologist. Among women, the prevalence of rheumatoid arthritis, adjusted for age of the Manitoba population, was 1,822 per 100,000 and was comparable with that observed in other populations; no cases of rheumatoid arthritis in men were confirmed. The age-adjusted prevalence of osteoarthritis, 1,219 per 100,000 in men and 2,144 per 100,000 in women, was apparently low. A moderately high incidence of Reiter's syndrome, 24.9 per 100,000, was found. The findings in children suggested a high frequency of seronegative spondylarthropathies (yearly incidence 60.1 per 100,000), although the adjusted yearly incidence for juvenile rheumatoid arthritis also appeared to be high, 23.6 per 100,000. The frequencies of HLA antigens in patient groups were compared with those found in 19 patients with musculoskeletal complaints but no rheumatic disease. Both HLA-B27 and HLA-DR4 appeared to be common in these controls, 36.8% and 63.2%, respectively. Nevertheless, there was a higher frequency of HLA-B27 in patients with seronegative spondylarthropathies (87%) than in controls (P = 0.001). Because of the small numbers of patients who had rheumatoid arthritis, no associations with HLA were made for this condition. Although the findings suggest differences in the distribution of rheumatic diseases compared with those found in other populations, more complete studies are required to confirm these observations.

Objectives-To estimate the cost effectiveness of giving prophylactic antibiotics routinely to reduce the incidence of wound infection after caesarean section.Design-Estimation of cost effectiveness was based, firstly, on a retrospective overview of 58 controlled trials and, secondly, on evidence about costs derived from data and observations of practice.Setting-Trials included in the overview were from obstetric units in several different countries, including the United Kingdom. The costing study was based on data referring to the John Radcliffe Maternity Hospital, Oxford.Subjects-A total of 7777 women were included in the 58 controlled trials comparing the effects of giving routine prophylactic antibiotics at caesarean section with either treatment with a placebo or no treatment. Cost estimates were based on data on 486 women who had caesarean sections between January and September 1987.Main outcome measure-Cost effectiveness of prophylaxis with antibiotics.Results Recovery from caesarean section is more difficult for women who develop postoperative infection. These infections may affect the pelvic organs, the surgical wound, and the respiratory and urinary tracts. Such infections are not uncommon and often not trivial.

The objective of this study was to optimize a planned audit and feedback (A&F) intervention for home and community care through incorporating user-centered design principles. Phase 1 comprised the development of a paper prototype, followed by testing of the prototype using semistructured interviews and focus groups. Phase 2 involved the development of a revised and online prototype based on the results of Phase 1, followed by user testing. A total of 39 participants across Phase 1 (n = 33) and Phase 2 (n = 6) provided input into the design of the A&F intervention. Key changes included improving clarity of the variables, reducing cognitive load, and highlighting opportunities for action. Preliminary findings suggest potential usefulness in this approach to optimize home care management.

While Indonesia's efforts at countering violent extremism have enjoyed some successes, a section of its Islamist community remains committed to militant jihadism. The return from overseas of hundreds of militants linked to ISIS means that there is now a greater need than ever for interventions to prevent radicalisation-and for programs to reintegrate militants back into society. Drawing on 20 selected interviews with former jihadists, this article asks how successful official efforts have been at disengaging those convicted under Indonesia's Anti-Terrorism Law from violent extremism. A significant minority remain welded to a militant mindset: "committed jihadists" who are likely to reoffend. Some former jihadists have "disengaged provisionally" but remain vulnerable: they have only disengaged for tactical or practical reasons. Yet some have also begun to disengage emotionally. While they may not disavow completely the use of force, these "provisionally deradicalised" activists have moved closer to that minority of interviewees who are "fully deradicalised". Using this four-part typology of the pathways by which some militant jihadists have disengaged but others have not, this article finds that disengagement is a gradual process shaped by social networks. Consequently, it is suggested that a variety of methods be used to promote disengagement both before and after inmates leave prison.

Over a period of 4 years in a large African teaching hospital, only 8 patients with ankylosing spondylitis were seen. This small number supports the impression that the disease is rare in African blacks. Patients tended to be relatively old and to have severe disease. None had iritis or a positive family history. The HLAB27 antigen was found in found in only 1 patient.