Hearts in the sky: understanding the cardiovascular implications of air travel

Abstract

Air travel is widely regarded as the safest mode of transportation, with the United States leading in airline passengers. However, travelers with pre-existing heart conditions face acute cardiovascular risks. Flight pilots and cabin crew are particularly vulnerable to air travel's physiological changes, which can significantly impair their health and performance. Cabin pressure differences and reduced oxygen levels at cruising altitudes of 5000–8000 feet make air travel challenging for individuals with underlying cardiac and pulmonary problems. This, along with dry air, sleep deprivation, missed medication and prolonged sitting, can lead to physiological changes. In-flight and pre-flight stressors contribute to increased health issues, and studies show a rise in medical emergencies during flights. Prolonged exposure to the airplane environment can lead to various health issues for pilots and cabin crew. These changes include impaired judgment, cognitive function and discomfort in the sinuses and ears due to pressure differentials. Therefore, thorough medical screening, skilled instrument use and compliance with safety measures are essential to mitigate these risks. This article reviews the cardiac implications of air travel, discussing the underlying pathophysiology, associated risks and preventive measures to ensure safer flights for individuals with cardiovascular diseases.

Plain Language Summary

This review examines the health risks of air travel for individuals with heart and lung conditions. Changes in cabin pressure and oxygen levels can lower blood oxygen, causing discomfort and health issues. Dry air, sleep problems and prolonged sitting also affect those with existing conditions. Pilots and flight attendants are especially vulnerable due to their continuous exposure.

The authors reviewed how air travel impacts heart and lung health and found that in-flight medical emergencies are rising, affecting passengers and flight staff. Common issues include impaired cognitive function and discomfort from pressure changes. The article emphasizes the importance of pre-flight medical check-ups, carrying medical documents and having travel insurance. It also calls for thorough medical screening and skilled instrument use to ensure safety.

Results show that current air travel conditions pose significant health risks for those with cardiovascular diseases. The study advocates for improvements in in-flight medical technology, cabin environments and personalized healthcare solutions to enhance safety. These findings suggest that future air travel should focus on reducing cardiovascular complications through advancements in medical support and cabin design.

The study provides valuable insights into the physiological effects of flying and recommends measures to make air travel safer for people with heart and lung conditions. It highlights the need for ongoing research and collaboration among healthcare professionals, researchers and aviation authorities to address these health risks effectively.

Plain language summary

Article highlights.

Introduction

• Over 2.3 billion people travel by plane annually, with an increasing number of travelers having chronic medical conditions.

• The aging population will result in more passengers with cardiovascular diseases and other chronic conditions.

Pathophysiology

• Reduced oxygen pressure at high altitudes can cause hypobaric hypoxia, impacting individuals with pre-existing conditions.

• Acute altitude exposure increases sympathetic activity, potentially worsening symptoms in those with cardiovascular diseases.

Cardiovascular response

• Altitude exposure increases heart rate and cardiac output, which may exacerbate ischemic symptoms in individuals with heart disease.

• Anemia and pre-existing cardiac conditions can worsen hypoxic symptoms during flight.

Pulmonary response

• Reduced partial pressure of oxygen increases alveolar ventilation and pulmonary artery pressure.

• Immobility during flights increases the risk of venous thromboembolism (VTE) and pulmonary embolism (PE).

Prevention

• Patients with severe heart failure should avoid air travel when possible.

• Supplemental oxygen and avoiding high-sodium meals can help mitigate risks during flights.

• Mild physical activities and proper hydration are recommended to prevent VTE.

Future perspective

• Innovations in in-flight medical technology and monitoring systems could improve safety for passengers with cardiovascular conditions.

• Future airplane designs may better control air pressure and oxygen levels, reducing stress on the cardiovascular system.

1. Introduction

Airplane travel is one of the safest and robust modes of transportation with around 2.3 billion people flying annually. The United States leads in the number of airline passengers with over 665 million per year, followed by China, Russia and India [1]. Currently, about 5% of passengers have chronic medical conditions, and with medical advancements and an aging population, it is projected that by 2030, over half of all travelers will be aged 50 or older, leading to more passengers with cardiovascular diseases and other chronic conditions [2].

However, airplane travel enforces a great deal of physiological burden on the human body, which arises primarily due to the difference in pressures in the aircraft cabin environment compared with that at sea level. These acute alterations in barometric pressure, along with the compressed air in the aircraft that lacks humidity, sleep deprivation, medicine misses and prolonged immobilization during air travel, can lead to physiological changes that are nonetheless tolerated by most but could potentially exacerbate pre-existing conditions in susceptible passengers, particularly those with cardiorespiratory issues, who may already have a reduced PaO2 on the ground [3].

Apart from these in-flight stressors, pre-flight stressors can also contribute to increased physiological burdens due to airplane travel which include walking long distances, carrying heavy luggage and the anxiety associated with reaching to gates on time, further contributing to the adverse clinical outcomes [4,5]. Studies have also shown an escalating number of medical emergencies during flights. An observational study from 2008 to 2010 found that out of 744 million passengers, about 1.6 per 100,000 required medical assistance for medical symptoms such as syncope or near-syncope (32.7%) and gastrointestinal (14.8%), respiratory (10.1%) and cardiovascular (7.0%) symptoms [6]. Of these, 36 passengers ultimately died and cardiac arrest was the most common cause of medical death seen in 31 out of 36 of those who died [7,8].

From the standpoint of flight-based staff such as pilots and cabin crew, the physiological changes experienced during flights can significantly impair their health and performance, making them the most susceptible group due to the significant exposure. Concerns extend beyond cardiorespiratory distress; prolonged exposure to such a hypoxic environment can manifest in various ways. Hypoxia can impair judgment and cognitive function, while pressure differentials can cause pain and discomfort in the sinuses and ears [9]. Additionally, increased exposure to UV and cosmic rays contributes to melanoma development among these individuals. Thus, thorough pre-flight medical screening, skilled instrument use and compliance with safety measures to alleviate risks are essential for the well-being of flight personnel [10].

Hence, a deeper understanding of the complex link between air travel and cardiovascular health is needed, and our review article focuses on the multifaceted risks and importance of pre-flight medical screening for travelers with pre-existing or chronic conditions. A comprehensive literature search was conducted to identify relevant studies on the effect of airplane travel on cardiovascular health from 2001 to 2024, which included both peer-reviewed academic articles and grey literature. The databases used for the peer-reviewed articles included PUBMED, Google Scholar and Scopus with terms including “Airplane travel,” “Airplane travel and cardiovascular system,” “Airplane travel and Pulmonary disease,” “Airplane travel and Pulmonary Embolism,” (PE) while grey literature was sourced from International Civil Aviation Organization reports and government publications which helped us capture a wider range of information and insights, particularly those not covered in traditional academic publications. To ensure a comprehensive review, we included studies and reports published in English, excluding non-English articles, editorials, opinion pieces and anecdotal reports to focus on empirical evidence.

2. Pathophysiology

Ascending to an altitude of 10,000 feet leads to a notable reduction in alveolar oxygen partial pressure. Specifically, the partial pressure of oxygen falls from 159 mmHg at sea level to 109 mmHg at 10,000 feet, corresponding to the fall in atmospheric pressure from 760 mmHg at sea level to 522 mmHg. Despite this, the decrease in the hemoglobin oxygen saturation at 10,000 feet is relatively small due to the relationship between oxygen tension and hemoglobin saturation [3]. However, at higher altitudes, the hemoglobin saturation also drops rapidly, leading to hypobaric hypoxia, which impairs an individual's ability to perform tasks.

Commercial aircraft typically operate at altitudes ranging from 22,000 to 44,000 feet. Consequently, regulations mandate that cabin pressure must not fall below the pressure equivalent to an altitude of 2438 meters (8000 feet) (565 mmHg) to ensure passenger safety and comfort [11]. Typically, short-haul flights maintain cabin pressures close to this minimum of approximately 565 mmHg, while long-haul widebody aircraft often maintain higher pressures (5000–6000 ft) (632–609 mmHg) [12].

At an elevation of 8,000 feet, the partial pressure of oxygen is 118 mmHg which is similar to breathing air with a 15% oxygen concentration at sea level (SpO2: 85–91%). With physiologic adaptations of the cardiovascular, pulmonary and endocrine systems, healthy individuals can endure this alteration without experiencing any symptoms (Figure 1) [13,14].

Figure 1.

Relationship between Cabin Altitude and Alveolar Oxygen Tension (PAO2).

X-axis: PAO2 (alveolar oxygen tension) (mmHg).

Y-axis: Cabin altitude (Feet).

The figure illustrates the relationship between cabin altitude and computed PAO2 under different conditions.

Violet line: The relationship between cabin altitude and computed PAO2 in a person with normal PAO2 at sea level.

Blue line: The relationship between cabin altitude and computed PAO2 in an individual with lowered PAO2 within normal ranges, considered “at risk.”

Red line: The relationship between cabin altitude and computed PAO2 in an individual with lowered PAO2 within normal ranges, considered “at risk.”

Annotations on the graph include:

1. Altitude levels at which supplemental oxygen is required for pilots, aircrew and healthy passengers as per Federal Aviation Administration standards. 2. Altitude at which cognitive issues are noted in healthy individuals.

3. Ambient cabin altitude range.

4. Altitude at which night vision is impaired.

3. Cardiovascular response

Acute altitude exposure boosts sympathetic and reduces parasympathetic activity, compensating for low PO2 and tissue hypoxia. This primarily occurs via alpha- and beta-adrenergic stimulation which increases the heart rate and thereby elevates the cardiac output (CO). Vasodilation lowers systemic vascular resistance, resulting in minimal systemic blood pressure alterations (5–15 mmHg) up to 4600 m (15,000 ft) after which paradoxical vasoconstriction occurs leading to high blood pressure. However, in the presence of cardiac disease, the heightened sympathetic activity and hypoxia may exacerbate cardiac dysfunction and lead to the development of ischemic symptoms with lesser exertion compared with sea level. As a result, the person may encounter increased breathlessness, worsening the already limited exercise capacity. Additionally, anemia if present, significantly lowers oxygen-delivering capacity, and will exacerbate the hypoxic symptoms regardless of the lung function and cardiac output levels [15–18].

A person exposed to high altitude experiences high altitude hypobaric hypoxia. Hypoxia activates peripheral chemoreceptors, leading to hypoxia diuresis and pulmonary vasoconstriction. Activation of peripheral chemoreceptors results in increased ventilation and activation of the sympathetic nervous system. Increased ventilation causes respiratory alkalosis, which contributes to pulmonary vasoconstriction and pulmonary hypertension. Activation of the sympathetic nervous system increases heart rate, stroke volume, and cardiac output, leading to systemic hypertension. Over time, sustained hypertension can result in cardiac decompensation. This whole process has been explained in Figure 2.

Figure 2.

Pathophysiological effects of high altitude hypobaric hypoxia on the cardiopulmonary system.

This figure outlines the pathophysiological cascade initiated by high altitude hypobaric hypoxia. Starting from “High Altitude Hypobaric Hypoxia” at the center, the sequence includes activation of peripheral chemoreceptors, leading to hypoxia diuresis and pulmonary vasoconstriction. Increased ventilation due to hypoxia results in respiratory alkalosis, contributing to pulmonary hypertension. Activation of the sympathetic nervous system increases heart rate, stroke volume, and cardiac output, leading to systemic hypertension. Over time, sustained hypertension can cause cardiac decompensation.

Passengers with ischemic heart diseases and heart failure, particularly with concurrent lung issues, may face even worse symptoms, especially during turbulence or adverse weather as higher cruising altitudes are necessary at that time, which further lowers cabin pressure. However, cabin altitudes exceeding 10,000 feet require supplemental oxygen for all passengers [7]. The association between cardiovascular health and air travel is multifaceted, involving flight duration, passenger demographics and individual health conditions.

Studies have shown that airline pilots, cockpit crew, and passengers face an elevated risk of cardiovascular disease due to prolonged sitting, frequent time zone changes, nighttime work and exposure to noise and vibration [19–21]. According to von Klot et al., extended travel, particularly by air, might be linked to a transiently heightened risk of nonfatal acute myocardial infarction (MI) among susceptible populations [22]. Similarly, Ingle et al. discovered a notable occurrence of cardiovascular complications in ambulatory patients with stable chronic heart failure during air travel, with 9% experiencing symptoms like breathlessness, dizziness, and chest pain, signifying an elevated risk of acute cardiovascular events while airborne [23].

However, there have been contradicting findings as suggested by Bernheim et al. that patients with stable coronary artery disease and adequate exercise tolerance are typically not prone to cardiac complications when traveling in a commercial aircraft cabin at altitudes up to 8000 feet [24]. Similarly, Macovei's study suggests that cabin altitude poses no risk to individuals with stable coronary artery disease [25].

4. Pulmonary response

The sudden drop in the partial pressure of oxygen (PO2), results in an increase of alveolar ventilation in a hyperbolic manner lowering the partial pressure of arterial carbon dioxide (PaCO2) resulting in alkalemia [26,27]. This results in a left shift of the oxyhemoglobin dissociation curve enhancing oxygen uptake through diffusion [28]. In addition to the left shift of the dissociation curve low altitude pressure results in pulmonary vasoconstriction, leading to an elevated pulmonary arterial pressure [29]. However this physiological response is heightened in patients suffering from pulmonary hypertension, negatively impacting the already stressed right heart causing acute decompensation of the right heart [30,31].

Patients with pulmonary artery hypertension tolerate short-haul flights of around 3.6 h. However, those in NYHA grade III/IV or on long-term oxygen therapy require additional recommendations based on their functional class and oxygen levels [31]. Patients with acute endocarditis, pericarditis, myocarditis or uncontrolled symptoms are generally unfit to fly, but post-recovery, flight fitness depends on NYHA functional class and clinical stability. Similarly, for congenital heart disease, cyanotic conditions like Eisenmenger syndrome pose significant flight risks due to baseline hypoxemia and hyperviscosity, the pathophysiological changes lead to a rightward shift of the oxygen dissociation curve with decreased hemoglobin affinity for oxygen molecules, further attenuating the effect of lower oxygen tension in the aircraft cabin during flight [30].

Studies have shown that the median age of those requiring medical support is 45 years, with 53.2% of them being females [2]. However, given cardiac arrest, the Air Medical Journal in 2021, demonstrated that the average age was 59 +/- 19 years, and a majority were male [32].

In addition to pulmonary hypertension, immobility poses a significant challenge in aircraft that increases the risk of deep venous thrombosis and venous thromboembolism (VTE) [7]. According to the WRIGHT project (WHO Research Into Global Hazards of Travel) [33], the incidence of VTE is twofold on flights exceeding 4 hours [30]. This can be attributed to prolonged sitting, relative cabin hypoxemia and dehydration in addition to individual risk factors which include age over 40 years, female gender, women on oral contraceptives, varicose veins in lower limbs, obesity and genetic thrombophilia [34]. High-risk groups, such as those who have recently undergone major surgery or cardiac procedures, or have a current or history of malignancy, recent MI or large varicosities, typically need a risk stratification approach for VTE prevention which includes compression stockings or prophylactic low molecular weight heparin during or day before long flights [30]. The VTE often poses a significant threat to pulmonary vasculature through dislodgement of thrombus causing PE. In patients with PE, there is redistribution of blood to non-occluded areas of the lungs, causing decrease in regional perfusion and subsequent regional bronchoconstriction. This bronchoconstriction often leads to reduced ventilation, skewing the V/Q ratio and resulting in Type 1 respiratory failure. Along with this, PE also strains the right ventricle by increasing the afterload causing deleterious effects on the heart [15]. The European Society of Cardiology places air travel as a weak risk factor predisposing to PE with an OR <2, precautions however are required after the diagnosis of deep venous thrombosis or PE to prevent recurrence [35].

In addition to the effects of hypoxia, the cabin-air quality and the expansion of gasses at high altitudes also induce various physiological changes in the body. The cabin air undergoes a process where it is drawn from the external environment, heated, filtered and then recirculated. This process leads to a significant reduction in humidity levels, typically ranging from 10 to 20%. Consequently, this low-humidity environment contributes to increased plasma and urine osmolarity that can result in hemoconcentration and heightened mucosal water loss during flights, which poses a potential risk, particularly for individuals with conditions such as COPD and asthma [36]. Gaseous expansion with rapid ascent, on the other hand, poses a problem for non-communicating gasses as they may cause rupturing of lung bullae and trigger tension pneumothorax in patients recovering from chest surgeries (like CABG), further resulting in desaturation and hemodynamic compromise [37]. Lastly, aviation-related stressors, including fear of flying, flight delays, security measures and baggage handling, have the potential to induce anxiety, which often contributes to the development of arrhythmias and heart disease [38].

5. Pregnancy

Air travel can induce physiological changes in pregnant women, including hemoconcentration, tachycardia and hypertension, due to the reduced barometric pressure at altitude [39]. While commercial air travel is generally considered safe for those with uncomplicated pregnancies, fetal heart rate typically remains unaffected. Most airlines permit air travel up to 37 weeks gestation for singleton pregnancies and 32 weeks for twins, although individual carrier policies vary [40].

Despite the normal oxygen saturation levels typically observed in pregnancy, supplemental oxygen may be indicated for women who cannot tolerate the relatively hypoxic environment of air travel [41]. The inherent increased risk of VTE during pregnancy is exacerbated by prolonged immobility associated with air travel. Additionally, there is an increased risk of exposure to infectious diseases such as travelers' diarrhea, Malaria, COVID, influenza, etc. [42].

Pregnant women with underlying medical or obstetrical complications that may be aggravated by flight conditions or necessitate urgent care should abstain from air travel [42].

In the Multiple Environmental and Genetic Assessment project, researchers discovered that the risk of developing deep vein thrombosis during long-haul flights can be up to 40-times higher among women using oral contraceptives, with female sex identified as a distinct risk factor for PE, leading to severe complications such as asystole and exacerbating pre-existing conditions like pulmonary hypertension and right-sided heart failure [43]. Additionally, similar results were affirmed by the World Health Organization's 2001 report that the risk of VTE doubles after 4 h of flight, with longer durations exacerbating this risk, especially among individuals with factors like obesity and oral contraceptive use and flights exceeding 6 h are particularly linked to a 2.3-fold higher risk of VTE compared with shorter flights, with the risk escalating by 26% for every additional two hours of travel time [34,44,45].

However, there have been contradictory findings such as a study by Toff WD simulating an 8-h long-haul flight at 8000-feet altitude, exploring the prothrombotic states of health showed no significant variations in prothrombotic states, indicating minimal risk under these conditions [46]. Similarly, the European Commission-sponsored Ideal Cabin Environment (ICE) project simulated a 7-h flight at 8000 feet and found no adverse effects on individuals with stable heart failure and reduced ejection fraction (classified as NYHA II functional status) [47].

6. Travelers' perspective

A study highlighted the perspective and experiences of cardiac patients on air travel. Participants emphasized the importance of managing their heart health before traveling, including securing travel insurance, carefully packing medications and pre-booking travel arrangements to reduce airport stress. While airport navigation was generally manageable, long layovers due to flight delays were physically taxing. Moreover, pre-travel checkups and medical advice was found to be useful and medical documentation, including physician letters and device identification, helped streamline security processes [18].

7. Airport security & implanted devices

While airport security systems can detect pacemakers and defibrillators, they pose no risk to device function. However, there's a theoretical concern about handheld metal detectors potentially interfering with these devices. Despite this, research has shown that passing through airport security gates doesn't impact implanted devices [48,49].

To minimize any potential issues, patients should walk through security gates at a normal pace and avoid lingering. If a manual search is necessary, they should request a non-metal detector search. If a handheld metal detector must be used, it should be kept away from the implanted device for more than a few seconds, with a 30-s interval between scans [50].

8. Travel insurance

Experience of medical events or deterioration in cardiovascular condition requiring hospitalization overseas has been rarely reported but the importance of travel insurance is emphasised, as it provides reassurance apart from reducing the medical expenses if needed [18].

9. Medical tourism

The term “medical tourism” refers to the trend of patients traveling to different countries for high-quality care, which frequently entails complex surgery that is easily accessible at comparatively low costs [51]. The cardiac surgeries typically offered are coronary artery bypass grafting, replacement or repair of heart valves, percutaneous coronary angioplasty with stenting and specialized treatments which may be available only in certain countries, like stem cell therapy for heart failure [52]. Specific air travel guidelines should be provided to individuals traveling for this reason.

10. Protocols of airlines for managing medical emergencies

Airlines handle in-flight medical emergencies on a case-by-case basis, with unique protocols for each carrier. Typically, when a medical issue arises, the cabin crew assesses the situation and informs the captain. If necessary, the crew seeks assistance from onboard medical professionals and requests medical support from ground personnel [53]. The captain decides how to proceed based on the passenger's condition. This could involve continuing the flight as planned but arranging for medical help upon arrival, speeding up the landing at the original destination, or diverting to a closer airport. Any medical professional on board assists the crew, but the captain always has the final say in all decisions concerning the aircraft [54].

The International Civil Aviation Organization sets guidelines for commercial aviation, including the types of medical kits required on airplanes. These kits include: first aid kits, emergency medical kits and universal precaution kits. First aid kits are for basic injuries, while Emergency medical kits are for more serious medical situations and are typically found on larger planes for longer flights. Universal precaution kits protect healthcare providers from exposure to infectious diseases [55]. The specific contents and quantities of these kits can vary widely between airlines and to ensure the safe and effective use of these kits, the FAA (United States Federal Aviation Administration) mandates that only trained personnel can access and use the emergency medical equipment [55,56].

11. Prevention

Passengers with preexisting cardiac and pulmonary conditions must exercise extra caution while traveling by aircraft. Patients with severe heart failure, particularly those with New York Heart Association grade IV symptoms, are advised to avoid air travel whenever possible. Additionally, individuals with significantly reduced functional status or ejection fraction may require supplemental oxygen during flights to mitigate potential risks associated with hypobaric conditions and it is also recommended to avoid high-sodium onboard meals and to abstain from alcohol and caffeinated beverages [57–59].

In addition, congestive heart failure patients undergoing open thoracotomy surgery, may encounter risks related to trapped air in the chest during flights, potentially causing curtain hemodynamic problems thereby guidelines recommend waiting 10–14 days post-surgery before flying to allow complete air resorption and minimize these risks. Similarly, following the implantation of an implantable cardioverter-defibrillator or pacemaker, there is a slight increase in the risk of pneumothorax, often necessitating a delay in air travel until complete radiographic resolution is evident. Additionally, the vibrations associated with flying, especially during takeoff and landing, may affect activity-sensing rate-adaptive pacemakers and implantable cardioverter-defibrillators. To mitigate this concern, passengers can consider reconfiguring the device to reduce or eliminate the rate-response function before takeoff, or utilize a magnet to disable a pacemaker's rate-adaptive function if necessary [49,60,61].

Patients with stable coronary artery disease and a history of MI can safely travel with their regular medications and short-acting nitrates [62]. To mitigate the challenges posed by deep vein thrombosis and subsequent PE, engaging in mild physical activities such as calf muscle exercises during flights is often recommended, which can help prevent VTE. In addition, abstaining from alcohol and tobacco products and maintaining proper hydration levels are additional strategies to minimize the risk of deep vein thrombosis during air travel [59,63].

12. Conclusion

The correlation between cardiovascular health and air travel entails various risks that can cause acute exacerbations of cardiovascular diseases, requiring careful evaluation. However, research is limited by the lack of large-scale, longitudinal studies and the variability in individual responses to stressors like hypobaric hypoxia. Further studies are needed to explore the long-term effects of repeated air travel and to develop standardized protocols for in-flight medical emergencies. Personalized prevention strategies and collaboration among healthcare professionals, researchers and aviation authorities are crucial to address these risks.

13. Future perspective

Future aspects of airplane travel are anticipated to focus on mitigating cardiovascular complications. Advancements in in-flight medical technology and monitoring systems could provide real-time health data to passengers and crew, ensuring early detection and management of cardiac events. Aircraft cabins are anticipated to be designed to better control air pressure and oxygen levels, reducing stress on the cardiovascular system. Personalized healthcare solutions, including in-flight telemedicine consultations, will offer immediate medical advice and support.

Additionally, future airplanes could feature improved seating ergonomics and space, encouraging more frequent movement and reducing the risk of deep vein thrombosis. These innovations promise to make air travel safer and more comfortable for passengers with cardiovascular conditions. By integrating promising medical advancements, environmental improvements and personalized healthcare options, the future of air travel seeks to ensure a safer and more enjoyable experience for all passengers, particularly those with cardiovascular concerns.

Author contributions

T Katoch – Writing Original Draft, Writing Review and Editing; S Pinnamaneni – Writing Original Draft, Writing Review and Editing; R Medatwal –Writing Original Draft, Writing Review and Editing; FNU Anamika – Writing Original Draft, Writing Review and Editing; K Aggarwal – Writing Original Draft, Writing Review and Editing; S Garg –Writing Review and Editing; R Jain – Project Oversight.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.