key: cord-299269-ylyhlyzw authors: Luo, X.; Lv, M.; Wang, X.; Long, X.; Ren, M.; Zhang, X.; Liu, Y.; Li, W.; Zhou, Q.; Ma, Y.; Fukuoka, T.; Ahn, H. S.; Lee, M. S.; Luo, Z.; Liu, E.; Chen, Y. title: Supportive Care for Patient with Respiratory Diseases: An Umbrella Review date: 2020-04-17 journal: nan DOI: 10.1101/2020.04.13.20064360 sha: doc_id: 299269 cord_uid: ylyhlyzw Abstract Background: Supportive treatment is an important and effective part of the management for patients with life-threatening diseases. This study aims to identify and evaluate the forms of supportive care for patients with respiratory diseases. Methods: An umbrella review of supportive care for patient respiratory diseases was undertaken. We comprehensively searched the following databases: Medline, EMBASE, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Data and CBM (SinoMed) from their inception to 31 March 2020, and other sources to identify systematic reviews and meta-analyses related to supportive treatments for patient with respiratory diseases including COVID-19, SARS, MERS and influenza. We assessed the methodological quality using the AMSTAR score and the quality of the evidence for the primary outcomes of each included systematic review and meta-analysis. Results: We included 18 systematic reviews and meta-analyses in this study. Most studies focused on the respiratory and circulatory support. Ten studies were of high methodological quality, five studies of medium quality, and three studies of low quality. According to four studies extracorporeal membrane oxygenation did not reduce mortality in adults (OR/RR ranging from 0.71 to 1.28), but two studies reported significantly lower mortality in patients receiving venovenous extracorporeal membrane oxygenation than in the control group (OR/RR ranging from 0.38 to 0.73). Besides, monitoring of vital signs and increasing the number of medical staff may also reduce the mortality in patients with respiratory diseases. Conclusions: Our overview suggests that supportive care may reduce the mortality of patients with respiratory diseases to some extent. However, the quality of evidence for the primary outcomes in the included studies was low to moderate. Further systematic reviews and meta-analyses are needed to address the evidence gap regarding the supportive care for SARS, MERS and COVID-19. The aim of supportive care is to prevent or treat the symptoms of a disease, side effects caused by treatment of a disease, and psychological and social problems related to a disease or its treatment as early as possible (1) . Supportive care can also be called comfort care, palliative care, or symptom management. Supportive care can improve the quality of life of patients who have a serious or life-threatening disease, such as cancer (2) . Besides, for patients with respiratory diseases, supportive care also is an important and effective part of the management (3) . A systematic review related to severe acute respiratory syndrome (SARS) treatment suggested that meticulous supportive care is the only form of treatment that can be recommended (4) . Another systematic review showed that continuous monitoring of vital signs outside the critical care setting is feasible and may provide a benefit in terms of improved patient outcomes and cost efficiency (5) . According to the World Health Organization (WHO) guidelines there is currently no treatment recommended for coronavirus infections except supportive care as needed (6) . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . https://doi.org/10.1101/2020.04. 13.20064360 doi: medRxiv preprint In early 2020, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China, and rapidly spread to more than 100 countries around the world (7) . As of 12 April 2020, more than 1,690,000 cases and more than 100,000 deaths have been confirmed according to the WHO (8) . The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID- 19) , has had been declared a global pandemic (9) However, there is so far no effective treatment or vaccine to curb the spread of the epidemic. Thus, we conducted this overview to identify the available and effective forms of supportive care for patients with respiratory diseases. We hope this review will help physicians working on COVID-19 to understand more about supportive care and make decisions on treatment selection for COVID-19. We performed a systematic search of Medline via PubMed, EMBASE, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Data and CBM (China Biology Medicine disc ) from their inception to 31 March 2020 with the terms All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . https://doi.org/10.1101/2020.04. 13.20064360 doi: medRxiv preprint ("COVID-19" OR "SARS-CoV-2" OR "2019 novel coronavirus" OR "2019-nCoV" OR "Wuhan coronavirus" OR "novel coronavirus" OR "Wuhan seafood market pneumonia virus" OR "MERS" OR "SARS" OR "Severe Acute Respiratory Syndrome" OR "Middle East Respiratory Syndrome Coronavirus" OR "Influenza") AND ("Meta-analysis" OR "Systematic Review" OR "rapid review") (The details of the search strategy can be found in the Supplementary Material 1). Search strategies for other databases are adapted from PubMed. In addition, we searched Google Scholar as well as reference lists of the identified articles, to find additional studies. Three preprint services, including medRxiv (https://www.medrxiv.org/), bioRxiv (https://www.biorxiv.org/) and SSRN (https://www.ssrn.com/index.cfm/en/) were also searched to find relevant studies. We included systematic reviews and meta-analyses related to supportive treatment for patient with respiratory diseases including COVID-19, SARS, MERS and influenza published in English and Chinese without other restrictions. We included systematic All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . https://doi.org/10.1101/2020.04. 13.20064360 doi: medRxiv preprint reviews and meta-analyses that focused on the proportion of medical staff, monitoring of vital signs, respiratory and circulatory support, and psychological intervention. We also considered systematic reviews and meta-analyses with related indirect evidence if no sufficient literature on COVID-19, SARS, MERS and influenza was found. We excluded duplicates, conference abstracts and articles where we failed to access full text and data despite contacting the authors. Two reviewers (X Luo and M Lv) screened all titles, abstracts and full texts independently and solved disagreements by consensus or consultation with a third reviewer. We extracted the following basic information: 1) title, 2) first author, 3) publication year, 4) journal, 5) number of included studies, 6) study design of included studies, and 7) sample size; and the following information on the results; 1) primary outcome, 2) effect size (odds ratio, OR; relative risk, RR), 3) 95% confidence interval (CI), 4) heterogeneity, and 5) main conclusion. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Two researchers (X Wang and X Zhang) independently evaluated the quality of the included studies and cross-checked the results. If necessary, a third reviewer (X Luo) participated in the discussion. Methodological quality assessment of included literature was performed using the AMSTAR tool (10) . The AMSTAR score has a total of 11 points, with studies scoring between 9 and 11 being considered to be of high quality, studies scoring between 6 and 8 of medium quality, and studies scoring between 0 and 5 of low quality. We evaluated the quality of evidence for the primary outcomes of each included systematic review and meta-analysis using the GRADE method (11) . We conducted a descriptive analysis of the included literature. We analyzed studies on the proportion of medical staff, monitoring of vital signs, respiratory and circulatory support, and psychological intervention for patients with respiratory diseases separately. All statistical analyses were conducted in STATA 14.0. A random-effects model was used to show the primary outcomes from each systematic review and meta-analysis. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. A total of 3536 records were identified. After reading the full texts, eighteen systematic reviews and meta-analyses were included (5,12-28) (Figure 1 ). Twelve reviews (13, 14, (16) (17) (18) (22) (23) (24) (25) (26) (27) (28) studied respiratory and circulatory support, three (5, 15, 21) the monitoring of vital signs, two (19, 20) the proportion of medical staff, and one (12) psychological impact. ( Table 1 ) According to the AMSTAR scores, ten studies (13) (14) (15) (20) (21) (22) (23) (24) (25) (26) were of high quality, five studies (5, 16, 17, 19, 28) of medium quality, and three studies (12, 18, 27) of low quality ( Table 2 ). According to our assessment using the GRADE approach, five of the 15 primary outcomes were based on moderate-quality evidence, and ten on low-quality evidence ( Table 3) . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . Heterogeneity was not significant in any combination of four of the five included primary studies (I 2 =0-21%; P>0. 25) . The last of the four reviews reported the outcomes of severe influenza infection with respiratory failure. The overall risk of death was 37% [95% CI, 30%-45%], the median duration for ECMO was 10 days and for mechanical ventilation 19 days, and the median length of ICU stay was 33 days. However, the heterogeneity among studies was large (I 2 =65%). One review reviewed the influence of ventilation in prone position on patients with ARDS. Seven of the 12 included studies in this review evaluated the effect of the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Besides, the syndromic surveillance for influenza and influenza-like-illness from the emergency department is becoming more common to detect yearly influenza outbreaks, as shown in a systematic review. Two systematic reviews reported the impact of the number of medical staff on disease outcomes ( Figure 2) . One examined the association between registered nurse (RN) staffing and patient outcomes in acute care hospitals. The results showed that increased RN staffing was associated with lower mortality in intensive care units (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . A rapid review published in 2020 focused on the psychological impact of quarantine to explore its likely effects on mental health and psychological wellbeing, and the factors that contribute to, or mitigate, these effects. A total of 24 studies were included and the results showed that stressors during quarantine were 1) duration of (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . https://doi.org/10.1101/2020.04.13.20064360 doi: medRxiv preprint altruism and the public health benefits of isolation rather than compulsion. Overall, the psychological impact of quarantine is wide-ranging, substantial, and can be long lasting. Officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Our study showed that for patients with respiratory diseases, especially H1N1 patients, ECMO may effectively reduce mortality, but attention should be paid to the risk of bleeding. For patients in non-critical wards, monitoring and recording of vital signs can effectively reduce mortality. In addition, increasing the number of medical staff in intensive care units can also reduce mortality. At the same time, psychological intervention is equally important for isolating patients. All systematic reviews were of low to moderate quality. Supportive treatment is an important and effective part of the management for patients with respiratory diseases (29) . After systematic searching, we did not find systematic reviews or meta-analyses for supportive care in SARS, MERS or COVID-19-patients, and only five systematic reviews and meta-analyses for influenza. In the absence of direct evidence, we focused on systematic reviews and meta-analysis of ECMO for ARDS. Overall, compared with the control group, ECMO did not reduce mortality in adult patients with ARDS, and the quality of evidence was relatively low due to the large heterogeneity between studies. ECMO can improve All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . https://doi.org/10.1101/2020.04.13.20064360 doi: medRxiv preprint severe hypoxemia in patients with ARDS, keep the lungs at rest, and wait for lung tissue to repair, but the clinical research results on the prognosis of patients with ARDS are not consistent. At the same time, two systematic reviews have shown that venovenous ECMO can reduce ARDS-related mortality, however the risk of bleeding needs to be considered. For patients with H1N1, one of the two currently available systematic reviews also reported that ECMO was associated with reduced risk of death (13, 16) . A systematic review (16) Monitoring vital signs with non-critical patients can reduce patient mortality and shorten the length of hospital stay, but the specific circumstances of the patient need to be considered, such as affordability and acceptability (31). Increasing the number of medical staff in the intensive care unit can reduce the mortality of patients. The likely reason is that due to the increase in the number of caregivers, patients can receive more time, attention and care. However, given the limited medical resources, investing in more medical staff into the ICU may need to be balanced by savings in some other expenditure, for example staff in other departments. Therefore, investing more medical staff into the ICU still needs further evaluation. In addition, for infectious diseases like SARS, MERS and COVID-19, psychological intervention is equally important. We found systematic reviews that analyzed the factors that may cause mental illness and provides psychological All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. We used the AMSTAR tool to evaluate the methodological quality of the included systematic reviews and meta-analyses and found that the overall quality is relatively high. In terms of evidence quality, the main problem was the large heterogeneity between included studies. The included studies contained only indirect evidence, and the reliability of the overall quality of evidence was low to moderate, which must be taken into consideration when the evidence is used for making clinical practice guidelines. To our knowledge, this is the first overview of systematic review focusing on the supportive care for patient with respiratory diseases. We comprehensively searched systematic reviews and meta-analyses on SARS, MERS, COVID-19 and influenza and evaluated the quality of methodology and evidence. Nevertheless, our work has several limitations. First, we conducted a rapid literature searching and screening, and some relevant studies may have been missed. Second, none of the included systematic reviews focused on COVID-19, SARS or MERS, so they can be only used as indirect evidence. Finally, there was large heterogeneity between the included studies, and most primary studies included in these systematic reviews were observational studies, which may influence the reliability of the reviews. However, systematic reviews and meta-analyses of non-randomized studies can be meaningful and guide clinical research and practice, even if only by emphasizing the limitations of the available clinical evidence. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. In conclusion, our overview suggests that supportive cares may reduce the mortality of patients with respiratory diseases to some extent. Having more medical staff in ICU, using of ECMO, monitoring vital signs and conducting counselling to patients (VII) Final approval of manuscript: All authors. We thank Janne Estill, Institute of Global Health of University of Geneva for providing guidance and comments for our review. We thank all the authors for their wonderful collaboration. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. We are very confident that the true effect lies close to that of the estimate of the effect. Moderate: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. a Quality of included studies poor because of inadequate study design and follow-up time. b Serious inconsistency for the scattered 95% CI. c Indirect evidence for target population. d Wide confidence intervals, serious imprecision. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . https://doi.org/10.1101/2020.04.13.20064360 doi: medRxiv preprint Figure 2 Results of meta-analyses on mortality from the included systematic reviews. The effect sizes are reported either as risk ratio or odds ratio comparing the risk/odds of death in the intervention with control group. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 17, 2020. . The role of palliative care at the end of life Utilization of supportive and palliative care services among oncology outpatients at one academic cancer center: determinants of use and barriers to access The potential of palliative care for patients with respiratory diseases SARS: systematic review of treatment effects The impact of continuous versus intermittent vital signs monitoring in hospitals: A systematic review and narrative synthesis Novel Coronavirus (2019-nCoV) technical guidance: Patient management World Health Organization; c2020 Evaluation and Treatment Coronavirus (COVID-19) World Health Organization; c2020 WHO characterizes COVID-19 as a pandemic Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews GRADE: an emerging consensus on rating quality of evidence and strength of recommendations The psychological impact of quarantine and how to reduce it: rapid review of the evidence Extracorporeal membrane oxygenation in severe influenza infection with respiratory failure: A systematic review and meta-analysis Extracorporeal Membrane Oxygenation in Pregnant and Postpartum Women With H1N1-Related Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis Syndromic surveillance for influenza in the emergency department-A systematic review Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO A systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the H1N1 influenza pandemic The role of extracorporeal membrane oxygenation for treatment of the adult respiratory distress syndrome: review and quantitative analysis The association of registered nurse staffing levels and patient outcomes: systematic review and meta-analysis The effect of nurse-to-patient ratios on nurse-sensitive patient outcomes in acute specialist units: a systematic review and meta-analysis Effectiveness of continuous or intermittent vital signs monitoring in preventing adverse events on general wards: a systematic review and meta-analysis Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis Extracorporeal Life Support: The Next Step in Moderate to Severe ARDS-A Review and Meta-Analysis of the Literature Extracorporeal membrane oxygenation (ECMO) as a treatment strategy for severe acute respiratory distress syndrome (ARDS) in the low tidal volume era: A systematic review Systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome A meta-analysis of extracorporeal membrane oxygenation for acute respiratory distress syndrome Influence of Ventilation in Prone Position on Patients with Acute Respiratory Distress Syn-drome: A Meta Analysis Use of Extracorporeal Membrane Oxygenation on Adults with adult Acute Respiratory Distress Syndrome: A meta-analysis and Systematic Review Supporting patients self-managing respiratory health: a qualitative study on the impact of the Breathe Easy voluntary group network