Table 1.

RCTs of the effectiveness of HCW mask wearing and hand hygiene to prevent transmission of influenza.

Author, date country	Participants and intervention	Study design	Comparison	Influenza rate in community, vaccination status of participants	Outcome	Compliance with mask wearing	Results
Health care workers, mask wearing directly observed, outcome = laboratory confirmed influenza in HCW
Loeb 2009, Canada [38]	Emergency departments, medical and pediatric units in 8 Ontario tertiary care hospitals during 2008/9 influenza season. When caring for febrile respiratory patients during influenza season: (1) 225 nurses randomized to surgical masks, and (2) 221 fit-tested N95 respirators. [It was routine practice to wear gowns and gloves in room of patient with febrile respiratory illness); no data on training or fit testing (although fit testing of masks was compulsory for nurses in Ontario]	C-RCT; randomization by independent clinical trials coordinating group; lab staff conducting influenza tests blinded; 225 randomized to surgical mask (212 included in analysis); 221 randomized to N95 (210 included in analysis)	No control	“Largely unvaccinated cohort of nurses followed closely during a period of relatively mild influenza-like illness and into the beginning of what is now considered a pandemic period” [H1N1 pandemic]. Vaccinated against influenza: 30.2% surgical mask group, 28.1% N95 respirator group	Web based self-report of influenza signs and symptoms weekly (those who did not report were contacted) and those with new symptoms performed nasal swab; Influenza by RT-PCR or 4 fold rise in serum titres	Research assistant called medical and pediatric units to ask if any patients admitted with droplet precautions for influenza or febrile respiratory illness; “a trained auditor was sent to the unit to observe for compliance. The auditor was instructed to stand a short distance from the patient isolation room …to accurately record the audit.” Only 1 room entry reported per observation. No audits within patient rooms or emergency department, no audit of hand hygiene or use of gloves or gowns.	Influenza by RT-PCR or 4 fold rise in serum titres (per protocol not intention-to-treat analysis): 23.6% mask, 22.9% N95; RD = -0.73% (95%CI -8.8%, 7.3%), p = 0.86 Attrition: [212/225 surgical mask and 210/221 N95 analyzed] Macintyre 2013 argues was “probably underpowered”; “care was “only during care of identified febrile patients with ILI or having high-risk procedures;” and “the study does not disclose the serologic status of those participants who received influenza vaccination, who seem to have been included in the denominator for analysis.”
MacIntyre 2011, China [39]	Beijing emergency departments and respiratory wards (high risk for respiratory exposure) in 15 hospitals (5 Level 2, 10 Level 3 with more sophisticated equipment) for respiratory outbreaks during study period Dec 2008 to Jan 2009; participants wore masks or N95 every shift x 4 weeks; (1) surgical masks (492 HCWs in 5 hospitals); (2) N95 fit-tested 461 HCWs in 5 hospitals; (3) N95 not fit-tested 488 HCWs in 5 hospitals; staff instructed on hand hygiene putting on and removing masks	C-RCT, hospitals computer randomized; power computation for 5% attack rate N95 arm (fit tested), N95 arm (not fit tested) and 12% medical mask arm, 80% power, alpha = 5%, intra cluster correlation 0.01 required 500/arm	Non-random sample emergency departments and hospital wards in 9 hospitals of HCWs who did not wear masks (randomized control group not acceptable to Chinese ethics board as mask wearing was widespread)	All hospitals monitored for respiratory outbreaks during study period Dec 2008 to Jan 2009 and none detected; participants contacted daily or face-to-face identify cases of respiratory infection and head nurse on each ward followed up reports and identified illness; District CDC also monitored sites daily.	Laboratory confirmed Influenza RT-PCR; given thermometer to record daily temperature or if symptoms; self reported ILI on daily diary cards monitored weekly by researchers, self-reported CRI	Not stated how reports of compliance by supervisors and daily diary cards integrated. Mask wearing during 80% of working days: N95 fit-tested 74%; N95 non fit-tested 68%, medical mask 76%. Duration of mask wearing: N95 fit-tested 5.2 hours; N95 non fit-tested 4.9 h, medical mask 5 h.	Intention-to treat multivariate analysis laboratory RT-PCR confirmed influenza: fit-tested N95 mask 3/461 OR = 0.64 (0.15, 2.68), p = 0.54; non fit-tested N95 0/488; surgical mask 5/492. Intention-to treat multivariate analysis any laboratory confirmed respiratory virus: fit-tested N95 mask 8/461 OR = 0.69 (0.24, 2.03), p = 0.50; non fit-tested N95 5/488 OR = 0.39 (0.12, 1.22, p = 0.11; surgical mask 13/492. Study underpowered Mask group included only level 3 (most sophisticated) hospitals; Authors suggest “study may have been underpowered because attack rates were lower than expected.”
Health care workers, mask wearing, not directly observed, outcome = laboratory confirmed influenza
Jacobs 2009, Japan [54]	17 HCWs wore surgical mask on duty		15 only if task required		Self-reported “cold” symptoms, no lab tests	84% self report	“cold symptoms” No significant differences. Study underpowered
MacIntyre 2013, Beijing [55]	Beijing, medical staff on 68 wards in 19 hospitals. (1) medical masks at all times on shift (n = 592), or (2) N95 respirators at all times on shift (n = 581) or (3) N95 respirators only when doing high risk procedures (n = 516)	C-RCT (by ward); observed for 4 weeks of intervention and 4 weeks thereafter to monitor for infections incubated in the first 4 weeks; power computation to detect significant difference between arms: 80% power, two sided 5%, assumed clinical respiratory rate 3.9% in N95 and 9.2% in mask arms, ICC = 0.027, needed 560/arm; intention-to-treat	No control	28 Dec 2009 to 7 Feb 2010 (winter season); staff vaccination rate A(H1N1)pdm09 2009–10 mask (19.1%), targeted N95 (25.2%), N95 (29.4%); p <0.001); Seasonal influenza 2009–10 mask (15.4%), targeted N95 (9.9%), N95 (14.6%); p = 0.017); Reported hand washing after patient contact at all times --mask (72.9%), targeted N95 (60.7%), N95 (77.1%); p = 0.0001)	1. Laboratory-confirmed Influenza, adenoviruses, human metapneumovirus, coronavirus, parainfluenza 1,2,3, RSV A and B, rhinoviruses A/B 2. ILI (T 38 °C + one respiratory symptom) 3. Clinical respiratory illness (2 respiratory or 1 respiratory and 1 systemic symptom)	Self-report (thermometer; diary cards collected daily), contacted daily to identify respiratory infections; “significantly poorer adherence in the continuous use N95 arm.”	Intention-to-treat laboratory-confirmed respiratory viruses: mask (19/572, 3.3%), targeted N95 (17/516, 3.3%), N95 (13/581, 2.2%), [Targeted N95 vs. mask p = 0.985; N95 vs mask p = 0.44] Study underpowered ILI: mask (4/572, 3/3%), targeted N95 (2/516, 3.3%), N95 (6/581, 2.2%), [Targeted N95 vs. mask p = 0.49; N95 vs mask p = 0.54] [6 cases of influenza A or B; other respiratory viruses in 43 staff (of which 17 RSV)] Intention-to-treat laboratory confirmed bacteria in HCWs with clinical respiratory illness: medical mask 84/572 (14.7%); targeted N95 52/516 (10.1%); N95 36/581 (6.2% (p = 0.012)
MacIntyre 2015, Vietnam	1607 HCWs on 74 high risk wards (emergency, infectious/respiratory disease, ICU, paediatrics)	HCWs randomized to medical masks, cloth mask or control (usually masks) every shift x 4 consecutive weeks		“Circulating influenza and RSV were almost completely absent during this study;” HCW influenza vaccination rates 3%	Laboratory confirmed for 17 viruses; compliance with mask wearing ≥70% of work shift hours		Intention-to-treat laboratory confirmed viruses in HCWs: cloth masks 31/569 (5.4%), control 18/458, (4.0%), medical masks 19/580 (3%); (no Influenza A, one Influenza B/rhinovirus co-infection)
Atrie 2011, Canada	221 nurses in emergency, medical and pediatric wards assigned to wear N95 respirators, 225 surgical masks	Randomization centrally, investigators and lab personnel blinded. Noninferiority trials of N95 respirators vs. surgical masks, no control group. Investigators specified lower limit of 95%CI for N95 respirators as 9% lower than for incidence if in HCWs surgical masks	No control	No data on HCW vaccination rates or community rates or HCW influenza exposure in non-clinical settings	Incidence of influenza in HCW, assessed by PCR or fourfold rise in hemagglutinin titres	No data on mask wearing	No significant difference in influenza infection surgical masks 23.6%, N95 respirators 22.9%, p = 0.86

HCW: health care worker; ILI: influenza like illness; CRI: clinically reported illness .