Surgery for nasal polyposis in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly. OBJECTIVES: To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched other databases (Pubmed, Embase, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Virtual Health Library and ClinicalTrials.gov). Date of last search: 18 September 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing groups who underwent endoscopic sinus surgery and groups with medical treatment alone. DATA COLLECTION AND ANALYSIS: The review authors independently selected studies, extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE. They contacted the authors of the included study for additional information. MAIN RESULTS: We identified 66 publications relating to 50 studies from electronic searches. Only one study fulfilled the inclusion criteria, and only limited information was available. In this study, 28 participants aged 19 to 28 years were randomized in equal numbers to either nasal irrigation alone or nasal irrigation with surgery (endoscopic polypectomy with extended sinusotomy). The certainty of the evidence was very low according to the GRADE approach. We are uncertain whether, compared to medical treatment alone, the addition of surgical intervention improves nasal symptoms, or reduces bacterial colonization, the use of antibiotics and pulmonary exacerbations. We are also uncertain whether the addition of surgery to medical treatment leads to changes in pulmonary function. There was one episode of bleeding during surgery that was corrected during the procedure with no further consequences. The study did not report on survival. AUTHORS' CONCLUSIONS: Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps.

Pharmacological interventions for asymptomatic carotid stenosis.

BACKGROUND: Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem. OBJECTIVES: To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes. SEARCH METHODS: We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE. MAIN RESULTS: We included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life. Antiplatelet agent (acetylsalicylic acid) versus placebo Acetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life. Antihypertensive agents (metoprolol and chlorthalidone) versus placebo The antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life. Anticoagulant agent (warfarin) versus placebo The evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life. Lipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment Lipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life. AUTHORS' CONCLUSIONS: Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.

Duplex ultrasound for surveillance of lower limb revascularisation.

BACKGROUND: Lower extremity atherosclerotic disease (LEAD) - also known as peripheral arterial disease - refers to the obstruction or narrowing of the large arteries of the lower limbs, most commonly caused by atheromatous plaque. Although in many cases of less severe disease patients can be asymptomatic, the major clinical manifestations of LEAD are intermittent claudication (IC) and critical limb ischaemia, also known as chronic limb-threatening ischaemia (CLTI). Revascularisation procedures including angioplasty, stenting, and bypass grafting may be required for those in whom the disease is severe or does not improve with non-surgical interventions. Maintaining vessel patency after revascularisation remains a challenge for vascular surgeons, since approximately 30% of vein grafts may present with restenosis in the first year due to myointimal hyperplasia. Restenosis can also occur after angioplasty and stenting. Restenosis and occlusions that occur more than two years after the procedure are generally related to progression of the atherosclerosis. Surveillance programmes with duplex ultrasound (DUS) scanning as part of postoperative care may facilitate early diagnosis of restenosis and help avoid amputation in people who have undergone revascularisation. OBJECTIVES: To assess the effects of DUS versus pulse palpation, arterial pressure index, angiography, or any combination of these, for surveillance of lower limb revascularisation in people with LEAD. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared DUS surveillance after lower limb revascularisation versus clinical surveillance characterised by medical examination with pulse palpation, with or without any other objective test, such as arterial pressure index measures (e.g. ankle-brachial index (ABI) or toe brachial index (TBI)). Our primary outcomes were limb salvage rate, vessel or graft secondary patency, and adverse events resulting from DUS surveillance. Secondary outcomes were all-cause mortality, functional walking ability assessed by walking distance, clinical severity scales, quality of life (QoL), re-intervention rates, and functional walking ability assessed by any validated walking impairment questionnaire. We presented the outcomes at two time points: two years or less after the original revascularisation (short term) and more than two years after the original revascularisation (long term). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We used the Cochrane RoB 1 tool to assess the risk of bias for RCTs and GRADE to assess the certainty of evidence. We performed meta-analysis when appropriate. MAIN RESULTS: We included three studies (1092 participants) that compared DUS plus pulse palpation and arterial pressure index (ABI or TBI) versus pulse palpation and arterial pressure index (ABI or TBI) for surveillance of lower limb revascularisation with bypass. One study each was conducted in Sweden and Finland, and the third study was conducted in the UK and Europe. The studies did not report adverse events resulting from DUS surveillance, functional walking ability, or clinical severity scales. No study assessed surveillance with DUS scanning after angioplasty or stenting, or both. We downgraded the certainty of evidence for risk of bias and imprecision. Duplex ultrasound plus pulse palpation and arterial pressure index (ABI or TBI) versus pulse palpation plus arterial pressure index (ABI or TBI) (short-term time point) In the short term, DUS surveillance may lead to little or no difference in limb salvage rate (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.45; I² = 93%; 2 studies, 936 participants; low-certainty evidence) and vein graft secondary patency (RR 0.92, 95% CI 0.67 to 1.26; I² = 57%; 3 studies, 1092 participants; low-certainty evidence). DUS may lead to little or no difference in all-cause mortality (RR 1.11, 95% CI 0.70 to 1.74; 1 study, 594 participants; low-certainty evidence). There was no clear difference in QoL as assessed by the 36-item Short Form Health Survey (SF-36) physical score (mean difference (MD) 2 higher, 95% CI 2.59 lower to 6.59 higher; 1 study, 594 participants; low-certainty evidence); the SF-36 mental score (MD 3 higher, 95% CI 0.38 lower to 6.38 higher; 1 study, 594 participants; low-certainty evidence); or the EQ-5D utility score (MD 0.02 higher, 95% CI 0.03 lower to 0.07 higher; 1 study, 594 participants; low-certainty evidence). DUS may increase re-intervention rates when considered any therapeutic intervention (RR 1.38, 95% CI 1.05 to 1.81; 3 studies, 1092 participants; low-certainty evidence) or angiogram procedures (RR 1.53, 95% CI 1.12 to 2.08; 3 studies, 1092 participants; low-certainty evidence). Duplex ultrasound plus pulse palpation and arterial pressure index (ABI or TBI) versus pulse palpation plus arterial pressure index (ABI or TBI) (long-term time point) One study reported data after two years, but provided only vessel or graft secondary patency data. DUS may lead to little or no difference in vessel or graft secondary patency (RR 0.83, 95% CI 0.19 to 3.51; 1 study, 156 participants; low-certainty evidence). Other outcomes of interest were not reported at the long-term time point. AUTHORS' CONCLUSIONS: Based on low certainty evidence, we found no clear difference between DUS and standard surveillance in preventing limb amputation, morbidity, and mortality after lower limb revascularisation. We found no studies on DUS surveillance after angioplasty or stenting (or both), only studies on bypass grafting. High-quality RCTs should be performed to better inform the best medical surveillance of lower limb revascularisation that may reduce the burden of peripheral arterial disease.

Interventions for motor rehabilitation in people with transtibial amputation due to peripheral arterial disease or diabetes.

BACKGROUND: Amputation is described as the removal of an external part of the body by trauma, medical illness or surgery. Amputations caused by vascular diseases (dysvascular amputations) are increasingly frequent, commonly due to peripheral arterial disease (PAD), associated with an ageing population, and increased incidence of diabetes and atherosclerotic disease. Interventions for motor rehabilitation might work as a precursor to enhance the rehabilitation process and prosthetic use. Effective rehabilitation can improve mobility, allow people to take up activities again with minimum functional loss and may enhance the quality of life (QoL). Strength training is a commonly used technique for motor rehabilitation following transtibial (below-knee) amputation, aiming to increase muscular strength. Other interventions such as motor imaging (MI), virtual environments (VEs) and proprioceptive neuromuscular facilitation (PNF) may improve the rehabilitation process and, if these interventions can be performed at home, the overall expense of the rehabilitation process may decrease. Due to the increased prevalence, economic impact and long-term rehabilitation process in people with dysvascular amputations, a review investigating the effectiveness of motor rehabilitation interventions in people with dysvascular transtibial amputations is warranted. OBJECTIVES: To evaluate the benefits and harms of interventions for motor rehabilitation in people with transtibial (below-knee) amputations resulting from peripheral arterial disease or diabetes (dysvascular causes). SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 9 January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCT) in people with transtibial amputations resulting from PAD or diabetes (dysvascular causes) comparing interventions for motor rehabilitation such as strength training (including gait training), MI, VEs and PNF against each other. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. prosthesis use, and 2. ADVERSE EVENTS: Our secondary outcomes were 3. mortality, 4. QoL, 5. mobility assessment and 6. phantom limb pain. We use GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included two RCTs with a combined total of 30 participants. One study evaluated MI combined with physical practice of walking versus physical practice of walking alone. One study compared two different gait training protocols. The two studies recruited people who already used prosthesis; therefore, we could not assess prosthesis use. The studies did not report mortality, QoL or phantom limb pain. There was a lack of blinding of participants and imprecision as a result of the small number of participants, which downgraded the certainty of the evidence. We identified no studies that compared VE or PNF with usual care or with each other. MI combined with physical practice of walking versus physical practice of walking (one RCT, eight participants) showed very low-certainty evidence of no difference in mobility assessment assessed using walking speed, step length, asymmetry of step length, asymmetry of the mean amount of support on the prosthetic side and on the non-amputee side and Timed Up-and-Go test. The study did not assess adverse events. One study compared two different gait training protocols (one RCT, 22 participants). The study used change scores to evaluate if the different gait training strategies led to a difference in improvement between baseline (day three) and post-intervention (day 10). There were no clear differences using velocity, Berg Balance Scale (BBS) or Amputee Mobility Predictor with PROsthesis (AMPPRO) in training approaches in functional outcome (very low-certainty evidence). There was very low-certainty evidence of little or no difference in adverse events comparing the two different gait training protocols. AUTHORS' CONCLUSIONS: Overall, there is a paucity of research in the field of motor rehabilitation in dysvascular amputation. We identified very low-certainty evidence that gait training protocols showed little or no difference between the groups in mobility assessments and adverse events. MI combined with physical practice of walking versus physical practice of walking alone showed no clear difference in mobility assessment (very low-certainty evidence). The included studies did not report mortality, QoL, and phantom limb pain, and evaluated participants already using prosthesis, precluding the evaluation of prosthesis use. Due to the very low-certainty evidence available based on only two small trials, it remains unclear whether these interventions have an effect on the prosthesis use, adverse events, mobility assessment, mortality, QoL and phantom limb pain. Further well-designed studies that address interventions for motor rehabilitation in dysvascular transtibial amputation may be important to clarify this uncertainty.

Digital technology for delivering and monitoring exercise programs for people with cystic fibrosis.

BACKGROUND: Although exercise is recommended as part of the cystic fibrosis (CF) therapeutic routine, adherence to exercise is still limited. Digital health technologies can provide easy-to-access health information and may help improve healthcare and outcomes in individuals with long-term conditions. However, its effects for delivering and monitoring exercise programs in CF have not yet been synthesized. OBJECTIVES: To evaluate the benefits and harms of digital health technologies for delivering and monitoring exercise programs, increasing adherence to exercise regimens, and improving key clinical outcomes in people with CF. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 November 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) or quasi-RCTs of digital health technologies for delivering or monitoring exercise programs in CF. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. physical activity, 2. self-management behavior, and 3. pulmonary exacerbations. Our secondary outcomes were 4. usability of technologies, 5. quality of life, 6. lung function, 7. muscle strength, 8. exercise capacity, 9. physiologic parameters, and 10. ADVERSE EVENTS: We used GRADE to assess certainty of evidence. MAIN RESULTS: We identified four parallel RCTs (three single-center and one multicenter with 231 participants aged six years or older). The RCTs evaluated different modes of digital health technologies with distinct purposes, combined with diverse interventions. We identified important methodologic concerns in the RCTs, including insufficient information on the randomization process, blinding of outcome assessors, balance of non-protocol interventions across groups, and whether the analyses performed corrected for bias due to missing outcome data. Non-reporting of results may also be a concern, especially because some planned outcome results were reported incompletely. Furthermore, each trial had a small number of participants, resulting in imprecise effects. These limitations on the risk of bias, and on the precision of effect estimates resulted in overall low- to very low-certainty evidence. We undertook four comparisons and present the findings for our primary outcomes below. There is no information on the effectiveness of other modes of digital health technologies for monitoring physical activity or delivering exercise programs in people with CF, on adverse events related to the use of digital health technologies either for delivering or monitoring exercise programs in CF, and on their long-term effects (more than one year). Digital health technologies for monitoring physical activity Wearable fitness tracker plus personalized exercise prescription compared to personalized exercise prescription alone One trial (40 adults with CF) evaluated this outcome, but did not report data for any of our primary outcomes. Wearable fitness tracker plus text message for personalized feedback and goal setting compared to wearable fitness tracker alone The evidence is very uncertain about the effects of a wearable fitness tracker plus text message for personalized feedback and goal setting, compared to wearable technology alone on physical activity measured by step count at six-month follow-up (mean difference [MD] 675.00 steps, 95% confidence interval [CI] -2406.37 to 3756.37; 1 trial, 32 participants). The same study measured pulmonary exacerbation rates and reported finding no difference between groups. Web-based application to record, monitor, and set goals on physical activity plus usual care compared to usual care alone Using a web-based application to record, monitor, and set goals on physical activity plus usual care may result in little to no difference on time spent in moderate-to-vigorous physical activity measured via accelerometry compared to usual care alone at six-month follow-up (MD -4 minutes/day, 95% CI -37 to 29; 1 trial, 63 participants). Low certainty-evidence from the same trial suggests that the intervention may result in little to no difference on pulmonary exacerbations during 12 months of follow-up (median 1 respiratory hospitalization, interquartile range [IQR] 0 to 3) versus control (median 1 respiratory hospitalization, IQR 0 to 2; P = 0.6). Digital health technologies for delivering exercise programs Web-based versus face-to-face exercise delivery The evidence is very uncertain about the effects of web-based compared to face-to-face exercise delivery on adherence to physical activity as assessed by the number of participants who completed all exercise sessions after three months of intervention (risk ratio 0.92, 95% CI 0.69 to 1.23; 1 trial, 51 participants). AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of an exercise program plus the use of a wearable fitness tracker integrated with a social media platform compared with exercise prescription alone and on the effects of receiving a wearable fitness tracker plus text message for personalized feedback and goal setting, compared to a wearable fitness tracker alone. Low-certainty evidence suggests that using a web-based application to record, monitor, and set goals on physical activity plus usual care may result in little to no difference in time spent in moderate-to-vigorous physical activity, total time spent in activity, pulmonary exacerbations, quality of life, lung function, and exercise capacity compared to usual care alone. Regarding the use of digital health technologies for delivering exercise programs in CF, the evidence is very uncertain about the effects of using a wearable fitness tracker plus personalized exercise prescription compared to personalized exercise prescription alone. Further high-quality RCTs, with blinded outcome assessors, reporting the effects of digital health technologies on clinically important outcome measures, such as physical activity participation and intensity, self-management behavior, and the occurrence of pulmonary exacerbations in the long term are needed. The results of six ongoing RCTs identified through our searches may help clarify the effects of different modes of digital health technologies for delivering and monitoring exercise programs in people with CF.

Anticoagulants for people hospitalised with COVID-19.

BACKGROUND: 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. OBJECTIVES: To assess the benefits and harms of anticoagulants versus active comparator, placebo or no intervention in people hospitalised with COVID-19. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Ultrasound guidance for arterial (other than femoral) catheterisation in adults.

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.

Prophylactic anticoagulants for people hospitalised with COVID-19.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Interventions for morphea.

BACKGROUND: Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened cutaneous areas. Morphea has different clinical features according to the subtype and stage of evolution of the disease. There is currently no consensus on optimal interventions for morphea. OBJECTIVES: To assess the effects of treatments for people with any form of morphea. SEARCH METHODS: We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and five trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials of topical, intralesional, or systemic treatments (isolated or combined) in anyone who has been clinically diagnosed by a medical practitioner with any form of morphea. Eligible controls were placebo, no intervention, any other treatment, or different doses or duration of a treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcomes were global improvement of disease activity or damage assessed by a medical practitioner or by participants, and adverse effects. Secondary outcomes were improvement of disease activity and improvement of disease damage. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included 14 trials, with a total of 429 randomised participants, aged between 3 and 76 years. There were juvenile and adult participants; over half were female, and the majority had circumscribed morphea, followed by linear scleroderma. The settings of the studies (where described) included a dermatologic centre, a national laboratory centre, paediatric rheumatology and dermatology centres, and a university hospital or medical centre.The studies evaluated heterogenous therapies for different types of morphea, covering a wide range of comparisons. We were unable to conduct any meta-analyses. Seven studies investigated topical medications, two evaluated intralesional medications, and five investigated systemic medications. The study duration ranged from seven weeks to 15 months from baseline.We present here results for our primary outcomes for our four key comparisons. All of these results are based on low-quality evidence.The included studies were at high risk of performance, detection, attrition, and reporting bias.Global improvement of disease activity or damage after treatment may be higher with oral methotrexate (15 mg/m², maximum 20 mg, once a week, for 12 months or until disease flare) plus oral prednisone (1 mg/kg a day, maximum of 50 mg, in a single morning dose, for three months, and one month with gradually decreased dose until discontinuation) than with placebo plus oral prednisone in children and adolescents with active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed) (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.20 to 4.45; number needed to treat for an additional beneficial outcome (NNTB) 3; 1 randomised controlled trial (RCT); 70 participants, all juvenile). This outcome was measured 12 months from the start of treatment or until flare of the disease. Data were not available separately for each morphea type. There may be little or no difference in the number of participants experiencing at least one adverse event with oral methotrexate (26/46) or placebo (11/24) (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT; 70 participants assessed during the 12-month follow-up). Adverse events related to methotrexate included alopecia, nausea, headache, fatigue and hepatotoxicity, whilst adverse events related to prednisone (given in both groups) included weight gain (more than 5% of body weight) and striae rubrae.One three-armed RCT compared the following treatments: medium-dose (50 J/cm²) UVA-1; low-dose (20 J/cm²) UVA-1; and narrowband UVB phototherapy. There may be little or no difference between treatments in global improvement of disease activity or damage, as assessed through the modified skin score (where high values represent a worse outcome): medium-dose UVA-1 phototherapy versus low-dose UVA-1 group: MD 1.60, 95% CI -1.70 to 4.90 (44 participants); narrowband UVB phototherapy versus medium-dose UVA-1 group: MD -1.70, 95% CI -5.27 to 1.87 (35 participants); and narrowband UVB versus low-dose UVA-1 group: MD -0.10, 95% CI -2.49 to 2.29 (45 participants). This RCT included children and adults with active morphea (circumscribed morphea, linear scleroderma (with trunk/limb variant and head variant), generalised morphea, or mixed morphea), who received phototherapy five times a week, for eight weeks. Outcomes were measured at eight weeks from the start of treatment.Safety data, measured throughout treatment, from the same RCT (62 participants) showed that treatment with UVA-1 phototherapy may cause mild tanning compared to narrowband UVB: narrowband UVB versus medium-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.42; 35 participants; narrowband UVB versus low-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.41; 45 participants. However, there may be no difference in the number of participants reporting mild tanning when comparing medium and low dose UVA-1 phototherapy (RR 1.00, 95% CI 0.91 to 1.10; 44 participants). Transient erythema was reported in three participants with narrowband UVB and no participants in the low- or medium-dose UVA-1 groups. AUTHORS' CONCLUSIONS: Compared to placebo plus oral prednisone, oral methotrexate plus oral prednisone may improve disease activity or damage in juvenile active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed), but there may be a slightly increased chance of experiencing at least one adverse event.When medium-dose UVA-1 (50 J/cm²), low-dose UVA-1 (20 J/cm²), and narrowband UVB were compared against each other in treating children and adults with active morphea (circumscribed morphea, linear scleroderma, generalised morphea and mixed morphea), there may be little or no difference between these treatments on global improvement of disease activity or damage. UVA-1 phototherapy may cause more mild tanning than narrowband UVB, but there may be no difference between medium- and low-dose UVA-1 phototherapy. These results are based on low-quality evidence.Limitations of data and analyses include risk of bias and imprecision (small number of participants or events and wide confidence intervals). We encourage multicentre RCTs to increase sample size and evaluate, with validated tools, different treatment responses according to the subtypes of morphea and age groups.