10 Thomas et al: Physiotherapy and COVID-19 update kidney disease, blood cancer, epilepsy, chronic obstructive pulmonary proning’ has evolved during the pandemic, where non-intubated disease, coronary heart disease, stroke, atrial fibrillation, heart failure, patients with severe COVID-19 who require supplemental oxygen thromboembolism, peripheral vascular disease, and type 2 diabetes.11 are encouraged to lie prone for prolonged periods to improve oxygenation.44 Awake proning has previously been used in ARDS Medical management of severe and critical COVID-19 patients45 and in COVID-19 has been used in conjunction with res- piratory support such as high-flow oxygen46 and CPAP using helmet Therapies for the management of COVID-19 continue to be eval- interfaces.47 While awake proning is recommended and appears to uated. Some treatments that were initially used have been shown to achieve improvements in oxygenation without any serious adverse have no benefit, including azithromycin and hydroxychloroquine.6 events, further evaluation is needed as there is significant variability Corticosteroids (eg, dexamethasone) when administered for a in its application within current publications and its impact on out- period up to 10 days in patients who are receiving supplemental comes such as rate of intubation or mortality rates is unclear.48–51 oxygen or are mechanically ventilated may increase ventilator-free Early implementation of awake proning, for example within 24 days and reduce mortality.28,29 Other medications, including bude- hours of a patient requiring high-flow oxygen, may be an important sonide, baricitinib, sarilumab, remdesivir, sotrovimab and tocilizu- factor.52 However, awake proning may be uncomfortable for some mab, may also be considered for their role in reducing the patients, leading to low adherence.47 progression or severity of symptoms related to COVID-19.6 Impor- tantly, variations exist around their indications (eg, whether they are Post-COVID conditions prescribed for patients who do or do not require oxygen or me- chanical ventilation) for specific age groups and/or need consider- Knowledge is increasing about the long-term impacts of COVID- ation of risk factors like immunodeficiency.6 19, which are referred to as post-COVID conditions,53 post-COVID syndrome54 or Long COVID.55 Post-COVID conditions can affect peo- Among patients with severe COVID-19, the time course of dete- ple with mild disease through to those hospitalised with severe and rioration is often delayed, with the median time from the onset of critical disease.56 The WHO’s definition of post-COVID conditions is illness to experiencing dyspnoea being 5 to 8 days and to signs of symptoms usually occurring 3 months from the onset of COVID-19, acute respiratory distress syndrome (ARDS) being 8 to 12 days.30 This that last for 2 months and cannot be explained by an alternative may lead to ICU admission around 9 to 12 days after the onset of diagnosis.57 Symptoms may be persistent from the time of the initial illness.30 Clinicians should be aware of this time course and the po- COVID-19 infection or be new in onset and can be fluctuating or tential for patients with COVID-19 to rapidly deteriorate with respi- remitting over time. The incidence of post-COVID conditions appears ratory failure and sepsis, especially on days 5 to 10 after symptom high and symptoms can have an impact on everyday living.58 Com- onset.6,30 mon symptoms include fatigue, dyspnoea and cognitive dysfunc- tion57,59 but other symptoms may be present, including cough, loss of The basic tenets of providing respiratory support to maintain or taste, cardiac abnormalities (eg, myocarditis, chest pain, autonomic achieve oxygen saturation targets are unchanged, although the use of dysfunction), concentration problems, sleep disturbances, post- non-invasive ventilation (NIV) is more widely accepted.6,31 Conven- traumatic stress disorder, muscle pain and headache.55,59 It is diffi- tional oxygen therapy devices with low flow rates are still used if cult to predict who will experience post-COVID conditions, although oxyhaemoglobin saturations (SpO2) can be maintained within desired it appears to be more likely in females, those of older age or higher ranges. When clinically indicated for worsening hypoxaemia, NIV and BMI, and those with more than five symptoms in the first week.60 high-flow oxygen devices are often used, with patients located within a negative pressure room whenever possible. Internationally, there is Recommendations significant variability in guidelines for the application of NIV and high-flow oxygen32,33 and larger trials comparing the use of high- The original manuscript1 consisted of 66 recommendations. After flow oxygen to different forms of NIV, including continuous positive review of the original recommendations, two recommendations were airway pressure (CPAP), in COVID-19 populations have had varying revoked (item 3.5: BubblePEP is not recommended for patients with outcomes.34,35 As the common presentation of COVID-19 pneumo- COVID-19 because of uncertainty around the potential for aerosolisation, nitis is hypoxaemic respiratory failure (without hypercapnia), CPAP which is similar to the caution the WHO places on bubble CPAP; and may be recommended rather than other forms of NIV.6 As more item 5.4: For all confirmed or suspected cases, droplet precautions research specific to COVID-19 becomes available, it may guide the should be implemented, at a minimum. Staff must wear the following selection of therapy for patients with worsening acute respiratory items: surgical mask; fluid-resistant long-sleeved gown; goggles or face failure. For patients monitored by pulse oximetry, there is new un- shield; and gloves), 20 recommendations were revised and 30 new derstanding on potential for under-detection of occult hypoxaemia, recommendations were drafted. After review and voting by all au- especially among people with dark skin.36 thors, all revised or new recommendations gained consensus. The final 94 recommendations are presented in Boxes 1 to 5 and updated Silent or ‘happy’ hypoxaemia is a term that has evolved to describe guidance for screening COVID-19 patients is presented in Appendix 1. an atypical clinical phenomenon in severe and critical COVID-19 pa- Endorsements and translations listed in Appendix 2 are current at the tients where significant hypoxaemia is present, but subjectively pa- time of publication. Appendices 1 to 2 are available on the eAddenda. tients have a feeling of wellbeing, often with the absence of dyspnoea or respiratory distress.37 Despite the severe hypoxaemia, patients Physiotherapy workforce planning and preparation may be calm, awake and have near-normal lung compliance.38 The pathophysiological cause of silent hypoxaemia is unclear, but it may Box 1 outlines recommendations related to physiotherapy work- be due to intrapulmonary shunting, loss of lung perfusion regulation, force planning and preparation. Surges in hospital admissions due to endothelial injury and impaired diffusion capacity.39,40 These patients COVID-19 have required significant organisational change, including require close monitoring. Desaturation may be transient but is often within physiotherapy services, with resources being re-distributed prolonged or associated with rapid respiratory decompensation. Si- across hospitals to bolster services to frontline COVID-19 areas61,62 lent hypoxaemia appears to be associated with cardiac disease41 and and in some cases, restructuring to create extended shift patterns carries greater mortality.38,42 There are currently no defined thera- to improve access to physiotherapy services.62 Physiotherapy services peutic approaches for it beyond supportive management via to non-COVID-19 patients have still been essential, contributing to increasing supplemental oxygen; using high-flow oxygen devices and efficiencies in patient flow and discharge, and continuing to provide NIV; prone positioning; and mechanical ventilation using the com- vital outpatient and ambulatory care services. Services provided by mon principles for ARDS ventilation.38,40 In some centres, patients hospital-based outpatient services have been impacted and resulted with severe refractory hypoxaemia may be offered extracorporeal membrane oxygenation.43 Prone positioning of mechanically ventilated adults with COVID- 19 is used for periods of 12 to 16 hours.6,44 Additionally, ‘awake
Invited Topical Review 11 Box 1. Physiotherapy workforce planning and preparation recommendations. Capacity 1.1 Plan for an increase in the required physiotherapy workforce. For example: allow additional shifts for part-time staff offer staff the ability to electively cancel leave recruit a pool of casual staff recruit academic and research staff, staff who have recently retired or who are currently working in non-clinical roles work different shift patterns (eg, 12-hour shifts, extended evening shifts) 1.2 Identify potential additional staff who could be deployed to areas of higher activity associated with COVID-19 admissions (eg, infectious disease ward, ICU and/or high dependency unit and other acute areas). Prioritise staff for deployment who have previous cardiorespiratory and critical care experience. 1.3 Workforce planning should include consideration for pandemic-specific requirements such as additional workload from donning and doffing PPE, and the need to allocate staff to key non-clinical duties such as enforcing infection control procedures. 1.4 Identify hospital-wide plans for allocation/cohorting patients with COVID-19. Utilise these plans to prepare resource plans that may be required. Refer to the original manuscript1 for an example of a resource plan for ICU physiotherapy. 1.5b Consider organisation of the workforce into teams that will manage patients with confirmed or suspected COVID-19 versus non- infectious patients: minimise or prevent movement of staff between teams consider rotating teams after periods between caring for people with COVID-19 versus non-COVID-19 ensure the teams have an even distribution of skill mix limit movement of staff across wards within the hospital or across hospital campuses 1.6a Physiotherapy departments should plan for potential changes to workload management including: furlough of staff who are diagnosed with COVID-19 or have had a close contact exposure to a person with COVID-19 in the community or at work (without appropriate PPE) shielding of staff who are at higher risk from COVID-19 and require plans to reduce their exposure to patients with confirmed or suspected COVID-19 1.7a When staff are furloughed, consider the ability to provide telehealth or other remote access modalities in order to provide clinical and/ or administrative support and reduce the workload of physiotherapy staff within the hospital. 1.8 Senior physiotherapists should be involved in determining the appropriateness of physiotherapy interventions for patients with confirmed or suspected COVID-19 in consultation with senior medical staff and according to a referral guidelines. Training and education 1.9 Physiotherapists are required to have specialised knowledge, skills and decision-making to work within ICU. Physiotherapists with previous ICU experience should be identified by hospitals and facilitated to return to ICU. 1.10 Physiotherapists who do not have recent cardiorespiratory physiotherapy experience should be identified by hospitals and facilitated to return to support additional hospital services. For example, staff without acute hospital or ICU training may facilitate rehabilitation, discharge pathways or hospital avoidance for patients without COVID-19. 1.11 Staff with advanced ICU physiotherapy skills should be supported to screen patients with COVID-19 assigned to physiotherapy caseloads and provide junior ICU staff with appropriate supervision and support, particularly with decision-making for complex patients with COVID-19. Hospitals should identify appropriate physiotherapy clinical leaders to implement this recommendation. 1.12b Identify existing learning resources for staff who could be deployed to acute, ICU or rehabilitation areas of the hospital. For example: PPE training local ICU orientation programs cardiorespiratory and/or ICU eLearning packages educational resources from professional bodies pulmonary rehabilitation guidelines and resources 1.13a In periods of low community COVID-19 transmission, physiotherapy staff in acute hospital settings should maintain readiness through ongoing education, simulation and revision of COVID-19 protocols. Communication and welfare 1.14 Keep staff informed of plans. Communication is crucial to the successful delivery of safe and effective clinical services. 1.15a Physiotherapy managers and clinical leaders should regularly engage with staff to maintain an awareness of staff wellbeing (eg, mental and physical health) during and after the pandemic. 1.16b It should be recognised that staff will likely have an increased workload with a heightened risk of anxiety both at work and home. Staff should be supported during and beyond the pandemic (eg, via access to employee assistance programs, counselling, facilitated debriefing sessions). 1.17 Consider and/or promote debriefing and psychological support; staff morale may be adversely affected due to the increased workload, anxiety over personal safety and the health of family members. Staff vaccination and health 1.18a All physiotherapists should be vaccinated for COVID-19 (unless an approved medical exemption applies), including boosters as required. 1.19a Physiotherapists who are providing direct care to patients with confirmed or suspected COVID-19 or who are required to maintain other physiotherapy services during periods of high community COVID-19 transmission (eg, services to medical wards or outpatient services) should be among the healthcare providers who are given priority access to vaccination programs for COVID-19.
12 Thomas et al: Physiotherapy and COVID-19 update Box 1. Continued 1.20a If a physiotherapy staff member is unable to be vaccinated due to an approved medical exemption, they should be reallocated to non- COVID areas. 1.21a Physiotherapists should follow and role model methods for limiting the transmission of COVID-19, including regular hand hygiene, physical distance and wearing of a mask, consistent with public health recommendations. 1.22a All physiotherapists should participate in workplace surveillance testing as per local procedures. For example, rapid antigen saliva testing after working with confirmed or suspected COVID-19 patients. 1.23b Staff who are deemed to be at high risk should not enter COVID-19 areas. When planning staffing and rosters, some people may be at higher risk of developing more serious illness from COVID-19 and should avoid exposure to patients with COVID-19. This includes staff who: are pregnant have significant chronic respiratory illnesses are immunosuppressed are older (eg, . 60 years) have severe chronic health conditions such as heart disease, lung disease, diabetes have a condition causing immunodeficiency 1.24b Be aware of and comply to relevant international, national, state and/or hospital guidelines for infection control in healthcare facilities. 1.25a Hospital services or physiotherapy departments should collect and maintain records on: staff vaccination status staff who need to shield from exposure PPE training and competence mask fit testing ICU trained staff other training (eg, for prone positioning, NIV/CPAP, oxygen therapy) Equipment 1.26 Identify additional physical resources that may be required for physiotherapy interventions and how the risk of cross-infection can be minimised (eg, respiratory equipment; mobilisation, exercise and rehabilitation equipment; and equipment storage). 1.27b Identify and develop a facility inventory of respiratory, mobilisation, exercise and rehabilitation equipment and determine process of equipment allocation as pandemic levels increase: if resources permit, limit the movement of equipment between infectious and non-infectious areas if resources are limited, equipment can be moved between areas with appropriate cleaning Clinical education 1.28a Physiotherapy student placements should continue where this is safe and possible, balancing the short versus long-term risks and benefits to students and the health workforce. 1.29a Physiotherapy students’ requirements for vaccination and PPE should align with requirements of physiotherapy staff. 1.30a When demands of the pandemic response require alterations to traditional clinical placements for physiotherapy students and alternative clinical options are offered, they should ensure appropriate learning opportunities, levels of supervision and feedback can be provided, ensuring accreditation standards are met. CPAP = continuous positive airway pressure, COVID-19 = coronavirus disease 2019, ICU = intensive care unit, NIV = non-invasive ventilation, PPE = personal protective equipment. a New recommendation. b Revised recommendation. in the rapid uptake of telehealth services, which have proven effective may be its ability to reduce viral transmission, and vaccination of in the delivery of both individual and group services.63 healthcare workers has been associated with a reduction in COVID-19 Vaccination for COVID-19 is the key mechanism for control of among members of their households.68 COVID-19, and reductions in both the severity of illness experienced and demand on healthcare services have been observed. Vaccination For healthcare workers who are pregnant, guidelines continue to of healthcare workers in every country has been a key priority for the WHO, even in countries and areas that have reported few cases to recommend the allocation of duties that reduce their exposure to date.64 As vaccine rollouts have been implemented within countries, patients with confirmed or suspected COVID-19.69 Pregnant women healthcare workers have often been prioritised, including physio- are at increased risk of becoming severely unwell from COVID-19 therapists, particularly those on the frontline. In some countries, full vaccination of healthcare workers has now been mandated.65 infection in comparison to the general population, with increased risk for hospitalisation, admission to ICU and death.69–71 Vaccine Health professionals involved in the care of patients with COVID- 19 often express concerns about contracting COVID-19 themselves hesitancy has been observed amongst pregnant women, who are and infecting family members.66 Genomic analysis of COVID-19 in- often concerned about possible effects on their unborn children.72 fections in Australian healthcare workers demonstrated that the majority of staff who acquired COVID-19 did so within the work- However, vaccination appears to be safe for a pregnant woman and place.67 Major contributors to staff acquiring COVID-19 were the her child,70 providing humoral immunity via the transfer of immu- mobility of staff and patients between wards and facilities, as well as noglobulins through the placenta and breastmilk73 and is strongly characteristics and behaviours of individual patients, particularly recommended.69,70 Decisions around resource allocation are complex those with delirium or dementia who are often highly mobile due to wandering behaviours and exhibit aerosol-generating behaviours (eg, and when local jurisdictions require pregnant healthcare workers to coughing, shouting or singing). An additional benefit of vaccination work in high-risk COVID-19 areas, staff should be vaccinated and have full access to PPE. Access to information, wellbeing and support ini- tiatives that are designed specifically for staff who are pregnant are recommended.66 During a pandemic, healthcare workers are at higher risk of psy- chological distress and mental health problems.74 The demands of
Invited Topical Review 13 Box 2. Recommendations regarding personal protective equipment for physiotherapists. 2.1a Staff education and training should be responsive to ensure compliance with changes in PPE recommendations as required. 2.2a Only staff who have been trained in the proper application of PPE should care for patients with confirmed or suspected COVID-19. 2.3a Fit testing of face masks that offer airborne protection (eg, N95, FFP3, P2) is recommended, to ensure that staff can identify which size and style of mask is suitable for them. 2.4 All staff must be trained in correct donning and doffing of PPE, including performing a ‘fit-check’ for masks that offer airborne protection (eg, N95, FFP3, P2). A registry of staff who have completed PPE education and fit testing should be maintained. 2.5b Masks that offer airborne protection (eg, N95, FFP3, P2) rely on a good seal. Beards compromise the ability to achieve an adequate seal and maintain protection from aerosols. Staff should remove facial hair and be clean shaven to ensure good mask fit. 2.6a Physiotherapists should be aware of common skin adverse events from the effects of frequent handwashing and prolonged application of PPE, including contact dermatitis, acne, itching and pressure injuries from masks. Options for reducing adverse events should be available. 2.7a If staff are unable to achieve a fit test with available masks that offer airborne protection, they should be redeployed to non-COVID areas. 2.8b PPE for contact and airborne precautions should be used for suspected and confirmed COVID-19 patients. This includes: a face mask that offers airborne protection (eg, N95, FFP3, P2) a fluid-resistant long-sleeved gown goggles/face shield gloves 2.9 In addition, the following can be considered: hair cover for aerosol-generating procedures shoes that are impermeable to liquids and can be wiped down Use of shoe covers is not recommended, as repeated removal is likely to increase the risk of staff contamination. 2.10 PPE must remain in place and be worn correctly for the duration of exposure to potentially contaminated areas. PPE (particularly masks) should not be adjusted during patient care. 2.11 Use a step-by-step process for donning and doffing PPE as per local guidelines. 2.12a When powered air purifying respirators are being used by hospitals within COVID-19 clinical areas, physiotherapists should have appropriate training on the use of the devices. 2.13a If physiotherapists experience a PPE breach or COVID-19 exposure: exposure management should be managed according to defined organisational processes it should be recorded in an organisation’s incident management system as an occupational health and safety risk the physiotherapist’s wellbeing should be considered, particularly at the time of the incident and during quarantine or the duration of illness and recovery on return to work, a refresher infection control and prevention training should be offered to the staff member 2.14 Check local guidelines for information on laundering uniforms and/or wearing uniforms outside work if exposed to COVID-19. For example, changing into scrubs may be recommended in local guidelines and/or staff may be encouraged to get changed out of their uniform before leaving work and to transport worn uniforms home in a plastic bag for washing at home. 2.15 Minimise personal effects in the workplace. All personal items should be removed before entering clinical areas and donning PPE; this includes earrings, watches, lanyards, mobile phones, pagers, pens, etc. Stethoscope use should be minimised. If required, use dedicated stethoscopes within isolation areas. Hair should be tied back out of the face and eyes. 2.16 Staff caring for infectious patients must apply correct PPE, irrespective of physical isolation. For example, in ICU, if patients are cohorted into a pod with open rooms, staff working within the confines of the ICU pod but not directly involved in patient care should also wear PPE. The same applies once infectious patients are nursed on an open ward. Staff then use plastic aprons, a change of gloves and hand hygiene when moving between patients in open areas. 2.17 When a unit is caring for a patient with confirmed or suspected COVID-19, it is recommended that all donning and doffing are supervised by an additional appropriately trained staff member. 2.18 Avoid sharing equipment. Preferentially use only single-use equipment. 2.19 Wear an additional plastic apron if a large volume of fluid exposure is expected. 2.20 If reusable PPE items are used (eg, goggles), these must be cleaned and disinfected prior to re-use. 2.21a When patients with confirmed or suspected COVID-19 are receiving aerosol-generating therapies (eg, high-flow oxygen) or displaying aerosol-generating behaviours (eg, coughing, shouting, crying), consideration should be given to the patient’s ability to wear a fluid-resistant surgical mask over their face and oxygen delivery device, particularly when staff are providing treatment within close proximity to the patient. COVID-19 = coronavirus disease 2019, ICU = intensive care unit, PPE = personal protective equipment. a New recommendation. b Revised recommendation. dealing with a public health emergency, of indefinite duration, may interaction with colleagues and isolation from family. For example, in result in many changes, including higher workloads, being displaced from normal work areas, compassion fatigue, lost opportunities, less ICUs, 51% of physicians have had severe burnout during the pandemic compared with pre-pandemic rates of 25 to 30%.75,76 In United States
14 Thomas et al: Physiotherapy and COVID-19 update Box 3. Whom should physiotherapists treat? 3.1b The respiratory infection associated with COVID-19 is mostly associated with dry and non-productive cough; lower respiratory tract involvement usually involves pneumonitis rather than exudative consolidation. In these cases, respiratory physiotherapy interventions for airway clearance are not indicated. 3.2 Respiratory physiotherapy interventions in hospital wards or ICU may be indicated for patients who have confirmed or suspected COVID-19 and concurrently or subsequently develop exudative consolidation, mucous hypersecretion and/or difficulty clearing secretions. 3.3a Physiotherapists have a role in identifying patients with COVID-19 who may require additional respiratory support, including high- flow nasal oxygen, NIV/CPAP or the use of prone positioning. Their role may also include initiating and managing these interventions. 3.4 Physiotherapists will have an ongoing role in providing interventions for mobilisation, exercise and rehabilitation (eg, in patients with comorbidities creating significant functional decline and/or (at risk of) ICU-acquired weakness). 3.5b Physiotherapy interventions should only be provided when there are clinical indicators, so that staff exposure to patients with COVID- 19 is minimised: unnecessary review of patients with COVID-19 within their isolation room/areas may increase the risk of transmission in situations where PPE supply is limited, it may also have a negative impact on PPE supplies 3.6 Physiotherapists should meet regularly with senior medical staff to determine indications for physiotherapy review in patients with confirmed or suspected COVID-19 and screen according to set/agreed guidelines (Appendix 1 provides a suggested framework). 3.7a Resources should be prepared by physiotherapists for patients with COVID-19 (eg, handouts, information sheets) with consideration to the cultural and/or linguistic groups within a community and translations made available. 3.8 Physiotherapy staff should not be routinely entering isolation rooms, where patients with confirmed or suspected COVID-19 are isolated or cohorted, just to screen for referrals. 3.9 Options for screening of patients via subjective review and basic assessment whilst not being in direct contact with the patient should be trialled first, whenever possible (eg, calling the patients’ isolation room telephone and conducting a subjective assessment for mobility information and/or providing education on airway clearance techniques). COVID-19 = coronavirus disease 2019, CPAP = continuous positive airway pressure, ICU = intensive care unit, NIV = non-invasive ventilation. a New recommendation. b Revised recommendation. healthcare workers, 49% of 20,947 respondents across 42 organisa- stress.74 At an organisational level, formalised peer support or tions reported burnout during COVID-19.77 Levels of stress were higher in female workers, those with fewer years in their role and organisational support is critical. Providing healthcare workers with those working in inpatient settings.77 Among physiotherapists, burnout has also significantly increased during the COVID-19 the resources to manage the risk of infection may also reduce anxiety pandemic,78,79 with reports suggesting that physiotherapists who experience the greatest levels of burnout are those working directly (eg, having vaccination programs, adequate training for PPE and with COVID-19 patients and/or working in ICU.78,79 While anxiety can guidelines to direct patient care).74 The psychological distress from be high amongst staff who have direct contact with people who have COVID-19, staff who believe that their health service’s response and working during a pandemic can persist for 2 to 3 years after the staff support strategies are effective may experience lower levels of outbreak;74 therefore, monitoring and support mechanisms should depression, anxiety and stress.66 Additionally, staff who feel valued by continue beyond the outbreak period.81 their organisation have significantly lower levels of burnout.77 Allied health student placements have been demonstrated to have Physiotherapy department clinical leaders and managers should be aware of the impact of workloads and stress on their teams during at least a neutral or positive impact on patient activity and clinical the pandemic, including themselves. The mental health of staff can be time.82 They are essential to ensuring the future workforce and also protected if strategies are implemented to keep staff informed about inspire and influence career decisions.83 During the pandemic, their health service responses to the pandemic. Regular, effective and physiotherapy student clinical placements have been profoundly timely communication of health service information is important. The impacted.84 They may have been disrupted by the changing re- importance of timely communication through briefings (daily, if necessary), the dissemination of information in real-time via group quirements of healthcare facilities, the need to limit access to hos- messaging and feedback mechanisms for staff create a continuous cycle that is imperative during the pandemic. Ensuring that staff feel pitals from all but essential healthcare staff and the redeployment of prepared also arises through the completion of relevant education, orientation and competencies for tasks that are required during the clinical educators to support frontline clinical roles. The impact from pandemic.80 As workloads increase, staff can be supported by rein- forcing teams and checking that staff maintain appropriate shift lost clinical placements and/or modified physiotherapy placements as patterns and have the ability to take regular breaks, especially during a result of COVID-19 is not collectively known. In addition to place- service redesign. ment time, students may have been unable to complete or pass Staff support and wellbeing initiatives must be used, including opportunities to debrief, practise/foster gratitude and recognise and/ practical competency assessments that are required for registration. It or reward staff for achievements. Managers and clinical leaders should regularly check in on the health and wellbeing of their staff,81 is unknown whether these disruptions will result in an impact on particularly staff working on the front-line teams during the pandemic and those who may be furloughed. Social support from service quality delivered by graduating workforces in coming years. supervisors and colleagues can help to build resilience and reduce The continuation of clinical placements requires careful consid- eration of factors such as student safety (including access to PPE and mask fit testing where required), enacting current public health di- rectives (eg, physical distancing, limiting travel, conflicts between concurrent or essential employment and placement), insurance and implications for future workforce planning.85,86 Placement of stu- dents within clinical areas where there is high likelihood of exposure to patients with confirmed or suspected COVID-19 is often not rec- ommended87 unless there are critical workforce shortages.88 How- ever, continuation of placements within clinical areas that may benefit from the presence of students is recommended.85,87 Inclusion of students within the healthcare system during the pandemic may assist in overcoming workforce shortages85 and will also ensure that
Invited Topical Review 15 Box 4. Recommendations for physiotherapy respiratory interventions. Personal protective equipment 4.1b It is strongly recommended that standard and airborne precautions are utilised during respiratory physiotherapy interventions for patients with confirmed or suspected COVID-19. Cough etiquette 4.2 Both patients and staff should practice cough etiquette and hygiene. During techniques that may provoke a cough, education should be provided to enhance cough etiquette and hygiene: ask the patient to cover their mouth by coughing into their elbow or sleeve or into a tissue. Tissues should then be disposed and hand hygiene performed In addition, if possible, physiotherapists should position themselves 2 m from the patient and out of the likely path of dispersion Aerosol generation 4.3 Many respiratory physiotherapy interventions are potentially aerosol-generating procedures. While there are insufficient investigations confirming the aerosol-generating procedures of various physiotherapy interventions, the combination with cough for airway clearance makes all techniques potentially aerosol-generating procedures. These include: cough-generating procedures (eg, cough or huff during treatment) positioning or gravity-assisted drainage techniques and manual techniques (eg, expiratory vibrations, percussion and manually assisted cough) that may trigger a cough and sputum expectoration use of positive pressure breathing devices (eg, inspiratory positive pressure breathing, mechanical insufflation-exsufflation de- vices, intra/extra pulmonary high-frequency oscillation devices (eg, The Vest, MetaNeb, Percussionaire)) PEP and oscillating PEP devices bubble PEP nasopharyngeal or oropharyngeal suctioning manual hyperinflation open suction saline instillation via an open-circuit endotracheal tube inspiratory muscle training, particularly if used with patients who are ventilated and disconnection from a breathing circuit is required sputum inductions any mobilisation or therapy that may result in coughing and expectoration of mucus Therefore, there is a risk of creating an airborne transmission of COVID-19 during treatments. Physiotherapists should weigh-up the risk versus benefit in completing these interventions and use standard and airborne precautions. 4.4b Where aerosol-generating procedures are indicated and considered essential they should be undertaken in a negative pressure room. Access to negative pressure rooms may not be available when cohorting is required due to the volume of patients presenting with COVID-19. Physiotherapists should weigh up the risk versus benefit in completing these interventions within cohorted areas. 4.5b The decision to commence humidification, NIV, high-flow oxygen or other aerosol-generating procedures should be made in agreement with the multi-professional team and potential risks minimised. This may include consulting to develop work unit instructions/procedures to guide physiotherapy treatments, alleviating the need to gain medical approval for every individual patient. 4.6b Do not use saline nebulisation: nebulisation is considered to be aerosol-generating. Airway clearance techniques 4.7 Positioning, including gravity-assisted drainage: Physiotherapists can continue to advise on positioning requirements for patients. 4.8 Respiratory equipment for airway clearance: where respiratory equipment is used, whenever possible use single-patient-use disposable options (eg, single-patient-use PEP devices) re-usable respiratory equipment should be avoided where possible 4.9 There is no evidence for incentive spirometry in patients with COVID-19. 4.10b Mechanical aids for airway clearance: mechanical insufflation/exsufflation, NIV, inspiratory positive pressure breathing devices and intra/extra pulmonary high-frequency oscillation devices may be used, if clinically indicated and alternative options have been ineffective consult with both senior medical staff and infection prevention and monitoring services within local facilities prior to use If used, ensure machines can be decontaminated after use and protect machines with viral filters over machine and patient ends of circuits): use disposable circuits for these devices maintain a log of devices that includes patient details for tracking and infection monitoring (if required) use contact and airborne precautions 4.11b Hyperinflation for airway clearance in patients on mechanical ventilation and/or with a tracheostomy: hyperinflation techniques should only be used if indicated (eg, for suppurative presentations in ICU) application of hyperinflation techniques should carefully consider the patient’s presentation and clinical management (eg, lung- protective ventilation for acute respiratory distress syndrome) if indicated, use ventilator hyperinflation rather than manual hyperinflation, which involves disconnection/opening of a ventilator circuit ensure local procedures are in place for hyperinflation techniques
16 Thomas et al: Physiotherapy and COVID-19 update Box 4. Continued Techniques for the management of hypoxaemia 4.12a Physiotherapists may be involved in the initiation and management of high-flow nasal oxygen, NIV and continuous positive pressure breathing for the management of hypoxaemia. Application of these devices by physiotherapists should be in accordance with local guidance for respiratory support decision-making, infection control and escalation procedures in the event of deterioration. 4.13 Prone positioning: Physiotherapists may have a role in the implementation of prone positioning in ICU. This may include leadership within ICU ‘prone teams’, providing staff education on prone positioning (eg, simulation-based education sessions) or assisting in turns as part of the ICU team. 4.14a When prone positioning is used, physiotherapists should review patients regularly to advise on positioning strategies to prevent potential adverse effects of prone, including pressure injuries and neurological damage. Patients should be screened after prone turns and at discharge from ICU for potential neurological damage associated with the use of prone. 4.15a In patients who have not yet been intubated, physiotherapists can facilitate awake proning when indicated (eg, in patients with severe COVID-19 who are receiving any form of supplemental oxygen therapy). Request for sputum samples 4.16 Sputum inductions should not be performed in patients with confirmed or suspected COVID-19. 4.17 For sputum samples in non-intubated patients, first ascertain whether the patient is productive of sputum and able to clear sputum independently. If so, physiotherapy is not required for a sputum sample. If physiotherapy interventions are required to facilitate a sputum sample, PPE for contact and airborne precautions should be worn. The handling of sputum samples should adhere to local policies. Generally, once a sputum sample has been obtained the following points should be followed: all sputum specimens and request forms should be marked with a biohazard label the specimen should be double-bagged and placed in the first bag in the isolation room by a staff member wearing recommended PPE specimens should be hand-delivered to the laboratory by someone who understands the nature of the specimens. Pneumatic tube systems must not be used to transport specimens Tracheostomy management 4.18b The presence of a tracheostomy and related procedures are potentially aerosol generating. These include: open suction of the tracheostomy manual hyperinflation as an airway clearance technique weaning from mechanical ventilation to humidified oxygen circuits cuff deflation trials inner cannula tube changes/cleaning use of speaking valves and leak speech use of IMT During their infectious period, patients with COVID-19 and a tracheostomy should be managed within an isolation room: PPE for contact and airborne precautions is required closed, in-line suction is recommended if tracheostomy-related procedures are clinically indicated (eg, for airway clearance, to facilitate weaning or communication), the risks versus benefits should be considered. It is important to consider the role these procedures have for facilitating weaning and decannulation. when patients are weaned off the ventilator, consider the use of a fluid-resistant surgical mask placed over the tracheostomy and any oxygen delivery device to reduce aerosol and droplet dispersion. When patients with a tracheostomy have completed their isolation period, they are considered to be non-infectious and airborne precautions for COVID-19 are no longer required. Lung ultrasound 4.19a Where physiotherapists have the education and competence to perform lung ultrasound, it may be used as an assessment modality in patients with COVID-19. COVID-19 = coronavirus disease 2019, ICU = intensive care unit, IMT = inspiratory muscle training, NIV = non-invasive ventilation, PEP = positive expiratory pressure, PPE = personal protective equipment. a New recommendation. b Revised recommendation. the newly graduated workforce is prepared for pandemic re- Maintaining clinical placements within clinical areas away from the sponses.86 Physiotherapy clinical placements have occurred with frontline COVID-19 response is paramount for cardiorespiratory students assisting in the management of patients with COVID-19.89 physiotherapy. If workload and staffing pressures require different supervision models, they should ensure appropriate learning oppor- As the pandemic response evolves, the potential contribution of tunities, levels of supervision and feedback can be provided so that students do not get lost in the chaos of the pandemic.91 New rec- students to the direct care of patients with COVID-19 and risks need ommendations related to physiotherapy clinical education are pre- sented in Box 1, items 1.28 to 1.30. to be evaluated by universities and healthcare providers. Delivery of physiotherapy interventions, including PPE As a result of COVID-19, innovation in education and clinical requirements placement models is required.87 Within some physiotherapy disci- When the original recommendations1 were first prepared early in plines, virtual placements and telehealth have been used and tools the pandemic, transmission of COVID-19 between people was that are used to assess student competencies on clinical placement have been modified to encompass these areas.84,90 However, tele- health has been less applicable to placements in acute hospital set- tings and there remains potential to investigate alternative placement models for acute care and cardiorespiratory skills training.
Invited Topical Review 17 Box 5. Recommendations for physiotherapy mobilisation, exercise and rehabilitation interventions. Personal protective equipment 5.1b PPE for contact and airborne precautions should be used when providing mobilisation, exercise and rehabilitation. Physiotherapists are likely to be in close contact with the patient (eg, for mobilisation, exercise or rehabilitation interventions that require assistance). Mobilisation and exercise may also result in the patient coughing or expectorating mucus, and there may be circuit disconnections with ventilated patients. Refer to local guidelines regarding ability to mobilise patients outside of their isolation room. If mobilising outside of the isolation room, ensure that the patient is wearing a fluid-resistant surgical mask. Screening 5.2 Physiotherapists will actively screen and/or accept referrals for mobilisation, exercise and rehabilitation. When screening, discussion with nursing staff, the patient (eg, via phone) or family is recommended before deciding to enter 5.3a the patient’s isolation room. For example, to try to minimise staff who come in to contact with patients with COVID-19, 5.4b physiotherapists may screen to determine an appropriate aid to trial. A trial of the aid may then be performed by the nursing staff already in an isolation room, with guidance provided, if needed, by the physiotherapist who is outside the room. Physical assessment including (but not limited to) manual muscle testing, functional assessment of bed mobility, transfers and gait should be considered in patients who have had severe disease with prolonged bed rest and/or critical disease where the presence of weakness and functional limitation may be increased. Physiotherapy interventions should be considered when there is a clinical indication (eg, to address functional decline due to illness or injury, frailty, multiple comorbidities, advanced age; or the prevention or recovery from ICU-acquired weakness). Mobilisation and exercise prescription 5.5 Early mobilisation is encouraged. Actively mobilise the patient early in the course of illness when safe to do so. 5.6 Patients should be encouraged to maintain function as able within their rooms: 5.7b sit out of bed perform simple exercises and activities of daily living Mobilisation and exercise prescription should involve careful consideration of the patients’ physiological state and reserve (eg, degree of respiratory and haemodynamic dysfunction). This includes consideration of: the presence and severity of hypoxaemia exertional hypoxaemia cardiac impairments autonomic dysfunction and orthostatic intolerance post-exertional symptom exacerbation Mobility and exercise equipment 5.8 The use of equipment should be carefully considered and discussed with local infection monitoring and prevention service staff before being used with patients with COVID-19 to ensure it can be properly decontaminated. 5.9 Use equipment that can be single patient use. For example, use elastic resistance bands rather than distributing hand weights. 5.10 Larger equipment (eg, mobility aids, ergometers, chairs, tilt tables) must be easily decontaminated. Avoid use of specialised equipment, unless necessary, for basic functional tasks. For example, stretcher chairs or tilt tables may be deemed appropriate if they can be decontaminated with appropriate cleaning and are indicated for progression of sitting/standing. 5.11 When mobilisation, exercise or rehabilitation interventions are indicated: plan well identify/use the minimum number of staff required to safely perform the activity ensure that all equipment is available and working before entering rooms ensure that all equipment is appropriately cleaned or decontaminated if equipment needs to be shared among patients, clean and disinfect between each patient use specific staff training for cleaning of equipment within isolation rooms may be required whenever possible, prevent the movement of equipment between infectious and non-infectious areas whenever possible, keep dedicated equipment within the isolation zones, but avoid storing extraneous equipment within the patient’s room 5.12 When performing activities with ventilated patients or patients with a tracheostomy, ensure that airway security is considered and maintained (eg, a dedicated airway person to prevent inadvertent disconnection of ventilator connections/tubing). COVID-19 = coronavirus disease 2019, ICU = intensive care unit, PPE = personal protective equipment. a New recommendation. b Revised recommendation. believed to be primarily through droplet and contact routes,14 but generation caused by other respiratory techniques and coughing. there was concern regarding its potential for airborne spread. Sub- sequently, the recommendations1 referred to both droplet and More recently, coughing has been shown to produce higher aerosol airborne precautions, depending on the type of physiotherapy being provided. For example, airborne precautions were recommended for emissions than breathing on CPAP (with an exhalation port filter in respiratory physiotherapy due to: the close proximity of therapists to situ) or via high-flow nasal cannula.93 Evidence for the aerosol- patients; use of techniques that are commonly considered aerosol- generating properties of patient care activities and subsequent generating, including airway suctioning, NIV, tracheostomy proced- ures and manual ventilation;92 and uncertain but possible aerosol transmission risk to healthcare workers is limited to a small number of studies, which are generally of low quality.93,94 While further evaluation of aerosol-generating potential of activities, including physiotherapy techniques, is required, there is now substantial
18 Thomas et al: Physiotherapy and COVID-19 update evidence indicating airborne transmission of COVID-19;16–20 thus, healthcare workers remain vaccination, PPE for contact and airborne precautions, fit testing and hand hygiene, encouraging patients to recommendations have been revised to reflect the use of airborne wear a surgical mask continues to be a recommended practice for precautions during all direct physiotherapy interactions with people physiotherapists (Box 2, item 2.21). with confirmed or suspected COVID-19 (Box 2). All patients with confirmed or suspected COVID-19 continue to be Face masks that offer airborne protection (eg, N95, FFP3, P2) have placed in isolation rooms or cohorted into COVID-19 designated areas. The risk of patients who present with non-COVID-19 conditions been shown to provide adequate protection against respiratory vi- also being COVID-19 positive will increase when community trans- mission is high. At these times, staffing models may change; for ruses when there is a good fit and adequate seal. Due to the example, physiotherapists who are treating patients with confirmed pandemic, there is increased awareness of the role of mask fit testing, or suspected COVID-19 may be instructed to avoid treating non- which is increasingly recommended for healthcare workers as a COVID patients in the same shift (ie, establishing COVID and non- necessary occupational health and safety standard.95 Mask fit de- COVID physiotherapy teams). Hospitals may require staff to adhere pends on a variety of factors, including an individual’s face shape and to the separation of COVID and non-COVID teams, for example by size, as well as brand and size of mask used.96,97 Without proper fit providing separate tea and meeting rooms and change facilities. It is testing, many staff may have insufficient airborne protection.97 Fit important to consider the need to maintain skill mix between sepa- testing does incur costs associated with proper testing equipment rated teams, so that if one team is furloughed, staff replacing them may have the skills required to maintain services in critical areas. and staff, PPE usage and time for the testing and education of staff. The isolation period for people who have been hospitalised with However, the benefit is considered to outweigh the high cost of staff severe COVID-19 varies depending on local hospital guidelines and sick leave and furloughing due to viral exposure.96 Fit checking, the severity of illness experienced. For adults who have not required hospital admission, isolation can be discontinued 10 days after where people test the seal of a mask after its application by inhaling symptom onset and 24 hours after resolution of fever along with improvement in other symptoms.110 When hospitalisation, ICU, NIV and exhaling quickly, should not be confused with the process of fit or other ventilatory support has been required, or patients are testing. Fit checking remains an important step with the application severely immunocompromised, a longer period of isolation of up to 20 days after symptom onset and after resolution of fever and of face masks that offer airborne protection, but is not a reliable test improvement in other symptoms is recommended.110 When patients to guide mask fitting.95,96 It is important for organisations and/or are removed from isolation, although the virus may still be detectable departments to be aware of levels of staff PPE training and fit testing in some patients, airborne PPE are no longer required as infectious- compliance in order to appropriately safeguard staff and fit testing ness is considered unlikely.110 should be repeated annually.98,99 Guidelines for PPE and environmental protections continue to Powered air-purifying respirators (PAPRs) are a type of face mask evolve, and it is important for physiotherapists to be aware of changes and practices within their healthcare setting. Heating, ventilation and with a small fan assembly that takes ambient, potentially contami- air-conditioning systems and ventilation in general are considered to be engineering controls that can reduce the risk of COVID-19 trans- nated air and passes it through high-efficiency, particulate-absorbing mission111 and many hospitals are reviewing and/or upgrading their viral filters before delivering the clean air to the user’s face. PAPRs heating, ventilation and air-conditioning systems. The use of portable may be used for several reasons, including as an alternative for high-efficiency particulate air filters has been demonstrated to significantly reduce the time required for aerosols to be cleared from providing a high level of respiratory protection in individuals who fail a patient’s room.112 Personal ventilation hoods have also evolved and have been shown to reduce aerosol counts by . 98% during nebu- fit testing, when performing aerosol-generating procedures (eg, lisation and NIV.113,114 intubation), or when viral exposure time is prolonged (eg, a shift If a direct exposure to COVID-19 or breach of PPE occurs, assess- performed within a COVID-19 isolation room). Although PAPRs may ment of the breach and risk categorisation should be performed and the incident should be recorded in a hospital’s incident management be more comfortable to wear due to improved heat tolerance, they system as an occupational health and safety risk.31 For periods of staff may restrict mobility and impede communication100 and there is no illness or post-exposure management, staff wellbeing should be considered, and psychosocial support provided if required during evidence to indicate that they reduce healthcare worker infection due quarantine or for the duration of their illness and recovery. On return to COVID-19 or other airborne diseases.100,101 Fit testing specific to to work, a refresher infection control and prevention training should PAPR devices is also required, and education in correct donning and be offered for the staff member. doffing procedures is essential, as there is a high risk of self- Recommendations for physiotherapy management principles – contamination during removal of the PAPR device.102 Access to respiratory care PAPR devices may be limited due to their high cost and associated While many patients with COVID-19 have a non-productive cough,115 some may develop suppurative presentations with a large expenses for training, cleaning and maintenance. Variations in the secretion load and/or thick and viscous respiratory secretions.116,117 With severe COVID-19 infection, elevated plasma levels of pro- use of PAPR devices between centres and/or their use by physio- inflammatory cytokines trigger and the overexpression of mucin may result in mucus hypersecretion, with alterations in the compo- therapists has not been reported. When they are used by a healthcare sition and impairments in mucociliary clearance leading to airway obstruction and/or ARDS and thrombosis.118,119 A higher proportion of facility, it is recommended that physiotherapists are PAPR fit tested patients with viscous sputum has been reported in critical COVID- and have appropriate training on the use of the devices and their don/ 19120 and researchers are beginning to evaluate the potential role of therapies like mucolytics.117 doff procedures (Box 2, item 2.12). Physiotherapy respiratory interventions for the primary purpose Prolonged application of PPE and frequent hand hygiene can lead of airway clearance are recommended only in severe and critical COVID-19 when there is evidence of pneumonia and difficulties with to adverse events such as contact dermatitis, acne and itching. Masks that offer airborne protection increase the risk of these conditions occurring over the nasal bridge and cheeks, and the duration that PPE is worn appears to be the most common risk factor.103,104 Hydrocol- loid dressings can be used to prevent the development of adverse skin reactions related to masks.103,104 While limited, evidence continues to grow to support the original recommendation1 that spontaneously breathing patients with confirmed or suspected COVID-19 should be encouraged to wear a fluid-resistant surgical mask to reduce the risk of transmission to other contacts.19,21,22,105,106 This has not always been reflected in hospital guidelines, where the wearing of masks was predominantly encouraged during transport for retrievals or movement between clinical areas. However, even asymptomatic patients with COVID-19 can have high viral load in the upper and lower respiratory tract107 and asking patients to cover their nose and mouth with a surgical mask when staff are in the room has been recommended by several organisations.108,109 Significant reductions in aerosol dispersion occur when masks are worn over the top of conventional oxygen or high- flow nasal cannula or when patients cough105 and may improve arterial oxygenation.109 Although the mainstays of protection for
Invited Topical Review 19 Box 6. Recommendations for recovery after COVID-19. frequently on computed tomography (CT). Lung ultrasound (LUS) continues to emerge as a useful tool in practice, due to its accuracy in 6.1a Physiotherapists should encourage physical activity and diagnosing pulmonary conditions.136,137 In the era of COVID-19, ICUs support healthy lifestyle programs for patients, the general may be reluctant to transport COVID-19 patients to CT, due to both community and people recovering from COVID-19. the risk of transmission and their acuity. The advantage of LUS is its portability and bedside application, which negates the need to 6.2a Physiotherapists should support multi-professional transport the patient outside the ICU for a CT scan. Use of LUS can rehabilitation programs for people recovering from COVID- assist with the diagnosis of COVID-19 and assist with clinical decision 19 along the trajectory from acute illness, through to the making for clinicians regarding therapy such as the need for prone ambulatory settings and onwards into the community. positioning and the need for intubation.138,139 Further, LUS is being used as an assessment tool by physiotherapists who have appropriate 6.3a Increased demand for outpatient and community training.140 Where physiotherapists have the education and compe- rehabilitation services, particularly pulmonary and cardiac tence to perform LUS, it may be used as an assessment modality in rehabilitation programs should be anticipated, and health patients with COVID-19 (Box 4, item 4.19). services should aim to increase modalities to make access available to the post COVID-19 population. Physiotherapy management principles – mobilisation, exercise and rehabilitation interventions COVID-19 = coronavirus disease 2019. a New recommendation. secretion clearance.1 On bronchoscopic evaluation of patients with Mobilisation, exercise and rehabilitation continue to be recom- mended for patients with severe and critical COVID-1944 and has COVID-19, mucus secretions were common (82%) but evidence of been widely implemented,62,125,126,133,141–143 so only one new mucous plugging was less frequent (18%).121 This supports the prin- recommendation has been added (Box 5, item 5.3). Immobility and the development of muscle weakness and functional limitations ciple that not all severe or critical COVID-19 patients will require appear common amongst hospitalised patients with severe and critical COVID-19.142,144,145 While mobilisation, exercise and rehabil- respiratory physiotherapy, and a personalised approach is recom- itation are an essential part of care, the ideal frequency, intensity, volume and type are unknown. One retrospective study suggested mended with screening performed to determine which patients that a higher frequency and longer duration of physiotherapy for hospitalised patients with COVID-19 are associated with improved may benefit from physiotherapy (Box 3, and Appendix 1 on the levels of mobility at hospital discharge and increased likelihood of eAddenda). Several reports reflect the role that respiratory physio- discharge home.142 However, increased frequency of physiotherapy therapy has had during COVID-19 in the acute hospital setting for may not influence changes in muscle strength144 and further research ward and ICU patients.122–126 and evaluation are needed. Physiotherapists may take an active role in the prone positioning of In ICU and acute care settings, the safety and feasibility of early patients,127 including awake proning. When prone positioning is used, mobilisation, exercise and rehabilitation interventions are well established.146,147 While guidelines for commencing these in- physiotherapists should review patients regularly to advise on posi- terventions exist, it is important to consider certain characteristics specific to COVID-19. tioning strategies to prevent potential adverse effects, including pres- sure injuries128,129 and neurological damage.130 Patients should be Cardiac dysfunction is a known complication of COVID-19 and may include signs of heart failure, cardiogenic shock, arrhythmia and screened after prone turns for pressure injuries and observed for myocarditis.148 Physiotherapists should be aware that cardiac dysfunction may occur during their interventions and screen for potential neurological damage associated with the use of prone posi- identified cardiac dysfunction prior to implementing mobility, exer- cise and rehabilitation interventions. This includes ensuring aware- tioning. While awake proning may be a strategy used to improve arterial ness of known and/or provisional diagnoses of cardiac abnormalities and ongoing investigations (eg, cardiac-specific biomarkers like oxygenation, not all patients tolerate it for prolonged periods and trial of troponin and NT-proBNP). Additionally, physiotherapists should uti- lise clinical surveillance during physiotherapy interventions to pre- different positions like side lie, semi-recumbent, sitting, forward lean, vent exacerbating cardiac signs and symptoms and/or to be aware of and identify possible new presentations of cardiac dysfunction. prone and semi-prone may identify positions that maximise arterial or Autonomic dysfunction and orthostatic intolerances may also be peripheral oxygenation and comfort for individuals.131–133 present.149 Interventions should not push patients to the point of symptom exacerbation (both during and after the exertion) or The use of inspiratory muscle training (IMT) in patients with fatigue. COVID-19 has been reported.126,134 In a pilot study, 2 weeks of IMT significantly improved dyspnoea, quality of life and exercise tolerance relative to usual care.134 Larger studies evaluating the role of IMT are needed. The Italian consensus on pulmonary rehabilitation in COVID- 19135 recommends that IMT should not be used routinely, but should be administered in patients with respiratory muscle weakness and persistent dyspnoea. It may also be considered for patients with a tracheostomy as they progress to decannulation.135 Disposable, single patient use respiratory devices are recommended for people with COVID-19, including IMT devices.135 Clinical decision making about pulmonary pathology in critically ill patients often relies on portable chest radiographs and less Table 2 The International Classification of Functioning, Disability and Health related to COVID-19. Factors to consider by physiotherapistsa. Body structure and function Activities (examples) Participation (examples) Dyspnoea Unable to walk long distances Unable to perform activities of daily living and/or return to work Persistent cough Unable to perform activities that trigger coughing Emotional impact, social isolation, reduced productivity182 Weakness Unable to stand for long periods Reduced health-related quality of life Fatigue Unable to do household tasks (cleaning, shopping) Difficulties with community activities Pain (headache, chest and Unable to participate in physical and recreational activities Altered family roles and relationships musculoskeletal pain) Poor memory, executive Unable to concentrate on a task and unable to multitask Return to work or studies (school, university, personal development functioning and problem solving courses) may be limited or impossible Nightmares, flashbacks to ICU, Unable to sleep Emotional impact, unable to enjoy usual activities, work or community roles anxiety, depression ICU = intensive care unit. a Adapted from the Australian and New Zealand Intensive Care Society’s COVID-19 Guidelines.31
20 Thomas et al: Physiotherapy and COVID-19 update Table 3 group. Patients should be closely monitored (eg, dyspnoea/exertion, SpO2, blood pressure, heart rate) during exercise, mobilisation and Assessment that may be considered by physiotherapists for patients with COVID-19 rehabilitation interventions and for a period afterwards due to the during transitions of care: ICU dischargea, hospital dischargeb and 6 to 8 weeks after potential for later deterioration. Patients should not be pushed to the COVID-19 infectionc. point of fatigue. Commencement of interventions in patients who are already below their targeted SpO2 ranges should be avoided or Clinical area Assessment items limited to only essential functional activities (eg, transfer to a commode). Respiratory Oxygen therapy requirements SpO2 at rest and with exercise Recovery after COVID-19 Dyspnoea at rest and with exertion Cough Recommendations for recovery after COVID-19 is a new category Presence of sputum and indications for airway clearance techniques within the physiotherapy recommendations and reflects the increasing awareness and evaluation of the long-term impairments Physical Autonomic dysfunction and orthostatic intolerances that result from COVID-19 (Box 6). Many patients who are discharged Post-exertional symptom exacerbation from hospital after COVID-19 will have ongoing symptoms and Muscle strength functional impairment.58 To address post-COVID conditions, it is Physical function important that patients are assessed for ongoing or new symptoms Exercise capacity/endurance (eg, 6-minute walk test) prior to hospital discharge, to identify potential therapies or health Level of mobility, walking aids required, walking services that can be organised. Whether hospitalised or not, people distance and assistance required who have had COVID-19 should also be evaluated at an appropriate Balance period after initial infection to monitor and address symptoms of Safety on stairs post-COVID conditions. Ongoing rehabilitation needs Pain Table 2 provides examples of the impact that post-COVID condi- Pelvic floor and continence183 tions may have on function and participation. Muscle weakness, fa- tigue, impaired concentration and dyspnoea are commonly reported Other Fatigue – activity-related or general malaise symptoms.58 People may experience post-COVID conditions, regard- Sleep less of whether they have been hospitalised or received home-based Delirium care.151 Reduced functional capacity is common in COVID-19 ICU Cognitive function, including memory and concentration survivors152 and inpatient rehabilitation may be required for some Social supports people. Return to work, family roles and recreational activities Consider referral to other healthcare professionals if indicated At discharge from acute care, all patients and caregivers should be provided with advice and written information on recovery following SpO2 = oxyhaemoglobin saturation. COVID-19.153 This should include what to expect during recovery, a Clinical handover should occur with the ward staff about ongoing concerns at ICU how to self-manage symptoms, and how to contact a health profes- sional if they are worried about new, ongoing or worsening symp- discharge. toms. Systematic screening of patients at 6 to 8 weeks after COVID-19 b Prepare a discharge letter to the primary health practitioner if patients require infection is useful to identify those patients with persistent symp- toms who may require additional management.154 Earlier review may ongoing need for support. be considered in patients who had critical COVID-19, were admitted c People with persistent symptoms post COVID-19 should be reviewed, either in to ICU and those with significant physical function limitations at hospital discharge. Persistent symptoms vary widely and are not al- person or via telehealth. Communicate with primary care practitioner regarding ways related to respiratory or physical function (eg, sleep distur- bance, impairment of smell, memory and concentration151), so a rehabilitation needs and ongoing support. multidisciplinary approach to care is frequently required. Interna- tionally, resources have been created to assist people in recovery after The presentation of silent hypoxaemia in acutely unwell patients COVID-19155–158 and guidelines and screening tools have also is important for physiotherapists to consider, particularly during emerged during the pandemic to guide multidisciplinary resource mobilisation, exercise and rehabilitation interventions. In the absence planning after hospital discharge.31,149,154,159 of evidence-based guidelines that may improve patient outcomes, caution is required and strategies should be used to attenuate desa- For physiotherapists, a suggested approach for screening across turation associated with mobilisation, exercise and rehabilitation the continuum of hospital admission to discharge and return to the strategies. In addition to identifying how different positions – for community is outlined in Table 3. Physiotherapy management of example, side lie, semi-recumbent, sitting, forward lean, prone and patients with impairments in physical function should include semi-prone – may affect arterial or peripheral oxygenation and referral to inpatient or outpatient rehabilitation services, as clinically comfort for individuals,131–133 functional activities, mobility and ex- indicated. Rehabilitation programs should be individualised and ercise should be trialled when deemed safe. A graduated and/or adapted to the needs of the patient. In some cases, specialist reha- paced approach is recommended: for example, in a patient with bilitation services (eg, neurological rehabilitation) may be required. critical COVID-19 who is on high-flow oxygen, first assessing the ef- Patients may also integrate into existing services, like ICU follow-up fect of a stepping transfer from bed to chair on dyspnoea, SpO2 and clinics. blood pressure and allowing a period of observation or recovery before allowing the patient to walk or perform more vigorous Large population studies are required to investigate the long-term activities. impact of severe COVID-19 on pulmonary function and exercise ca- pacity.58 Emerging reports indicate that reductions in pulmonary In patients who have hypoxaemia and/or are receiving high levels function and exercise capacity are common. When monitored for of oxygen, have exertional hypoxaemia or silent hypoxaemia, several periods up to 6 months after COVID-19 infection, changes in diffusing strategies may prevent desaturation. Interventions should be care- capacity for carbon monoxide and/or forced vital capacity were fully graduated, commencing with low-intensity activities (eg, exer- common160–163 and 6-minute walk test results were significantly cise performed in bed, simple limb exercises, or a passive transfer via lower163 than expected in 23 to 27% of patients.160,161 Alterations in slide board to a chair). Supplemental oxygen concentration and/or lung function, exercise capacity, and symptoms may be similar to flow may be increased prior to mobilisation to maintain SpO2 within individuals with interstitial lung disease and exercise-induced desa- targeted ranges (eg, 92 to 96% in most patients, or 88 to 92% in pa- turation may be more severe than seen in people with chronic tients with hypercapnia due to chronic respiratory disease6). Short intervals of exercise or mobilisation and recovery can be used rather than continuous interventions and demand moderated by exercising partitioned muscle mass (eg, single limb exercises).150 Ventilation with NIV should be considered, particularly if it is already in use and with consideration to environmental controls135 and all patients should be informed about performing activities conservatively and at a safe pace that is manageable for their energy levels and within the limits of current symptoms.149 Performing activities at the bedside rather than moving away from the bed may be an important safety strategy for this patient
Invited Topical Review 21 obstructive pulmonary disease.164 However, exercise-induced desa- international authorship panel. The overwhelming uptake and turation appears to occur in a small proportion (2 to 9%) of survivors adoption of the publication is testament to its strengths and reso- of severe COVID-19.161,163 nance within the physiotherapy community world-wide. At the time of preparation of this manuscript, the original manuscript1 had been Pulmonary rehabilitation models have been shown to be effective downloaded more than 180,000 times, endorsed by 10 organisations in chronic lung disease165–167 and may reduce symptoms such as and translated into 26 languages. dyspnoea and fatigue,165,167 which are common to post-COVID condi- tions. They are often applied in traditional outpatient models but are While more is being learnt about COVID-19, and an exponential evolving, with efficacy shown with alternative models, including tele- rise in research specific to COVID-19 is now presenting, rehabilitation.168 The use of pulmonary rehabilitation models that physiotherapy-specific publications are limited and often confined to have been adapted for COVID-19 appear to show potential benefit, observational reports or audits. Information from these resources has including the implementation of inpatient pulmonary rehabilitation been used whenever possible, but further evidence describing the models169 and outpatient-based pulmonary rehabilitation.170,171 Tele- role of physiotherapy world-wide and/or clinical studies are needed. rehabilitation after hospitalisation has also shown benefits in exercise A further limitation is the focus of the recommendations on adult capacity, muscle strength and physical components of quality of life in acute hospital settings. Definitions for COVID-19 disease severity exist COVID-19.172 Other models of rehabilitation (eg, cardiac rehabilitation) for children and differ to that of adults.5 The long-term implications and types of physical activity may be utilised and options will vary of COVID-19 are also now being documented, with the potential role depending on the individual factors, including age, access to services, of outpatient or community-based rehabilitation becoming apparent degree of disability and identified risk factors. and specific recommendations in this context have been incorporated into the updated recommendations. Regardless of the model used for exercise-based rehabilitation, programs that include or are designed specifically for people with Footnotes: a These updated recommendations are intended for COVID-19 should incorporate disease-specific education on post-COVID use in adults only. This document has been constructed using existing conditions, screening related to specific complications and monitoring medical guidelines, relevant literature and expert opinion. The au- for post-exertional symptom exacerbation. When prescribing physical thors have made considerable effort to ensure that the information interventions to people who have post-COVID conditions, they should contained with the recommendation is accurate at time of publica- be screened for new or worsened cardiac impairment, post-exertional tion. The information provided in this document is not designed to symptom exacerbation, exertional oxygen desaturation, autonomic replace local institutional policies, override public health directives or dysfunction and orthostatic intolerance.149 replace clinical reasoning for individual patient management. The authors are not liable for the accuracy, information that may be Providing guidance for exercise training to people post-COVID perceived as misleading, or completeness of information in this should always be done with caution, as it is possible for symptoms document. to be exacerbated. This may include worsening of fatigue, cognitive dysfunction or any other symptoms experienced following COVID- b These recommendations have been endorsed by American 19.149 Where post-exertional symptom exacerbation is identified, Physical Therapy Association, APTA Acute Care Academy, Associação adaptations may include the “Stop. Rest. Pace” approach, activity Brasileira de Fisioterapia Cardiorrespiratória e Fisioterapia em Terapia management or pacing.149 Patients should be encouraged to contact Intensiva, Association of Chartered Physiotherapists in Respiratory their healthcare team if they experience any ‘red flag’ symptoms with Care, Australian Physiotherapy Association, AXXON Physical Therapy exercise, including new or worsening breathlessness, chest pain, in Belgium, Canadian Physiotherapy Association, Cardiopulmonary tachycardia, palpitations, confusion, difficulty speaking or under- Rehabilitation Group of the South African Society of Physiotherapy, standing speech, or weakness in their face, arm or leg.173 Hong Kong Physiotherapy Association, International Confederation of Cardiorespiratory Physical Therapists, Japanese Society of Cardiovas- There is a need to recognise the demand that respiratory pan- cular Physical Therapy, Japanese Society of Intensive Care Medicine, demics are likely to place on rehabilitation teams as people move Japanese Society of Physical Therapy for Diabetes Mellitus, Japanese along the disease trajectory from acute and inpatient care, through to Society of Respiratory Physical Therapy, Physiotherapy New Zealand, the ambulatory settings and onwards into the community.174 To be Société de Kinésithérapie de Réanimation, and World Physiotherapy. effective in reducing disability-related outcomes, COVID-19 in- terventions, including rehabilitation programs, must be considered as eAddenda: Appendices 1 to 2 can be found online at DOI: 10.1016/ part of early planning and additional resources allocated as part of the j.jphys.2021.12.012. pandemic response.174 Ethics approval: Not applicable. While not yet part of any international or national guidance on Competing interests: All authors completed a World Health Or- prevention, there is increasing understanding of the role of health ganization conflict of interest form. Direct financial and industry- and lifestyle risk factors in the susceptibility to COVID-19 infection related conflicts of interest were not permitted. The development of and severity. Physical activity is a modifiable risk factor and these recommendations did not include any industry input, funding, contributor to the disease burden for multiple chronic conditions, and or financial or non-financial contribution. No author received hono- physiotherapists play an important role in health promotion. Having a raria or remuneration for any role in the development process. higher habitual level of physical activity can lower a person’s risk of Source(s) of support: Nil. acquiring community-acquired infectious diseases.175 Regular phys- Acknowledgements: Nil. ical activity before vaccinations may also increase the subsequent Provenance: Invited. Peer reviewed. level of antibody produced.175 Physical inactivity has been identified Correspondence: Peter Thomas, Department of Physiotherapy, as a strong predictor of the impact of severe COVID-19 infection, with Royal Brisbane and Women’s Hospital, Australia. Email: people who were inactive prior to the pandemic at greater risk of [email protected] hospitalisation, ICU admission and death.176 Physiotherapists must promote effective health education programs, including smoking References cessation, nutrition, weight control and physical activity, to improve the health of their community and potentially minimise the impact of 1. 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Journal of Physiotherapy 68 (2022) 43–50 j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j p hy s Research Prehabilitation sessions can be provided more frequently in a shortened regimen with similar or better efficacy in people with non-small cell lung cancer: a randomised trial Francis-Edouard Gravier a,b, Pauline Smondack a, Fairuz Boujibar c,d, Guillaume Prieur b,e, Clément Medrinal e,f,g, Yann Combret h, Jean-François Muir a,b, Jean-Marc Baste c,d, Antoine Cuvelier b,i, David Debeaumont j, Tristan Bonnevie a,b a ADIR Association, Rouen University Hospital, Rouen, France; b Normandie University, UNIROUEN, UPRES EA 3830, Haute Normandie Research and Biomedical Innovation, Rouen, France; c Department of Thoracic Surgery, Rouen University Hospital, Rouen, France; d Normandie University, UNIROUEN, INSERM U1096, Haute Normandie Research and Biomedical Innovation, Rouen, France; e Intensive Care Unit Department, Le Havre Hospital, Le Havre, France; f Université Paris-Saclay, UVSQ, UR 20201 ERPHAN, Versailles, France; g IFMK Saint Michel, Paris, France; h Physiotherapy Department, Le Havre Hospital, Le Havre, France; i Pulmonary, Thoracic Oncology and Respiratory Intensive Care Department, Rouen University Hospital, Rouen, France; j Department of Respiratory and Exercise Physiology and CIC-CRB 1404, Rouen University Hospital, Rouen, France KEY WORDS ABSTRACT Non-small cell lung cancer Question: In people with non-small cell lung cancer, what is the effect of condensing 15 prehabilitation Lung resection sessions into a 3-week regimen compared with a 5-week regimen? Design: Randomised controlled trial Preoperative care with concealed allocation, intention-to-treat analysis and blinded assessment of the primary outcome. Exercise training Participants: People with diagnosed or suspected non-small cell lung cancer and moderate-to-high risk of Prehabilitation postoperative complications. Intervention: Fifteen supervised prehabilitation sessions delivered with either a dense regimen of five sessions/week for 3 weeks (experimental group) or a non-dense regimen of three sessions/week for 5 weeks (control group). Outcome measures: The primary outcome was the change in cardiorespiratory fitness measured by the V_ O2peak in ml/kg/min. The secondary outcomes were the change in other variables of interest measured during cardiopulmonary exercise testing, non-invasive nutritional markers, quadriceps maximal voluntary isometric contractions, maximal inspiratory pressure, quality of life, adherence and postoperative complications. Results: Changes with the experimental regimen were similar to or better than changes with the control regimen for: V_ O2peak (MD 1.2 ml/kg/min, 95% CI 20.1 to 2.6); V_ E/V_ CO2 slope (MD 23.6 points, 95% CI 28.7 to 1.5); and work rate at ventilatory threshold (MD 3.7 W, 95% CI 25.6 to 13.0). The two regimens had similar effects on: peak work rate (MD 1.3 W, 95% CI 26.4 to 9.0), V_ O2 at ventilatory threshold (MD 0.0 ml/kg/min, 95% CI 21.4 to 1.4); body mass index (MD 20.2 kg/m2, 95% CI 20.5 to 0.1); and maximal inspiratory pressure (MD 20.7 cmH2O, 95% CI 29.8 to 8.4). The relative effect was uncertain for quadriceps maximal voluntary isometric contractions, quality of life and complications. Conclusion: Condensing prehabilitation sessions led to similar or better improvement in cardiorespiratory fitness and did not decrease adherence or increase adverse events. This could increase the number of patients who can be referred for prehabilitation, despite short presurgical periods. Trial registration: NCT03936764. [Gravier F-E, Smondack P, Boujibar F, Prieur G, Medrinal C, Combret Y, Muir J-F, Baste J-M, Cuvelier A, Debeaumont D, Bonnevie T (2022) Prehabilitation sessions can be pro- vided more frequently in a shortened regimen with similar or better efficacy in people with non-small cell lung cancer: a randomised trial. Journal of Physiotherapy 68:43–50] © 2021 Australian Physiotherapy Association. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction termed prehabilitation, which involves exercise training, support with smoking cessation, nutritional advice, respiratory physiotherapy Lung cancer is the most common type of cancer and the leading and postoperative education, is increasingly being prescribed and cause of cancer death worldwide.1 Lung resection is currently the delivered to this clinical population. recommended curative treatment for early-stage non-small cell lung cancer (NSCLC).2 Measurement of peak oxygen uptake (V_ O2peak) by Prehabilitation was initially undertaken to allow patients who cardiopulmonary exercise testing is recommended to assess periop- were inoperable due to their poor cardiorespiratory fitness to benefit erative risk in frail patients.3,4 Physical preparation for surgery, from curative surgery. Today, as evidenced by a growing number of randomised trials from various regions of the world, the challenge is https://doi.org/10.1016/j.jphys.2021.12.010 1836-9553/© 2021 Australian Physiotherapy Association. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
44 Gravier et al: Prehabilitation density before NSCLC surgery to offer this intervention to reduce the occurrence and severity of Intervention postoperative complications and to shorten length of hospital stay, including in patients with moderate postoperative risk.5 Despite Prehabilitation sessions these benefits, some teams might be reluctant to offer prehabilitation All participants in both groups were allocated to receive 15 to operable patients with high/moderate surgical risk so that surgery is not delayed. prehabilitation sessions. Each prehabilitation session lasted approxi- mately 90 minutes. The first session was individual and the following Related to this concern, the organisation of prehabilitation must sessions were performed in groups of around six patients. The pro- consider both the need for rapid surgery and the need to provide a gram was supervised by a physiotherapist. The program included the sufficient training load to obtain physiological benefits. In a pre- following four components. liminary retrospective cohort study, we found that the subgroup of patients who completed 15 sessions showed more improvement in Aerobic endurance training: aerobic endurance training on a cycle cardiorespiratory measures after the prehabilitation program than ergometer at the ventilatory threshold (VT) determined during the those who performed fewer sessions.6 The program was therefore initial cardiopulmonary exercise testing. The first session lasted for 15 designed to have 15 sessions. Programs involving daily training could to 20 minutes. The duration increased by 5 minutes each session to provide considerable physiological stimulation in a shorter timeframe reach 45 minutes (including a 5-minute warmup and a 5-minute compared with a more conventional frequency of two to three ses- active recovery). The intensity was then increased by 5 or 10 watts, sions per week in pulmonary rehabilitation.7 However, such intense as tolerated.9 training could cause significant fatigue or limit adherence. Patients scheduled for NSCLC resection undergo many preoperative consul- Peripheral muscle strengthening: peripheral muscle strengthening tations and examinations and may struggle to also participate in on weight machines performed at 60 to 70% of the 1-repetition prehabilitation. maximum (1RM) (three exercises: whole-leg extension, whole-arm pull down and whole-arm extension). Three sets of 12 movements To date, no study has evaluated the relative effect of condensing were carried out for each exercise and the load was increased regu- the delivery of a fixed number of exercise sessions on the physio- larly as tolerated.10 logical benefits and safety of prehabilitation. Inspiratory muscle training: inspiratory muscle training using an Therefore, the research question for this randomised controlled inspiratory threshold valve calibrated to at least 30% of the maximal trial was: inspiratory pressure (MIP). Patients were encouraged to carry out 15 minutes of independent training daily and to increase the resistance In people with NSCLC, what is the effect of condensing 15 pre- regularly.11 habilitation sessions into a 3-week regimen compared with a 5- week regimen? Support and education: smoking cessation support12 and education regarding mucus clearance techniques, deep-breathing, directed and Method protected coughing, and postoperative mobilisation.13 The last two components were mainly delivered during the first individual ses- Study design sion, and reminders and advice were provided during the following 14 group sessions. The exercises were prescribed and progressed by a This randomised controlled trial was conducted by ADIR Associ- physiotherapist in accordance with the safety criteria recommended ation, Rouen, France, in partnership with Rouen University Hospital. by the physician after cardiopulmonary exercise testing. Consecutive adult patients with suspected or confirmed NSCLC and a moderate-to-high perioperative risk at the pulmonary rehabilitation Randomised regimens centre of the ADIR Association were screened for eligibility. Eligible, Participants were randomly assigned to one of two regimens for consenting patients were randomly assigned after baseline assess- ment to one of two prehabilitation regimens: five sessions per week 15 sessions of prehabilitation. The experimental group was scheduled for 3 weeks (experimental group) or three sessions per week for 5 to attend five 90-minute sessions per week for 3 weeks. The control weeks (control group). The 1:1 randomisation sequence was group was scheduled to attend three 90-minute sessions per week for computer-generated before initiation of the trial using the Research 5 weeks. Randomizer website and concealed until enrolment in the first pre- habilitation session. Before and after prehabilitation, participants Outcome measures underwent cardiopulmonary exercise testing and measurement of non-invasive nutritional markers, quadriceps strength, maximal A comprehensive medical history was collected for each patient. inspiratory pressure, quality of life and adherence. Complications Cardiorespiratory fitness and spirometry were assessed by a physi- were assessed postoperatively. A blinded researcher assessed the cian who was blind to patient allocation before and after the 15 primary outcome (cardiorespiratory fitness). Analysis followed the planned prehabilitation sessions. The same physiotherapist, who was intention-to-treat principle. The results of the study are reported not blind to patient allocation, assessed quadriceps strength, maximal according the Consolidated Standards of Reporting Trials (CONSORT) inspiratory pressure, and non-invasive nutritional variables at the statement.8 first and last sessions. A quality of life questionnaire was completed during the first and last sessions. The primary outcome was the post-training change in cardio- respiratory fitness measured by the V_ O2peak in ml/kg/min. Sec- ondary outcomes were the post-training change in the other variables of interest measured during cardiopulmonary exercise testing, non-invasive nutritional markers, quadriceps maximal voluntary isometric contractions, maximal inspiratory pressure, quality of life, adherence and postoperative complications. Participants Cardiopulmonary exercise testing The inclusion criteria were suspected or confirmed NSCLC and a Cardiopulmonary exercise testing was performed on an electro- moderate-to-high perioperative risk, defined as V_ O2peak , 20 ml/kg/ magnetic ergometera. A face mask, pneumotach and gas analyserb min. The exclusion criteria were: cardiological contraindications to were used to assess oxygen uptake (V_ O2) and carbon dioxide pro- training; neoadjuvant radio-chemotherapy; refusal to carry out a duction (V_ CO2), breath by breath. Heart rate was continuously training program; a comorbidity that limited cycling (eg, orthopaedic, monitored using a 12-lead electrocardiogram and perceived exertion vascular or neurologic limitations); exacerbation; or medical recom- mendation for early cessation of the prehabilitation program. was assessed using the Borg scale. After a 3-minute warm-up period, incremental ramp exercise (aimed to last for about 10 minutes using steps from 5 to 15 W/min depending on the physician’s evaluation,
Research 45 the patient’s history and usual physical activity levels) was applied to methods,23,24 and the widest estimate was conservatively used before exhaustion.14 V_ O2 measured during the last fully sustained ramp was calculating the MDs. Statistical analyses were performed with an defined as the V_ O2peak and expressed as a percentage of the predicted intention-to-treat approach using the last observation carried for- value according to age, weight and sex.14,15 Ventilatory threshold was ward method for preoperative variables,25 and no postoperative complication was considered for patients who did not undergo sur- manually identified using a three-criterion discrimination tech- gery. Commercial statistical softwareg was used for analyses. nique.14 Linear regression of the ratio between the increase in minute ventilation (V_ E) and the expired carbon dioxide flow (V_ CO2) gener- Results ated the V_ E/V_ CO2 slope. Flow of participants through the study Pulmonary function Thirty-six participants were recruited between May 2019 and Pulmonary function tests were carried out according to the April 2021. The flow of participants through the study is presented in Figure 1. The baseline characteristics of the participants are presented American Thoracic Society and the European Respiratory Society in Table 1 and in the first two columns of data in Table 2. guidelines with a commercial spirometerc. Values were expressed as percentages of established predicted values for European pop- ulations.16 MIP was measured before and after prehabilitation using an electronic manometerd. Quality of life Primary outcome Quality of life was estimated using the European Organization for The mean between-group difference in the change in V_ O2peak was Research and Treatment of Cancer Core Quality of Life Questionnaire 1.2 ml/kg/min (95% CI 20.1 to 2.6). The two-sided 95% CI (20.1 to 2.6) and modular supplement for Lung Cancer patients (EORTC QLQ-C30 / spanned from close to 0 (no between-group difference) to greater LC13), a 30-question questionnaire with a 13-question modular spe- than the prespecified smallest worthwhile effect of 1.75 ml/kg/min in cific supplement for patients with lung cancer.17 Scores range from favour of the dense training regimen, indicating similar or better 0 to 100, and a higher score reflects either better function or milder benefits from the dense training regimen relative to the control symptoms. regimen. (Table 2 and Figure 2). Nutritional status Secondary outcomes Nutritional status was estimated non-invasively by measuring Preoperative outcomes body mass index and bioimpedance analysise of fat-free mass calcu- Changes in the secondary outcomes from before to after pre- lated as percentage of total body weight. The measurement was carried out before exercise, in a standardised supine position, after habilitation for each group and the corresponding between-group urination and 10 minutes of rest.18 Since the patient then performed comparisons are presented in Table 2. As for primary outcome, the the exercise training session, fasting was not required. The pre- and effect from the dense prehabilitation was similar to or better than the post-prehabilitation measurements were taken at the same time of control regimen for V_ E/V_ CO2 slope (MD 23.6 points, 95% CI 28.7 to day. 1.5) and work rate at the ventilatory threshold (3.7 W, 25.6 to 13.0). The dense prehabilitation regimen was estimated to have similar Quadriceps strength effects to the control regimen on peak work rate (MD 1.3 W, 95% Bilateral quadriceps maximal voluntary isometric contractions CI 26.4 to 9.0), V_ O2VT (MD 0.0 ml/kg/min, 95% CI 21.4 to 1.4), body mass index (MD 20.2 kg/m2, 95% CI 20.5 to 0.1), and maximal were evaluated with hand-held dynamometryf according to a inspiratory pressure (MD 20.7 cmH2O, 95% CI 29.8 to 8.4). Although standardised methodology.19 The obtained results were expressed in the mean between-group differences for quadriceps maximal absolute values and as a percentage of the corresponding theoretical voluntary isometric contractions and quality of life were all too small normal values for each lower limb.20 to be perceived as clinically relevant, the large 95% CIs demonstrate that these estimates had important inherent uncertainty that does Adherence and adverse event not exclude the possibility of worthwhile differences in effect. Indi- Adherence to the prehabilitation program was defined as the ratio vidual participant data are presented in Table 3 on the eAddenda. of the number of sessions attended to the 15 sessions prescribed. Any Adherence and adverse events adverse event during or related to exercise training was recorded. The mean adherence rate for scheduled sessions was 86% (SD 11) Postoperative complications in the experimental group and 87% (SD 11) in the control group, Postoperative complications were collected from the medical giving a mean difference of 1% (95% CI 29 to 7). No patient dropped out due to intolerance to the prehabilitation program. Only one pa- records at 30 days and graded according to the Clavien-Dindo tient had to discontinue the program early, because the date of sur- classification.21 gery was brought forward. No adverse events occurred. Data analysis Postoperative outcomes Twenty-six participants (72%) underwent surgery at the end of This study aimed to assess the relative effects of a dense and a non-dense supervised outpatient prehabilitation program on im- their prehabilitation program (Table 4). Ten surgical interventions provements in cardiorespiratory fitness measured by the change in (five in each group) were not carried out for the following reasons: V_ O2peak. Taking into account an expected between-group difference three participants had stable nodules under surveillance, three par- (mA 2 mB) of zero, alpha of 0.05, power of 80%, a two-sided 95% CI, a ticipants had metastases discovered, two participants had unfav- smallest worthwhile effect on the change in V_ O2peak of 1.75 ml/kg/ ourable onco-geriatric opinions, one participant had a benign biopsy min, and a standard deviation of 1.62 ml/kg/min,6 it was determined result and one participant refused surgery. Six postoperative com- that a total of 30 participants was required, divided into two groups.22 plications were reported: two in the experimental group and four in Assuming a 20% dropout risk, the sample size was set to 36 the control group, RR 0.5 (95% CI 0.1 to 2.1). Most of the postoperative participants. complications were pulmonary and clinically significant (Clavien- Dindo classification 2) (Table 5). Categorial data were expressed as numbers (percentages). Continuous data were expressed as means (SD) or median (IQR) according to distribution. Normality was assessed using the Kolmogorov-Smirnov test. Between-group differences were expressed as MD (95% CI). If necessary, skewed data were prelimi- narily converted into means (SD) with the Luo et al and Shi et al
46 Gravier et al: Prehabilitation density before NSCLC surgery Assessed for eligibility (n = 61) Excluded (n = 25) neoadjuvant chemotherapy (n = 6) COVID-19 containment (n = 6) surgical date < 5 weeks away (n = 6) comorbidity limiting training (n = 4) d.eclined to participate (n = 1) VO2peak > 20 ml/kg/min (n = 1) tracheostomy (n = 1) Week 0 Underwent cardiopulmonary exercise testing and measured body mass index, fat-free mass, quadriceps torque, maximum inspiratory pressure and quality of life Randomised (n = 36) (n = 18) (n = 18) Lost to follow-up (n = 0) Experimental group Control group Lost to follow-up (n = 0) prehabilitation prehabilitation 5 sessions/week 3 sessions/week 3 weeks 5 weeks Preop Underwent cardiopulmonary exercise testing and measured body mass index, fat-free mass, quadriceps torque, maximum inspiratory pressure, quality of life, adherence and adverse events (n = 18) (n = 18) Lost to follow-up (n = 5) Lost to follow-up (n = 5) surgery cancelled (n surgery cancelled (n = 5) = 5) Postop Assessed postoperative complications (n = 13) (n = 13) Figure 1. Design and flow of participants through the trial. COVID-19 = coronavirus disease 2019, CPET = cardiopulmonary exercise testing, V_ O2peak = peak oxygen uptake. Discussion this value represents approximately 10% of the baseline median The main finding of this study was that a shorter dense pre- (Table 2) and can potentially allow some patients to fall below the habilitation program (five sessions/week for 3 weeks) had a similar or previously reported postoperative risk threshold of 35.27 However, better effect than a longer regimen (three sessions/week for 5 weeks) on cardiorespiratory fitness measured with V_ O2peak. The between- the uncertainty around this estimate ranges from a very worthwhile group difference in change in V_ O2peak was 1.2 ml/kg/min (95% reduction in favour of dense prehabilitation regimen through to CI 20.1 to 2.6) in favour of the dense regimen, although the uncer- tainty in that estimate ranged from quite similar to better than negligible differences (95% CI 28.7 to 1.5). control to a clinically worthwhile degree (ie, greater than the pre- The two outcome measures discussed above (ie, V_ O2peak and V_ E/ specified smallest worthwhile effect of 1.75 ml/kg/min). As no rele- vant smallest worthwhile effect has been published for this clinical V_ CO2 slope) are powerful predictive markers of complications after scenario, the threshold that was prespecified requires further clari- pulmonary resection.4,27 Given that mean estimates favoured the fication. This value corresponded to the mean difference previously observed between patients who completed 15 training sessions or dense prehabilitation regimen and the confidence intervals indicated more and those who received a lower training load.6 Furthermore, that the effects are as good as or better than the control regimen, a this value of 1.75 ml/kg/min is equal to a half metabolic equivalent of task (1 MET = 3.5 ml/kg/min)2a value that can distinguish different reduction in postoperative complications might be anticipated. Un- levels of functional activity.26 Ultimately, whatever smallest worth- while effect threshold is chosen, this study provides an estimate that fortunately, the study did not confirm this assumption. Although the is accurate enough to support that a dense prehabilitation regimen overall complication rate in the present cohort (23%) was close to the leads to benefits that are at least similar to those achieved with a longer less-dense regimen. overall complication rate of 19% reported by the European Society of Thoracic Surgeons from their database, this produced a very uncer- A previous study found that ventilatory efficiency was probably less sensitive than oxygen uptake to prehabilitation.6 In the present tain estimate of the relative effect of the interventions on this study, only the experimental group showed a substantial mean outcome. Additionally, the distribution of surgical procedures per- reduction in the V_ E/V_ CO2 slope, resulting in a mean difference be- tween the two groups of 23.6 (slope coefficient). Although there is formed did not allow this comparison to be interpreted without currently no established threshold for a smallest worthwhile effect, possible confounding. Future adequately powered trials are war- ranted to further explore the effects of prehabilitation density on postoperative complications. The estimated effect of the dense prehabilitation regimen on peak power on the cycle ergometer (WRpeak) was a mean between-group difference of 1.3 W (95% CI 26.4 to 9.0). This can be considered clinically similar to the control regimen, based on a MCID of 10.5 W.28 The upper limit of the confidence interval could perhaps be judged as a worthwhile benefit from the dense regimen, since in clinical prac- tice the variation in Watts on cycle ergometers is generally rounded
Research 47 Table 1 Baseline characteristics of the study participants. Characteristic All Exp Con (n = 36) (n = 18) (n = 18) Age (yr), mean (SD) 66 (8) 68 (8) 65 (8) Sex, n male (%) 23 (64) 14 (78) 9 (50) Body mass index (kg/m2), mean (SD) 29 (6) 29 (7) 29 (5) V_ O2peak (% pred), mean (SD) 64 (15) 61 (15) 67 (15) FEV1 (L), mean (SD) 1.9 (0.7) 1.9 (0.7) 1.9 (0.7) FEV1 (% pred), mean (SD) 74 (28) 73 (31) 75 (26) FVC (L), mean (SD) 3.0 (0.8) 3.2 (0.9) 2.9 (0.8) FVC (% pred), mean (SD) 90 (22) 90 (26) 90 (19) DLCO (% pred), median (IQR) 56 (45 to 70) 58 (46 to 70) 55 (45 to 69) Comorbidities, n (%) 22 (61) 14 (78) 8 (44) COPD 19 (53) 9 (50) 10 (56) hypertension 14 (39) 6 (33) 8 (44) hypercholesterolaemia 13 (36) 8 (44) 5 (28) cardiovascular disease 10 (28) 6 (33) 4 (22) diabetes 5 (14) 2 (11) 3 (17) anxiety-depression syndrome 8 (22) 4 (22) 4 (22) orthopaedic/rheumatic disease 6 (3 to 7) 6 (4 to 7) 5 (3 to 8) Medications (n/patient), median (IQR) Tobacco use category, n (%) 2 (6) 1 (6) 1 (6) non-smoker 11 (31) 6 (33) 5 (28) smoker 23 (64) 11 (61) 12 (67) former 42 (36 to 60) 48 (35 to 60) 40 (34 to 54) Tobacco exposure (pack-yr), median (IQR) NSCLC stage, n (%) 22 (61) 13 (72) 9 (50) I 7 (19) 2 (11) 5 (28) II 3 (8) 1 (6) 2 (11) III 1 (3) 0 (0) 1 (6) IV 3 (8) 2 (11) 1 (6) NS Con = control group, COPD = chronic obstructive pulmonary disease, DLCO = diffusing capacity of the lung for carbon monoxide, Exp = experimental, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, NS = not specified, V_ O2peak = peak oxygen uptake. off to 5 W higher or lower, and an average gain of 10 W at WRpeak opportunity to perform more inspiratory muscle training sessions generally results in an additional increment during cardiopulmonary due to the longer duration of the program; however, this did not exercise testing.14 produce clinically relevant increases in the amount of improvement in maximal inspiratory pressure. Concerning a submaximal marker, the difference in V_ O2VT be- tween the two groups was unimportant (MD 0.0 ml/kg/min, 95% We were concerned that participants undertaking an outpatient CI 21.4 to 1.4). For WRVT, although the difference was clinically trivial, training program 5 days per week might experience a reduction in the uncertainty around this estimate ranged from similar to better in quality of life and/or adhere poorly to the prescribed sessions. Both favour of the dense regimen (MD 3.7 W, 95% CI 25.6 to 13.0). Due to groups underwent an identical total prescribed training load with a uncertainty, further research is needed to clarity the relative effects of similar rate of adherence: 86% in the experimental group and 87% in different training densities on submaximal cardiorespiratory fitness the control group. The study produced very imprecise estimates biomarkers. about the relative effects of the two prehabilitation regimens on quality of life. For example, the confidence interval around the mean The evaluated nutritional markers did not clinically change after between-group difference in the EORTC-QLQ-C30 LC13 subscale prehabilitation in either group, with trivial between-group differ- spanned the published smallest worthwhile effects of a 3-point in- ences. These measures have not been previously reported in lung crease and a 6-point decrease.33 Therefore, we were unable to draw cancer patients but the results are consistent with the effect of a any clear conclusion about whether and by how much one regimen similar prehabilitation program in patients with scheduled colorectal might be superior to the other for quality of life. This requires further surgery.29 clarification with future trials. However, the current results confirm that it is possible to obtain physiological benefits in a short period of To interpret the effects on quadriceps strength, the smallest time with a condensed program without generating adverse events or worthwhile effect of 7.5 Nm (established in patients with COPD30) a negative effect on adherence. could be used. Against this threshold, the between-group difference of 0.3 Nm and 4.7 Nm were both clinically trivial (Table 2). The es- The positive effects of prehabilitation in patients scheduled timates were, however, very imprecise; on the left side, for example, for lung resection for NSCLC are increasingly being scientifically the 95% CI spanned clinically worthwhile differences in either di- supported; however, these programs are very heterogeneous.5 rection. Although there are no data in the literature for NSCLC pa- One-week programs with twice-daily training and multimodal tients, a meta-analysis reported that healthy untrained subjects management have recently been described, but they involve hospi- benefit more from higher training frequencies with moderate loads talisation,34,35 which cannot be generalised to a large number of rather than low training frequencies with higher resistive load.31 Due patients in most healthcare systems. The durations of supervised to uncertainty, further research is needed to clarify the relative effects outpatient programs described in prospective trials are 3 weeks, of more-frequent resistance training on peripheral muscle strength and training frequencies range from three to five times per week.5 during prehabilitation. Regarding inspiratory muscle strength Since patients with risk factors frequently require a larger set of measured with MIP, a smallest worthwhile effect threshold of 17.2 examinations, we observed locally that those who benefited from cmH2O was used.32 The relative improvement in MIP can be judged prehabilitation did not have a longer surgical delay, while reducing as clinically similar because both the main estimate (20.7 cmH2O) the incidence and the severity of postoperative complications.36 In and its confidence interval (29.8 to 8.4) are smaller in magnitude order to facilitate the implementation of such prehabilitation pro- than the smallest worthwhile effect. It is worth noting that in addi- grams, this must be considered in parallel with their diagnosis in a tion to the supervised exercise training sessions, participants in both global oncological care pathway. As the flowchart shows, a sizeable groups also had the opportunity to perform daily unsupervised proportion of patients referred for prehabilitation do not ultimately inspiratory muscle training. Therefore, the control group had the
48 Gravier et al: Prehabilitation density before NSCLC surgery Table 2 Mean (SD) of groups, mean (SD) within-group difference and mean (95% CI) between-group difference for outcome measures. Outcome Groups Within-group difference Between-group difference Preoperative minus baseline Preoperative minus baseline Baseline Preoperative Exp minus Con Exp Con Exp Con Exp Con (n = 18) (n = 18) (n = 18) (n = 18) Cardiorespiratory exercise testing V_ O2peak (ml/kg/min) 12.9 14.1 15.3 15.3 2.4 1.2 1.2 V_ O2VT (ml/kg/min) (3.3) (3.2) (3.6) (3.7) (2.1) (20.1 to 2.6) WRpeak (W) 9.6 9.9 10.4 10.6 (1.8) 0.8 WRVT (W) (1.8) (1.7) (1.9) (2.0) (2.0) 0.0 V_ E/V_ CO2 slope 73.9 77.2 85.3 87.5 0.8 9.8a (21.4 to 1.4) (19.2) (26.4) (19.6) (31.7) (11.3) 45.0a,b 43.0a,b 50.9a,b 48.5a,b (2.1) 6.7a 1.3 (12.8) (17.4) (14.4) (19.7) 11.1a (10.3) (26.4 to 9.0) 38.9a 39.0 35.5 38.8 (10.4) (9.9) (6.2) (11.0) (12.3) 20.2 3.7 10.4a (6.6) (25.6 to 13.0) (17.2) 23.6 23.8a (28.7 to 1.5) (8.9) Nutrition 29.5 29.3 29.5 29.5 0.0 0.2a 20.2 Body mass index (kg/m2) (6.8) (5.1) (6.7) (5.1) (0.5) (0.5) (20.5 to 0.1) 66.3 62.2 66.0 62.0 20.3 20.1 Fat-free mass (%) (8.4) (8.6) (7.9) (7.9) (1.5) (2.8) 20.2 (21.8 to 1.3) Muscle strength 82.7c 86.7 91.2c 94.9 8.5 8.2 0.3 QMVIC left (Nm) (20.7) (42.6) (21.8) (39.5) (12.5) (18.3) (210.8 to 11.4) QMVIC right (Nm) 76.4c 83.5 86.1c 89.2 10.4a MIP (cmH2O) (21.7) (43.0) (22.4) (39.2) (14.4) 5.7 4.7 60.9 60.5 70.5 68.4a (13.8) (22.4 to 11.8) (16.3) (20.6) (17.1) (24.9) 9.6 10.3a (9.3) (17.3) 20.7 (29.8 to 8.4) EORTC QLQ-30 78.3a 71.1 86.2 81.9a 7.7 11.0 23.3 Functional score (0 to 100) (7.3) (212.6 to 5.9) Symptom score (0 to 100) (11.6) (23.0) 83.0 (17.2) (8.9) (17.1) Global score (0 to 100) 81.3a 82.8a (12.0) 83.9a 1.5a 4.0a 22.5 LC13 score (0 to 100) (11.7) (14.0) 71.3 (13.8) (12.6) (211.1 to 6.1) 59.3a 64.7a (14.1) (14.1) 12.5a 10.2a (22.1) (20.0) 88.0 74.1a (25.1) (19.1) 2.3 85.7 83.6 (8.2) 2.3 1.4 (212.3 to 16.9) (8.2) (12.6) (16.0) (5.2) (7.5) 84.9a 1.4 (28.7 to 6.5) (13.3) Small anomalies in subtraction in the unconverted data are due to the effects of rounding. Shaded row = primary outcome. Con = control group, EORTC QLQ-30 = European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire, Exp = experimental group, FEV1 = forced expiratory volume in 1 second, FEF25-75 = forced expiratory flow at 25 to 75% of the expiratory volume, FVC = forced vital capacity, LC13 = lung cancer-specific module of the EORTC QLQ-30, MIP = maximal inspiratory pressure, QMVIC = quadriceps maximum voluntary isometric contraction, V_ E/V_ CO2 slope = linear regression of the ratio between the increase in minute ventilation (V_ E) and the expired carbon dioxide flow (V_ CO2), V_ O2peak = peak oxygen uptake, V_ O2VT = oxygen uptake at ventilatory threshold, WRpeak = peak power on cycle ergometer, WRVT = power at ventilatory threshold. a Data converted. b n = 17. c n = 16. undergo their planned surgery. Routine referral of all NSCLC patients postoperative stress will help a patient to better tolerate other to prehabilitation programs may incur expenditure on patients therapeutic strategies, as suggested by the positive effects of exercise whose planned surgery does not eventuate. However, the clinical training on exercise capacity and disease-specific health-related benefits that were intended to overcome the surgical and quality of life for patients with advanced lung cancer.37 Future work should consider long-term follow-up and analysis of cost- Favours control Favours dense prehabilitation effectiveness in order to answer this issue. Our current results show that prehabilitation sessions can be provided more frequently in a shortened regimen with similar or better efficacy in people with NSCLC. This could increase the number Table 4 Characteristics of participants’ surgery. Characteristic All Exp Con (n = 26) (n = 13) (n = 13) –4 –3 –2 –1 0 1 2 3 4 Between-group difference (ml/kg/min) Surgical approach, n (%) 20 (77) 12 (92) 8 (62) Figure 2. Mean between-group difference (95% CI) between the experimental group VATS/RATS 6 (23) 1 (8) 5 (39) thoracotomy (dense regimen; five sessions/week for 3 weeks) and the control group (standard 3 (12) 0 (0) 3 (23) regimen; three sessions/week for 5 weeks) in change in peak oxygen uptake (V_ O2peak) Type of surgery, n (%) 12 (46) 5 (39) 7 (54) after the prescribed 15-session prehabilitation program. The two-sided 95% CI (20.1 to pneumonectomy/bilobectomy 11 (42) 8 (62) 3 (23) 2.6) spanned from close to 0 (no between-group difference) to greater than the pre- lobectomy wedge/segmentectomy specified smallest worthwhile effect of 1.75 ml/kg/min, indicating similar or better benefits from the dense training regimen relative to the control regimen. Con = control group, Exp = experimental, RATS = robot-assisted thoracoscopic surgery, VATS = video-assisted thoracoscopic surgery.
Research 49 Table 5 eAddenda: Table 3 can be found online at https://doi.org/10.1016/j. Postoperative complications. jphys.2021.12.010. Complications Exp Con Ethics approval: The French ethics committee SUD-EST IV (n = 13) (n = 13) approved this study (n19.01.29.69434). All participants gave written informed consent before data collection began. Type, n 0 1 subcutaneous emphysema 0 0 Competing interests: All the authors have completed the ICMJE arrhythmia 1 0 uniform disclosure form. Francis-Edouard Gravier declares personal air leak . 5 d 1 1 fee from Asten Santé unrelated to this study. Tristan Bonnevie de- pneumonia 0 1 clares receiving grants from Fisher and Paykel, a personal fee from atelectasis 0 1 Asten Santé and another from KerNel Biomedical, both unrelated to ARDS this study. None of the authors have any conflicts of interest to 0 1 declare. Clavien-Dindo classification, n 2 1 I 0 1 Source(s) of support: This work was supported by ADIR II 0 1 Association. IIIa IVa Acknowledgements: We thank Johanna Robertson for language assistance. ARDS = adult respiratory distress syndrome, Con = control group, Exp = experimental group. Provenance: Not invited. Peer reviewed. Correspondence: Francis-Edouard Gravier, Pulmonary Rehabilita- of patients with postoperative risk who can be referred for pre- tion, ADIR Association, Rouen, France. Email: f.gravier@adir- habilitation, despite short presurgical delays. hautenormandie.com This study had several strengths, including compliance with the References pre-registered protocol, concealed allocation, blinded assessment of the primary outcome, intention-to-treat analysis and reporting ac- 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer sta- cording to the CONSORT recommendations. Moreover, we provided a tistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 clinical interpretation of each estimate based on the relative mean cancers in 185 countries. 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50 Gravier et al: Prehabilitation density before NSCLC surgery 19. Beaumont M, Kerautret G, Peran L, Pichon R, Le Ber C, Cabillic M. Reproducibility of 31. Peterson MD, Rhea MR, Alvar BA. Applications of the dose-response for muscular strength development: a review of meta-analytic efficacy and reliability for strength and endurance measurements of the quadriceps in patients with COPD. designing training prescription. J Strength Cond Res. 2005;19:950–958. Rev Malad Respir. 2017;34:1000–1006. 32. Iwakura M, Okura K, Kubota M, Sugawara K, Kawagoshi A, Takahashi H, et al. 20. Hogrel JY, Payan CA, Ollivier G, Tanant V, Attarian S, Couillandre A, et al. Devel- Estimation of minimal clinically important difference for quadriceps and inspira- tory muscle strength in older outpatients with chronic obstructive pulmonary opment of a French isometric strength normative database for adults using disease: a prospective cohort study. Phys Ther Res. 2021;24:35–42. quantitative muscle testing. Arch Phys Med Rehabil. 2007;88:1289–1297. 21. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new 33. Hong F, Bosco JL, Bush N, Berry DL. Patient self-appraisal of change and minimal proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann clinically important difference on the European organization for the research and Surg. 2004;240:205–213. treatment of cancer quality of life questionnaire core 30 before and during cancer 22. Chow S, Shao J, Wang H. Sample Size Calculations in Clinical Research. 2nd Ed. therapy. BMC Cancer. 2013;13:165. Florida, USA: Taylor & Francis Group, LLC; 2008. 23. Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample 34. Lai Y, Wang X, Zhou K, Su J, Che G. Impact of one-week preoperative physical size, median, mid-range, and/or mid-quartile range. Statist Methods Med Res. training on clinical outcomes of surgical lung cancer patients with limited lung 2018;27:1785–1805. function: a randomized trial. Ann Translat Med. 2019;7:544. 24. Shi J, Luo D, Weng H, Zeng XT, Lin L, Chu H, et al. Optimally estimating the sample standard deviation from the five-number summary. Res Synth Methods. 35. Lai Y, Su J, Qiu P, Wang M, Zhou K, Tang Y, et al. Systematic short-term pulmonary 2020;11:641–654. rehabilitation before lung cancer lobectomy: a randomized trial. Interact Cardiovasc 25. Streiner D, Geddes J. Intention to treat analysis in clinical trials when there are Thorac Surg. 2017;25:476–483. missing data. Evid Based Ment Health. 2001;4:70–71. 26. Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR, Tudor-Locke C, 36. Boujibar F, Bonnevie T, Debeaumont D, Bubenheim M, Cuvellier A, Peillon C, et al. et al. 2011 Compendium of Physical Activities: a second update of codes and MET Impact of prehabilitation on morbidity and mortality after pulmonary lobectomy values. Med Sci Sports Ex. 2011;43:1575–1581. by minimally invasive surgery: a cohort study. J Thorac Dis. 2018;10:2240–2248. 27. Brunelli A, Belardinelli R, Pompili C, Xiumé F, Refai M, Salati M, et al. Minute ventilation-to-carbon dioxide output (VE/VCO2) slope is the strongest predictor of 37. Peddle-McIntyre CJ, Singh F, Thomas R, Newton RU, Galvão DA, Cavalheri V. Exercise respiratory complications and death after pulmonary resection. Ann Thorac Surg. training for advanced lung cancer. Cochrane Database Syst Rev. 2019;2:CD012685. 2012;93:1802–1806. 28. Sutherland ER, Make BJ. Maximum exercise as an outcome in COPD: minimal 38. Neder JA, Marillier M, Bernard AC, James MD, Milne KM, O’Donnell DE. The integrative clinically important difference. COPD. 2005;2:137–141. physiology of exercise training in patients with COPD. COPD. 2019;16:182–195. 29. Suen M, Liew A, Turner JD, Khatri S, Lin Y, Raso KL, et al. Short-term multimodal prehabilitation improves functional capacity for colorectal cancer patients prior to 39. Folland JP, Williams AG. The adaptations to strength training: morphological and surgery. Asia-Pac J Clin Oncol. 2021. neurological contributions to increased strength. Sports Med. 2007;37:145–168. 30. Vaidya T, Beaumont M, de Bisschop C, Bazerque L, Le Blanc C, Vincent A, et al. Determining the minimally important difference in quadriceps strength in in- 40. Del Vecchio A, Casolo A, Negro F, Scorcelletti M, Bazzucchi I, Enoka R, et al. The increase dividuals with COPD using a fixed dynamometer. Int J COPD. 2018;13:2685– in muscle force after 4 weeks of strength training is mediated by adaptations in motor 2693. unit recruitment and rate coding. J Physiol. 2019;597:1873–1887. Websites Research Randomizer. www.randomizer.org
Journal of Physiotherapy 68 (2022) 76–79 Appraisal j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j p hy s Research Note: Thematic analysis in qualitative research Qualitative research, the analysis of language and other non- When should I conduct qualitative research? numerical data, is critical to applied (including interventional) research.1 It provides unique insight into peoples’ experiences, Qualitative research can be undertaken before, during or after an including those related to healthcare systems, services and pro- intervention or program of implementation, and with patients, cli- grams, in a manner that quantitative methods cannot.1 Its value is nicians and other stakeholders (Table 1, Figure 1). Some qualitative increasingly being recognised by public health and funding bodies research may not be directly tied to the development of an inter- such as the US National Institute of Health.2 However, qualitative vention or implementation effort, and the study simply aims to better research tends to be underrepresented in musculoskeletal and pain understand a phenomenon (termed ‘Standalone’ in Table 1); this type literature,3 despite the highly subjective and complex nature of the is common in social science disciplines. topic area. Before quantitative research is undertaken qualitative research Added to this, applied health science researchers must often can help to understand the underlying context of the target popula- manage tension between practical constraints (such as time, tion, their needs and their preferences for intervention goals, content funding, discipline-specific standards and required outputs) and and delivery formats. The goal of this research is often to inform the depth of qualitative analysis. This research note focuses on a intervention design; this can include analysis of qualitative data from type of qualitative analysis that is widely used in applied sci- co-design workshops (eg, transcripts, field notes) that depict how ences – thematic analysis – and aims to help readers reflect on stakeholder input shaped the resulting intervention. how this qualitative analysis method can best achieve their research goals. Qualitative research undertaken concurrently with quantitative research can take several forms. For example, ‘think-aloud’ studies, in Table 1 Points at which qualitative research can contribute to a research program. Study type/relationship to quantitative study Purpose Aim from example study Standalone To understand phenomena or experiences, To seek physiotherapists’ perspectives on patient including those relating to usual practice adherence to exercise prescription for falls prevention and/or risk reduction in the Singapore setting7 May provide background context Research questions: What are the decision-making May inform intervention design or methods for criteria and facilitating strategies that clinical educators use when increasing physiotherapy evaluation students’ autonomy on clinical placement; and How do the criteria and strategies used by clinical Conducted prior to quantitative research To understand stakeholder (including patients and educators relate to students’ perceptions of their health professionals) needs and preferences readiness to accept greater autonomy?8 Conducted concurrently with quantitative research regarding an intervention or implementation To identify the current practices of physiotherapists Conducted after quantitative data is collected strategy regarding promotion of physical activity within daily clinical practice, with a focus on referral to Often underpinned by a theoretical framework community-based structured physical activity op- Participants may be involved in developing solu- portunities for older clients and people of all ages with physical disabilities; to obtain input from phys- tions (co-design) iotherapists to develop and refine strategies to help physiotherapists improve physical activity promotion To iteratively revise an intervention or imple- and referral.9 mentation strategy To refine intervention to reduce inappropriate imag- ing referrals, increase psychosocial-oriented patient May be combined with quantitative data (eg, assessment and increase provision of patient educa- through surveys or analytics) tion information (mixed methods study)4 Often more pragmatic (depth of analysis more To explore the feasibility of delivering ESCAPE-pain in superficial) community venues, and the experiences of organi- sations and facilitators delivering it.10 To evaluate and/or further refine intervention or To explore the role of leadership by physiotherapists implementation strategies; to understand the in implementing and sustaining an evidence-based impact of the intervention complex intervention (ESCAPE-pain) for osteoarthritis.11 May be combined with quantitative data (eg, through surveys or analytics) Often more pragmatic (depth of analysis more superficial) Often underpinned by a theoretical framework https://doi.org/10.1016/j.jphys.2021.11.002 1836-9553/© 2021 Australian Physiotherapy Association. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Appraisal Research Note 77 Standalone Analysis informs Understanding of Qualitative data phenomena or experiences Before quantitative research Qualitative data Analysis informs Development of Quantitative data intervention, survey, implementation strategies, discrete choice experiment parameters or evaluation study design (eg, outcome measures) Concurrently with quantitative research Qualitative data Analysis informs Development of intervention Analysis informs Quantitative data iterative revisions and implementation iterative revisions strategies, formative research and process evaluation After quantitative data are collected Development of Quantitative data Analysis informs Understanding of intervention, implementation Qualitative data impact, formative research, (process) strategies, or quantitative evaluation, further study design (eg, outcome refinement measures) Figure 1. Points at which qualitative research can contribute to a research program. which participants speak their thoughts out loud while engaging researcher’s relationship to knowledge); both will shape the resulting with an intervention, are widely used for evaluating and refining analysis, and we encourage readers to take up the suggested readings digital technologies, including innovative apps for pain management. in Table 2 on this topic.12 Braun and Clarke have categorised thematic Focus groups, interviews and field notes can also assist with iterative analysis into three broad approaches: coding reliability, reflexive development of pilot programs (see Lin et al,4 Table 1, as an example). thematic analysis and codebook analysis.13 The benefits and trade- offs for each approach are now discussed. After quantitative research is undertaken (eg, after an intervention is implemented) qualitative research is fundamental to process Coding reliability thematic analysis (or content analysis)13 is an evaluation efforts.5 This often takes the form of a qualitative study approach to qualitative research that may feel most familiar to nested within a trial. These findings elucidate the experience of the quantitative researchers. It is characterised by topic or domain intervention and can shed further light on its success (or not), summaries (or content codes) that capture the frequency of ideas, providing opportunities for further improvement and strategies to concepts and meanings expressed by participants, often at a more adapt it for different settings. Research questions could explore, for surface (explicit) level.14 This approach inherently assumes that example, acceptability, adoption, feasibility and patient-reported objective facts are ‘in’ the data, uncovered by the researcher. For this outcomes such as satisfaction and quality of life.6 reason, researcher subjectivity is considered a bias that must be minimised, and interrater reliability statistics (agreement between Which analytical approach should I take? coders) are often reported to demonstrate rigour. The benefit of this approach is that the data can be collected easily, for example, through Thematic analysis comprises several analytical approaches, that open-ended survey questions, and analysis is relatively quick. How- each have different aims, philosophical underpinnings and methods. ever, this approach may not provide sufficient depth; coding reli- The philosophical underpinnings encompass ontology (beliefs about ability analysis will answer ‘What is the most common barrier to the nature of the world and what we can know about it), and epis- adhering to an exercise program?’ but won’t necessarily help you temology (ways of knowing about the world, including the understand why. Table 2 Description Suggested further reading. Describes differences between quantitative and qualitative research in the context of public health, with additional Topic further reading Comparison of qualitative and quantitative research24 General conceptual overview of qualitative research, ontology and epistemology, with more detail about quality reflexive thematic analysis Qualitative analysis25 General conceptual overview of qualitative research, ontology and epistemology, with more detail about framework analysis methods, a type of codebook analysis Framework analysis12 Comparison of content and thematic analysis Overview of how qualitative research can be used to develop interventions Content analysis26 Further detail outlining how qualitative research can contribute to implementation outcomes Person-centred intervention development27 Systematic review investigating how use of the theoretical domains framework impacts on research findings Implementation science6,15 Discussion of ‘information power’ as an alternative to ‘saturation’ Using theoretical frameworks in qualitative research21 Sample size19
78 Appraisal Research Note Reflexive thematic analysis presents analyses as ‘themes’, funding applications. Vasileiou et al18 summarise various expert rules described as patterns of shared meaning.13 Themes may incorporate of thumb, which range from 15 to 20 individual interviews through to explicit ideas, concepts and meanings (eg, frustration when physio- estimates of 50 to 60 participants, and emphasise that whilst a lower therapists give vague or conflicting advice), as well as those that are and upper range may be identified a priori, the final sample size is a implicit (eg, that physiotherapists who acknowledge uncertainty have product of ongoing reflection as the research progresses. Sample size inadequate skills or expertise). Quality reflexive thematic analysis will also depend on aspects such as the narrowness of the study aim, recognises the inherent role of the researcher in constructing themes specificity of the sample, how established the existing research/the- as they engage with the data.13 As such, rigour is demonstrated ory is, the quality of the interview dialogue, and whether analysis through continual reflection, questioning and awareness of the re- focuses on singular experiences (eg, case studies) versus patterns searchers’ roles in generating themes, rather than seeking consensus. across participants.19 Larger samples may be appropriate for stratified Coding can be inductive (‘data driven’) or deductive (data are inter- analysis (eg, comparing findings for younger versus older preted through existing research or theory), or a mixture of both. participants). Although this approach is slower and more involved, it takes full advantage of the richness of qualitative data. Should I (or how should I) use a theoretical framework in my work? Codebook thematic analysis lies between codebook reliability and reflexive thematic analysis and is recommended for applied This will depend on the norms within your discipline and other health research.13 In this approach, themes are generated and criteria by which the research is judged.20 As discussed above, using a charted into a framework; however, this framework does not theoretical framework to deductively code qualitative data for an determine reliability or accuracy, as it would for content analysis. implementation project can ensure that findings align with concepts Rather, the framework exists to help further develop themes, and is used in implementation science and may identify gaps or opportu- particularly useful for integrating efforts from multiple re- nities through the mapping process. But this must be weighed against searchers.14 Whilst the output of the analysis is ‘themes’, these can the risk of missing or ignoring themes that don’t align with the theory range from topic/domain summaries through to more fully devel- and developing superficial themes that feel ‘done’ simply because oped themes. Similar to reflexive thematic analysis, codebook they have been mapped to the framework.21 Three alternatives that thematic analysis affords flexibility in the extent that inductive and allow for largely inductive coding but can still be informed by theo- deductive coding are used. Given implementation science’s retical frameworks are: emphasis on theoretical frameworks, these studies often take a mostly deductive approach (themes align with components of a. Develop an interview schedule that incorporates important ele- these frameworks), whilst remaining open to other themes, which ments from the theoretical framework but still has flexibility to are developed through an inductive approach.15 This approach is uncover additional unexpected concepts (see, for example, discussed in greater detail in the final section. McDonald et al22). Further decisions in thematic analysis b. Apply the theoretical framework only after themes are largely finalised (for the purposes of publication). This entails switching The most appropriate approach to thematic analysis will depend to a more deductive approach at the end of the analysis. In a on the research goals, desired outputs and practical constraints. The journal manuscript, tables in the discussion section can help to field of sport and exercise science has previously been criticised for make these links to theoretical framework and the practical im- conducting superficial and poor-quality qualitative analyses.16 The plications of the research more explicit. following questions may help researchers to justify their approach and make deliberate decisions that balance pragmatic factors and c. Ramanadhan et al20 suggest that a two-step process may be quality and depth of analysis.17 appropriate when fast output is needed (eg, deductive coding into a framework followed by a second, more in-depth analysis that What level of depth is needed? has a less rigid coding framework). This will depend on the extent that the research question focuses How do I know if my themes are superficial and how can I develop on internal, experiential and highly subjective narratives, and them further? potentially the sensitivity of the topic area. For example, perspectives on the relationship between pain and exercise will almost certainly There is no clear ‘endpoint’ in qualitative analysis and there is no be better explored within the context of a person’s life, goals and ‘one quality standard criterion’.13 However, the following may flag values. As such, this type of research question may be better suited to opportunities to increase the depth of analysis when using codebook codebook or reflexive thematic analysis. Conversely, any of the three or reflective thematic analyses: approaches described above may be appropriate for narrower research questions (eg, evaluating use of heat packs for managing a. Themes read as topics or domain summaries, or simply mirror the back pain or identifying barriers and enablers). interview questions.23 Braun and Clarke describe these as descriptive summaries of all information on a topic, but which do What method of data collection is most appropriate? not reflect shared patterns of meaning or differences.17 These themes often comprise a single word. Data collection methods should ideally suit the level of depth expected for analysis. For a more superficial analysis, open-ended b. The scope of themes overlaps. survey questions may provide adequate and insightful data (eg, c. Themes feel disjointed and do not tell a coherent narrative. What are the barriers to using heat packs for back pain in emergency departments?). Focus groups are less resource-intensive than in- Developing themes further is fundamentally about reflecting on terviews, but are more logistically complex, including scheduling connections between the data, themes and researcher. A researcher (especially clinicians), travel and catering; they are most useful for might refine themes, for example, by reflecting on the assumptions observing group discussion and reactions on a topic. they or participants have made about the data (eg, asking; ‘Why might the participant have said that?’, ‘Why didn’t they say the Sample size for codebook and reflexive thematic analysis should opposite?’, ‘Which sections of the data stand out to me, and why?’). balance data breadth and depth against complexity of the analytic Involving other researchers (including consumers and other stake- task. Although a priori sample sizes are not appropriate for qualitative holders) in theme development provides a different perspective on research, an estimated sample size is often required for ethics or the data and can facilitate reflection.17 Drawing diagrams or ‘maps’ can also be useful to explore relationships between themes.23 This can
Appraisal Research Note 79 reduce conceptual overlap between themes and refine their de- References scriptions and scope. 1. Southam-Gerow MA, et al. J Clin Child Adolesc Psychol. 2014;43:845–850. Conclusion 2. National Cancer Institute. https://cancercontrol.cancer.gov/sites/default/files/202 This research note discusses the value of qualitative research to 0-09/nci-dccps-implementationscience-whitepaper.pdf. Accessed 13 August, 2021. applied health sciences. To make the most of qualitative studies, re- 3. Tutelman PR, et al. Can J Pain. 2020;4:1–5. searchers must carefully consider which analytic approach will best 4. Lin IB, et al. BMC Family Practice. 2016;17:44. achieve their research goals. We encourage researchers to make 5. Moore GF, et al. BMJ. 2015;350:h1258. deliberate and reasoned decisions to balance the depth of analysis, 6. Proctor E, et al. Adm Policy Ment Health. 2011;38:65–76. whilst still providing timely and practical outputs. Further reading is 7. Teng B, et al. Disabil Rehabil. 2021:1–9. provided in Table 2. 8. Clouder L, et al. Physiother Theory Pract. 2021:1–11. 9. West K, et al. Int J Environ Res Public Health. 2021;18:2963. Competing interests: None declared. 10. Hurley M, et al. Musculoskelet Care. 2021;n/a. Sources of Support: Nil. 11. Walker A, et al. Disabil Rehabil. 2020:1–8. Acknowledgements: Nil. 12. Ritchie J, et al. Qualitative research practice: A guide for social science students and Provenance: Invited. Peer reviewed. Correspondence: Julie Ayre, Sydney Health Literacy Lab, Faculty of researchers. SAGE; 2013. Medicine and Health, Sydney School of Public Health, The University 13. Braun V, et al. Qual Res Psychol. 2020:1–25. of Sydney, Australia. Email: [email protected] 14. Braun V, et al. Couns Psychother Res. 2020;21:37–47. 15. Hamilton AB, et al. Psychiatry Res. 2019;280:112516. Julie Ayre and Kirsten J McCaffery 16. Braun V, et al. Qual Res Sport Exerc Health. 2019;11:589–597. Sydney Health Literacy Lab, Faculty of Medicine and Health, Sydney 17. Braun V, et al. Thematic Analysis. In: Liamputtong P, ed. Handbook of Research School of Public Health, The University of Sydney, Australia Methods in Health Social Sciences. Singapore: Springer Singapore; 2019:843–860. 18. Vasileiou K, et al. BMC Med Res Methodol. 2018;18:148. 19. Malterud K, et al. Qual Health Res. 2015;26:1753–1760. 20. Ramanadhan S, et al. Implement Sci Comm. 2021;2:70. 21. McGowan LJ, et al. Br J Health Psychol. 2020;25:677–694. 22. McDonald S, et al. Int J Behav Nutr Phys Act. 2015;12:25. 23. Braun V, et al. Qual Res Psychol. 2006;3:77–101. 24. Carter SM, et al. NSW Pub Health Bull. 2009;20:105–111. 25. Braun V, et al. Successful Qualitative Research: A Practical Guide for Beginners. SAGE; 2013. 26. Vaismoradi M, et al. Nurs Health Sci. 2013;15:398–405. 27. Yardley L, et al. J Med Internet Res. 2015;17:e30.
Journal of Physiotherapy 68 (2022) 1–4 j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j p hy s Editorial Statistical inference through estimation: recommendations from the International Society of Physiotherapy Journal Editors1 Mark R Elkins a,b, Rafael Zambelli Pinto a,c, Arianne Verhagen a,b, Monika Grygorowicz d, Anne Söderlund e, Matthieu Guemann f, Antonia Gómez-Conesa g, Sarah Blanton h, Jean-Michel Brismée i, Clare Ardern j, Shabnam Agarwal k, Alan Jette l, Sven Karstens m, Michele Harms n, Geert Verheyden o, Umer Sheikh p a International Society of Physiotherapy Journal Editors executive; b Journal of Physiotherapy; c Brazilian Journal of Physical Therapy/Revista Brasileira de Fisioterapia; d BMC Sports Science, Medicine and Rehabilitation; e European Journal of Physiotherapy; f European Rehabilitation Journal; g Fisioterapia; h Journal of Humanities in Rehabilitation; i Journal of Manual & Manipulative Therapy; j Journal of Orthopaedic & Sports Physical Therapy; k Journal of Society of Indian Physiotherapists; l Physical Therapy; m physioscience; n Physiotherapy; o Physiotherapy Research International; p The Journal of Physiotherapy & Sports Medicine Null hypothesis statistical tests are often conducted in healthcare Because the reasoning behind these tests is linked to imagined research,1 including in the physiotherapy field.2 Despite their wide- repetition of the study, they are said to be conducted within a ‘fre- spread use, null hypothesis statistical tests have important limita- quentist’ framework. In this framework, the focus is on how much a tions. This co-published editorial explains statistical inference using statistical result (eg, a mean difference, a proportion or a correlation) null hypothesis statistical tests and the problems inherent to this would vary among the repeats of the study. If the data obtained from approach; examines an alternative approach for statistical inference the study sample indicate that the result is likely to be similar among (known as estimation); and encourages readers of physiotherapy the imagined repeats of the study, this is interpreted as an indication research to become familiar with estimation methods and how the that the result is in some way more credible. results are interpreted. It also advises researchers that some physio- therapy journals that are members of the International Society of One type of null hypothesis statistical test is significance testing, Physiotherapy Journal Editors (ISPJE) will be expecting manuscripts to developed by Fisher.4–6 In significance testing, if a result at least as use estimation methods instead of null hypothesis statistical tests. large as the result observed in the study would be unlikely to occur in the imagined repeats of the study if the null hypothesis is true (as What is statistical inference? reflected by p , 0.05), then this is interpreted as evidence that the null hypothesis is false. Another type of null hypothesis statistical test Statistical inference is the process of making inferences about is hypothesis testing, developed by Neyman and Pearson.4–6 Here, two populations using data from samples.1 Imagine, for example, that hypotheses are posited: the null hypothesis (ie, that there is no dif- some researchers want to investigate something (perhaps the effect ference in the population) and the alternative hypothesis (ie, that of an intervention, the prevalence of a comorbidity or the usefulness there is a difference in the population). The p-value tells the re- of a prognostic model) in people after stroke. It is unfeasible for the searchers which hypothesis to accept: if p 0.05, retain the null researchers to test all stroke survivors in the world; instead, the re- hypothesis; if p , 0.05, reject the null hypothesis and accept the searchers can only recruit a sample of stroke survivors and conduct alternative. Although these two approaches are mathematically their study with that sample. Typically, such a sample makes up a similar, they differ substantially in how they should be interpreted miniscule fraction of the population, so the result from the sample is and reported. Despite this, many researchers do not recognise the likely to differ from the result in the population.3 Researchers must distinction and analyse their data using an unreasoned hybrid of the therefore use their statistical analysis of the data from the sample to two methods. infer what the result is likely to be in the population. Problems with null hypothesis statistical tests What are null hypothesis statistical tests? Regardless of whether significance testing or hypothesis testing (or a hybrid) is considered, null hypothesis statistical tests have numerous Traditionally, statistical inference has relied on null hypothesis problems.4,5,7 Five crucial problems are explained in Box 1. Each of statistical tests. Such tests involve positing a null hypothesis (eg, that there is no effect of an intervention on an outcome, that there is no these problems is fundamental enough to make null hypothesis sta- effect of exposure on risk or that there is no relationship between two variables). Such tests also involve calculating a p-value, which quan- tistical tests unfit for use in research. This may surprise many readers, tifies the probability (if the study were to be repeated many times) of given how widely such tests are used in published research.1,2 observing an effect or relationship at least as large as the one that was observed in the study sample, if the null hypothesis is true. Note that It is also surprising that the widespread use of null hypothesis the null hypothesis refers to the population, not the study sample. statistical tests has persisted for so long, given that the problems in 1This article is a joint publication by several member journals of the International Society of Physiotherapy Journal Editors. Box 1 have been repeatedly raised in healthcare journals for de- cades,8,9 including physiotherapy journals.10,11 There has been some movement away from null hypothesis statistical tests, but the use of alternative methods of statistical inference has increased slowly over decades, as seen in analyses of healthcare research, including phys- iotherapy trials.2,12 This is despite the availability of alternative https://doi.org/10.1016/j.jphys.2021.12.001 1836-9553/© 2021 Published by Elsevier B.V. on behalf of Australian Physiotherapy Association. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
2 Editorial Box 1. Problems with null hypothesis statistical tests. Modified from Herbert (2019).26 Problem Explanation A p-value is not the probability that Researchers need to know the probability that the null hypothesis is true given the data observed in a hypothesis is (or is not) true their study. A p-value instead is the probability of observing the observed data given that the null hypothesis is true. These two probabilities may seem interchangeable but they are not. Therefore, p-values do not equate to a probability that researchers need to know. A p-value does not constitute As explained above, a p-value is the probability of an observation given that a particular hypothesis is evidence true. Any probability of an observation given a particular hypothesis cannot provide evidence for or against that hypothesis. It is only possible to quantify the strength of evidence for a hypothesis by comparing it with another hypothesis. Statistically significant findings If a study is repeated with a new random sample from the same population, the result (and therefore are not very replicable the p-value) is likely to vary. Imagine a study with a p-value between 0.005 and 0.05. If this study was repeated with a new random sample from the same population, there would be a 33% chance that the p-value would be non-significant.27 In most clinical trials, the null The null hypothesis is that the effect of interest is exactly nil. hypothesis must be false Almost all interventions would be expected to have some effect, even if that effect was trivially small. Almost all trials (even those with the most robust methods) would be expected to have some bias, even if that bias was trivially small. All trials should therefore identify an effect (because the null hypothesis is not true, ie, the effect of interest is not exactly nil). This implies that every statistically non-significant result is actually a failure to detect an effect that does exist. Researchers need information Researchers need to know more than just whether an effect does or does not exist. about the size of effects Researchers need to know about the size of the effect. A p-value gives no information about the size or direction of an effect. methods of statistical inference and promotion of those methods in to estimation methods is littered with examples of researchers statistical, medical and physiotherapy journals.10,13–16 calculating confidence intervals at the behest of editors, but then ignoring the confidence intervals and instead interpreting their Estimation as an alternative approach for statistical inference study’s result dichotomously as statistically significant or non- significant depending on the p-value.20 Interpretation is crucial. Although there are multiple alternative approaches to statistical inference,13 the simplest is estimation.17 Estimation is based on a Some authors have proposed a ban on terms related to interpre- frequentist framework but, unlike null hypothesis statistical tests, its tation of null hypothesis statistical testing. One prominent example is aim is to estimate parameters of populations using data collected an editorial published in The American Statistician,13 which introduced from the study sample. The uncertainty or imprecision of those es- a special issue on statistical inference. It states: timates is communicated with confidence intervals.10,14 The American Statistical Association Statement on P-Values and A confidence interval can be calculated from the observed study Statistical Significance stopped just short of recommending that data, the size of the sample, the variability in the sample and the declarations of “statistical significance” be abandoned. We take confidence level. The confidence level is chosen by the researcher, that step here. We conclude, based on our review of the articles in conventionally at 95%. This means that if hypothetically the study this special issue and the broader literature, that it is time to stop were to be repeated many times, 95% of the confidence intervals using the term “statistically significant” entirely. Nor should var- would contain the true population parameter. Roughly speaking, a iants such as “significantly different,” “p , 0.05,” and “nonsignif- 95% confidence interval is the range of values within which we can be icant” survive, whether expressed in words, by asterisks in a table, 95% certain that the true parameter in the population actually lies. or in some other way. Confidence intervals are often discussed in relation to treatment This may seem radical and unworkable to researchers with a long effects in clinical trials,18,19 but it is possible to put a confidence in- history of null hypothesis statistical testing, but many concerns can be terval around any statistic, regardless of its use, including mean dif- allayed. First, such a ban would not discard decades of existing ference, risk, odds, relative risk, odds ratio, hazard ratio, correlation, research reported with null hypothesis statistical tests; the data proportion, absolute risk reduction, relative risk reduction, number generated in such studies maintain their validity and will often be needed to treat, sensitivity, specificity, likelihood ratios, diagnostic reported in sufficient detail for confidence intervals to be calculated. odds ratios, and difference in medians. Second, reframing the study’s aim involves a simple shift in focus from whether the result is statistically significant to gauging how Interpretation of the results of the estimation approach large and how precise the study’s estimate of the population parameter is. (For example, instead of aiming to determine whether a To use the estimation approach well, it is not sufficient simply to treatment has an effect in stroke survivors, the aim is to estimate the report confidence intervals. Researchers must also interpret the size of the average effect. Instead of aiming to determine whether a relevance of the information portrayed by the confidence intervals prognostic model is predictive, the aim is to estimate how well the and consider the implications arising from that information. The path model predicts.) Third, the statistical imprecision of those estimates of migration of researchers from statistical significance and p-values can be calculated readily. Existing statistical software packages
Editorial 3 Box 2. Resources that provide additional information to respond to questions about the transition from null hypothesis statistical tests to estimation methods. Question Resources Where can I find more detailed This short paper details the problems inherent in significance testing and hypothesis testing.25 information about null hypothesis https://doi.org/10.1016/j.jphys.2019.05.001 statistical testing and its problems? This American Statistical Association’s statement on p-values28 shows that the problems are Is there widespread recognition of widely recognised by statisticians. Numerous fields of research have recognised the need to move these problems and the need for an beyond significance testing, such as medicine,29 specific medical subdisciplines,30,31 nursing,32 alternative? psychology,33 neuroscience,34 pharmacy,35 toxicology,36 anthropology37 and animal research.38 Is there a publication that explains These two editorials explain confidence intervals for continuous and dichotomous variables:10,14 confidence intervals from first https://doi.org/10.1016/S0004-9514(14)60334-2 principles? https://doi.org/10.1016/s0004-9514(14)60292-0 Are there published examples of how These two short papers explain confidence intervals and show examples of how they can be confidence intervals should be described in words:18,19 interpreted? https://doi.org/10.1016/j.bjpt.2019.01.003 https://www.jospt.org/doi/10.2519/jospt.2019.0706 How can I calculate confidence Existing statistical software packages already calculate confidence intervals, including free intervals from my raw data? software such as R.21,22 How can I quickly calculate A free Excel-based confidence interval calculator is available to download from the PEDro website: confidence intervals from the https://pedro.org.au/english/resources/confidence-interval-calculator/ summary data in a published paper? already calculate confidence intervals, including free software such as values around the study’s main estimate where the true population R.21,22 Lastly, learning to interpret confidence intervals is relatively result probably lies. To interpret a confidence interval, we simply straightforward. describe the practical implications of all values inside the confidence interval.24 For example, in a diagnostic test accuracy study, the posi- Many researchers and readers initially come to understand how to tive likelihood ratio tells us how much more likely a positive test interpret confidence intervals around estimates of the effect of a finding is in people who have the condition than it is in people who do treatment. In a study comparing a treatment versus control with a not have the condition. A diagnostic test with a positive likelihood continuous outcome measure, the study’s best estimate of the effect ratio greater than about 3 is typically useful and greater than about 10 of the treatment is usually the average between-group difference in is very useful.25 Therefore, if a diagnostic test had a positive likelihood outcome. To account for the fact that estimates based on a sample ratio of 4.8 with a 95% confidence interval of 4.1 to 5.6, we could may differ by chance from the true value in the population, the anticipate that the true positive likelihood ratio in the population is confidence interval provides an indication of the range of values both useful and similar to the study’s main estimate. Conversely, if a above and below that estimate where the true average effect in the study estimated the prevalence of depression in people after anterior relevant clinical population may lie. The estimate and its confidence cruciate ligament rupture at 40% with a confidence interval from 5% to interval should be compared against the ‘smallest worthwhile effect’ 75%, we may conclude that the main estimate is suggestive of a high of the intervention on that outcome in that population.23 The prevalence but too imprecise to conclude that confidently. smallest worthwhile effect is the smallest benefit from an interven- tion that patients feel outweighs its costs, risk and other in- ISPJE member journals’ policy regarding the estimation approach conveniences.23 If the estimate and the ends of its confidence interval are all more favourable than the smallest worthwhile effect, then the The executive of the ISPJE strongly recommends that member treatment effect can be interpreted as typically considered worth- journals seek to foster use of the estimation approach in the papers while by patients in that clinical population. If the effect and its they publish. In line with that recommendation, the editors who have confidence interval are less favourable than the smallest worthwhile co-authored this editorial advise researchers that their journals will effect, then the treatment effect can be interpreted as typically expect manuscripts to use estimation methods instead of null hy- considered trivial by patients in that clinical population. Results with pothesis statistical tests. We acknowledge that it will take time to confidence intervals that span the smallest worthwhile effect indicate make this transition, so editors will give authors the opportunity to a benefit with uncertainty about whether it is worthwhile. Results revise manuscripts to incorporate estimation methods if the manu- with a narrow confidence interval that spans no effect indicate that script seems otherwise potentially viable for publication. Editors may the treatment’s effects are negligible, whereas results with a wide assist authors with those revisions where required. confidence interval that spans no effect indicate that the treatment’s effects are uncertain. For readers unfamiliar with this sort of inter- Readers who require more detailed information to address ques- pretation, some clear and non-technical papers with clinical physio- tions about the topics raised in this editorial are referred to the re- therapy examples are available.10,14,18,19 sources in Box 2, such as the Research Note on the problems of significance and hypothesis testing25 and an excellent textbook that Interpretation of estimates of treatment effects and their confi- addresses confidence intervals and the application of estimation dence intervals relies on knowing the smallest worthwhile effect methods in various research study designs with clinical physio- (sometimes called the minimum clinically important difference).23 therapy examples.26 Both are readily accessible to researchers and For some research questions, such a threshold has not been estab- clinicians without any prior understanding of the issues. lished or has been established with inadequate methods. In such cases, researchers should consider conducting a study to establish the Quantitative research studies in physiotherapy that are analysed threshold or at least to nominate the threshold prospectively. and interpreted using confidence intervals will provide more valid and relevant information than those analysed and interpreted using Readers who understand the interpretation of confidence intervals null hypothesis statistical tests. The estimation approach is therefore around treatment effect estimates will find interpretation of confi- of great potential value to the researchers, clinicians and consumers dence intervals around many other types of estimates quite familiar. Roughly speaking, the confidence interval indicates the range of
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