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.

Rutosides for prevention of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of PTS. This is the second update of the review first published in 2013. OBJECTIVES: To determine the effectiveness and safety of rutosides for prevention of post-thrombotic syndrome (PTS) in patients with deep vein thrombosis (DVT), compared to placebo, no intervention, or reference medication. SEARCH METHODS: 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 registers to 21 August 2018. SELECTION CRITERIA: We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and intended to extract information from the trials. MAIN RESULTS: No studies were identified comparing rutosides versus any alternative in the prevention of PTS. AUTHORS' CONCLUSIONS: As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

Rutosides for treatment of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. This is the second update of the review first published in 2013. OBJECTIVES: To determine the effectiveness (improvement or deterioration in symptoms) and safety of rutosides for treatment of post-thrombotic syndrome (PTS) in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. SEARCH METHODS: 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 registers to 21 August 2018. SELECTION CRITERIA: Two review authors independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two review authors extracted information from the trials. Disagreements were resolved by discussion. DATA COLLECTION AND ANALYSIS: Data were extracted using designated data extraction forms. The Cochrane 'Risk of bias' tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of DVT or pulmonary embolism, compliance with therapy, and adverse effects. All of the outcome measures were analysed using Mantel-Haenzel fixed-effect model odds ratios. The unit of analysis was the number of patients. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: Ten reports of nine studies were identified following searching and three studies with a total of 233 participants met the inclusion criteria. Overall quality of evidence using the GRADE approach was low, predominantly due to the lack of both participant and researcher blinding in the included studies. The quality of the evidence was further limited as only three small studies contributed to the review findings. A subjective scoring system was used to obtain the symptoms of PTS so it was important that the assessors were blinded to the intervention. One study compared rutosides with placebo, one study compared rutosides with ECS and rutosides plus ECS versus ECS alone, and one study compared rutosides with an alternative venoactive remedy. Occurrence of leg ulceration was not reported in any of the included studies. There was no clear evidence to support a difference in PTS improvement between the rutosides or placebo/no treatment groups (OR 1.29, 95% CI 0.69 to 2.41; 164 participants; 2 studies; low-quality evidence); or between the rutosides and ECS groups (OR 0.80, 95% CI 0.31 to 2.03; 80 participants; 1 study ; low-quality evidence). Results from one small study reported less PTS improvement in the rutosides group compared to an alternative venoactive remedy (OR 0.18, 95% CI 0.04 to 0.94; 29 participants; 1 study; low-quality evidence). There was no clear evidence to support a difference in PTS deterioration when comparing rutosides with placebo/no treatment (OR 0.61, 95% CI 0.19 to 1.90; 80 participants; 1 study); with ECS (OR 0.61, 95% CI 0.19 to 1.90; 80 participants; 1 study); or an alternative venoactive remedy (OR 0.19, 95% CI 0.01 to 4.24; 29 participants; 1 study). No clear evidence of a difference in adverse effects between the rutosides and placebo/no treatment groups was seen ('mild side effects' reported in 7/41 and 5/42 respectively). In the study comparing rutosides with ECS, 2/80 could not tolerate ECS and 6/80 stopped medication due to side effects. The study comparing rutosides with an alternative venoactive remedy did not comment on side effects AUTHORS' CONCLUSIONS: There was no evidence that rutosides were superior to the use of placebo or ECS. Overall, there is currently limited low-quality evidence that 'venoactive' or 'phlebotonic' remedies such as rutosides reduce symptoms of PTS. Mild side effects were noted in one study. The three studies included in this review provide no evidence to support the use of rutosides in the treatment of PTS.

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.

Debridement for venous leg ulcers.

BACKGROUND: Venous ulcers (also known as varicose or venous stasis ulcers) are a chronic, recurring and debilitating condition that affects up to 1% of the population. Best practice documents and expert opinion suggests that the removal of devitalised tissue from venous ulcers (debridement) by any one of six methods helps to promote healing. However, to date there has been no review of the evidence from randomised controlled trials (RCTs) to support this. OBJECTIVES: To determine the effects of different debriding methods or debridement versus no debridement, on the rate of debridement and wound healing in venous leg ulcers. SEARCH METHODS: In February 2015 we searched: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting. In addition we handsearched conference proceedings, journals not cited in MEDLINE, and the bibliographies of all retrieved publications to identify potential studies. We made contact with the pharmaceutical industry to enquire about any completed studies. SELECTION CRITERIA: We included RCTs, either published or unpublished, which compared two methods of debridement or compared debridement with no debridement. We presented study results in a narrative form, as meta-analysis was not possible. DATA COLLECTION AND ANALYSIS: Independently, two review authors completed all study selection, data extraction and assessment of trial quality; resolution of disagreements was completed by a third review author. MAIN RESULTS: We identified 10 RCTs involving 715 participants. Eight RCTs evaluated autolytic debridement and included the following agents or dressings: biocellulose wound dressing (BWD), non-adherent dressing, honey gel, hydrogel (gel formula), hydrofibre dressing, hydrocolloid dressings, dextranomer beads, Edinburgh University Solution of Lime (EUSOL) and paraffin gauze. Two RCTs evaluated enzymatic preparations and one evaluated biosurgical debridement. No RCTs evaluated surgical, sharp or mechanical methods of debridement, or debridement versus no debridement. Most trials were at a high risk of bias.Three RCTs assessed the number of wounds completely debrided. All three of these trials compared two different methods of autolytic debridement (234 participants), with two studies reporting statistically significant results: one study (100 participants) reported that 40/50 (80%) ulcers treated with dextranomer beads and 7/50 (14%) treated with EUSOL achieved complete debridement (RR 5.71, 95% CI 2.84 to 11.52); while the other trial (86 participants) reported the number of ulcers completely debrided as 31/46 (76%) for hydrogel versus 18/40 (45%) for paraffin gauze (RR 0.67, 95% CI 0.45 to 0.99). One study (48 participants) reported that by 12 weeks, 15/18 (84%) ulcers treated with BWD had achieved a 75% to 100% clean, granulating wound bed versus 4/15 (26%) treated with non-adherent petrolatum emulsion-impregnated gauze.Four trials assessed the mean time to achieve debridement: one (86 participants) compared two autolytic debridement methods, two compared autolytic methods with enzymatic debridement (71 participants), and the last (12 participants) compared autolytic with biosurgical debridement; none of the results achieved statistical significance.Two trials that assessed autolytic debridement methods reported the number of wounds healed at 12 weeks. One trial (108 participants) reported that 24/54 (44%) ulcers treated with honey healed versus 18/54 (33%) treated with hydrogel (RR (adjusted for baseline wound diameter) 1.38, 95% CI 1.02 to 1.88; P value 0.037). The second trial (48 participants) reported that 7/25 (28%) ulcers treated with BWD healed versus 7/23 (30%) treated with non-adherent dressing.Reduction in wound size was assessed in five trials (444 participants) in which two autolytic methods were compared. Results were statistically significant in one three-armed trial (153 participants) when cadexomer iodine was compared to paraffin gauze (mean difference 24.9 cm², 95% CI 7.27 to 42.53, P value 0.006) and hydrocolloid compared to paraffin gauze (mean difference 23.8 cm², 95% CI 5.48 to 42.12, P value 0.01). A second trial that assessed reduction in wound size based its results on median differences and, at four weeks, produced a statistically significantly result that favoured honey over hydrogel (P value < 0.001). The other three trials reported no statistically significant results for reduction in wound size, although one trial reported that the mean percentage reduction in wound area was greater at six and 12 weeks for BWD versus a non-adherent dressing (44% versus 24% week 6; 74% versus 54% week 12).Pain was assessed in six trials (544 participants) that compared two autolytic debridement methods, but the results were not statistically significant. No serious adverse events were reported in any trial. AUTHORS' CONCLUSIONS: There is limited evidence to suggest that actively debriding a venous leg ulcer has a clinically significant impact on healing. The overall small number of participants, low number of studies and lack of meta-analysis in this review precludes any strong conclusions of benefit. Comparisons of different autolytic agents (hydrogel versus paraffin gauze; Dextranomer beads versus EUSOL and BWD versus non-adherent dressings) and Larvae versus hydrogel all showed statistically significant results for numbers of wounds debrided. Larger trials with follow up to healing are required.

Rutosides for treatment of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. This is an update of the review first published in 2013. OBJECTIVES: To determine the effectiveness (improvement or deterioration in symptoms) and safety of rutosides for treatment of post-thrombotic syndrome (PTS) in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. SEARCH METHODS: For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) (CENTRAL (2015, Issue 8)). Clinical trials databases were searched for details of ongoing and unpublished studies. SELECTION CRITERIA: Two review authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two review authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. DATA COLLECTION AND ANALYSIS: Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the outcome measures were analysed using Mantel-Haenzel fixed-effect model odds ratios. The unit of analysis was the number of patients. MAIN RESULTS: Ten reports of nine studies were identified following searching and three studies with a total of 233 participants met the inclusion criteria. Overall quality of the evidence using the GRADE approach was low or very low, predominantly due to the lack of both participant and researcher blinding in the included studies. The quality of the evidence was further limited as only three small studies contributed to the review findings. A subjective scoring system was used to obtain the symptoms of PTS so it was important that the assessors were blinded to the intervention. One study compared rutoside with placebo, one study compared rutosides with ECS and rutosides plus ECS versus ECS alone, and one study compared rutosides with an alternative venoactive remedy. Occurrence of leg ulceration was not reported in any of the included studies. There was a 29% odds of an improvement in PTS in the rutoside treated group versus placebo or no treatment, and lower rates of improvement in PTS in the rutoside treated group when compared with ECS, however these were statistically non-significant. Lower rates of improvement in PTS were shown in the rutoside treated group when compared with an alternative venoactive remedy. More PTS deterioration was shown in the placebo or no treatment group when compared with rutosides but this was not statistically significant. Compared with ECS, rutosides showed higher odds of PTS deterioration but this was also not statistically significant. One study reported on adverse effects showing higher odds of mild adverse effects in the rutoside treated group compared to placebo but this was not statistically significant. AUTHORS' CONCLUSIONS: There was no evidence that rutosides were superior to the use of placebo or ECS. Overall, there is currently limited and low or very low quality evidence that 'venoactive' or 'phlebotonic' remedies such as rutosides reduce symptoms of PTS. Mild side effects were noted in one study. The three studies included in this review provide no evidence for the use of rutosides in the treatment of PTS.

Rutosides for prevention of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. This is an update of the review first published in 2013. OBJECTIVES: To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. SEARCH METHODS: For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) ((CENTRAL) 2015, Issue 8). Clinical trials databases were searched for details of ongoing and unpublished studies. SELECTION CRITERIA: We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and intended to extract information from the trials. MAIN RESULTS: No studies were identified comparing rutosides versus any alternative in the prevention of PTS. AUTHORS' CONCLUSIONS: As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

Non-pharmacological interventions for preventing venous insufficiency in a standing worker population.

BACKGROUND: Chronic venous insufficiency (CVI) is a common problem, affecting up to 50% of the population in industrialised countries. It is a chronic condition which, if untreated, can progress to serious complications that in turn can interfere with working ability. Standing at work is a known risk factor for CVI, yet the true effect of non-pharmacological preventive strategies remains unknown. This is an update of a review first published in 2012. OBJECTIVES: To assess the efficacy of non-pharmacological strategies and devices to prevent CVI in a standing worker population. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2013) and CENTRAL (2013, Issue 8). We also handsearched reference lists of relevant studies. SELECTION CRITERIA: Randomised and non-randomised controlled trials that recruited standing workers to evaluate non-pharmacological devices or strategies used to prevent CVI were eligible for inclusion. Trials had to report an objective measure of clinical features of CVI or complaints associated with this condition in order to be included. DATA COLLECTION AND ANALYSIS: Selection of the trials, quality assessment and data abstraction were completed independently by two review authors. We resolved disagreements by discussion. Only one trial was eligible for inclusion in the review so we did not perform meta-analyses. MAIN RESULTS: The primary outcomes of this review were clinical features of CVI and its associated symptoms. No new included studies were identified for this update. One prospective cross-over trial was included in this review. It measured the effect of no compression followed by two phases with different gradients of compression stockings on symptoms in 19 female flight attendants who were required to stand, almost continuously, for long periods of time. The included study provided some evidence that compression stockings improved symptoms of leg fatigue in standing workers. However, the strength of the evidence in this review is weak as it is based on only one very small trial which was at high risk of bias. The included study did not address any of the secondary outcomes including quality of life or economic impact of the interventions. Nor did the study report the length of time that the population were required to stand at work. Furthermore, no trials were found which measured the effectiveness of other non-pharmacological interventions or strategies aimed at preventing CVI in standing workers. AUTHORS' CONCLUSIONS: Due to the extremely limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of non-pharmacological interventions for preventing CVI in standing workers. Further large-scale studies examining all possible non-pharmacological interventions and outcomes are required.

Rutosides for treatment of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. OBJECTIVES: To determine the effectiveness and safety of rutosides for treatment of PTS in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. SELECTION CRITERIA: Two authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. DATA COLLECTION AND ANALYSIS: Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the outcome measures were analysed using Mantel-Haenzel fixed-effect model odds ratios. The unit of analysis was the number of patients. MAIN RESULTS: Ten reports of nine studies were identified following searching and three studies with a total of 233 participants met the inclusion criteria. One study compared rutoside with placebo, one study compared rutosides with ECS and rutosides plus ECS versus ECS alone, and one study compared rutosides with an alternative venoactive remedy. Occurrence of leg ulceration was not reported in any of the included studies. There was a 29% odds of an improvement in PTS in the rutoside treated group versus placebo or no treatment, and lower rates of improvement in PTS in the rutoside treated group when compared with ECS, however these were statistically non-significant. Lower rates of improvement in PTS were shown in the rutoside treated group when compared with an alternative venoactive remedy. More PTS deterioration was shown in the placebo or no treatment group when compared with rutosides but this was not statistically significant. Compared with ECS, rutosides showed higher odds of PTS deterioration but this was also not statistically significant. One study reported on adverse effects showing higher odds of mild adverse effects in the rutoside treated group compared to placebo but this was not statistically significant. AUTHORS' CONCLUSIONS: There was no evidence that rutosides were superior to the use of placebo or ECS. Overall, there is currently limited evidence that 'venoactive' or 'phlebotonic' remedies such as rutosides reduce symptoms of PTS. Mild side effects were noted in one study. The three studies included in this review provide no evidence for the use of rutosides in the treatment of PTS.

Rutosides for prevention of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. OBJECTIVES: To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. SELECTION CRITERIA: We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and intended to extract information from the trials. MAIN RESULTS: No studies were identified comparing rutosides versus any alternative in the prevention of PTS. AUTHORS' CONCLUSIONS: As there were no studies identified in this review it is not possible to support the use of rutosides in the prevention of PTS. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

Non-pharmacological interventions for preventing venous insufficiency in a standing worker population.

BACKGROUND: Chronic venous insufficiency (CVI) is a common problem, affecting up to 50% of the population in industrialised countries. It is a chronic condition which, if untreated, can progress to serious complications that in turn can interfere with working ability. Standing at work is a known risk factor for CVI, yet the true effect of non-pharmacological preventive strategies remains unknown. OBJECTIVES: To undertake a systematic review of randomised or controlled clinical trials to assess the efficacy of non-pharmacological strategies and devices to prevent CVI in a standing worker population. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialised Register (last searched April 2011) and CENTRAL (Issue 2, 2011). No date or language restrictions were applied. We also handsearched reference lists of relevant studies. SELECTION CRITERIA: Randomised and non-randomised controlled trials that recruited standing workers to evaluate non-pharmacological devices or strategies used to prevent CVI were eligible for inclusion. Trials had to report an objective measure of clinical features of CVI or complaints associated with this condition in order to be included. DATA COLLECTION AND ANALYSIS: Selection of the trials, quality assessment and data abstraction were completed independently by two review authors. We resolved disagreements by discussion. Only one trial was eligible for inclusion in the review so we did not perform meta-analyses. MAIN RESULTS: The primary outcomes of this review were clinical features of CVI and its associated symptoms. One prospective cross-over trial was included in this review. It measured the effect of no compression followed by two phases with different gradients of compression stockings on symptoms in 19 female flight attendants who were required to stand, almost continuously, for long periods of time. The included study provided some evidence that compression stockings improved symptoms of leg fatigue in standing workers. However, the strength of the evidence in this review is weak as it is based on only one very small trial which was at high risk of bias. The included study did not address any of the secondary outcomes including quality of life or economic impact of the interventions. Nor did the study report the length of time that the population were required to stand at work. Furthermore, no trials were found which measured the effectiveness of other non-pharmacological interventions or strategies aimed at preventing CVI in standing workers. AUTHORS' CONCLUSIONS: Due to the extremely limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of non-pharmacological interventions for preventing CVI in standing workers. Further large-scale studies examining all possible non-pharmacological interventions and outcomes are required.

Influence of mutation type on clinical expression of Leber hereditary optic neuropathy.

PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined. DESIGN: Observational, retrospective population cohort study. METHODS: The clinical characteristics of LHON patients of 25 families, previously described in 1963, were reevaluated. The mutation and haplotype were determined in the DNA of one affected LHON patient per family. The genotype of their relatives could be deducted, enabling us to evaluate retrospectively the genotype-phenotype correlation. The prevalence of LHON was determined on the basis of anamnestic evaluation of patients in 1963 and by using population registers of that period. RESULTS: The LHON mutation does not influence disease penetrance (50% in male subjects; 10% to 20% in female subjects). More than half of the patients with the 14484 mutation exhibit a partial recovery of vision, regardless of the acuteness of disease onset (P = .001), whereas only 22% of the 11778 carriers and 15.4% of the 3460 carriers recovered. The recovery did not take place within the first year after onset and was uncommon after four years. The onset of LHON is in general very acute but might be more gradual in 11778 carriers and in children. The calculated prevalence of LHON in the Dutch population (1/39,000) is very likely an underestimation caused by a selection bias of familial cases in the original study. CONCLUSIONS: The LHON genotype influences the recovery of vision and disease onset but is unrelated to age, acuteness of onset, or gender. The genotype does not influence disease penetrance. Children might exhibit a slower onset of disease.

Identifying inappropriate hospital stay in patients with venous thromboembolism.

Background: Traditionally, venous thromboembolism has been treated in a hospital setting. Nowadays, low molecular weight heparin (LMWH) preparations allow most deep venous thrombosis (DVT) patients to benefit from home therapy. The objective of this study was to evaluate whether the previous treatment of deep venous thrombosis in a hospital setting was appropriate in the context of modern opinion, using the Dutch Appropriateness Evaluation Protocol (DAEP). If so, the DAEP could be used to assess the appropriateness of the present hospital stay of other patient groups. Methods: A retrospective study of patients treated from 1995 to 1998 for DVT or for pulmonary embolism (PE), before the implementation of ambulatory treatment, was conducted that assessed the appropriateness of the patient's hospital stay using the DAEP. Results: Only 27.1% of the treatments for DVT were found to be appropriate in a hospital setting and related to specific hospital care. Inappropriate stay was mostly related to delays in hospital and discharge procedures. Of the patients with PE, 50.2% needed a hospital stay. This proportion was statistically significantly higher than in DVT patients (p<0.001). The extent of the DVT was not related to the length of bed rest prescribed. Conclusions: The DAEP was able to identify inappropriate hospital stay in the past within the DVT patient group. Further exploration of the potential of the DAEP to identify patient groups who could be treated at home is warranted.