Worldwide Expert Agreement on Updated Recommendations for the Treatment of Systemic Sclerosis.

OBJECTIVE: To evaluate agreement of the updated European League Against Rheumatism and European Scleroderma Trials and Research group (EUSTAR) recommendations for treatment of systemic sclerosis (SSc) among international experts. In addition, to determine factors that might influence agreement. METHODS: Level of agreement (10-point scale: 0 = not at all, 10 = completely agree) and local drug availability (yes/no) were assessed using an online survey. The Web link to the survey was shared with 481 unique e-mail addresses and SSc networks (Scleroderma Clinical Trials Consortium, Australian Scleroderma Interest Group, International Systemic Sclerosis Inception Cohort). Level of agreement was compared between subgroups stratified for participant characteristics. RESULTS: In total, 263 experts participated, of whom n = 209 (79%) completed each single item. The majority were rheumatologists (n = 200, 76%) working in Europe (n = 185; 71%); 59% (n = 156) were EUSTAR members; and 57% (n = 151) had > 10 years of clinical experience. Overall level of agreement was high (mean 8.0, SD 2.5). The 3 highest mean agreements included (1) angiotensin-converting enzyme inhibitors for scleroderma renal crisis (9.2, SD 2.1); (2) blood pressure control in SSc-patients treated with corticosteroids (9.0, SD 2.2); (3) proton pump inhibitors to prevent reflux complications (9.0, SD 2.2). The 3 lowest mean agreements included (1) fluoxetine for Raynaud phenomenon (RP; 4.6, SD 2.8); (2) hematopoietic stem cell transplantation (HSCT) for severe SSc (7.1, SD 2.9); (3) phosphodiesterase inhibitors 5 for RP (7.3, SD 2.7). Agreement differed between Europe and non-Europe for the use of iloprost, bosentan, methotrexate, HSCT, and cyclophosphamide. Treatment availability could partially explain differential agreement for iloprost, bosentan, and HSCT. CONCLUSION: In general, worldwide expert agreement on updated recommendations for treatment of SSc is high, supporting their value. Differences in agreement are partially explained by geographical area and treatment availability.

Behaviour change interventions for the management of Raynaud's phenomenon: a systematic review protocol.

INTRODUCTION: Raynaud's phenomenon (RP) describes excessive peripheral vasospasm to cold exposure and/or emotional stress. RP episodes are associated with digital colour changes, pain and reduced quality of life. Pharmacological interventions are of low to moderate efficacy and often result in adverse effects such as facial flushing and headaches. Recommended lifestyle and behavioural interventions have not been evaluated. The objectives of the proposed systematic review are to assess the comparative safety and efficacy of behaviour change interventions for RP and identify what we can learn to inform future interventions. METHODS AND ANALYSIS: Studies eligible for inclusion include randomised controlled trials testing behaviour change interventions with a control comparator. A comprehensive search strategy will include peer review and grey literature up until 30 April 2017. Search databases will include Medline, Embase, PsychINFO and Cochrane. Initial sifting, eligibility, data extraction, risk of bias and quality assessment will be subject to review by two independent reviewers with a third reviewer resolving discrepancies. Risk of bias assessment will be performed using Cochrane risk of a bias assessment tool with quality of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation(GRADE). A meta-analysis will be performed if there are sufficient data. Two subgroup analyses are planned: primary versus secondary RP outcomes; comparison of theoretically informed interventions with pragmatic interventions. ETHICS AND DISSEMINATION: This review does not require ethical approval as it will summarise published studies with non-identifiable data. This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Findings will be disseminated in peer-reviewed articles and reported according to PRISMA. This review will make a significant contribution to the management of RP where no review of behaviour-change interventions currently exist. The synopsis and protocol for the proposed systematic review is registered in the International Prospective Register of Systematic Reviews (registration number CRD42017049643).

[Guidelines for occupational exposures to mechanical vibration.] / I valori guida nella valutazione del rischio da vibrazioni meccaniche.

OBJECTIVES: In this study, the daily exposure action values (EAV) and the daily exposure limit values (ELV) for hand-transmitted vibration (HTV) and whole-body vibration (WBV), established by the EU Directive 2002/44/EC and the Italian Decree 81/2008, and expressed in terms of 8-hr frequency weighted r.m.s. acceleration magnitude, are discussed upon consideration of the findings of experimental and epidemiological studies. METHODS: There is some epidemiological support for the EAV A(8) of 2.5 ms-2 r.m.s. and the ELV A(8) of 5 ms-2 r.m.s. for HTV, at least for the vascular component (secondary Raynaud's phenomenon) of the hand-arm vibration syndrome. RESULTS: There is some experimental evidence for the EAV A(8) of 0.5 ms-2 r.m.s. for WBV, while there is neither biodynamic nor epidemiological validation for the ELV A(8) of 1.15 ms-2 r.m.s. for WBV, this latter lowered to 1 ms-2 r.m.s. in the Italian legislation.

A double-blind, randomized, placebo-controlled crossover trial of the α2C-adrenoceptor antagonist ORM-12741 for prevention of cold-induced vasospasm in patients with systemic sclerosis.

OBJECTIVES: Our primary purpose was to evaluate the efficacy of the high-potency α2C-adrenoceptor antagonist ORM-12741 in the attenuation of a cold-induced reduction in finger blood flow and temperature in patients with RP secondary to SSc. Secondary objectives were to assess safety and tolerability. METHODS: This was a phase IIa, randomized, double-blind, crossover, single-dose, placebo-controlled, single-centre study. Patients attended five times: initial screening, treatment visits 1-3 (each at least 1 week apart) and 1-2 weeks after the last treatment. At each treatment visit, each subject received a single oral dose of 30 mg or 100 mg of ORM-12741 or placebo. Thirty minutes later the subject underwent a cold challenge. Blood flow to the fingers was assessed by three methods [temperature by probe, laser Doppler imaging (LDI) and infrared thermography] performed before, during and after the cold challenge. RESULTS: Twelve patients (10 female, mean age 58 years) were included. The area under the rewarming curve (LDI) of the right index finger (arbitrary flux units × time) was lower for both 30 mg (P = 0.043) and 100 mg (P = 0.025) of ORM-12741 compared with placebo, indicating delayed reperfusion. The time to 70% temperature recovery (middle finger probe) was longer with active than placebo treatment: mean (s.d.) values for placebo, 30 mg of ORM-12741 and 100 mg of ORM-12741 were 21.4 min (12.4), 25.7 min (12.2) and 26.9 min (13.9), respectively. Overall ORM-12741 was well tolerated. CONCLUSION: ORM-12741 did not expedite recovery from a cold challenge in the fingers of patients with SSc. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/; no. 2010-024005-13.

Auricular electroacupuncture reduces frequency and severity of Raynaud attacks.

BACKGROUND: Acupuncture has been shown to influence skin perfusion and the subjective cold perception threshold. Therefore, we hypothesized that auricular electroacupuncture (EA) might reduce symptoms in primary Raynaud's phenomenon (PRP). METHODS: Twenty-six patients with PRP received 6 cycles of auricular EA. After 3, 6 and 24 weeks attack frequency and severity were reevaluated using standardized questionnaires and a visual analogue scale (VAS). Skin temperature was assessed by infrared thermography and laser Doppler perfusion imaging was used to determine skin perfusion. RESULTS: Compared to baseline we found a significant reduction of attack frequency after 3 (p = 0.001) and 6 weeks (p < 0.001) of auricular EA. This improvement sustained following cessation of EA, after 24 weeks (p < 0.001). Furthermore, attack associated pain was reduced after 3 (p = 0.003), 6 (p = 0.003) and 24 weeks (p = 0.001) of treatment, while skin temperature and skin perfusion did not change significantly throughout the study period. CONCLUSIONS: Auricular EA reduces symptoms by means of frequency and severity of attacks in PRP but has no influence on skin perfusion and skin temperature.

Conquering common breast-feeding problems.

Meeting mothers' personal breast-feeding goals depends on a number of factors, including the timely resolution of any problems she encounters. Nurses are often the first providers who interact with the mother during the perinatal period and are positioned to guide mothers through the prevention and solving of breast-feeding problems. Although many problems may be "common," failure to remedy conditions that cause pain, frustration, and anxiety can lead to premature weaning and avoidance of breast-feeding subsequent children. This article describes strategies and interventions to alleviate common problems that breast-feeding mothers frequently encounter.

A potential role for imatinib and other small molecule tyrosine kinase inhibitors in the treatment of systemic and localized sclerosis.

Small molecule tyrosine kinase (TK) inhibitor, such as imatinib, is well established in the treatment of malignancy. Oral administration, high efficacy, and an excellent safety profile have made imatinib a drug of choice for several malignancies and benign conditions. Recent progress in the understanding of several benign conditions has led to the use of TK inhibitors in the treatment of hypereosinophilic syndrome and mastocytosis. Systemic sclerosis (SS) is a recalcitrant disease featuring multiorgan fibrosis and dysfunction. Molecular and biological evidence point to a central role for platelet-derived growth factor receptor, a TK-associated entity, in the pathogenesis of SS. The ability of several TK inhibitors, namely imatinib, to abrogate the activation of platelet-derived growth factor receptor-TK may entail their use in the treatment of SS and possibly more limited forms of sclerosis. Several human studies aiming to examine the use of imatinib in the treatment of SS are currently underway.

Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril.

OBJECTIVE: To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for 2-3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent-to-treat analysis was used. RESULTS: Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one-half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one-fifth of the patients, with dry cough being the most frequent side effect. CONCLUSION: Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population.

Anakinra prevents symptoms of familial cold autoinflammatory syndrome and Raynaud's disease.

OBJECTIVE: Familial cold autoinflammatory syndrome (FCAS) is a rare, hereditary disorder characterized by cold-induced inflammation. We describe the successful longterm treatment of a patient with FCAS with anakinra, an interleukin 1 receptor antagonist (IL-1Ra). The remarkable response of FCAS and associated Raynaud's disease in this patient suggests that IL-1 is an important mediator of these inflammatory diseases. Our report supports increasing evidence that anakinra plays an important role in the treatment of select chronic inflammatory diseases.

Influence on operator's health of hand-transmitted vibrations from handles of a single-axle tractor.

The operators of the single-axle tractors are especially exposed to hand-arm transmitted vibrations. These vibrations can cause the complex of vascular, neurological and musculoskeletal disorders, collectively named hand-arm vibration syndrome. Among these, the most common disorder is vibration-induced white finger (Raynaud's phenomenon). The vibration levels were measured in three tractor's working conditions, namely idling, transportation and soil tillage. The vibration level on the handles was measured and analysed and the frequency spectra for the chosen working conditions were obtained. The frequency-weighted acceleration, given in m/s2, was calculated and the obtained values are graphically presented. The measured vibration levels are then discussed with regard to the operator's daily exposure limits recommended by the ISO 5349. The vibration levels were much higher in the x and y directions than the z-direction in all working conditions. The vibration total values in idling, transportation and soil tillage were 3.37, 8.37 and 9.62 m/s2, respectively. Results showed that the 10% of workers are exposed to a risk of vibration-induced white finger disorder of the hands after relatively short periods (3-4 years), if the tractor is used 8 hour per day in soil tillage and transportation at full load. Considering the criteria of the ISO 5349, the daily working time with the single-axle tractor should be limited in order to protect the operator and work schedules should be arranged to include vibration-free periods.

7-oxo-DHEA and Raynaud's phenomenon.

Patients with Raynaud's phenomenon have abnormal digital vasoconstriction in response to cold. The pathogenesis remains unknown but may involve a local neurovascular defect leading to vasoconstriction. Diagnosis of primary Raynaud's phenomenon is based on typical symptomatology coupled with normal physical examination, normal laboratory studies and lack of observable pathology by nail fold capillaroscopy. Secondary Raynaud's phenomenon is known to occur associated with several connective tissue diseases, vascular injury due to repeated vibrational trauma, and other causes which produce demonstrable vascular and microcirculatory damage. Treatment of Raynaud's symptoms is conservative and aimed at prevention of attacks. Patients are advised to remain warm and, if possible, to live in warm climates. We suggest that an ergogenic (thermogenic) steroid, 7-oxo-DHEA (3-acetoxyandrost-5-ene-7,17-dione), which is available without prescription as the trademarked 7-keto DHEA, may be very helpful in prevention of primary Raynaud's attacks by increasing the basal metabolic rate and inhibiting vasospasm.