International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Compression therapy for treating post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep vein thrombosis (DVT) characterised by chronic complaints such as oedema and skin changes including; venous ectasia, varicose veins, redness, eczema, hyperpigmentation, and in severe cases fibrosis of the subcutaneous adipose in the affected limb. These chronic complaints are the effects of venous outflow restriction that can cause symptoms such as heaviness, itching, pain, cramps, and paraesthesia. Twenty to fifty percent of people with DVT develop post-thrombotic complications. Several non-pharmaceutical measures are used for prevention of PTS during the acute phase of DVT. These include elevation of the legs and compression therapy. There have been limited studies regarding the effectiveness of compression therapy for prevention or treatment of PTS. As a result, clinicians and guidelines differ in their assessment of compression therapy during treatment of DVT and in the treatment of PTS. This is an update of a review first published in 2003. OBJECTIVES: To assess the effectiveness of compression therapy for treatment of post-thrombotic syndrome, including elastic compression stockings and mechanical devices compared with no intervention, placebo and with each other. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries on 2 July 2018. SELECTION CRITERIA: We included trials that evaluated compression therapy for the treatment of PTS. The primary outcomes were severity of PTS and adverse effects. There were no restrictions on date or language. Two review authors (SA, DNK) independently assessed whether potentially relevant studies met the inclusion criteria. DATA COLLECTION AND ANALYSIS: One review author extracted and summarised data and one review author (DNK) verified them. We resolved disagreements by discussion. We assessed methodological study quality with the Cochrane 'Risk of bias' tool. We used GRADE to assess the overall certainty of the evidence supporting the outcomes assessed in this review. MAIN RESULTS: We identified four trials, with 116 participants, investigating the effectiveness of compression therapy for treatment of PTS. The methodology used by each trial was too heterogeneous to perform a meta-analysis, so we reported our findings narratively.Two trials studied the effect of graduated elastic compression stockings (GECS) on improvement of PTS symptoms. One study reported beneficial haemodynamic effects, while the other found no benefits on PTS severity compared to placebo (very low-certainty evidence). There was very limited evidence available for adverse effects and quality of life (QoL). The two studies did not report on compliance rates during the study period.Two trials studied the effects of intermittent mechanical compression devices. Both reported improvement in PTS severity (low-certainty evidence). Improvement of the severity of PTS was defined by treatment 'success' or 'failure'. Only one study comparing compression devices evaluated adverse effects and QoL. Although 9% of the participants experienced adverse effects such as leg swelling, irritation, superficial bleeding, and skin itching (moderate-certainty evidence), QoL was improved (moderate-certainty evidence). Studies did not assess compliance using intermittent mechanical compression devices.None of the studies evaluated patient satisfaction. AUTHORS' CONCLUSIONS: There is very low-certainty evidence regarding the use of GECS for treatment of PTS as assessed by two small studies of short duration. One study reported beneficial haemodynamic effects, while one found no benefits on PTS severity compared to control/placebo stockings. There is very limited evidence for adverse effects, patient satisfaction, QoL, and compliance rates. There is low-certainty evidence favouring use of intermittent pneumatic compression devices compared to a control device for the treatment of severity owing to different measurements used by the studies reporting on this outcome and small studies of short duration. There is moderate-certainty evidence of improved QoL but possible increased adverse effects related to compression device use owing to small studies of short duration. High-certainty evidence to support the use of compression therapy in prevention of PTS is lacking and any conclusions drawn from current evidence should be interpreted with care. Further research is needed to assess whether compression can result in long-term reduction and relief of the symptoms caused by PTS, or prevent deterioration and leg ulceration.

Compression therapy for prevention of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep vein thrombosis (DVT) that is characterised by chronic pain, swelling, and skin changes in the affected limb. One of every three people with DVT will develop post-thrombotic complications within five years. Several non-pharmaceutical measures are used for prevention of post-thrombotic syndrome during the acute phase of DVT. These include elevation of the legs and compression therapy. Clinicians and guidelines differ in their assessment of the utility of compression therapy for treatment of DVT. This is an update of a review first published in 2003. OBJECTIVES: To determine relative effectiveness and rate of complications when compression therapy is used in people with deep vein thrombosis (DVT) for prevention of post-thrombotic syndrome (PTS). SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register (20 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched trial registries for details of ongoing or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) of compression therapy, such as bandaging and elastic stockings, in people with clinically confirmed DVT. The primary outcome was the occurrence of PTS. DATA COLLECTION AND ANALYSIS: Two review authors (DK and EvL) identified and assessed titles and abstracts for relevance, and a third review author (DA) verified this assessment independently. Review authors imposed no restrictions on date or language of publications. Three review authors (DA, DK, EvL) used data extraction sheets to independently extract study data. We resolved disagreements by discussion. MAIN RESULTS: We identified 10 RCTs with a total of 2361 participants that evaluated compression therapy. The overall methodological quality of these trials was low. We used only five studies in meta-analysis owing to differences in intervention types and lack of data. Three studies compared elastic compression stockings (pressure of 30 to 40 mmHg at the ankle) versus no intervention. Two studies compared elastic compression stockings (pressure 20 to 40 mmHg) versus placebo stockings. Overall, use of elastic compression stockings led to a clinically significant reduction in the incidence of PTS (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.38 to 1.01; P = 0.05; 1393 participants; 5 studies; low-quality evidence); no reduction in the incidence of severe PTS (RR 0.78, 95% CI 0.53 to 1.15; P = 0.21; 1224 participants; 4 studies; low-quality evidence); and no clear difference in DVT recurrence (RR 0.94, 95% CI 0.69 to 1.28; 1212 participants; 4 studies; P = 0.69; low-quality evidence). We did not pool data on the incidence of pulmonary embolism because this information was poorly reported, but we observed no differences between groups included in individual studies (low-quality evidence).Two studies evaluated effects of compression in the acute phase versus no compression treatment and found no differences in the incidence of PTS (RR 0.76, 95% CI 0.49 to 1.16; P = 0.2; 101 participants). One study reported that thigh-length stockings did not provide better protection against development of PTS than knee-length stockings (RR 0.92, 95% CI 0.66 to 1.28; P = 0.6; 267 participants). Another trial reported that wearing compression stockings for two years seemed to be superior to wearing them for one year in terms of PTS incidence.Two of the 10 included studies described patient satisfaction and quality of life (moderate-quality evidence), using different measurement systems. The first study showed significant improvement in well-being and DVT-related quality of life with compression treatment (P < 0.05) compared with bed rest, and the second study showed no differences in quality of life scores between compression and placebo groups. Four studies poorly reported side effects (low-quality evidence) that included itching, erythema, and other forms of allergic reaction and described no serious adverse events. Compliance with wearing of compression stockings was generally high but varied across studies. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that elastic compression stockings may reduce the occurrence of PTS after DVT. We downgraded the quality of evidence owing to considerable heterogeneity between studies and lack of or unclear risk of blinding due to clinical assessment scores. No serious adverse effects occurred in these studies. Large randomised controlled trials are needed to confirm these findings because of current lack of high-quality evidence and considerable heterogeneity.