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Antiandrogens for COVID-19: real-time meta analysis of 39 studies
Covid Analysis, August 14, 2022, DRAFT
https://c19early.com/aameta.html
0 0.5 1 1.5+ All studies 26% 39 89,992 Improvement, Studies, Patients Relative Risk Mortality 31% 27 86,012 Ventilation 43% 10 1,296 ICU admission 26% 9 6,181 Hospitalization 16% 11 6,901 Progression 49% 3 221 Recovery 42% 10 1,285 Cases 9% 11 92,725 Viral clearance 37% 3 560 RCTs 48% 12 910 RCT mortality 51% 9 637 Peer-reviewed 24% 35 89,396 Prophylaxis 8% 20 61,661 Early 55% 3 26,865 Late 59% 16 1,466 Antiandrogens for COVID-19 c19early.com/aa Aug 2022 Favorsantiandrogen Favorscontrol after exclusions
Statistically significant improvements are seen for mortality, ventilation, recovery, cases, and viral clearance. 22 studies from 20 independent teams in 12 different countries show statistically significant improvements in isolation (14 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 26% [17‑35%] improvement. Results are better for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies.
Results are robust — in exclusion sensitivity analysis 20 of 39 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
0 0.5 1 1.5+ All studies 26% 39 89,992 Improvement, Studies, Patients Relative Risk Mortality 31% 27 86,012 Ventilation 43% 10 1,296 ICU admission 26% 9 6,181 Hospitalization 16% 11 6,901 Progression 49% 3 221 Recovery 42% 10 1,285 Cases 9% 11 92,725 Viral clearance 37% 3 560 RCTs 48% 12 910 RCT mortality 51% 9 637 Peer-reviewed 24% 35 89,396 Prophylaxis 8% 20 61,661 Early 55% 3 26,865 Late 59% 16 1,466 Antiandrogens for COVID-19 c19early.com/aa Aug 2022 Favorsantiandrogen Favorscontrol after exclusions
This analysis combines the results of several different antiandrogens. Results for individual treatments may vary. Proxalutamide is analyzed separately.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 13% of antiandrogen studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments are more effective.
No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.
All data to reproduce this paper and sources are in the appendix. [Kotani] present another meta analysis for antiandrogens, showing significant improvements for mortality and progression.
Highlights
Antiandrogens reduce risk for COVID-19 with very high confidence for mortality, ventilation, recovery, viral clearance, and in pooled analysis, high confidence for cases, and very low confidence for ICU admission, hospitalization, and progression. This analysis combines the results of several different antiandrogens. Proxalutamide is analyzed separately.
We show traditional outcome specific analyses and combined evidence from all studies, incorporating treatment delay, a primary confounding factor in COVID-19 studies.
Real-time updates and corrections, transparent analysis with all results in the same format, consistent protocol for 43 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Cadegiani 77% 0.23 [0.08-0.66] recov. time 8 (n) 262 (n) Improvement, RR [CI] Treatment Control Cadegiani (DB RCT) 62% 0.38 [0.18-0.82] no recov. 7/44 18/43 Hunt 39% 0.61 [0.51-0.73] death 167/1,788 1,445/24,720 Tau​2 = 0.13, I​2 = 55.5%, p = 0.0037 Early treatment 55% 0.45 [0.26-0.77] 174/1,840 1,463/25,025 55% improvement Vicenzi 93% 0.07 [0.04-0.53] death 30 (n) 39 (n) OT​1 Improvement, RR [CI] Treatment Control Goren 81% 0.19 [0.03-1.28] ICU 1/12 17/36 Mareev (RCT) 11% 0.89 [0.65-1.22] no recov. 33 (n) 33 (n) CT​2 Zarehoseinz.. (RCT) 75% 0.25 [0.03-2.14] death 1/40 4/40 Ghandehari (RCT) -22% 1.22 [0.08-18.2] death 1/18 1/22 Ersoy (ICU) 46% 0.54 [0.36-0.81] death 14/30 26/30 ICU patients Welén (RCT) 80% 0.20 [0.01-4.65] death 0/29 1/10 Davarpanah 78% 0.22 [0.08-0.55] hosp. 6/103 23/103 CT​2 Kotfis (RCT) 17% 0.83 [0.25-2.74] death 4/24 5/25 Abbasi (SB RCT) 55% 0.45 [0.18-1.13] death 5/51 19/87 Gomaa (DB RCT) 91% 0.09 [0.01-1.56] death 0/25 5/25 CT​2 Hsieh 88% 0.12 [0.01-2.22] death 0/117 4/143 CT​2 Nickols (DB RCT) 18% 0.82 [0.32-1.82] death 11/62 7/34 Gordon (DB RCT) 82% 0.18 [0.03-0.94] death n/a n/a Wadhwa (RCT) 72% 0.28 [0.09-0.85] progression 4/74 9/46 Barnette (DB RCT) 55% 0.45 [0.27-0.74] death 19/94 23/51 Tau​2 = 0.22, I​2 = 55.2%, p < 0.0001 Late treatment 59% 0.41 [0.28-0.59] 66/742 144/724 59% improvement Montopoli 95% 0.05 [0.00-0.77] death 0/5,273 18/37,161 Improvement, RR [CI] Treatment Control Koskinen 46% 0.54 [0.06-5.16] death 1/134 3/218 Patel 55% 0.45 [0.11-1.47] death 4/22 10/36 Bennani 95% 0.05 [0.00-2063] death 0/4 18/114 Lazzeri -23% 1.23 [0.81-1.87] death/ICU Kwon 21% 0.79 [0.10-6.40] death 1/799 7/4,412 Klein -124% 2.24 [0.86-5.85] death 6/304 13/1,475 Jeon 77% 0.23 [0.08-0.64] cases case control Shaw (PSM) 6% 0.94 [0.88-1.01] cases 47 (n) 97 (n) Israel 38% 0.62 [0.41-0.91] hosp. case control Jiménez-Alcaide 33% 0.67 [0.26-1.74] death 3/11 17/50 Kazan -229% 3.29 [0.61-17.7] hosp. 4/138 2/227 Schmidt (PSM) 20% 0.80 [0.46-1.34] death 25/169 44/308 Duarte 11% 0.89 [0.59-1.11] death 100/156 32/43 Welén 2% 0.98 [0.61-1.59] death 21/358 167/4,980 Gedeborg -25% 1.25 [0.95-1.65] death case control Lyon 17% 0.83 [0.42-1.63] death 15/944 19/994 Lee (PSW) 21% 0.79 [0.62-0.97] severe case 76/295 727/2,427 MacFadden 7% 0.93 [0.88-0.98] cases n/a n/a Shah -16% 1.16 [0.68-1.98] death 148 (n) 317 (n) Tau​2 = 0.01, I​2 = 58.3%, p = 0.075 Prophylaxis 8% 0.92 [0.83-1.01] 256/8,802 1,077/52,859 8% improvement All studies 26% 0.74 [0.65-0.83] 496/11,384 2,684/78,608 26% improvement 39 antiandrogen COVID-19 studies c19early.com/aa Aug 2022 Tau​2 = 0.04, I​2 = 73.9%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors antiandrogen Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Cadegiani 77% recovery Improvement Relative Risk [CI] Cadegiani (DB RCT) 62% recovery Hunt 39% death Tau​2 = 0.13, I​2 = 55.5%, p = 0.0037 Early treatment 55% 55% improvement Vicenzi 93% death OT​1 Goren 81% ICU admission Mareev (RCT) 11% recovery CT​2 Zarehoseinz.. (RCT) 75% death Ghandehari (RCT) -22% death Ersoy (ICU) 46% death ICU patients Welén (RCT) 80% death Davarpanah 78% hospitalization CT​2 Kotfis (RCT) 17% death Abbasi (SB RCT) 55% death Gomaa (DB RCT) 91% death CT​2 Hsieh 88% death CT​2 Nickols (DB RCT) 18% death Gordon (DB RCT) 82% death Wadhwa (RCT) 72% progression Barnette (DB RCT) 55% death Tau​2 = 0.22, I​2 = 55.2%, p < 0.0001 Late treatment 59% 59% improvement Montopoli 95% death Koskinen 46% death Patel 55% death Bennani 95% death Lazzeri -23% death/ICU Kwon 21% death Klein -124% death Jeon 77% case Shaw (PSM) 6% case Israel 38% hospitalization Jiménez-Alcaide 33% death Kazan -229% hospitalization Schmidt (PSM) 20% death Duarte 11% death Welén 2% death Gedeborg -25% death Lyon 17% death Lee (PSW) 21% severe case MacFadden 7% case Shah -16% death Tau​2 = 0.01, I​2 = 58.3%, p = 0.075 Prophylaxis 8% 8% improvement All studies 26% 26% improvement 39 antiandrogen COVID-19 studies c19early.com/aa Aug 2022 Tau​2 = 0.04, I​2 = 73.9%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors antiandrogen Favors control
Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix. B. Scatter plot showing the distribution of effects reported in studies. C. History of all reported effects (chronological within treatment stages).
Introduction
We analyze all significant studies concerning the use of antiandrogens for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for individual outcomes, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.
Preclinical Research
An In Silico study supports the efficacy of antiandrogens [Saih].
An In Vivo animal study supports the efficacy of antiandrogens [Leach].
Preclinical research is an important part of the development of treatments, however results may be very different in clinical trials. Preclinical results are not used in this paper.
Results
Figure 3 shows a visual overview of the results, with details in Table 1 and Table 2. Figure 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, viral clearance, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION PROGRESSION RECOVERY CASES VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Antiandrogens for COVID-19 C19EARLY.COM/AA AUG 2022
Figure 3. Overview of results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Early treatment 3 3 100% 55% improvement
RR 0.45 [0.26‑0.77]
p = 0.0037
Late treatment 15 16 93.8% 59% improvement
RR 0.41 [0.28‑0.59]
p < 0.0001
Prophylaxis 15 20 75.0% 8% improvement
RR 0.92 [0.83‑1.01]
p = 0.075
All studies 33 39 84.6% 26% improvement
RR 0.74 [0.65‑0.83]
p < 0.0001
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 3955% [23‑74%]59% [41‑72%]8% [-1‑17%] 89,992 448
With exclusions 3639% [27‑49%]59% [41‑72%]9% [-0‑17%] 89,270 430
Peer-reviewed 3544% [20‑60%]54% [33‑69%]10% [0‑18%] 89,396 406
Randomized Controlled TrialsRCTs 1262% [18‑82%]45% [21‑62%] 910 161
Table 2. Results by treatment stage for all studies and with different exclusions.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Cadegiani 77% 0.23 [0.08-0.66] recov. time 8 (n) 262 (n) Improvement, RR [CI] Treatment Control Cadegiani (DB RCT) 62% 0.38 [0.18-0.82] no recov. 7/44 18/43 Hunt 39% 0.61 [0.51-0.73] death 167/1,788 1,445/24,720 Tau​2 = 0.13, I​2 = 55.5%, p = 0.0037 Early treatment 55% 0.45 [0.26-0.77] 174/1,840 1,463/25,025 55% improvement Vicenzi 93% 0.07 [0.04-0.53] death 30 (n) 39 (n) OT​1 Improvement, RR [CI] Treatment Control Goren 81% 0.19 [0.03-1.28] ICU 1/12 17/36 Mareev (RCT) 11% 0.89 [0.65-1.22] no recov. 33 (n) 33 (n) CT​2 Zarehoseinz.. (RCT) 75% 0.25 [0.03-2.14] death 1/40 4/40 Ghandehari (RCT) -22% 1.22 [0.08-18.2] death 1/18 1/22 Ersoy (ICU) 46% 0.54 [0.36-0.81] death 14/30 26/30 ICU patients Welén (RCT) 80% 0.20 [0.01-4.65] death 0/29 1/10 Davarpanah 78% 0.22 [0.08-0.55] hosp. 6/103 23/103 CT​2 Kotfis (RCT) 17% 0.83 [0.25-2.74] death 4/24 5/25 Abbasi (SB RCT) 55% 0.45 [0.18-1.13] death 5/51 19/87 Gomaa (DB RCT) 91% 0.09 [0.01-1.56] death 0/25 5/25 CT​2 Hsieh 88% 0.12 [0.01-2.22] death 0/117 4/143 CT​2 Nickols (DB RCT) 18% 0.82 [0.32-1.82] death 11/62 7/34 Gordon (DB RCT) 82% 0.18 [0.03-0.94] death n/a n/a Wadhwa (RCT) 72% 0.28 [0.09-0.85] progression 4/74 9/46 Barnette (DB RCT) 55% 0.45 [0.27-0.74] death 19/94 23/51 Tau​2 = 0.22, I​2 = 55.2%, p < 0.0001 Late treatment 59% 0.41 [0.28-0.59] 66/742 144/724 59% improvement Montopoli 95% 0.05 [0.00-0.77] death 0/5,273 18/37,161 Improvement, RR [CI] Treatment Control Koskinen 46% 0.54 [0.06-5.16] death 1/134 3/218 Patel 55% 0.45 [0.11-1.47] death 4/22 10/36 Bennani 95% 0.05 [0.00-2063] death 0/4 18/114 Lazzeri -23% 1.23 [0.81-1.87] death/ICU Kwon 21% 0.79 [0.10-6.40] death 1/799 7/4,412 Klein -124% 2.24 [0.86-5.85] death 6/304 13/1,475 Jeon 77% 0.23 [0.08-0.64] cases case control Shaw (PSM) 6% 0.94 [0.88-1.01] cases 47 (n) 97 (n) Israel 38% 0.62 [0.41-0.91] hosp. case control Jiménez-Alcaide 33% 0.67 [0.26-1.74] death 3/11 17/50 Kazan -229% 3.29 [0.61-17.7] hosp. 4/138 2/227 Schmidt (PSM) 20% 0.80 [0.46-1.34] death 25/169 44/308 Duarte 11% 0.89 [0.59-1.11] death 100/156 32/43 Welén 2% 0.98 [0.61-1.59] death 21/358 167/4,980 Gedeborg -25% 1.25 [0.95-1.65] death case control Lyon 17% 0.83 [0.42-1.63] death 15/944 19/994 Lee (PSW) 21% 0.79 [0.62-0.97] severe case 76/295 727/2,427 MacFadden 7% 0.93 [0.88-0.98] cases n/a n/a Shah -16% 1.16 [0.68-1.98] death 148 (n) 317 (n) Tau​2 = 0.01, I​2 = 58.3%, p = 0.075 Prophylaxis 8% 0.92 [0.83-1.01] 256/8,802 1,077/52,859 8% improvement All studies 26% 0.74 [0.65-0.83] 496/11,384 2,684/78,608 26% improvement 39 antiandrogen COVID-19 studies c19early.com/aa Aug 2022 Tau​2 = 0.04, I​2 = 73.9%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors antiandrogen Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Cadegiani 77% recovery Improvement Relative Risk [CI] Cadegiani (DB RCT) 62% recovery Hunt 39% death Tau​2 = 0.13, I​2 = 55.5%, p = 0.0037 Early treatment 55% 55% improvement Vicenzi 93% death OT​1 Goren 81% ICU admission Mareev (RCT) 11% recovery CT​2 Zarehoseinz.. (RCT) 75% death Ghandehari (RCT) -22% death Ersoy (ICU) 46% death ICU patients Welén (RCT) 80% death Davarpanah 78% hospitalization CT​2 Kotfis (RCT) 17% death Abbasi (SB RCT) 55% death Gomaa (DB RCT) 91% death CT​2 Hsieh 88% death CT​2 Nickols (DB RCT) 18% death Gordon (DB RCT) 82% death Wadhwa (RCT) 72% progression Barnette (DB RCT) 55% death Tau​2 = 0.22, I​2 = 55.2%, p < 0.0001 Late treatment 59% 59% improvement Montopoli 95% death Koskinen 46% death Patel 55% death Bennani 95% death Lazzeri -23% death/ICU Kwon 21% death Klein -124% death Jeon 77% case Shaw (PSM) 6% case Israel 38% hospitalization Jiménez-Alcaide 33% death Kazan -229% hospitalization Schmidt (PSM) 20% death Duarte 11% death Welén 2% death Gedeborg -25% death Lyon 17% death Lee (PSW) 21% severe case MacFadden 7% case Shah -16% death Tau​2 = 0.01, I​2 = 58.3%, p = 0.075 Prophylaxis 8% 8% improvement All studies 26% 26% improvement 39 antiandrogen COVID-19 studies c19early.com/aa Aug 2022 Tau​2 = 0.04, I​2 = 73.9%, p < 0.0001 Effect extraction pre-specifiedRotate device for footnotes/details Favors antiandrogen Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Hunt 39% 0.61 [0.51-0.73] 167/1,788 1,445/24,720 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 39% 0.61 [0.51-0.73] 167/1,788 1,445/24,720 39% improvement Vicenzi 93% 0.07 [0.04-0.53] 30 (n) 39 (n) OT​1 Improvement, RR [CI] Treatment Control Goren -50% 1.50 [0.15-15.1] 1/12 2/36 Zarehoseinz.. (RCT) 75% 0.25 [0.03-2.14] 1/40 4/40 Ghandehari (RCT) -22% 1.22 [0.08-18.2] 1/18 1/22 Ersoy (ICU) 46% 0.54 [0.36-0.81] 14/30 26/30 ICU patients Welén (RCT) 80% 0.20 [0.01-4.65] 0/29 1/10 Kotfis (RCT) 17% 0.83 [0.25-2.74] 4/24 5/25 Abbasi (SB RCT) 55% 0.45 [0.18-1.13] 5/51 19/87 Gomaa (DB RCT) 91% 0.09 [0.01-1.56] 0/25 5/25 CT​2 Hsieh 88% 0.12 [0.01-2.22] 0/117 4/143 CT​2 Nickols (DB RCT) 18% 0.82 [0.32-1.82] 11/62 7/34 Gordon (DB RCT) 82% 0.18 [0.03-0.94] n/a n/a Barnette (DB RCT) 55% 0.45 [0.27-0.74] 19/94 23/51 Tau​2 = 0.11, I​2 = 28.5%, p < 0.0001 Late treatment 56% 0.44 [0.30-0.64] 56/532 97/542 56% improvement Montopoli 95% 0.05 [0.00-0.77] 0/5,273 18/37,161 Improvement, RR [CI] Treatment Control Koskinen 46% 0.54 [0.06-5.16] 1/134 3/218 Patel 55% 0.45 [0.11-1.47] 4/22 10/36 Bennani 95% 0.05 [0.00-2063] 0/4 18/114 Kwon 21% 0.79 [0.10-6.40] 1/799 7/4,412 Klein -124% 2.24 [0.86-5.85] 6/304 13/1,475 Jiménez-Alcaide 33% 0.67 [0.26-1.74] 3/11 17/50 Schmidt (PSM) 20% 0.80 [0.46-1.34] 25/169 44/308 Duarte 11% 0.89 [0.59-1.11] 100/156 32/43 Welén 2% 0.98 [0.61-1.59] 21/358 167/4,980 Gedeborg -25% 1.25 [0.95-1.65] case control Lyon 17% 0.83 [0.42-1.63] 15/944 19/994 Shah -16% 1.16 [0.68-1.98] 148 (n) 317 (n) Tau​2 = 0.04, I​2 = 37.8%, p = 0.75 Prophylaxis 3% 0.97 [0.79-1.18] 176/8,322 348/50,108 3% improvement All studies 31% 0.69 [0.55-0.87] 399/10,642 1,890/75,370 31% improvement 27 antiandrogen COVID-19 mortality results c19early.com/aa Aug 2022 Tau​2 = 0.14, I​2 = 68.6%, p = 0.0015 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors antiandrogen Favors control
Figure 5. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Ghandehari (RCT) 85% 0.15 [0.01-2.82] 0/18 3/22 Improvement, RR [CI] Treatment Control Welén (RCT) 31% 0.69 [0.07-6.81] 2/29 1/10 Abbasi (SB RCT) 34% 0.66 [0.30-1.48] 7/51 18/87 Gomaa (DB RCT) 91% 0.09 [0.01-1.56] 0/25 5/25 CT​1 Hsieh 51% 0.49 [0.10-2.47] 2/117 5/143 CT​1 Nickols (DB RCT) -19% 1.19 [0.50-2.84] 13/62 6/34 Gordon (DB RCT) 76% 0.24 [0.03-1.63] n/a n/a Barnette (DB RCT) 49% 0.51 [0.33-0.76] 98 (n) 52 (n) Tau​2 = 0.00, I​2 = 0.0%, p = 0.00045 Late treatment 44% 0.56 [0.41-0.77] 24/400 38/373 44% improvement Patel 69% 0.31 [0.05-1.81] 22 (n) 36 (n) Improvement, RR [CI] Treatment Control Shah 19% 0.81 [0.25-2.66] 148 (n) 317 (n) Tau​2 = 0.00, I​2 = 0.0%, p = 0.31 Prophylaxis 39% 0.61 [0.23-1.58] 0/170 0/353 39% improvement All studies 43% 0.57 [0.42-0.77] 24/570 38/726 43% improvement 10 antiandrogen COVID-19 mechanical ventilation results c19early.com/aa Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.00027 1 CT: study uses combined treatment Favors antiandrogen Favors control
Figure 6. Random effects meta-analysis for ventilation.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Goren 81% 0.19 [0.03-1.28] 1/12 17/36 Improvement, RR [CI] Treatment Control Zarehoseinz.. (RCT) 0% 1.00 [0.06-15.4] 1/40 1/40 Kotfis (RCT) 11% 0.89 [0.35-2.28] 6/24 7/25 Abbasi (SB RCT) 19% 0.81 [0.42-1.59] 10/51 21/87 Hsieh 30% 0.70 [0.21-2.33]