Pre-deployment programmes for building resilience in military and frontline emergency service personnel.

BACKGROUND: Military personnel and frontline emergency workers may be exposed to events that have the potential to precipitate negative mental health outcomes such as depression, symptoms of post-traumatic stress and even post-traumatic stress disorder (PTSD). Programmes have been designed to build psychological resilience before staff are deployed into the field. This review presents a synthesis of the literature on these "pre-deployment resilience-building programmes". OBJECTIVES: The objective of this review was to assess the effectiveness of programmes that seek to build resilience to potentially traumatic events among military and frontline emergency service personnel prior to their deployment. These resilience programmes were compared to other interventions, treatment as usual or no intervention. SEARCH METHODS: Studies were identified through searches of electronic databases including Ovid MEDLINE, Embase, PsycINFO, Web of Science and Google Scholar. The initial search took place in January 2019, with an updated search completed at the end of September 2020. SELECTION CRITERIA: Only studies that used a randomised controlled trial (RCT)/cluster-RCT methodology were included. The programmes being evaluated must have sought to build resilience prior to exposure to trauma. Study participants must have been 18 years or older and be military personnel or frontline emergency workers. DATA COLLECTION AND ANALYSIS: Studies that met the inclusion criteria were assembled. Data extracted included methods, participants' details, intervention details, comparator details, and information on outcomes. The primary outcomes of interest were resilience, symptoms of post-traumatic stress and PTSD. Secondary outcomes of interest included acute stress disorder, depression, social support, coping skills, emotional flexibility, self-efficacy, social functioning, subjective levels of aggression, quality of sleep, quality of life and stress. Assessment of risk of bias was also completed. A total of 28 studies were included in a narrative synthesis of results. MAIN RESULTS: All 28 included studies compared an experimental resilience building intervention versus a control or no intervention. There was a wide range of therapeutic modalities used, including cognitive behavioural therapy (CBT) informed programmes, biofeedback based programmes, stress-management programmes, mindfulness and relaxation programmes, neuropsychological-based programmes, and psychoeducational-informed programmes. The main outcomes are specified here, secondary outcomes such as depression, social support, coping skills, self-efficacy, subjective levels of aggression and stress are reported in text. No studies reported on the following pre-specified outcomes; acute stress disorder, emotional flexibility, social functioning, quality of sleep and quality of life. Resilience Eight studies reported resilience as an outcome. We narratively synthesised the data from these studies and our findings show that five of these interventions had success in building resilience in their respective samples. Two of the studies that reported significant results utilised a CBT approach to build resilience, while the other three successful programmes were mindfulness-based interventions. Symptoms of post-traumatic stress Our narrative synthesis of results included eight studies. Two of the eight studies produced significant reductions in symptoms of post traumatic stress compared to controls. These interventions used neuropsychological and biofeedback intervention models respectively. PTSD caseness Four studies reported PTSD caseness as an outcome. Our narrative synthesis of results suggests that evidence is mixed as to the effectiveness of these interventions in reducing clinical diagnosis of PTSD. One study of a neuropsychology-orientated Attention Bias Modification Training (AMBT) programme had success in reducing both symptoms of post-traumatic stress and numbers of participants receiving a diagnosis of PTSD. A stress-management programme reported that, when baseline differences in rates of pre-deployment mental health issues were controlled for, participants in the control condition were at 6.9 times the risk of a diagnosis of PTSD when compared to the intervention group. Given the diversity of intervention designs and theoretical orientations used (which included stress-management, neuropsychological and psychoeducational programmes), a definitive statement on the efficacy of pre-deployment programmes at reducing symptoms of post-traumatic stress and PTSD cannot be confidently offered. AUTHORS' CONCLUSIONS: While a number of evaluations of relevant programmes have been published, the quality of these evaluations limits our ability to determine if resilience-building programmes 'work' in terms of preventing negative outcomes such as depression, symptoms of post-traumatic stress and diagnoses of PTSD. Based on our findings we recommend that future research should: a) report pre-/post-means and standard deviation scores for scales used within respective studies, b) take the form of large, RCTs with protocols published in advance, and c) seek to measure defined psychological facets such as resilience, PTSD and stress, and measure these concepts using established psychometric tools. This will provide more certainty in future assessments of the evidence base. From a clinical implications point of view, overall there is mixed evidence that the interventions included in this review are effective at safe guarding military personnel or frontline emergency workers from experiencing negative mental health outcomes, including PTSD, following exposure to potentially traumatic events. Based on this, practitioners seeking to build resilience in their personnel need to be aware of the limitations of the evidence base. Practitioners should have modest expectations in relation to the efficacy of resilience-building programmes as a prophylactic approach to employment-related critical incident traumas.

Behavioural activation therapy for depression in adults.

BACKGROUND: Behavioural activation is a brief psychotherapeutic approach that seeks to change the way a person interacts with their environment. Behavioural activation is increasingly receiving attention as a potentially cost-effective intervention for depression, which may require less resources and may be easier to deliver and implement than other types of psychotherapy. OBJECTIVES: To examine the effects of behavioural activation compared with other psychological therapies for depression in adults. To examine the effects of behavioural activation compared with medication for depression in adults. To examine the effects of behavioural activation compared with treatment as usual/waiting list/placebo no treatment for depression in adults. SEARCH METHODS: We searched CCMD-CTR (all available years), CENTRAL (current issue), Ovid MEDLINE (1946 onwards), Ovid EMBASE (1980 onwards), and Ovid PsycINFO (1806 onwards) on the 17 January 2020 to identify randomised controlled trials (RCTs) of 'behavioural activation', or the main elements of behavioural activation for depression in participants with clinically diagnosed depression or subthreshold depression. We did not apply any restrictions on date, language or publication status to the searches. We searched international trials registries via the World Health Organization's trials portal (ICTRP) and ClinicalTrials.gov to identify unpublished or ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of behavioural activation for the treatment of depression or symptoms of depression in adults aged 18 or over. We excluded RCTs conducted in inpatient settings and with trial participants selected because of a physical comorbidity. Studies were included regardless of reported outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all titles/abstracts and full-text manuscripts for inclusion. Data extraction and 'Risk of bias' assessments were also performed by two review authors in duplicate. Where necessary, we contacted study authors for more information. MAIN RESULTS: Fifty-three studies with 5495 participants were included; 51 parallel group RCTs and two cluster-RCTs. We found moderate-certainty evidence that behavioural activation had greater short-term efficacy than treatment as usual (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.10 to 1.78; 7 RCTs, 1533 participants), although this difference was no longer evident in sensitivity analyses using a worst-case or intention-to-treat scenario. Compared with waiting list, behavioural activation may be more effective, but there were fewer data in this comparison and evidence was of low certainty (RR 2.14, 95% CI 0.90 to 5.09; 1 RCT, 26 participants). No evidence on treatment efficacy was available for behavioural activation versus placebo and behavioural activation versus no treatment. We found moderate-certainty evidence suggesting no evidence of a difference in short-term treatment efficacy between behavioural activation and CBT (RR 0.99, 95% CI 0.92 to 1.07; 5 RCTs, 601 participants). Fewer data were available for other comparators. No evidence of a difference in short term-efficacy was found between behavioural activation and third-wave CBT (RR 1.10, 95% CI 0.91 to 1.33; 2 RCTs, 98 participants; low certainty), and psychodynamic therapy (RR 1.21, 95% CI 0.74 to 1.99; 1 RCT,60 participants; very low certainty). Behavioural activation was more effective than humanistic therapy (RR 1.84, 95% CI 1.15 to 2.95; 2 RCTs, 46 participants; low certainty) and medication (RR 1.77, 95% CI 1.14 to 2.76; 1 RCT; 141 participants; moderate certainty), but both of these results were based on a small number of trials and participants. No evidence on treatment efficacy was available for comparisons between behavioural activation versus interpersonal, cognitive analytic, and integrative therapies. There was moderate-certainty evidence that behavioural activation might have lower treatment acceptability (based on dropout rate) than treatment as usual in the short term, although the data did not confirm a difference and results lacked precision (RR 1.64, 95% CI 0.81 to 3.31; 14 RCTs, 2518 participants). Moderate-certainty evidence did not suggest any difference in short-term acceptability between behavioural activation and waiting list (RR 1.17, 95% CI 0.70 to 1.93; 8 RCTs. 359 participants), no treatment (RR 0.97, 95% CI 0.45 to 2.09; 3 RCTs, 187 participants), medication (RR 0.52, 95% CI 0.23 to 1.16; 2 RCTs, 243 participants), or placebo (RR 0.72, 95% CI 0.31 to 1.67; 1 RCT; 96 participants; low-certainty evidence). No evidence on treatment acceptability was available comparing behavioural activation versus psychodynamic therapy. Low-certainty evidence did not show a difference in short-term treatment acceptability (dropout rate) between behavioural activation and CBT (RR 1.03, 95% CI 0.85 to 1.25; 12 RCTs, 1195 participants), third-wave CBT (RR 0.84, 95% CI 0.33 to 2.10; 3 RCTs, 147 participants); humanistic therapy (RR 1.06, 95% CI 0.20 to 5.55; 2 RCTs, 96 participants) (very low certainty), and interpersonal, cognitive analytic, and integrative therapy (RR 0.84, 95% CI 0.32 to 2.20; 4 RCTs, 123 participants). Results from medium- and long-term primary outcomes, secondary outcomes, subgroup analyses, and sensitivity analyses are summarised in the text. AUTHORS' CONCLUSIONS: This systematic review suggests that behavioural activation may be more effective than humanistic therapy, medication, and treatment as usual, and that it may be no less effective than CBT, psychodynamic therapy, or being placed on a waiting list. However, our confidence in these findings is limited due to concerns about the certainty of the evidence. We found no evidence of a difference in short-term treatment acceptability (based on dropouts) between behavioural activation and most comparison groups (CBT, humanistic therapy, waiting list, placebo, medication, no treatment or treatment as usual). Again, our confidence in all these findings is limited due to concerns about the certainty of the evidence. No data were available about the efficacy of behaioural activation compared with placebo, or about treatment acceptability comparing behavioural activation and psychodynamic therapy, interpersonal, cognitive analytic and integrative therapies. The evidence could be strengthened by better reporting and better quality RCTs of behavioural activation and by assessing working mechanisms of behavioural activation.

Evaluation of the prescribing decision support system Synonyms in a primary care setting: a mixed-method study.

BACKGROUND: Primary care prescribers must cope with an increasing number and complexity of considerations. Prescribing decision support systems (DSS) have therefore been developed to assist prescribers. Previous studies have shown that although there is wide variance in the different DSS available within primary care, barriers and facilitators to uptake remain. The Drug Synonyms function ('Synonyms') is a DSS inherent in the commercial electronic medical record system EMIS. Synonyms functionality has been further developed by the NHS Greater Glasgow and Clyde (GG&C) Central Prescribing Team to promote safe and cost-effective prescribing; however, it does not support the collection of usage data. As there is no knowledge on the uptake nor on the perceived effect of using Synonyms on prescribing, quantitative and qualitative analyses of Synonyms usage are required to ascertain the impact Synonyms has on primary care prescribers, which will influence the continued maintenance and/or future development of this prescribing DSS. AIM: To determine the uptake of Synonyms and explore users' perceptions of its usefulness and future development. DESIGN AND SETTING: An exploratory sequential mixed-method observational study using quantitative questionnaires, followed by semi-structured interviews with primary care prescribers within NHS GG&C. METHOD: An electronic questionnaire (Questionnaire 1) accessible across 218 EMIS-compliant NHS GG&C GP practices ascertained Synonyms uptake by determining whether prescribers were aware of the DSS, whether they were aware of it and whether they used it. Prescribers who were aware of and used Synonyms were asked to opt in to participating further. This involved answering a second electronic questionnaire (Questionnaire 2), with the option of taking part in an additional one-to-one interview, to investigate their use and perceptions of Synonyms. RESULTS: Questionnaire 1 was completed by 201 respondents from 43.1% of eligible GP practices: 186 (92.5%) respondents were aware of Synonyms, of whom 163 (87.6%) had used it and 155 (83.3%) continued to use it. Questionnaire 2 was completed by 104 respondents: 90 (86.5%) indicated that Synonyms informed or influenced their choice of drug prescribed; 94 (90.4%) reported that Synonyms changed their prescribing choice towards medication on NHS GG&C formulary, and 104 (100%) reported that they trust Synonyms. Six interviews generated suggestions for improvements, mainly extending the clinical conditions listed. CONCLUSION: Most respondents were aware of and continued to use Synonyms. Respondents perceived Synonyms to influence prescribing choices towards local formulary medicines and improve adherence to local prescribing guidelines. Respondents trusted the DSS, but there is potential to increase awareness and training amongst non-users to encourage usage. Potentially, the NHS GG&C Synonyms function could be utilised by other health boards with supportive clinical systems.

Cancer Mortality, Early Detection and Treatment among Adult New Zealanders: Changes in Perceptions between 2001 and 2014/5

Background: Beliefs about cancer risk and experience of early detection and treatment can impact on willingness to engage with these initiatives. This study describes changes in perceptions of cancer mortality, early detection and treatment among adult New Zealanders (NZ) between two cross-sectional studies conducted in 2001 and 2014/5. Methods: Data was collected via telephone interviews conducted by trained interviewers in 2001 (231 females and 207 males, 64% response rate) and 2014/5 (588 females and 476 males, 64% response rate). Participants were asked to identify the most common three causes of cancer mortality among women and then men. They were also asked to note their agreement or otherwise with statements about early detection and treatment of cancer. Results: There was an increase in proportions of men who correctly identified prostate cancer as one of the top three causes of cancer mortality among men, and also an increase among women who correctly identified bowel cancer as one of the top three. Most participants agreed that there were benefits from early detection for cancer outcomes. Over time, there was a significant decline in proportions which felt that most cancer treatment is "so terrible it is worse than death" and that alternative therapy has an "equal or better chance of curing cancer." Conclusion: Internationally, there is little information available about changes in cancer perceptions over time, these findings suggest some changes in perceptions of treatment and awareness of types of cancer with the highest mortality in NZ, which should support timely engagement with early detection and treatment services.

Secondary prevention of recurrent venous thromboembolism after initial oral anticoagulation therapy in patients with unprovoked venous thromboembolism.

BACKGROUND: Currently, little evidence is available on the length and type of anticoagulation used for extended treatment for prevention of recurrent venous thromboembolism (VTE) in patients with unprovoked VTE who have completed initial oral anticoagulation therapy. OBJECTIVES: To compare the efficacy and safety of available oral therapeutic options (aspirin, warfarin, direct oral anticoagulants (DOACs)) for extended thromboprophylaxis in adults with a first unprovoked VTE, to prevent VTE recurrence after completion of an acceptable initial oral anticoagulant treatment period, as defined in individual studies. SEARCH METHODS: For this review, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (March 2017) as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). We also searched trials registries (March 2017) and reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials in which patients with a first, symptomatic, objectively confirmed, unprovoked VTE, who had been initially treated with anticoagulants, were randomised to extended prophylaxis (vitamin K antagonists (VKAs), antiplatelet agents, or DOACs) versus no prophylaxis or placebo. We also included trials that compared one type of extended prophylaxis versus another type of extended prophylaxis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed quality, and extracted data. We resolved disagreements by discussion. MAIN RESULTS: Six studies with a combined total of 3436 participants met the inclusion criteria. Five studies compared extended prophylaxis versus placebo: three compared warfarin versus placebo, and two compared aspirin versus placebo. One study compared one type of extended prophylaxis (rivaroxaban) versus another type of extended prophylaxis (aspirin). For extended prophylaxis versus placebo, we downgraded the quality of the evidence for recurrent VTE and all-cause mortality to moderate owing to concerns arising from risks of selection and performance bias in individual studies. For all other outcomes in this review, we downgraded the quality of the evidence to low owing to concerns arising from risk of bias for the studies stated above, combined with concerns over imprecision. For extended prophylaxis versus other extended prophylaxis, we downgraded the quality of the evidence for recurrent VTE and major bleeding to moderate owing to concerns over imprecision. Risk of bias in the individual study was low.Meta-analysis showed that extended prophylaxis was no more effective than placebo in preventing VTE-related mortality (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.14 to 6.98; 1862 participants; 4 studies; P = 0.98; low-quality evidence), recurrent VTE (OR 0.63, 95% CI 0.38 to 1.03; 2043 participants; 5 studies; P = 0.07; moderate-quality evidence), major bleeding (OR 1.84, 95% CI 0.87 to 3.85; 2043 participants; 5 studies; P = 0.86; low-quality evidence), all-cause mortality (OR 1.00, 95% CI 0.63 to 1.57; 2043 participants; 5 studies; P = 0.99; moderate-quality evidence), clinically relevant non-major bleeding (OR 1.78, 95% CI 0.59 to 5.33; 1672 participants; 4 studies; P = 0.30; low-quality evidence), stroke (OR 1.15, 95% CI 0.39 to 3.46; 1224 participants; 2 studies; P = 0.80; low-quality evidence), or myocardial infarction (OR 1.00, 95% CI 0.35 to 2.87; 1495 participants; 3 studies; P = 1.00; low-quality evidence).One study showed that the novel oral anticoagulant rivaroxaban was associated with fewer recurrent VTEs than aspirin (OR 0.28, 95% CI 0.15 to 0.54; 1389 participants; P = 0.0001; moderate-quality evidence). Data show no clear differences in the incidence of major bleeding between rivaroxaban and aspirin (OR 3.06, 95% CI 0.37 to 25.51; 1389 participants; P = 0.30; moderate-quality evidence) nor in the incidence of clinically relevant non-major bleeding (OR 0.84, 95% CI 0.37 to 1.94; 1389 participants; 1 study; P = 0.69; moderate-quality evidence). Data on VTE-related mortality, all-cause mortality, stroke, and myocardial infarction were not yet available for participants with unprovoked VTE and will be incorporated in future versions of the review. AUTHORS' CONCLUSIONS: Evidence is currently insufficient to permit definitive conclusions concerning the effectiveness and safety of extended thromboprophylaxis in prevention of recurrent VTE after initial oral anticoagulation therapy among participants with unprovoked VTE. Additional good-quality large-scale randomised controlled trials are required before firm conclusions can be reached.

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism.

BACKGROUND: Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism. OBJECTIVES: To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations. SELECTION CRITERIA: We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism. DATA COLLECTION AND ANALYSIS: Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). MAIN RESULTS: We included five randomised controlled trials with a total of 7897 participants. Two studies tested oral DTIs (dabigatran) and three studies tested oral factor Xa inhibitors (one rivaroxaban, one edoxaban and one apixaban).Analysis showed no difference in the effectiveness of oral DTIs and standard anticoagulation in preventing recurrent pulmonary embolism (OR 1.02, 95% CI 0.50 to 2.04; two studies; 1602 participants; high quality evidence), recurrent venous thromboembolism (OR 0.93, 95% CI 0.52 to 1.66; two studies; 1602 participants; high quality evidence), deep vein thrombosis (DVT) (OR 0.79, 95% CI 0.29 to 2.13; two studies; 1602 participants; high quality evidence) and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; two studies; 1527 participants; high quality evidence).For oral factor Xa inhibitors, when we combined the three included studies together in meta-analyses, there was significant heterogeneity for recurrent pulmonary embolism (OR 1.08, 95% CI 0.46 to 2.56; two studies; 4509 participants; I(2) = 58%; moderate quality evidence). The oral factor Xa inhibitors were no more or less effective in the prevention of recurrent venous thromboembolism (OR 0.85, 95% CI 0.63 to 1.15; three studies; 6295 participants; high quality evidence), DVT (OR 0.72, 95% CI 0.39 to 1.32; two studies; 4509 participants; high quality evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; one study; 4817 participants; moderate quality evidence) or major bleeding (OR 0.97, 95% CI 0.59 to 1.62; two studies; 4507 participants; high quality evidence). None of the studies measured quality of life. AUTHORS' CONCLUSIONS: Moderate to high quality evidence suggests that there are no differences between DOACs and standard anticoagulation for the long-term treatment of pulmonary embolism, for the outcomes recurrent pulmonary embolism, recurrent venous thromboembolism, DVT, all-cause mortality and major bleeding.

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately 1 in 1,000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of novel oral anticoagulants (NOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the treatment of DVT. OBJECTIVES: To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the treatment of DVT. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. SELECTION CRITERIA: We included randomised controlled trials in which people with a DVT confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor for the treatment of DVT. DATA COLLECTION AND ANALYSIS: Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third review author (PK). We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and PE. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). MAIN RESULTS: We included 11 randomised controlled trials of 27,945 participants. Three studies tested oral DTIs (two dabigatran and one ximelagatran), while eight tested oral factor Xa inhibitors (four rivaroxaban, two apixaban and two edoxaban). We deemed all included studies to be of high methodological quality and low risk of bias. The quality of the evidence was graded as high as the outcomes were direct and effect estimates were consistent and precise, as reflected in the narrow CIs around the ORs. Meta-analysis of three studies (7596 participants) comparing oral DTIs with standard anticoagulation groups showed no difference in the rate of recurrent VTE (OR 1.09; 95% CI 0.80 to 1.49), recurrent DVT (OR 1.08; 95% CI 0.74 to 1.58), fatal PE (OR 1.00; 95% CI 0.27 to 3.70), non-fatal PE (OR 1.12; 95% CI 0.66 to 1.90) or all-cause mortality (OR 0.82; 95% CI 0.60 to 1.13). However, oral DTIs were associated with reduced bleeding (OR 0.68; 95% CI 0.47 to 0.98). Meta-analysis of eight studies (16,356 participants) comparing oral factor Xa inhibitors with standard anticoagulation demonstrated a similar rate of recurrent VTE between the two treatments (OR 0.89; 95% CI 0.73 to 1.07). Oral factor Xa inhibitors were associated with a lower rate of recurrent DVT (OR 0.75; 95% CI 0.57 to 0.98). However, this was a weak association, heavily dependent on one study. The rate of fatal (OR 1.20; 95% CI 0.71 to 2.03), non-fatal PE (OR 0.94; 95% CI 0.68 to 1.28) and all-cause mortality (OR 0.90; 95% CI 0.65 to 1.23) was similar between the two treatment groups. Oral factor Xa inhibitors were also associated with reduced bleeding (OR 0.57; 95% CI 0.43 to 0.76). None of the included studies measured post-thrombotic syndrome or health-related quality of life. AUTHORS' CONCLUSIONS: NOACs such as DTIs and factor Xa inhibitors may be an effective and safe alternative to conventional anticoagulation treatment for acute DVT.

Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment.

BACKGROUND: Peripheral arterial disease (PAD) is frequently treated by balloon angioplasty. Restenosis/reocclusion of the dilated segments occurs often, depending on length of occlusion, lower leg outflow, stage of disease and presence of cardiovascular risk factors. To prevent reocclusion, patients are treated with antithrombotic agents. This is an update of a review first published in 2005. OBJECTIVES: To determine whether any antithrombotic drug is more effective in preventing restenosis or reocclusion after peripheral endovascular treatment, compared to another antithrombotic drug, no treatment, placebo or other vasoactive drugs. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 February 2012) and CENTRAL (2012, Issue 1). SELECTION CRITERIA: We selected randomised controlled trials (RCTs). Participants were patients with symptomatic PAD treated by endovascular revascularisation of the pelvic or femoropopliteal arteries. Interventions were anticoagulant, antiplatelet or other vasoactive drug therapy compared with no treatment, placebo or any other vasoactive drug. Clinical endpoints were reocclusion, restenosis, amputation, death, myocardial infarction, stroke, major bleeding and other side effects, such as minor bleeding, puncture site bleeding, gastrointestinal side effects and haematoma. DATA COLLECTION AND ANALYSIS: We independently extracted and assessed details of the number of randomised patients, treatment, study design, patient characteristics and risk of bias. Analysis was based on intention-to-treat data. To examine the effects of outcomes such as reocclusion, restenosis, amputation and major bleeding, we computed odds ratios (OR) with 95% confidence intervals (CI) using a fixed-effect model. MAIN RESULTS: Twenty-two trials with a total of 3529 patients are included (14 in the original review and a further eight in this update). For the majority of comparisons, only one trial was available so results were rarely combined in meta-analyses. Individual trials were generally small and risk of bias was often unclear due to limitations in reporting. Three trials reported on drug versus placebo/control; results were consistently available for a maximum follow-up of only six months. At six months post intervention, a statistically significant reduction in reocclusion was found for high-dose acetylsalicylic acid (ASA) combined with dipyridamole (DIP) (OR 0.40, 95% CI 0.19 to 0.84), but not for low-dose ASA combined with DIP (OR 0.69, 95% CI 0.44 to 1.10; P = 0.12) nor in major amputations for lipo-ecraprost (OR 0.89, 95% CI 0.44 to 1.80). The remaining trials compared different drugs; results were more consistently available for a longer period of 12 months. At 12 months post intervention, no statistically significant difference in reocclusion/restenosis was detected for any of the following comparisons: high-dose ASA versus low-dose ASA (OR 0.98, 95% CI 0.64 to 1.48; P = 0.91), ASA/DIP versus vitamin K antagonists (VKA) (OR 0.65, 95% CI 0.40 to 1.06; P = 0.08), clopidogrel and aspirin versus low molecular weight heparin (LMWH) plus warfarin (OR 0.31, 95% CI 0.06 to 1.68; P = 0.18), suloctidil versus VKA: reocclusion (OR 0.59, 95% CI 0.20 to 1.76; P = 0.34), restenosis (OR 1.87, 95% CI 0.66 to 5.31; P = 0.24) and ticlopidine versus VKA (OR 0.71, 95% CI 0.37 to 1.36; P = 0.30). Treatment with cilostazol resulted in statistically significantly fewer reocclusions than ticlopidine (OR 0.32, 95% CI 0.13 to 0.76; P = 0.01). Compared with aspirin alone, LMWH plus aspirin significantly decreased occlusion/restenosis (by up to 85%) in patients with critical limb ischaemia (OR 0.15, 95% CI 0.06 to 0.42; P = 0.0003) but not in patients with intermittent claudication (OR 1.73, 95% CI 0.97 to 3.08; P = 0.06) and batroxobin plus aspirin reduced restenosis in diabetic patients (OR 0.28, 95% CI 0.13 to 0.60). Data on bleeding and other potential gastrointestinal side effects were not consistently reported, although there was some evidence that high-dose ASA increased gastrointestinal side effects compared with low-dose ASA, that clopidogrel and aspirin resulted in fewer major bleeding episodes compared with LMWH plus warfarin, and that abciximab resulted in more severe bleeding episodes. AUTHORS' CONCLUSIONS: There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reduced by use of antiplatelet drugs compared with placebo/control, but associated information on bleeding and gastrointestinal side effects is lacking. There is also some evidence of variation in effect according to different drugs with cilostazol reducing reocclusion/restenosis at 12 months compared with ticlopidine and both LMWH and batroxobin combined with aspirin appearing beneficial compared with aspirin alone. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale RCTs, stratified by severity of disease, are required.