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Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people and the third most common cause of mortality in surgical patients. People undergoing bariatric surgery have the additional risk factor of being overweight. Although VTE prophylaxis in surgical patients is well established, the best way to prevent VTE in those undergoing bariatric surgery is less clear.To evaluate the benefits and harms of pharmacological interventions (alone or in combination) on venous thromboembolism and other health outcomes in people undergoing bariatric surgery compared to the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention or started at a different time point, another pharmacological intervention, no intervention or placebo.We used standard, extensive Cochrane search methods. The latest search date was 1 November 2021.We included randomised controlled trials (RCTs) and quasi-RCTs in males and females of any age undergoing bariatric surgery comparing pharmacological interventions for VTE (alone or in combination) with the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention started at a different time point, a different pharmacological intervention, no treatment or placebo.We used standard Cochrane methods. Our primary outcomes were 1. VTE and 2. major bleeding. Our secondary outcomes were 1. all-cause mortality, 2. VTE-related mortality, 3. PE, 4. DVT, 5. adverse effects and 6. quality of life. We used GRADE to assess certainty of evidence for each outcome.We included seven RCTs with 1045 participants. Data for meta-analysis were available from all participants. Four RCTs (597 participants) compared higher-dose heparin to standard-dose heparin: one of these studies (139 participants) used unfractionated heparin (UFH) and the other three (458 participants) used low-molecular-weight heparin (LMWH). One study compared heparin versus pentasaccharide (198 participants), and one study compared starting heparin before versus after bariatric surgery (100 participants). One study (150 participants) compared combined mechanical and pharmacological (enoxaparin) prophylaxis versus mechanical prophylaxis alone. The duration of the interventions ranged from seven to 15 days, and follow-up ranged from 10 to 180 days. Higher-dose heparin versus standard-dose heparin Compared to standard-dose heparin, higher-dose heparin may result in little or no difference in the risk of VTE (RR 0.55, 95% CI 0.05 to 5.99; 4 studies, 597 participants) or major bleeding (RR 1.19, 95% CI 0.48 to 2.96; IHigher-dose heparin may make little or no difference to venous thromboembolism or major bleeding in people undergoing bariatric surgery when compared to standard-dose heparin. Heparin may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to pentasaccharide. There are inadequate data to draw conclusions about the effects of heparin compared to pentasaccharide on major bleeding. Starting prophylaxis with heparin 12 hours before bariatric surgery may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to starting heparin after bariatric surgery. There are inadequate data to draw conclusions about the effects of heparin started before versus after surgery on major bleeding. Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery when compared to mechanical prophylaxis alone. No data are available relating to major bleeding. The certainty of the evidence is limited by small sample sizes, few or no events, and risk of bias concerns. Future trials must be sufficiently large to enable analysis of relevant clinical outcomes, and should standardise the time of treatment and follow-up. They should also address the effect of direct oral anticoagulants and antiplatelets, preferably grouping them according to the type of intervention.

Antiplatelet agents may be useful for the treatment of deep venous thrombosis (DVT) when used in addition to best medical practice (BMP), which includes anticoagulation, compression stockings, and clinical care such as physical exercise, skin hydration, etc. Antiplatelet agents could minimise complications such as post-thrombotic syndrome (PTS) and pulmonary embolism (PE). They may also reduce the recurrence of the disease (recurrent venous thromboembolism (recurrent VTE)). However, antiplatelet agents may increase the likelihood of bleeding events.To assess the effects of antiplatelet agents in addition to current BMP compared to current BMP (with or without placebo) for the treatment of DVT.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 7 December 2021. The review authors searched LILACS and IBECS databases (15 December 2021) and also checked the bibliographies of included trials for further references to relevant trials, and contacted specialists in the field, manufacturers and authors of the included trials.We considered randomised controlled trials (RCTs) examining antiplatelet agents compared to BMP following initial standard anticoagulation treatment for DVT. We included studies where antiplatelet agents were given in addition to current BMP compared to current BMP (with or without placebo) for the treatment of DVT (acute: treatment started within 21 days of symptom onset; chronic: treatment started after 21 days of symptom onset). We evaluated only RCTs where the antiplatelet agents were the unique difference between the groups (intervention and control).We used standard Cochrane methodological procedures. Two review authors independently extracted data and assessed risk of bias of the trials. Any disagreements were resolved by discussion with a third review author. We calculated outcome effects using risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) and the number needed to treat to benefit (NNTB).We included six studies with 1625 eligible participants, with data up to 37.2 months of follow-up. For one preplanned comparison (i.e. antiplatelet agents plus BMP versus BMP plus placebo) for acute DVT we identified no eligible studies for inclusion. In acute DVT, antiplatelet agents plus BMP versus BMP alone was assessed by one study (500 participants), which reported on four outcomes until 6 months of follow-up. There were no deaths and no cases of major bleeding reported. The participants who received antiplatelet agents showed a lower risk of PTS (RR 0.74, 95% CI 0.61 to 0.91; 1 study, 500 participants; very low-certainty evidence). The control group presented a lower risk of adverse events compared to the intervention group (RR 2.88, 95% CI 1.06 to 7.80; 1 study, 500 participants; very low-certainty evidence). This study did not provide information for recurrent VTE or PE. In chronic DVT, antiplatelet agents plus BMP versus BMP alone was assessed by one study (224 participants). The study authors reported four relevant outcomes, three of which (major bleeding, mortality and adverse events) showed no events during the 3 years of follow-up. Therefore, an effect estimate could only be reported for recurrent VTE, favouring antiplatelet agents plus BMP versus BMP alone (RR 0.12, 95% CI 0.05 to 0.34; 1 study, 224 participants; very low-certainty evidence). For the outcomes PE and PTS, this study did not present information which could be used for analysis. In chronic DVT, antiplatelet agents plus BMP versus BMP plus placebo was assessed by four studies (901 participants). The meta-analysis of this pooled data showed a lower risk of recurrent VTE for the antiplatelet agents group (RR 0.65, 95%, CI 0.43 to 0.96; NNTB = 14; low-certainty evidence). For major bleeding, we found no clear difference between placebo and intervention groups until 37.2 months of follow-up (RR 0.98, 95% CI 0.29 to 3.34; 1 study, 583 participants; moderate-certainty evidence). In PE fatal/non-fatal outcome, we found no clear difference with the use of antiplatelet agents (RR 0.52, 95% CI 0.23 to 1.14; 1 study, 583 participants; moderate-certainty evidence). For all-cause mortality, the overall effect of antiplatelet agents did not differ from the placebo group (RR 0.48, 95% CI 0.21 to 1.06; 3 studies, 649 participants; moderate-certainty evidence). The adverse events outcome did not show a clear difference (RR 1.57, 95% CI 0.34 to 7.19; 2 studies, 621 participants; moderate-certainty evidence). There is no assessment of PTS in these studies. We downgraded the certainty of evidence for risk of bias, indirectness, imprecision and publication bias.In chronic DVT settings, following the initial standard treatment with anticoagulants, there is low-certainty evidence that antiplatelet agents in addition to BMP may reduce recurrent VTE, (NNTB = 14) when compared to BMP plus placebo. Moderate-certainty evidence shows no clear difference in adverse events, major bleeding and PE when antiplatelet agents are used in addition to BMP compared to BMP plus placebo. In acute and chronic DVT settings, following the initial standard treatment with anticoagulants, we can draw no conclusions for antiplatelet agents in addition to BMP compared to BMP alone due to very low-certainty evidence. Trials of high methodological quality, that are large and of sufficient duration to detect significant clinical outcomes are needed. Trials should ideally last more than 4 years in order to estimate the long-term effect of antiplatelet agents. Trials should include people with acute and chronic DVT and provide relevant individual data, such as the outcome for each index event (DVT or PE), the use of an inferior vena cava (IVC) filter, whether the DVT is provoked or unprovoked, and the age of participants.

Coronavirus disease 2019 (COVID-19) is a serious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary manifestation is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis in people with COVID-19. This disease also causes thromboembolic events, such as pulmonary embolism, deep venous thrombosis, arterial thrombosis, catheter thrombosis, and disseminated intravascular coagulopathy. Recent studies have indicated a worse prognosis for people with COVID-19 who developed thromboembolism. Anticoagulants are medications used in the prevention and treatment of venous or arterial thromboembolic events. Several drugs are used in the prophylaxis and treatment of thromboembolic events, such as heparinoids (heparins or pentasaccharides), vitamin K antagonists and direct anticoagulants. Besides their anticoagulant properties, heparinoids have an additional anti-inflammatory potential, that may affect the clinical evolution of people with COVID-19. Some practical guidelines address the use of anticoagulants for thromboprophylaxis in people with COVID-19, however, the benefit of anticoagulants for people with COVID-19 is still under debate.To assess the effects of prophylactic anticoagulants versus active comparator, placebo or no intervention, on mortality and the need for respiratory support in people hospitalised with COVID-19.We searched CENTRAL, MEDLINE, Embase, LILACS and IBECS databases, the Cochrane COVID-19 Study Register and medRxiv preprint database from their inception to 20 June 2020. We also checked reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials.Randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cohort studies that compared prophylactic anticoagulants (heparin, vitamin K antagonists, direct anticoagulants, and pentasaccharides) versus active comparator, placebo or no intervention for the management of people hospitalised with COVID-19. We excluded studies without a comparator group. Primary outcomes were all-cause mortality and need for additional respiratory support. Secondary outcomes were mortality related to COVID-19, deep vein thrombosis (DVT), pulmonary embolism, major bleeding, adverse events, length of hospital stay and quality of life.We used standard Cochrane methodological procedures. We used ROBINS-I to assess risk of bias for non-randomised studies (NRS) and GRADE to assess the certainty of evidence. We reported results narratively.We identified no RCTs or quasi-RCTs that met the inclusion criteria. We included seven retrospective NRS (5929 participants), three of which were available as preprints. Studies were conducted in China, Italy, Spain and the USA. All of the studies included people hospitalised with COVID-19, in either intensive care units, hospital wards or emergency departments. The mean age of participants (reported in 6 studies) ranged from 59 to 72 years. Only three included studies reported the follow-up period, which varied from 8 to 35 days. The studies did not report on most of our outcomes of interest: need for additional respiratory support, mortality related to COVID-19, DVT, pulmonary embolism, adverse events, and quality of life. Anticoagulants (all types) versus no treatment (6 retrospective NRS, 5685 participants) One study reported a reduction in all-cause mortality (adjusted odds ratio (OR) 0.42, 95% confidence interval (CI) 0.26 to 0.66; 2075 participants). One study reported a reduction in mortality only in a subgroup of 395 people who required mechanical ventilation (hazard ratio (HR) 0.86, 95% CI 0.82 to 0.89). Three studies reported no differences in mortality (adjusted OR 1.64, 95% CI 0.92 to 2.92; 449 participants; unadjusted OR 1.66, 95% CI 0.76 to 3.64; 154 participants and adjusted risk ratio (RR) 1.15, 95% CI 0.29 to 2.57; 192 participants). One study reported zero events in both intervention groups (42 participants). The overall risk of bias for all-cause mortality was critical and the certainty of the evidence was very low. One NRS reported bleeding events in 3% of the intervention group and 1.9% of the control group (OR 1.62, 95% CI 0.96 to 2.71; 2773 participants; low-certainty evidence). Therapeutic-dose anticoagulants versus prophylactic-dose anticoagulants (1 retrospective NRS, 244 participants) The study reported a reduction in all-cause mortality (adjusted HR 0.21, 95% CI 0.10 to 0.46) and a lower absolute rate of death in the therapeutic group (34.2% versus 53%). The overall risk of bias for all-cause mortality was serious and the certainty of the evidence was low. The study also reported bleeding events in 31.7% of the intervention group and 20.5% of the control group (OR 1.8, 95% CI 0.96 to 3.37; low-certainty evidence). Ongoing studies We found 22 ongoing studies in hospital settings (20 RCTs, 14,730 participants; 2 NRS, 997 participants) in 10 different countries (Australia (1), Brazil (1), Canada (2), China (3), France (2), Germany (1), Italy (4), Switzerland (1), UK (1) and USA (6)). Twelve ongoing studies plan to report mortality and six plan to report additional respiratory support. Thirteen studies are expected to be completed in December 2020 (6959 participants), eight in July 2021 (8512 participants), and one in December 2021 (256 participants). Four of the studies plan to include 1000 participants or more.There is currently insufficient evidence to determine the risks and benefits of prophylactic anticoagulants for people hospitalised with COVID-19. Since there are 22 ongoing studies that plan to evaluate more than 15,000 participants in this setting, we will add more robust evidence to this review in future updates.INTRODUÇÃO: A doença coronavírus 2019 (COVID‐19) é uma doença grave causada por pelo coronavírus 2 da síndrome respiratória aguda grave (SARS‐CoV‐2). Sua manifestação primária é a insuficiência respiratória, que também pode estar relacionada à microtrombose pulmonar difusa vista em pacientes com COVID‐19. A doença também causa eventos tromboembólicos, tais como embolia pulmonar, trombose venosa profunda, trombose arterial, trombose de cateter e coagulopatia intravascular disseminada. Estudos recentes indicam que os pacientes com COVID‐19 que desenvolvem tromboembolismo têm um pior prognóstico. Os anticoagulantes são medicamentos utilizados na prevenção e no tratamento de eventos tromboembólicos venosos ou arteriais. Vários medicamentos são utilizados na profilaxia e no tratamento de eventos tromboembólicos, tais como heparinoides (heparinas ou pentasacarídeos), antagonistas da vitamina K e anticoagulantes diretos. Além de suas propriedades anticoagulantes, os heparinoides têm um potencial anti‐inflamatório adicional. Essa propriedade poderia afetar a evolução clínica dos pacientes com COVID‐19. Algumas diretrizes clínicas abordam o uso de anticoagulantes para tromboprofilaxia em pacientes com COVID‐19. Porém, o benefício dos anticoagulantes para esses pacientes ainda está em debate. OBJETIVOS: Avaliar os efeitos do uso de anticoagulantes profiláticos versus um comparador ativo, placebo ou nenhuma intervenção, na mortalidade e na necessidade de suporte respiratório em pacientes internados com COVID‐19. MÉTODOS DE BUSCA: Fizemos buscas nas seguintes bases de dados eletrônicas desde seu início até 20 de junho de 2020: CENTRAL, MEDLINE, Embase, LILACS e IBECS, Cochrane COVID‐19 Study Register e a base de dados de pré‐impressão medRxiv. Também revisamos as listas de referências das revisões sistemáticas relevantes e contatamos especialistas da área em busca de referências adicionais de ensaios clínicos. CRITÉRIO DE SELEÇÃO: Incluímos ensaios clínicos randomizados controlados (ECRs), quasi‐randomizados, ECR tipo cluster e coortes. Os estudos deveriam comparar o uso de anticoagulantes profiláticos (heparina, antagonistas da vitamina K, anticoagulantes diretos e pentasacarídeos) versus um comparador ativo, placebo ou nenhuma intervenção, em pacientes hospitalizadas com COVID‐19. Excluímos estudos sem um grupo de comparação. Os desfechos primários foram mortalidade por todas as causas e a necessidade de suporte respiratório adicional. Os desfechos secundários foram mortalidade relacionada à COVID‐19, trombose venosa profunda (TVP), embolia pulmonar, sangramento importante, eventos adversos, tempo de internação hospitalar e qualidade de vida. COLETA DOS DADOS E ANÁLISES: Adotamos os procedimentos metodológicos padrão da Cochrane. Utilizamos o ROBINS‐I para avaliar o risco de viés dos estudos não randomizados (NRS) e o GRADE para avaliar a certeza da evidência. Apresentamos os resultados de forma narrativa. PRINCIPAIS RESULTADOS: Não identificamos nenhum ECR ou quasi‐randomizado que preenchessem os critérios de inclusão. Incluímos sete estudos retrospectivos não randomizados (5929 participantes). Três desses estudos estavam disponíveis como pré‐impressões. Os estudos foram conduzidos na China, Itália, Espanha e nos EUA. Todos os estudos incluíram pessoas hospitalizadas com COVID‐19, em unidades de terapia intensiva, enfermarias ou departamentos de emergência. A idade média dos participantes (relatada em 6 estudos) variou de 59 a 72 anos. Apenas três estudos relataram qual foi o período de acompanhamento, que variou de 8 a 35 dias. Os estudos não relataram a maioria dos nossos desfechos de interesse: necessidade de suporte respiratório adicional, mortalidade relacionada à COVID‐19, TVP, embolia pulmonar, eventos adversos e qualidade de vida. Anticoagulantes (todos os tipos) versus nenhum tratamento (6 estudos não randomizados retrospectivos, 5685 participantes) Um estudo relatou redução na mortalidade por todas as causas (odds ratio ajustado (OR) 0,42, intervalo de confiança (IC) 95% 0,26 a 0,66; 2075 participantes). Um estudo relatou redução na mortalidade apenas num subgrupo de 395 pessoas que necessitaram de ventilação mecânica (hazard ratio (HR) 0,86, IC 95% 0,82 a 0,89). Três estudos não encontraram diferenças na mortalidade (OR ajustado 1,64, IC 95% 0,92 a 2,92; 449 participantes; OR não ajustado 1,66, IC 95% 0,76 a 3,64; 154 participantes e razão de risco ajustada (RR) 1,15, IC 95% 0,29 a 2,57; 192 participantes). Um estudo não teve nenhum caso de morte nos dois grupos (42 participantes). O risco geral de viés para mortalidade por todas as causas é crítico e a qualidade (certeza) da evidência é muito baixa. Um estudo não randomizado relatou que 3% dos participantes do grupo intervenção e 1,9% daqueles do grupo controle tiveram eventos de sangramento (OR 1,62, IC 95% 0,96 a 2,71; 2773 participantes; evidência de baixa qualidade). Anticoagulantes em dose terapêutica versus anticoagulantes em dose profilática (1 estudo retrospectivo não randomizado, 244 participantes) O estudo relatou redução na mortalidade por todas as causas (HR ajustado 0,21, IC 95% 0,10 a 0,46) e menor taxa absoluta de morte no grupo tratado com dose terapêutica (34,2% versus 53%). O risco geral de viés para mortalidade por todas as causas é grave e a qualidade da evidência é baixa. O estudo também relatou eventos de sangramento em 31,7% dos participantes do grupo intervenção e em 20,5% daqueles no grupo controle (OR 1,8, IC 95% 0,96 a 3,37; evidência de baixa qualidade). Estudos em andamento Encontramos 22 estudos em andamento em ambientes hospitalares (20 ECRs, 14.730 participantes; 2 estudos não randomizados, 997 participantes). Esses estudos estão sendo realizados em 10 países diferentes: Austrália (1), Brasil (1), Canadá (2), China (3), França (2), Alemanha (1), Itália (4), Suíça (1), Reino Unido (1) e EUA (6). Doze estudos em andamento pretendem avaliar mortalidade e seis vão avaliar suporte respiratório adicional. Espera‐se que 13 estudos sejam concluídos em dezembro de 2020 (6959 participantes), oito em julho de 2021 (8512 participantes) e um em dezembro de 2021 (256 participantes). Quatro dos estudos planejam incluir 1000 participantes ou mais. CONCLUSÃO DOS AUTORES: Atualmente não há evidência suficiente sobre os riscos e benefícios do uso de anticoagulantes profiláticos para pacientes hospitalizados com COVID‐19. Como há 22 estudos em andamento que planejam avaliar mais de 15.000 participantes internados, a evidência das futuras atualizações desta revisão será mais robusta.บทนำ: โรคโคโรนาไวรัส 2019 (COVID‐19) เป็นโรคร้ายแรงที่เกิดจากกลุ่มอาการทางเดินหายใจเฉียบพลันรุนแรง coronavirus 2 (SARS‐CoV‐2) อาการหลักคือ ระบบทางเดินหายใจทำงานไม่เพียงพอ ซึ่งอาจเกี่ยวข้องกับการเกิด microthrombosis ในปอดแบบกระจายในผู้ที่เป็น COVID‐19 โรคนี้ยังทำให้เกิดภาวะลิ่มเลือดอุดตัน เช่นเส้นเลือดในปอดอุดตัน หลอดเลือดดำส่วนลึกอุดตัน เส้นเลือดแดงอุดตัน สายสวนอุดตัน และการแข็งตัวของหลอดเลือดผิดปกติทั่วร่างกาย การศึกษาเมื่อเร็ว ๆ นี้ชี้ให้เห็นการพยากรณ์โรคที่แย่ลงสำหรับผู้ที่ติดเชื้อ COVID‐19 ซึ่งเป็นโรคลิ่มเลือดอุดตัน ยาต้านการแข็งตัวของเลือดเป็นยาที่ใช้ในการป้องกันและรักษาภาวะลิ่มเลือดอุดตันในหลอดเลือดดำหรือหลอดเลือดแดง มีการใช้ยาหลายชนิดในการป้องกันและการรักษาภาวะลิ่มเลือดอุดตันเช่น heparinoids (heparins หรือ pentasaccharides) ยาต้านวิตามินเค และยาต้านการแข็งตัวของเลือดโดยตรง นอกจากคุณสมบัติในการต้านการแข็งตัวของเลือดแล้ว heparinoids ยังมีฤทธิ์ต้านการอักเสบเพิ่มเติม ซึ่งอาจส่งผลต่อการเปลี่ยนแปลงทางคลินิกของผู้ที่เป็น COVID‐19 แนวทางปฏิบัติบางส่วน กล่าวถึงการใช้ยาต้านการแข็งตัวของเลือดในผู้ที่เป็นโรค COVID‐19 อย่างไรก็ตามประโยชน์ของยาต้านการแข็งตัวของเลือดสำหรับผู้ที่ติดเชื้อ COVID‐19 ยังคงเป็นที่ถกเถียงกันอยู่ วัตถุประสงค์: เพื่อประเมินผลของยาต้านการแข็งตัวของเลือด เมื่อเทียบกับตัวเปรียบเทียบที่ออกฤทธิ์ ยาหลอกหรือไม่มีการรักษา ต่อการเสียชีวิตและความจำเป็นในการช่วยหายใจในผู้ที่เข้ารับการรักษาในโรงพยาบาลด้วย COVID‐19 วิธีการสืบค้น: เราสืบค้นฐานข้อมูล CENTRAL, MEDLINE, Embase, LILACS และ IBECS, Cochrane COVID‐19 Study Register และฐานข้อมูล medRxiv preprint ตั้งแต่เริ่มต้นจนถึง 20 มิถุนายน 2020 นอกจากนี้เรายังตรวจสอบรายการอ้างอิงของการทบทวนวรรณกรรมอย่างเป็นระบบที่เกี่ยวข้องที่พบ และติดต่อผู้เชี่ยวชาญในสาขานั้นสำหรับเอกสารอ้างอิงเพิ่มเติมเกี่ยวกับการทดลอง เกณฑ์การคัดเลือก: การทดลองแบบสุ่มที่มีกลุ่มควบคุม (RCTs), quasi‐RCTs, cluster‐RCTs และการศึกษาแบบ cohort ที่เปรียบเทียบยาต้านการแข็งตัวของเลือด (heparin, vitamin K antagonists, direct anticoagulants และ pentasaccharides) เทียบกับ active comparator, placebo หรือไม่มีการรักษาใด ๆ สำหรับการดูแลผู้ที่เข้ารับการรักษาในโรงพยาบาลด้วย COVID ‐19 เราไม่รวมการศึกษาที่ไม่มีกลุ่มเปรียบเทียบ ผลลัพธ์หลักคือการเสียชีวิตจากทุกสาเหตุ และความจำเป็นต้องได้รับการช่วยหายใจเพิ่มเติม ผลลัพธ์รอง ได้แก่ การเสียชีวิตจาก COVID‐19, ลิ่มเลือดอุดตันในหลอดเลือดดำ (DVT), เส้นเลือดอุดตันในปอด, เลือดออกที่สำคัญ, เหตุการณ์ไม่พึงประสงค์, ระยะเวลาในการนอนโรงพยาบาลและคุณภาพชีวิต การรวบรวมและวิเคราะห์ข้อมูล: เราใช้ระเบียบวิธีการวิจัยตามมาตรฐานของ Cochrane เราใช้ ROBINS‐I เพื่อประเมินความเสี่ยงของอคติสำหรับการศึกษาแบบไม่สุ่ม (NRS) และ GRADE เพื่อประเมินความเชื่อมั่นของหลักฐาน เรารายงานผลแบบบรรยาย ผลการวิจัย: เราไม่พบ RCT หรือ quasi RCT ที่ตรงตามเกณฑ์การคัดเลือก เรารวม retrospective NRS 7 รายการ (ผู้เข้าร่วม 5929 คน) ซึ่ง 3 รายการ อยู่ในรูปแบบของฉบับร่างหรือเป็นฉบับก่อนที่ตีพิมพ์ การศึกษาดำเนินการในจีน อิตาลี สเปน และสหรัฐอเมริกา การศึกษาทั้งหมดรวมผู้ที่เข้ารับการรักษาในโรงพยาบาลด้วย COVID‐19 ทั้งในหอผู้ป่วยหนัก หอผู้ป่วยในโรงพยาบาลหรือแผนกฉุกเฉิน อายุเฉลี่ยของผู้เข้าร่วมการศึกษา (รายงานใน 6 การศึกษา) อยู่ระหว่าง 59 ถึง 72 ปี มีการศึกษาเพียง 3 รายการเท่านั้นที่รายงานระยะเวลาติดตามผลซึ่งแตกต่างกันไปตั้งแต่ 8 ถึง 35 วัน การศึกษาไม่ได้รายงานเกี่ยวกับผลลัพธ์ที่น่าสนใจส่วนใหญ่ของเรา: ความต้องการการช่วยหายใจเพิ่มเติม การเสียชีวิตที่เกี่ยวข้องกับ COVID‐19, DVT, เส้นเลือดอุดตันในปอด, เหตุการณ์ไม่พึงประสงค์และคุณภาพชีวิต ยาต้านการแข็งตัวของเลือด (ทุกประเภท) เทียบกับไม่มีการรักษา (Retrospective NRS 6 รายการ ผู้เข้าร่วม 5685 คน) การศึกษา 1 รายการรายงานว่าการเสียชีวิตจากทุกสาเหตุลดลง (อัตราส่วนที่ปรับแล้ว (OR) 0.42, ช่วงความเชื่อมั่น 95% (CI) 0.26 ถึง 0.66; ผู้เข้าร่วม 2075 คน) การศึกษา 1 รายการรายงานว่าการลดลงของอัตราการตายเฉพาะในกลุ่มย่อย 395 คนที่ต้องใช้เครื่องช่วยหายใจ (harzard ratio (HR) 0.86, 95% CI 0.82 ถึง 0.89) การศึกษา 3 รายการรายงานว่าไม่มีความแตกต่างในการตาย (adjusted OR 1.64, 95% CI 0.92 ถึง 2.92; ผู้เข้าร่วม 449 คน; unadjusted OR 1.66, 95% CI 0.76 ถึง 3.64; ผู้เข้าร่วม 154 คนและ adjusted risk ratio (RR) 1.15, 95% CI 0.29 ถึง 2.57; ผู้เข้าร่วม 192 คน) การศึกษา 1 รายการรายงานว่าไม่มีเหตุการณ์ในทั้งสองกลุ่มการรักษา (ผู้เข้าร่วม 42 คน) ความเสี่ยงของการมีอคติโดยรวมสำหรับการเสียชีวิตจากทุกสาเหตสูงมาก และความเชื่อมั่นของหลักฐานต่ำมาก NRS 1 รายการรายงานุการเลือดออกใน 3% ของกลุ่มรักษา และ 1.9% ของกลุ่มควบคุม (OR 1.62, 95% CI 0.96 ถึง 2.71; ผู้เข้าร่วม 2773 คน; หลักฐานที่มีความเชื่อมั่นต่ำ) ยาต้านการแข็งตัวของเลือดในขนาดที่ใช้รักษาเทียบกับยาต้านการแข็งตัวของเลือดในขนาดที่ใช้ป้องกันโรค (1 retrospective NRS ผู้เข้าร่วม 244 คน) การศึกษารายงานการลดลงของการเสียชีวิตจากทุกสาเหตุ (adjusted HR 0.21, 95% CI 0.10 ถึง 0.46) และอัตราการเสียชีวิตลดลงในกลุ่มรักษา (34.2% เทียบกับ 53%) ความเสี่ยงโดยรวมของอคติสำหรับการเสียชีวิตจากทุกสาเหตสูงมาก และความเชื่อมั่นของหลักฐานต่ำ การศึกษาได้รายงานการมีเลือดออกใน 31.7% ของกลุ่มรักษา และ 20.5% ของกลุ่มควบคุม (OR 1.8, 95% CI 0.96 ถึง 3.37; หลักฐานที่มีความเชื่อมั่นต่ำ) การศึกษาที่กำลังดำเนินการ เราพบการศึกษาที่กำลังดำเนินการ 22 เรื่องในสถานพยาบาล (20 RCTs ผู้เข้าร่วม 14,730 คน; 2 NRS ผู้เข้าร่วม 997 คน) ใน 10 ประเทศ (ออสเตรเลีย (1), บราซิล (1), แคนาดา (2), จีน (3), ฝรั่งเศส (2) , เยอรมนี (1), อิตาลี (4), สวิตเซอร์แลนด์ (1), สหราชอาณาจักร (1) และสหรัฐอเมริกา (6)) การศึกษาที่กำลังดำเนินการ 12 รายการวางแผนที่จะรายงานการเสียชีวิต และ 6 รายการวางแผนที่จะรายงานการสนับสนุนทางเดินหายใจเพิ่มเติม การศึกษา 13 รายการคาดว่าจะแล้วเสร็จในเดือนธันวาคม 2020 (ผู้เข้าร่วม 6959 คน) 8 การศึกษาในเดือนกรกฎาคม 2021 (ผู้เข้าร่วม 8512 คน) และหนึ่งในเดือนธันวาคม 2021 (ผู้เข้าร่วม 256 คน) การศึกษา 4 รายการมีแผนจะรวมผู้เข้าร่วม 1000 คนขึ้นไป ข้อสรุปของผู้วิจัย: ขณะนี้ยังไม่มีหลักฐานเพียงพอที่จะประเมินุความเสี่ยงและประโยชน์ของยาต้านการแข็งตัวของเลือดสำหรับผู้ที่เข้ารับการรักษาในโรงพยาบาลด้วย COVID‐19 เนื่องจากมีการศึกษาที่กำลังดำเนินการ 22 รายการที่วางแผนจะประเมินผู้เข้าร่วมมากกว่า 15,000 คนในบริบทนี้ เราจะเพิ่มหลักฐานที่ชัดเจนยิ่งขึ้นในการตรวจสอบนี้ในการอัปเดตในอนาคต.پیشینه: بیماری کروناویروس 2019 (COVID‐19) یک بیماری جدی است که توسط سندرم حاد تنفسی شدید کروناویروس ‐2 (SARS‐CoV‐2) ایجاد می‌شود. تظاهرات اولیه آن نارسایی تنفسی است که می‌تواند با میکروترومبوز منتشر ریوی در افراد مبتلا به COVID‐19 نیز مرتبط باشد. این بیماری همچنین باعث وقوع حوادث ترومبوآمبولیک، مانند آمبولی ریوی، ترومبوز وریدی عمقی، ترومبوز شریانی، ترومبوز کاتتر، و انعقاد داخل عروقی منتشر می‌شود. مطالعات اخیر پیش‌آگهی بدتری را برای افراد مبتلا به COVID‐19 که به ترومبوآمبولی دچار شده‌اند، نشان داده‌اند. آنتی‌کوآگولانت‌ها، داروهایی هستند که در پیشگیری و درمان حوادث ترومبوآمبولی وریدی یا شریانی استفاده می‌شوند. داروهای متعددی در پروفیلاکسی و درمان حوادث ترومبوآمبولیک استفاده می‌شوند، مانند هپارینوئیدها (هپارین‌ها یا پنتاساکاریدها (pentasaccharides))، آنتاگونیست‌های ویتامین K و آنتی‌کوآگولانت‌های مستقیم. هپارینوئیدها، علاوه بر خاصیت آنتی‌کوآگولانتی خود، پتانسیل ضد‐التهابی بیشتری هم دارند، که ممکن است بر تکامل بالینی افراد مبتلا به COVID‐19 تأثیر بگذارد. برخی از دستورالعمل‌های عملی استفاده از آنتی‌کوآگولانت‌ها را برای ترومبوپروفیلاکسی در افراد مبتلا به COVID‐19 توصیه می‌کنند، با این حال، مزیت آنتی‌کوآگولانت‌ها برای افراد مبتلا به COVID‐19 هنوز مورد بحث است. اهداف: ارزیابی اثرات آنتی‌کوآگولانت‌های پروفیلاکتیک در مقایسه با مقایسه کننده فعال، دارونما (placebo) یا عدم مداخله، بر مورتالیتی و نیاز به حمایت تنفسی در بیماران بستری با COVID‐19. روش‌های جست‌وجو: ما بانک‌های اطلاعاتی CENTRAL؛ MEDLINE؛ Embase؛ LILACS و IBECS، پایگاه ثبت مطالعات COVID‐19 در کاکرین، و بانک اطلاعاتی پیش از چاپ medRxiv را از بدو تاسیس آنها تا 20 جون 2020 جست‌وجو کردیم. همچنین فهرست منابع مرورهای سیستماتیک مرتبط را که شناسایی شدند، بررسی کرده و برای یافتن منابع بیشتر، با متخصصان این زمینه تماس گرفتیم. معیارهای انتخاب: کارآزمایی‌های تصادفی‌سازی و کنترل شده (randomised controlled trials; RCTs)، شبه‐RCTها، RCTهای خوشه‌ای و مطالعات کوهورت که آنتی‌کوآگولانت‌های پروفیلاکتیک (هپارین، آنتاگونیست‌ویتامین K، آنتی‌کوآگولانت‌های مستقیم و پنتاساکاریدها) را در برابر مقایسه کننده فعال، دارونما یا عدم مداخله برای مدیریت افراد بستری با COVID‐19 مقایسه کردند. ما مطالعات بدون گروه مقایسه کننده را حذف کردیم. پیامدهای اولیه عبارت بودند از مورتالیتی به هر علتی و نیاز به حمایت تنفسی بیشتر. پیامدهای ثانویه، مورتالیتی مرتبط با COVID‐19، ترومبوز ورید عمقی (DVT)، آمبولی ریوی، خونریزی عمده، عوارض جانبی، طول مدت بستری در بیمارستان و کیفیت زندگی بودند. گردآوری و تجزیه‌وتحلیل داده‌ها: از پروسیجرهای استاندارد روش‌شناسی کاکرین استفاده شد. ما از ROBINS‐I برای ارزیابی خطر سوگیری (bias) در مطالعات غیر‐تصادفی‌سازی شده (NRS) و روش درجه‌‏بندی توصیه‏، ارزیابی، توسعه و ارزشیابی (GRADE) برای ارزیابی قطعیت شواهد استفاده کردیم. نتایج را به صورت روایت‌گونه گزارش کردیم. نتایج اصلی: ما هیچ RCT‌ یا شبه‐RCTای را شناسایی نکردیم که معیارهای ورود را داشته باشند. ما هفت NRS گذشته‌نگر (5929 شرکت‌کننده) را وارد کردیم، که سه مورد از آنها به صورت پیش از چاپ (preprint) در دسترس بودند. مطالعات در چین، ایتالیا، اسپانیا و ایالات متحده انجام شدند. همه مطالعات شامل افرادی بودند که با COVID‐19، در بخش‌های مراقبت ویژه، بخش‌های بیمارستان یا بخش‌های اورژانس، بستری بودند. میانگین سنی شرکت‌کنندگان (در 6 مطالعه گزارش شد) از 59 تا 72 سال متغیر بود. فقط سه مطالعه وارد شده، دوره پیگیری را گزارش کردند، که از 8 تا 35 روز متفاوت بود. این مطالعات اغلب پیامدهای مورد نظر ما را گزارش نکردند: نیاز به حمایت تنفسی بیشتر، مورتالیتی مرتبط با COVID‐19؛ DVT، آمبولی ریوی، عوارض جانبی، و کیفیت زندگی. آنتی‌کوآگولانت‌ها (همه انواع) در مقابل عدم درمان (شش NRS گذشته‌نگر، 5685 شرکت‌کننده) یک مطالعه کاهش را در مورتالیتی به هر علتی گزارش کرد (نسبت شانس تعدیل شده (OR): 0.42؛ 95% فاصله اطمینان (CI): 0.26 تا 0.66؛ 2075 شرکت‌کننده). یک مطالعه کاهش مورتالیتی را فقط در زیرگروهی با 395 نفر که به تهویه مکانیکی نیاز داشتند، گزارش کرد (نسبت خطر (HR): 0.86؛ 95% CI؛ 0.82 تا 0.89). سه مطالعه هیچ تفاوتی را در میزان مورتالیتی گزارش نکردند (OR تعدیل ‌شده: 1.64؛ 95% CI؛ 0.92 تا 2.92؛ 449 شرکت‌کننده؛ OR تعدیل نشده: 1.66؛ 95% CI؛ 0.76 تا 3.64؛ 154 شرکت‌کننده و نسبت خطر (RR) تعدیل شده: 1.15؛ 95% CI؛ 0.29 تا 2.57؛ 192 شرکت‌کننده). یک مطالعه وقوع صفر مورد حوادث را در هر دو گروه مداخله (42 شرکت‌کننده) گزارش کرد. خطر کلی سوگیری برای مورتالیتی به هر علتی، بحرانی و قطعیت شواهد بسیار پائین بود. یک NRS، حوادث خونریزی دهنده را در 3% از شرکت‏‌کنندگان گروه مداخله و 1.9% از افراد گروه کنترل گزارش کرد (OR: 1.62؛ 95% CI؛ 0.96 تا 2.71؛ 2773 شرکت‌کننده؛ شواهد با قطعیت پائین). آنتی‌کوآگولانت‌ها با دوز درمانی در مقابل آنتی‌کوآگولانت‌ها با دوز پروفیلاکتیک (یک NRS گذشته‌نگر، 244 شرکت‌کننده) این مطالعه کاهش را در مورتالیتی به هر علتی (HR تعدیل شده: 0.21؛ 95% CI؛ 0.10 تا 0.46) و میزان مطلق پائین‌تر مرگ را در گروه دوز درمانی (34.2% در مقابل 53%) نشان داد. خطر کلی سوگیری برای مورتالیتی به هر علتی، جدی و قطعیت شواهد پائین بود. یک NRS همچنین حوادث خونریزی دهنده را در 31.7% از افراد گروه مداخله و 20.5% از بیماران گروه کنترل گزارش کرد (OR: 1.8؛ 95% CI؛ 0.96 تا 3.37؛ شواهد با قطعیت پائین). مطالعات در حال انجام ما 22 مطالعه در حال انجام را در شرایط بیمارستانی (20 RCT؛ 14,730 شرکت‌کننده؛ 2 NRS؛ 997 شرکت‌کننده) در 10 کشور مختلف (استرالیا (1)، برزیل (1)، کانادا (2)، چین (3)، فرانسه (2)، آلمان (1)، ایتالیا (4)، سوئیس (1)، انگلیس (1)، و ایالات متحده آمریکا (6)) یافتیم. دوازده مطالعه در حال انجام قصد دارند مورتالیتی و شش مطالعه می‌خواهند نیاز به پشتیبانی تنفسی بیشتر را گزارش کنند. انتظار می‌رود سیزده مطالعه در دسامبر 2020 (6959 شرکت‌کننده)، هشت مورد در جولای 2021 (8512 شرکت‌کننده)، و یک مطالعه در دسامبر 2021 (256 شرکت‌کننده) به پایان برسند. چهار مورد از این مطالعات شامل 1000 شرکت‌کننده یا بیشتر هستند. نتیجه‌گیری‌های نویسندگان: در حال حاضر شواهد کافی برای تعیین خطرات و مزایای آنتی‌کوآگولانت‌های پروفیلاکتیک برای افراد بستری با COVID‐19 وجود ندارد. از آنجا که 22 مطالعه در حال انجام هستند که قصد دارند بیش از 15,000 شرکت‌کننده را در این شرایط ارزیابی کنند، در به‌روزرسانی‌های آینده شواهد محکم‌تری را به این مرور اضافه خواهیم کرد.La maladie à coronavirus 2019 (COVID‐19) est une maladie grave causée par le coronavirus 2 du syndrome respiratoire aigu sévère (SARS‐CoV‐2). La principale manifestation est l'insuffisance respiratoire qui peut également être liée à la microthrombose pulmonaire diffuse chez les personnes atteintes de la COVID‐19. Cette maladie provoque également des événements thromboemboliques, tels que l'embolie pulmonaire, la thrombose veineuse profonde, la thrombose artérielle, la thrombose par cathéter et la coagulopathie intravasculaire disséminée. Des études récentes ont indiqué un pronostic plus défavorable pour les personnes atteintes de la COVID‐19 qui ont développé une thromboembolie. Les anticoagulants sont des médicaments utilisés dans la prévention et le traitement des événements thromboemboliques veineux ou artériels. Plusieurs médicaments sont utilisés dans la prophylaxie et le traitement des événements thromboemboliques, tels que les héparinoïdes (héparines ou pentasaccharides), les antagonistes de la vitamine K et les anticoagulants directs. Outre leurs propriétés anticoagulantes, les héparinoïdes ont un potentiel anti‐inflammatoire supplémentaire, qui pourrait affecter l'évolution clinique des personnes atteintes de COVID‐19. Certaines recommandations de bonnes pratiques cliniques traitent de l'utilisation des anticoagulants pour la thromboprophylaxie chez les personnes atteintes de la COVID‐19, cependant, le bénéfice de l’utilisation des anticoagulants chez les personnes atteintes de la COVID‐19 est toujours en débat.Évaluer les effets des anticoagulants à dose prophylactique par rapport à un comparateur actif, au placebo ou à l’absence d’intervention, sur la mortalité et le besoin d'assistance respiratoire chez les personnes hospitalisées pour la COVID‐19. STRATÉGIE DE RECHERCHE DOCUMENTAIRE: Nous avons effectué des recherches dans les bases de données CENTRAL, MEDLINE, Embase, LILACS et IBECS, dans le registre d'étude Cochrane sur la COVID‐19 et dans la base de données de prépublications medRxiv depuis leur création jusqu'au 20 juin 2020. Nous avons également vérifié les références bibliographiques de toutes les revues systématiques pertinentes identifiées et avons contacté les spécialistes du domaine pour obtenir des références supplémentaires sur les essais. CRITÈRES DE SÉLECTION: Essais contrôlés randomisés (ECR), essais quasi‐randomisés, essais randomisés en grappes et études de cohortes qui comparent les anticoagulants à dose prophylactique (héparine, antagonistes de la vitamine K, anticoagulants directs et pentasaccharides) à un comparateur actif, un placebo ou à l’absence d’intervention dans la prise en charge des personnes hospitalisées pour la COVID‐19. Nous avons exclu les études sans groupe de comparaison. Les critères de jugement principaux sont la mortalité toutes causes confondues et la nécessité d'une assistance respiratoire supplémentaire. Les critères de jugement secondaires étaient la mortalité liée à la COVID‐19, la thrombose veineuse profonde (TVP), l'embolie pulmonaire, les hémorragies graves, les événements indésirables, la durée du séjour à l'hôpital et la qualité de vie. RECUEIL ET ANALYSE DES DONNÉES: Nous avons utilisé les procédures méthodologiques standards de Cochrane. Nous avons utilisé ROBINS‐I pour évaluer le risque de biais pour les études non randomisées et GRADE pour évaluer le niveau de confiance des données probantes. Nous avons rapporté les résultats de manière narrative. RÉSULTATS PRINCIPAUX: Nous n'avons pas identifié d’ECR ou d’essais quasi‐randomisés répondant aux critères d'inclusion. Nous avons inclus sept études non randomisées rétrospectives (5 929 participants), dont trois étaient disponibles sous forme de prépublication. Les études ont été menées en Chine, en Italie, en Espagne et aux États‐Unis. Toutes les études ont porté sur des personnes hospitalisées pour la COVID‐19, dans des unités de soins intensifs, des services hospitaliers ou des services d'urgence. L'âge moyen des participants (indiqué dans 6 études) se situait entre 59 et 72 ans. Seules trois études incluses ont rapporté la période de suivi, qui variait de 8 à 35 jours. Les études n'ont pas rapporté la plupart de nos critères de jugement d'intérêt: besoin d'une assistance respiratoire supplémentaire, mortalité liée à la COVID‐19, TVP, embolie pulmonaire, événements indésirables et qualité de vie. Anticoagulants (tous types) par rapport à l’absence de traitement (6 études non randomisées rétrospectives, 5 685 participants) Une étude a rapporté une réduction de la mortalité toutes causes confondues (rapport des cotes ajusté (RC) 0,42, intervalle de confiance (IC) à 95% 0,26 à 0,66 ; 2 075 participants). Une étude a rapporté une réduction de la mortalité uniquement dans un sous‐groupe de 395 personnes qui avaient besoin d'une ventilation mécanique (rapport des risques instantanés (HR) 0,86, IC à 95% 0,82 à 0,89). Trois études n'ont pas rapporté de différence sur la mortalité (RC ajusté de 1,64, IC à 95 % de 0,92 à 2,92 ; 449 participants ; RC non ajusté de 1,66, IC à 95 % de 0,76 à 3,64 ; 154 participants et risque relatif (RR) ajusté de 1,15, IC à 95 % de 0,29 à 2,57 ; 192 participants). Une étude n’a pas rapporté d’événement dans les deux groupes d'intervention (42 participants). Le risque global de biais pour la mortalité toutes causes confondues était critique et le niveau de confiance des données probantes était très faible. Une étude non randomisée a rapporté des événements hémorragiques chez 3 % du groupe d'intervention et 1,9 % du groupe témoin (RC 1,62, IC à 95 % 0,96 à 2,71 ; 2 773 participants ; données probantes d’un niveau de confiance faible). Anticoagulants à dose thérapeutique par rapport aux anticoagulants à dose prophylactique (1 étude non randomisée rétrospective, 244 participants) L'étude a rapporté une réduction de la mortalité toutes causes confondues (HR ajusté 0,21, IC à 95 % 0,10 à 0,46) et un taux absolu de décès plus faible dans le groupe thérapeutique (34,2 % contre 53 %). Le risque global de biais pour la mortalité toutes causes confondues était sérieux et le niveau de confiance des données probantes était faible. L'étude a également rapporté des événements hémorragiques chez 31,7 % du groupe d’intervention et 20,5 % du groupe témoin (RC 1,8, IC à 95 % 0,96 à 3,37 ; données probantes d’un niveau de confiance faible). Etudes en cours Nous avons trouvé 22 études en cours en milieu hospitalier (20 ECR, 14 730 participants ; 2 études non randomisées, 997 participants) dans 10 pays différents (Australie (1), Brésil (1), Canada (2), Chine (3), France (2), Allemagne (1), Italie (4), Suisse (1), Royaume‐Uni (1) et États‐Unis (6)). Douze études en cours prévoient de rapporter la mortalité et six prévoient de rapporter l'assistance respiratoire supplémentaire. Treize études devraient être achevées en décembre 2020 (6 959 participants), huit en juillet 2021 (8 512 participants) et une en décembre 2021 (256 participants). Quatre de ces études prévoient d'inclure 1 000 participants ou plus.Il n'y a actuellement pas suffisamment de données probantes pour déterminer les risques et les bénéfices des anticoagulants à dose prophylactique chez les personnes hospitalisées pour la COVID‐19. Étant donné que 22 études qui sont en cours prévoient d'évaluer plus de 15 000 participants dans ce contexte, nous ajouterons des données probantes plus robustes à cette revue dans de futures mises à jour.La enfermedad por coronavirus 2019 (covid‐19) es grave y está causada por el síndrome respiratorio agudo grave por coronavirus 2 (SARS‐CoV‐2, del inglés). La manifestación principal es la insuficiencia respiratoria, que también se puede relacionar con la microtrombosis pulmonar difusa en personas con covid‐19. Esta enfermedad también causa eventos tromboembólicos como embolia pulmonar, trombosis venosa profunda, trombosis arterial, trombosis del catéter y coagulopatía intravascular diseminada. Estudios recientes han indicado un peor pronóstico para las personas con covid‐19 que desarrollaron tromboembolia. Los anticoagulantes son fármacos utilizados para la prevención y el tratamiento de eventos tromboembólicos venosos o arteriales. En la profilaxis y el tratamiento de los eventos tromboembólicos se utilizan varios medicamentos como los heparinoides (heparinas o pentasacáridos), los antagonistas de la vitamina K y los anticoagulantes directos. Además de sus propiedades anticoagulantes, los heparinoides tienen un potencial antiinflamatorio adicional, que puede afectar la evolución clínica de las personas con covid‐19. Algunas guías de práctica clínica abordan el uso de anticoagulantes para la tromboprofilaxis en personas con covid‐19; sin embargo, el efecto beneficioso de los anticoagulantes para las personas con covid‐19 aún es objeto de debate.Evaluar los efectos de los anticoagulantes profilácticos versus un comparador activo, placebo o ninguna intervención, sobre la mortalidad y la necesidad de asistencia respiratoria en personas hospitalizadas con covid‐19. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las bases de datos CENTRAL, MEDLINE, Embase, LILACS e IBECS, el Registro Cochrane de estudios de covid‐19 (Cochrane COVID‐19 Study Register) y en la bases de datos de prepublicaciones medRxiv, desde su creación hasta el 20 de junio de 2020. También se verificaron las listas de referencias de cualquier revisión sistemática relevante identificada y se estableció contacto con expertos en el tema para obtener referencias adicionales de ensayos. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA), cuasiECA, ECA grupales y estudios de cohortes que compararon anticoagulantes profilácticos (heparina, antagonistas de la vitamina K, anticoagulantes directos y pentasacáridos) versus comparador activo, placebo o ninguna intervención para el tratamiento de personas hospitalizadas con covid‐19. Se excluyeron los estudios sin un grupo de comparación. Los desenlaces principales fueron la mortalidad por todas las causas y la necesidad de asistencia respiratoria adicional. Los desenlaces secundarios fueron la mortalidad relacionada con covid‐19, la trombosis venosa profunda (TVP) la embolia pulmonar, la hemorragia grave, los eventos adversos, la duración de la estancia hospitalaria y la calidad de vida. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los procedimientos metodológicos Cochrane estándar. Se utilizó ROBINS‐I para evaluar el riesgo de sesgo para estudios no aleatorizados (ENA) y GRADE para evaluar la certeza de la evidencia. Los resultados se presentaron de forma narrativa.No se identificaron ECA ni cuasiECA que cumplieran con los criterios de inclusión. Se incluyeron siete ENA retrospectivos (5929 participantes), tres de las cuales estaban disponibles como prepublicaciones. Los estudios se realizaron en China, EE.UU., España e Italia. Todos los estudios incluyeron personas hospitalizadas con covid‐19 en unidades de cuidados intensivos, salas de hospital o servicios de urgencias. La media de edad de los participantes (informada en seis estudios) varió de 59 a 72 años. Solo tres estudios informaron sobre el período de seguimiento, que varió de ocho a 35 días. Los estudios no informaron la mayoría de los desenlaces de interés: necesidad de asistencia respiratoria, mortalidad relacionada con covid‐19, TVP, embolia pulmonar, episodios adversos y calidad de vida. Anticoagulantes (todos los tipos) versus ningún tratamiento (seis ENA retrospectivos, 5685 participantes) Un estudio informó de una reducción de la mortalidad por todas las causas (odds ratio [OR] 0,42; intervalo de confianza [IC] del 95%: 0,26 a 0,66; 2075 participantes). Un estudio informó de una reducción de la mortalidad solo en un subgrupo de 395 personas que necesitaron ventilación mecánica (cociente de riesgos instantáneos [CRI] 0,86; IC del 95%: 0,82 a 0,89). Tres estudios no informaron diferencias en la mortalidad (OR ajustado 1,64; IC del 95%: 0,92 a 2,92; 449 participantes; OR no ajustado 1,66; IC del 95%: 0,76 a 3,64; 154 participantes, y riesgo relativo [RR] ajustado 1,15; IC del 95%: 0,29 a 2,57; 192 participantes). Un estudio informó cero episodios en ambos grupos de intervención (42 participantes). El riesgo general de mortalidad por todas las causas fue crítico y la certeza de la evidencia fue muy baja. Un ENA informó de episodios de hemorragia en el 3% del grupo de intervención y el 1,9% del grupo control (OR 1,62; IC del 95%: 0,96 a 2,71; 2773 participantes; evidencia de certeza baja). Anticoagulantes en dosis terapéutica versus anticoagulantes en dosis profiláctica (un ENA retrospectivo, 244 participantes) Un estudio informó de una reducción de la mortalidad por todas las causas (CRI ajustado 0,21; IC del 95%: 0,10 a 0,46) y una tasa de mortalidad absoluta menor en el grupo terapéutico (34,2% versus 53%). El riesgo general de mortalidad por todas las causas fue grave y la certeza de la evidencia fue baja. El estudio también informó de episodios de hemorragia en el 31,7% del grupo de intervención y el 20,5% del grupo control (OR 1,8; IC del 95%: 0,96 a 3,37; evidencia de certeza baja). Estudios en curso Se encontraron 22 estudios en curso en entornos hospitalarios (20 ECA, 14 730 participantes; dos ENA, 997 participantes) en diez países diferentes (Australia [1], Brasil [1], Canadá [2], China [3], Francia [2], Alemania [1], Italia [4], Suiza [1], Reino Unido [1] y EE.UU. [6]). Doce estudios en curso tienen previsto informar sobre la mortalidad y seis tienen previsto informar sobre la asistencia respiratoria adicional. Está previsto que 13 estudios se completen en diciembre de 2020 (6959 participantes), ocho en julio de 2021 (8512 participantes) y uno en diciembre de 2021 (256 participantes). Cuatro de los estudios tienen previsto incluir 1000 participantes o más.Actualmente no hay evidencia suficiente para determinar los riesgos y los efectos beneficiosos de la profilaxis con anticoagulantes en personas hospitalizadas con covid‐19. Debido a que hay 22 estudios en curso que pretenden evaluar a más de 15 000 participantes en este entorno, se agregará evidencia más sólida a esta revisión en las actualizaciones futuras.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of telemedicine for the treatment of foot ulcers in people with diabetes.

BACKGROUND: Telangiectasias (spider veins) and reticular veins on the lower limbs are very common, increase with age, and have been found in 41% of women. The cause is unknown and the patients may be asymptomatic or can report pain, burning or itching. Treatments include sclerotherapy, laser, intense pulsed light, microphlebectomy and thermoablation, but none is established as preferable. OBJECTIVES: To assess the effects of sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy treatments for telangiectasias and reticular veins. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 16 March 2021. We undertook additional searches in LILACS and IBECS databases, reference checking, and contacted specialists in the field, manufacturers and study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi‐RCTs that compared treatment methods such as sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy for telangiectasias and reticular veins in the lower limb. We included studies that compared individual treatment methods against placebo, or that compared different sclerosing agents, foam or laser treatment, or that used a combination of treatment methods. DATA COLLECTION AND ANALYSIS: Three review authors independently performed study selection, extracted data, assessed risks of bias and assessed the certainty of evidence using GRADE. The outcomes of interest were resolution or improvement (or both) of telangiectasias, adverse events (including hyperpigmentation, matting), pain, recurrence, time to resolution, and quality of life. MAIN RESULTS: We included 3632 participants from 35 RCTs. Studies compared a variety of sclerosing agents, laser treatment and compression. No studies investigated intensive pulsed light, thermocoagulation or microphlebectomy. None of the included studies assessed recurrence or time to resolution. Overall the risk of bias of the included studies was moderate. We downgraded the certainty of evidence to moderate or low because of clinical heterogeneity and imprecision due to the wide confidence intervals (CIs) and few participants for each comparison. Any sclerosing agent versus placebo There was moderate‐certainty evidence that sclerosing agents showed more resolution or improvement of telangiectasias compared to placebo (standard mean difference (SMD) 3.08, 95% CI 2.68 to 3.48; 4 studies, 613 participants/procedures), and more frequent adverse events: hyperpigmentation (risk ratio (RR) 11.88, 95% CI 4.54 to 31.09; 3 studies, 528 participants/procedures); matting (RR 4.06, 95% CI 1.28 to 12.84; 3 studies, 528 participants/procedures). There may be more pain experienced in the sclerosing‐agents group compared to placebo (SMD 0.70, 95% CI 0.06 to 1.34; 1 study, 40 participants; low‐certainty evidence). Polidocanol versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.01, 95% CI −0.13 to 0.14; 7 studies, 852 participants/procedures), hyperpigmentation (RR 0.94, 95% CI 0.62 to 1.43; 6 studies, 819 participants/procedures), or matting (RR 0.82, 95% CI 0.52 to 1.27; 7 studies, 859 participants/procedures), but there were fewer cases of pain (SMD −0.26, 95% CI −0.44 to −0.08; 5 studies, 480 participants/procedures) in the polidocanol group. All moderate‐certainty evidence. Sodium tetradecyl sulphate (STS) versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD −0.07, 95% CI −0.25 to 0.11; 4 studies, 473 participants/procedures). There was more hyperpigmentation (RR 1.71, 95% CI 1.10 to 2.64; 4 studies, 478 participants/procedures), matting (RR 2.10, 95% CI 1.14 to 3.85; 2 studies, 323 participants/procedures) and probably more pain (RR 1.49, 95% CI 0.99 to 2.25; 4 studies, 409 participants/procedures). All moderate‐certainty evidence. Foam versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.04, 95% CI −0.26 to 0.34; 2 studies, 187 participants/procedures); hyperpigmentation (RR 2.12, 95% CI 0.44 to 10.23; 2 studies, 187 participants/procedures) or pain (SMD −0.10, 95% CI −0.44 to 0.24; 1 study, 147 participants/procedures). There may be more matting using foam (RR 6.12, 95% CI 1.04 to 35.98; 2 studies, 187 participants/procedures). All low‐certainty evidence. Laser versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD −0.09, 95% CI −0.25 to 0.07; 5 studies, 593 participants/procedures), or matting (RR 1.00, 95% CI 0.46 to 2.19; 2 studies, 162 participants/procedures), and maybe less hyperpigmentation (RR 0.57, 95% CI 0.40 to 0.80; 4 studies, 262 participants/procedures) in the laser group. All moderate‐certainty evidence. High heterogeneity of the studies reporting on pain prevented pooling, and results were inconsistent (low‐certainty evidence). Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol) Low‐certainty evidence suggests there may be more resolution or improvement (or both) of telangiectasias in the combined group (SMD 5.68, 95% CI 5.14 to 6.23; 2 studies, 710 participants), and no clear difference in hyperpigmentation (RR 0.83, 95% CI 0.35 to 1.99; 2 studies, 656 participants) or matting (RR 0.83, 95% CI 0.21 to 3.28; 2 studies, 656 participants). There may be more pain in the combined group (RR 2.44, 95% CI 1.69 to 3.55; 1 study, 596 participants; low‐certainty evidence). AUTHORS' CONCLUSIONS: Small numbers of studies and participants in each comparison limited our confidence in the evidence. Sclerosing agents were more effective than placebo for resolution or improvement of telangiectasias but also caused more adverse events (moderate‐certainty evidence), and may result in more pain (low‐certainty evidence). There was no evidence of a benefit in resolution or improvement for any sclerosant compared to another or to laser. There may be more resolution or improvement of telangiectasias in the combined laser and polidocanol group compared to polidocanol alone (low‐certainty evidence). There may be differences between treatments in adverse events and pain. Compared to other sclerosing agents polidocanol probably causes less pain; STS resulted in more hyperpigmentation, matting and probably pain; foam may cause more matting (low‐certainty evidence); laser treatment may result in less hyperpigmentation (moderate‐certainty evidence). Further well‐designed studies are required to provide evidence for other available treatments and important outcomes (such as recurrence, time to resolution and delayed adverse events); and to improve our confidence in the identified comparisons.

The primary manifestation of coronavirus disease 2019 (COVID-19) is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis and thromboembolic events, such as pulmonary embolism, deep vein thrombosis, or arterial thrombosis. People with COVID-19 who develop thromboembolism have a worse prognosis. Anticoagulants such as heparinoids (heparins or pentasaccharides), vitamin K antagonists and direct anticoagulants are used for the prevention and treatment of venous or arterial thromboembolism. Besides their anticoagulant properties, heparinoids have an additional anti-inflammatory potential. However, the benefit of anticoagulants for people with COVID-19 is still under debate.To assess the benefits and harms of anticoagulants versus active comparator, placebo or no intervention in people hospitalised with COVID-19.We searched the CENTRAL, MEDLINE, Embase, LILACS and IBECS databases, the Cochrane COVID-19 Study Register and medRxiv preprint database from their inception to 14 April 2021. We also checked the reference lists of any relevant systematic reviews identified, and contacted specialists in the field for additional references to trials.Eligible studies were randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cohort studies that compared prophylactic anticoagulants versus active comparator, placebo or no intervention for the management of people hospitalised with COVID-19. We excluded studies without a comparator group and with a retrospective design (all previously included studies) as we were able to include better study designs. Primary outcomes were all-cause mortality and necessity for additional respiratory support. Secondary outcomes were mortality related to COVID-19, deep vein thrombosis, pulmonary embolism, major bleeding, adverse events, length of hospital stay and quality of life.We used standard Cochrane methodological procedures. We used Cochrane RoB 1 to assess the risk of bias for RCTs, ROBINS-I to assess risk of bias for non-randomised studies (NRS) and GRADE to assess the certainty of evidence. We meta-analysed data when appropriate.We included seven studies (16,185 participants) with participants hospitalised with COVID-19, in either intensive care units, hospital wards or emergency departments. Studies were from Brazil (2), Iran (1), Italy (1), and the USA (1), and two involved more than country. The mean age of participants was 55 to 68 years and the follow-up period ranged from 15 to 90 days. The studies assessed the effects of heparinoids, direct anticoagulants or vitamin K antagonists, and reported sparse data or did not report some of our outcomes of interest: necessity for additional respiratory support, mortality related to COVID-19, and quality of life. Higher-dose versus lower-dose anticoagulants (4 RCTs, 4647 participants) Higher-dose anticoagulants result in little or no difference in all-cause mortality (risk ratio (RR) 1.03, 95% CI 0.92 to 1.16, 4489 participants; 4 RCTs) and increase minor bleeding (RR 3.28, 95% CI 1.75 to 6.14, 1196 participants; 3 RCTs) compared to lower-dose anticoagulants up to 30 days (high-certainty evidence). Higher-dose anticoagulants probably reduce pulmonary embolism (RR 0.46, 95% CI 0.31 to 0.70, 4360 participants; 4 RCTs), and slightly increase major bleeding (RR 1.78, 95% CI 1.13 to 2.80, 4400 participants; 4 RCTs) compared to lower-dose anticoagulants up to 30 days (moderate-certainty evidence). Higher-dose anticoagulants may result in little or no difference in deep vein thrombosis (RR 1.08, 95% CI 0.57 to 2.03, 3422 participants; 4 RCTs), stroke (RR 0.91, 95% CI 0.40 to 2.03, 4349 participants; 3 RCTs), major adverse limb events (RR 0.33, 95% CI 0.01 to 7.99, 1176 participants; 2 RCTs), myocardial infarction (RR 0.86, 95% CI 0.48 to 1.55, 4349 participants; 3 RCTs), atrial fibrillation (RR 0.35, 95% CI 0.07 to 1.70, 562 participants; 1 study), or thrombocytopenia (RR 0.94, 95% CI 0.71 to 1.24, 2789 participants; 2 RCTs) compared to lower-dose anticoagulants up to 30 days (low-certainty evidence). It is unclear whether higher-dose anticoagulants have any effect on necessity for additional respiratory support, mortality related to COVID-19, and quality of life (very low-certainty evidence or no data). Anticoagulants versus no treatment (3 prospective NRS, 11,538 participants) Anticoagulants may reduce all-cause mortality but the evidence is very uncertain due to two study results being at critical and serious risk of bias (RR 0.64, 95% CI 0.55 to 0.74, 8395 participants; 3 NRS; very low-certainty evidence). It is uncertain if anticoagulants have any effect on necessity for additional respiratory support, mortality related to COVID-19, deep vein thrombosis, pulmonary embolism, major bleeding, stroke, myocardial infarction and quality of life (very low-certainty evidence or no data). Ongoing studies We found 62 ongoing studies in hospital settings (60 RCTs, 35,470 participants; 2 prospective NRS, 120 participants) in 20 different countries. Thirty-five ongoing studies plan to report mortality and 26 plan to report necessity for additional respiratory support. We expect 58 studies to be completed in December 2021, and four in July 2022. From 60 RCTs, 28 are comparing different doses of anticoagulants, 24 are comparing anticoagulants versus no anticoagulants, seven are comparing different types of anticoagulants, and one did not report detail of the comparator group.When compared to a lower-dose regimen, higher-dose anticoagulants result in little to no difference in all-cause mortality and increase minor bleeding in people hospitalised with COVID-19 up to 30 days. Higher-dose anticoagulants possibly reduce pulmonary embolism, slightly increase major bleeding, may result in little to no difference in hospitalisation time, and may result in little to no difference in deep vein thrombosis, stroke, major adverse limb events, myocardial infarction, atrial fibrillation, or thrombocytopenia. Compared with no treatment, anticoagulants may reduce all-cause mortality but the evidence comes from non-randomised studies and is very uncertain. It is unclear whether anticoagulants have any effect on the remaining outcomes compared to no anticoagulants (very low-certainty evidence or no data). Although we are very confident that new RCTs will not change the effects of different doses of anticoagulants on mortality and minor bleeding, high-quality RCTs are still needed, mainly for the other primary outcome (necessity for additional respiratory support), the comparison with no anticoagulation, when comparing the types of anticoagulants and giving anticoagulants for a prolonged period of time.

Background Endovascular aortic aneurysm repair (EVAR) is used to treat aorto-iliac and isolated iliac aneurysms in selected patients, and prospective studies have shown advantages compared with open surgical repair, mainly in the first years of follow-up. Although this technique produces good results, anatomic issues (such as common iliac artery ectasia or an aneurysm that involves the iliac bifurcation) can make EVAR more complex and challenging and can lead to an inadequate distal seal zone for the stent-graft. Inadequate distal fixation in the common iliac arteries can lead to a type Ib endoleak. To avoid this complication, one of the most commonly used techniques is unilateral or bilateral internal iliac artery occlusion and extension of the iliac limb stent-graft to the external iliac arteries with or without embolisation of the internal iliac artery. However, this occlusion is not without harm and is associated with ischaemic complications in the pelvic territory such as buttock claudication, sexual dysfunction, ischaemic colitis, gluteal necrosis, and spinal cord injury. New endovascular devices and alternative techniques such as iliac branch devices and the sandwich technique have been described to maintain pelvic perfusion and decrease complications, achieving revascularisation of the internal iliac arteries in patients not suitable for an adequate seal zone in the common iliac arteries. These approaches may also preserve the quality of life of treated individuals and may decrease other serious complications including spinal cord ischaemia, ischaemic colitis, and gluteal necrosis, thereby decreasing the morbidity and mortality of EVAR. Objectives To assess the effects of internal iliac artery revascularisation versus internal iliac artery occlusion during endovascular repair of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation. Search methods The Cochrane Vascular Information Specialists searched the Cochrane Vascular Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 August 2019. The review authors searched Latin American Caribbean Health Sciences Literature (LILACS) and the Indice Bibliografico Espanol de Ciencias de la Salud (IBECS) on 28 August 2019 and contacted specialists in the field and manufacturers to identify relevant studies. Selection criteria We planned to include all randomised controlled trials (RCTs) that compared internal iliac artery revascularisation with internal iliac artery occlusion for patients undergoing endovascular treatment of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation. Data collection and analysis Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions. Main results We identified no RCTs that met the inclusion criteria. Authors' conclusions We found no RCTs that compared internal iliac artery revascularisation versus internal iliac artery occlusion for endovascular treatment of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation. High-quality studies that evaluate the best strategy for managing endovascular repair of aorto-iliac aneurysms with inadequate distal seal zones in the common iliac artery are needed.

Background Arterial vascular access is a frequently performed procedure, with a high possibility for adverse events (e.g. pneumothorax, haemothorax, haematoma, amputation, death), and additional techniques such as ultrasound may be useful for improving outcomes. However, ultrasound guidance for arterial access in adults is still under debate. Objectives To assess the effects of ultrasound guidance for arterial (other than femoral) catheterisation in adults. Search methods We searched CENTRAL, MEDLINE, Embase, LILACS, and CINAHL on 21 May 2021. We also searched IBECS, WHO ICTRP, and ClinicalTrials.gov on 16 June 2021, and we checked the reference lists of retrieved articles. Selection criteria Randomised controlled trials (RCTs), including cross-over trials and cluster-RCTs, comparing ultrasound guidance, alone or associated with other forms of guidance, versus other interventions or palpation and landmarks for arterial (other than femoral) guidance in adults. Data collection and analysis Two review authors independently performed study selection, extracted data, assessed risk of bias, and assessed the certainty of evidence using GRADE. Main results We included 48 studies (7997 participants) that tested palpation and landmarks, Doppler auditory ultrasound assistance (DUA), direct ultrasound guidance with B-mode, or any other modified ultrasound technique for arterial (axillary, dorsalis pedis, and radial) catheterisation in adults. Radial artery Real-time B-mode ultrasound versus palpation and landmarks Real-time B-mode ultrasound guidance may improve first attempt success rate (risk ratio (RR) 1.44, 95% confidence interval (CI) 1.29 to 1.61; 4708 participants, 27 studies; low-certainty evidence) and overall success rate (RR 1.11, 95% CI 1.06 to 1.16; 4955 participants, 28 studies; low-certainty evidence), and may decrease time needed for a successful procedure (mean difference (MD) -0.33 minutes, 95% CI -0.54 to -0.13; 4902 participants, 26 studies; low-certainty evidence) up to one hour compared to palpation and landmarks. Real-time B-mode ultrasound guidance probably decreases major haematomas (RR 0.35, 95% CI 0.23 to 0.56; 2504 participants, 16 studies; moderate-certainty evidence). It is uncertain whether real-time B-mode ultrasound guidance has any effect on pseudoaneurysm, pain, and quality of life (QoL) compared to palpation and landmarks (very low-certainty evidence). Real-time B-mode ultrasound versus DUA One study (493 participants) showed that real-time B-mode ultrasound guidance probably improves first attempt success rate (RR 1.35, 95% CI 1.11 to 1.64; moderate-certainty evidence) and time needed for a successful procedure (MD -1.57 minutes, 95% CI -1.78 to -1.36; moderate-certainty evidence) up to 72 hours compared to DUA. Real-time B-mode ultrasound guidance may improve overall success rate (RR 1.13, 95% CI 0.99 to 1.29; low-certainty evidence) up to 72 hours compared to DUA. Pseudoaneurysm, major haematomas, pain, and QoL were not reported. Real-time B-mode ultrasound versus modified real-time B-mode ultrasound Real-time B-mode ultrasound guidance may decrease first attempt success rate (RR 0.68, 95% CI 0.55 to 0.84; 153 participants, 2 studies; low-certainty evidence), may decrease overall success rate (RR 0.93, 95% CI 0.86 to 1.01; 153 participants, 2 studies; low-certainty evidence), and may lead to no difference in time needed for a successful procedure (MD 0.04 minutes, 95% CI -0.01 to 0.09; 153 participants, 2 studies; low-certainty evidence) up to one hour compared to modified real-time B-mode ultrasound guidance. It is uncertain whether real-time B-mode ultrasound guidance has any effect on major haematomas compared to modified real-time B-mode ultrasound (very low-certainty evidence). Pseudoaneurysm, pain, and QoL were not reported. In-plane versus out-of-plane B-mode ultrasound In-plane real-time B-mode ultrasound guidance may lead to no difference in overall success rate (RR 1.00, 95% CI 0.96 to 1.05; 1051 participants, 8 studies; low-certainty evidence) and in time needed for a successful procedure (MD -0.06 minutes, 95% CI -0.16 to 0.05; 1134 participants, 9 studies; low-certainty evidence) compared to out-of-plane B-mode ultrasound up to one hour. It is uncertain whether in-plane real-time B-mode ultrasound guidance has any effect on first attempt success rate or major haematomas compared to out-of-plane B-mode ultrasound (very low-certainty evidence). Pseudoaneurysm, pain, and QoL were not reported. DUA versus palpation and landmarks DUA may lead to no difference in first attempt success rate (RR 1.01, 95% CI 0.90 to 1.14; 666 participants, 2 studies; low-certainty evidence) or overall success rate (RR 0.99, 95% CI 0.92 to 1.07; 666 participants, 2 studies; low-certainty evidence) and probably increases time needed for a successful procedure (MD 0.45 minutes, 95% CI 0.20 to 0.70; 500 participants, 1 study; moderate-certainty evidence) up to 72 hours compared to palpation and landmarks. Pseudoaneurysm, major haematomas, pain, and QoL were not reported. Oblique-axis versus long-axis in-plane B-mode ultrasound Oblique-axis in-plane B-mode ultrasound guidance may increase overall success rate (RR 1.27, 95% CI 1.05 to 1.53; 215 participants, 2 studies; low-certainty evidence) up to 72 hours compared to long-axis in-plane B-mode ultrasound. It is uncertain whether oblique-axis in-plane B-mode ultrasound guidance has any effect on first attempt success rate, time needed for a successful procedure, and major haematomas compared to long-axis in-plane B-mode ultrasound. Pseudoaneurysm, pain, and QoL were not reported. We are uncertain about effects in the following comparisons due to very low-certainty evidence and unreported outcomes: real-time B-mode ultrasound versus palpation and landmarks (axillary and dorsalis pedis arteries), real-time B-mode ultrasound versus near-infrared laser (radial artery), and dynamic versus static out-of-plane B-mode ultrasound (radial artery). Authors' conclusions Real-time B-mode ultrasound guidance may improve first attempt success rate, overall success rate, and time needed for a successful procedure for radial artery catheterisation compared to palpation, or DUA. In addition, real-time B-mode ultrasound guidance probably decreases major haematomas compared to palpation. However, we are uncertain about the evidence on major haematomas and pain for other comparisons due to very low-certainty evidence and unreported outcomes. We are also uncertain about the effects on pseudoaneurysm and QoL for axillary and dorsalis pedis arteries catheterisation. Given that first attempt success rate and pseudoaneurysm are the most relevant outcomes for people who underwent arterial catheterisation, future studies must measure both. Future trials must be large enough to detect effects, use validated scales, and report longer-term follow-up.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis, to prevent neurological impairment, stroke, disability, death, and other complications.

Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by valvular incompetence, reflux, venous obstruction or a combination of these symptoms, with consequent distal venous hypertension. Clinical manifestations of CVI include oedema, pain, skin changes, ulcerations and dilated skin veins in the lower limbs. It places a large financial burden on health systems. There is a wide variety of treatment options for CVI, ranging from surgery and medication to compression and physiotherapy. Balneotherapy (treatments involving water) may be a relatively cheap and efficient way to deliver physiotherapy to people with CVI. This is an update of a review first published in 2019.To assess the effectiveness and safety of balneotherapy for the treatment of people with chronic venous insufficiency.We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022.We included randomised and quasi-randomised controlled trials comparing balneotherapy to no treatment or other types of treatment for CVI. We also included studies that used a combination of treatments.We used standard Cochrane methods. Our primary outcomes were 1. disease severity, 2. health-related quality of life (HRQoL) and 3.Our secondary outcomes were 1. pain, 2. oedema, 3. leg ulcer incidence and 4. skin pigmentation changes. We used GRADE to assess the certainty of evidence for each outcome.We included nine randomised controlled trials involving 1126 participants with CVI. Seven studies evaluated balneotherapy versus no treatment, one study evaluated balneotherapy versus a phlebotonic drug (melilotus officinalis), and one study evaluated balneotherapy versus dryland exercises. We downgraded our certainty in the evidence due to a lack of blinding of participants and investigators, participant-reported outcomes and imprecision. Balneotherapy versus no treatment Balneotherapy compared to no treatment probably results in slightly improved disease severity signs and symptoms scores as assessed by the Venous Clinical Severity Score (VCSS; mean difference (MD) -1.75, 95% confidence interval (CI) -3.02 to -0.49; 3 studies, 671 participants; moderate-certainty evidence). Balneotherapy compared to no treatment may improve HRQoL as assessed by the Chronic Venous Insufficiency Quality of Life Questionnaire 2 (CIVIQ2) at three months, but we are very uncertain about the results (MD -10.46, 95% CI -19.21 to -1.71; 2 studies, 153 participants; very low-certainty evidence). The intervention may improve HRQoL at 12 months (MD -4.48, 95% CI -8.61 to -0.36; 2 studies, 417 participants; low-certainty evidence). It is unclear if the intervention has an effect at six months (MD -2.99, 95% CI -6.53 to 0.56; 2 studies, 436 participants; low-certainty evidence) or nine months (MD -6.40, 95% CI -13.84 to 1.04; 1 study, 59 participants; very low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on the occurrence of adverse effects. The main adverse effects were thromboembolic events (odds radio (OR) 0.35, 95% CI 0.09 to 1.42; 3 studies, 584 participants; low-certainty evidence), erysipelas (OR 2.58, 95% CI 0.65 to 10.22; 2 studies, 519 participants; low-certainty evidence) and palpitations (OR 0.33, 95% CI 0.01 to 8.52; 1 study, 59 participants; low-certainty evidence). No studies reported any serious adverse effects. Balneotherapy compared with no treatment may improve pain scores slightly at three months (MD -1.12, 95% CI -1.35 to -0.88; 2 studies, 354 participants; low-certainty evidence); and six months (MD -1.02, 95% CI -1.25 to -0.78; 2 studies, 352 participants; low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on oedema (measured by leg circumference) at 24 days to three months, but we are very uncertain about the results (standardised mean difference (SMD) 0.32 cm, 95% CI -0.70 to 1.34; 3 studies, 369 participants; very low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on the incidence of leg ulcers at 12 months, but we are very uncertain about the results (OR 1.06, 95% CI 0.27 to 4.14; 2 studies, 449 participants; very low-certainty evidence). Balneotherapy compared with no treatment may slightly reduce skin pigmentation changes as measured by the pigmentation index at 12 months (MD -3.60, 95% CI -5.95 to -1.25; 1 study, 59 participants; low-certainty evidence). Balneotherapy versus melilotus officinalis For the comparison balneotherapy versus a phlebotonic drug (melilotus officinalis), there was little or no difference in pain symptoms (OR 0.29, 95% CI 0.03 to 2.87; 1 study, 35 participants; very low-certainty evidence) or oedema (OR 0.21, 95% CI 0.02 to 2.27; 1 study, 35 participants; very low-certainty evidence), but we are very uncertain about the results. The study reported no other outcomes of interest. Balneotherapy versus dryland exercise For the comparison balneotherapy versus dryland exercise, evidence from one study showed that balneotherapy may improve HRQoL as assessed by the Varicose Vein Symptom Questionnaire (VVSymQ), but we are very uncertain about the results (MD -3.00, 95% CI -3.80 to -2.20; 34 participants, very low-certainty evidence). Balneotherapy compared with dryland exercises may reduce oedema (leg volume) after five sessions of treatment (right leg: MD -840.70, 95% CI -1053.26 to -628.14; left leg: MD -767.50, 95% CI -910.07 to -624.93; 1 study, 34 participants, low-certainty evidence). The study reported no other outcomes of interest.For the comparison balneotherapy versus no treatment, we identified moderate-certainty evidence that the intervention improves disease severity signs and symptoms scores slightly, low-certainty evidence that it improves pain and skin pigmentation changes, and very low-certainty evidence that it improves HRQoL. Balneotherapy compared with no treatment made little or no difference to adverse effects, oedema or incidence of leg ulcers. Evidence comparing balneotherapy with other interventions was very limited. To ensure adequate comparison between trials, future trials should standardise measurements of outcomes (e.g. disease severity signs and symptoms score, HRQoL, pain and oedema) and follow-up time points.

Background Telangiectasias (spider veins) and reticular veins on the lower limbs are very common, increase with age, and have been found in 41% of women. The cause is unknown and the patients may be asymptomatic or can report pain, burning or itching. Treatments include sclerotherapy, laser, intense pulsed light, microphlebectomy and thermoablation, but none is established as preferable. Objectives To assess the effects of sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy treatments for telangiectasias and reticular veins. Search methods The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 16 March 2021. We undertook additional searches in LILACS and IBECS databases, reference checking, and contacted specialists in the field, manufacturers and study authors to identify additional studies. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs that compared treatment methods such as sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy for telangiectasias and reticular veins in the lower limb. We included studies that compared individual treatment methods against placebo, or that compared different sclerosing agents, foam or laser treatment, or that used a combination of treatment methods. Data collection and analysis Three review authors independently performed study selection, extracted data, assessed risks of bias and assessed the certainty of evidence using GRADE. The outcomes of interest were resolution or improvement (or both) of telangiectasias, adverse events (including hyperpigmentation, matting), pain, recurrence, time to resolution, and quality of life. Main results We included 3632 participants from 35 RCTs. Studies compared a variety of sclerosing agents, laser treatment and compression. No studies investigated intensive pulsed light, thermocoagulation or microphlebectomy. None of the included studies assessed recurrence or time to resolution. Overall the risk of bias of the included studies was moderate. We downgraded the certainty of evidence to moderate or low because of clinical heterogeneity and imprecision due to the wide confidence intervals (CIs) and few participants for each comparison. Any sclerosing agent versus placebo There was moderate-certainty evidence that sclerosing agents showed more resolution or improvement of telangiectasias compared to placebo (standard mean difference (SMD) 3.08, 95% CI 2.68 to 3.48; 4 studies, 613 participants/procedures), and more frequent adverse events: hyperpigmentation (risk ratio (RR) 11.88, 95% CI 4.54 to 31.09; 3 studies, 528 participants/procedures); matting (RR 4.06, 95% CI 1.28 to 12.84; 3 studies, 528 participants/procedures). There may be more pain experienced in the sclerosing-agents group compared to placebo (SMD 0.70, 95% CI 0.06 to 1.34; 1 study, 40 participants; low-certainty evidence). Polidocanol versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.01, 95% CI -0.13 to 0.14; 7 studies, 852 participants/procedures), hyperpigmentation (RR 0.94, 95% CI 0.62 to 1.43; 6 studies, 819 participants/procedures), or matting (RR 0.82, 95% CI 0.52 to 1.27; 7 studies, 859 participants/procedures), but there were fewer cases of pain (SMD -0.26, 95% CI -0.44 to -0.08; 5 studies, 480 participants/procedures) in the polidocanol group. All moderate-certainty evidence. Sodium tetradecyl sulphate (STS) versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD -0.07, 95% CI -0.25 to 0.11; 4 studies, 473 participants/procedures). There was more hyperpigmentation (RR 1.71, 95% CI 1.10 to 2.64; 4 studies, 478 participants/procedures), matting (RR 2.10, 95% CI 1.14 to 3.85; 2 studies, 323 participants/procedures) and probably more pain (RR 1.49, 95% CI 0.99 to 2.25; 4 studies, 409 participants/procedures). All moderate-certainty evidence. Foam versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.04, 95% CI -0.26 to 0.34; 2 studies, 187 participants/procedures); hyperpigmentation (RR 2.12, 95% CI 0.44 to 10.23; 2 studies, 187 participants/procedures) or pain (SMD -0.10, 95% CI -0.44 to 0.24; 1 study, 147 participants/procedures). There may be more matting using foam (RR 6.12, 95% CI 1.04 to 35.98; 2 studies, 187 participants/procedures). All low-certainty evidence. Laser versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD -0.09, 95% CI -0.25 to 0.07; 5 studies, 593 participants/procedures), or matting (RR 1.00, 95% CI 0.46 to 2.19; 2 studies, 162 participants/procedures), and maybe less hyperpigmentation (RR 0.57, 95% CI 0.40 to 0.80; 4 studies, 262 participants/procedures) in the laser group. All moderate-certainty evidence. High heterogeneity of the studies reporting on pain prevented pooling, and results were inconsistent (low-certainty evidence). Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol) Low-certainty evidence suggests there may be more resolution or improvement (or both) of telangiectasias in the combined group (SMD 5.68, 95% CI 5.14 to 6.23; 2 studies, 710 participants), and no clear difference in hyperpigmentation (RR 0.83, 95% CI 0.35 to 1.99; 2 studies, 656 participants) or matting (RR 0.83, 95% CI 0.21 to 3.28; 2 studies, 656 participants). There may be more pain in the combined group (RR 2.44, 95% CI 1.69 to 3.55; 1 study, 596 participants; low-certainty evidence). Authors' conclusions Small numbers of studies and participants in each comparison limited our confidence in the evidence. Sclerosing agents were more effective than placebo for resolution or improvement of telangiectasias but also caused more adverse events (moderate-certainty evidence), and may result in more pain (low-certainty evidence). There was no evidence of a benefit in resolution or improvement for any sclerosant compared to another or to laser. There may be more resolution or improvement of telangiectasias in the combined laser and polidocanol group compared to polidocanol alone (low-certainty evidence). There may be differences between treatments in adverse events and pain. Compared to other sclerosing agents polidocanol probably causes less pain; STS resulted in more hyperpigmentation, matting and probably pain; foam may cause more matting (low-certainty evidence); laser treatment may result in less hyperpigmentation (moderate-certainty evidence). Further well-designed studies are required to provide evidence for other available treatments and important outcomes (such as recurrence, time to resolution and delayed adverse events); and to improve our confidence in the identified comparisons.

Buerger's disease is characterized by recurring progressive inflammation and occlusions in small and medium arteries and veins of the limbs. Its cause is unknown, but it is most common in young men with a history of tobacco use. It is responsible for ischemic ulcers and extreme pain in the hands and feet. In many cases, notably in patients with the most severe presentations, there is no possibility of improving the condition with surgery (limb revascularisation), and therefore, alternative therapies (e.g. sympathectomy) is used. This review assessed the effectiveness of surgical sympathectomy compared with any other therapy in patients with Buerger's disease. As a result, only one randomised controlled study (162 participants) compared sympathectomy with prostacyclin analogue (iloprost) was incorporated to the review. Such comparison shown that iloprost is more effective than sympathectomy to complete healing ulcers at four weeks (risk ratio 0.65; 95% confidence interval 0.45 to 0.95; P = 0.02; very low quality evidence) and at twenty four weeks (risk ratio 0.62; 95% confidence interval 0.48 to 0.82; P We concluded, with very low quality of evidence, that intravenous iloprost is more effective than lumbar sympathectomyin the healing of ischemic ulcers and pain at rest in patients with Buerger's disease. Therefore, until now, the preference of the usage of intravenous iloprost over the lumbar sympathectomy (and vice versa) does not find robust evidence for its routine use.