|Year : 2021 | Volume
| Issue : 1 | Page : 16-23
Critical care preparedness and conduct in COVID-2019 crisis
Manoj Kumar Sahu, Prateek Vaswani
Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||13-Aug-2020|
|Date of Decision||08-Mar-2021|
|Date of Acceptance||17-Mar-2021|
|Date of Web Publication||24-Apr-2021|
Manoj Kumar Sahu
Department of Cardiothoracic and Vascular Surgery, CTVS office, 7th floor, Cardiothoracic and Neurosciences Centre, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Background: COVID-19 pandemic has stirred an unexpected turmoil in health care worldwide. The strategic conduct of critical care would warrant an effective preparedness plan, thorough knowledge of the disease manifestations, and relevant therapeutic strategy to sail through this crisis. Methods: English medical literature with MeSh database was searched using the key words such as “COVID-19 pandemic,” “ICU preparedness,” “COVID-19 management,” “COVID-19 therapy,” and “COVID-19 systemic effects.” The relevant studies were included with significant inputs from interdepartmental meetings for the formulation of a plan. Results: The analysis of the respective studies highlighted the requirements of COVID-19 designated intensive care units (ICUs) with special provisions and the therapeutic agents being used in critical patients with emphasis on Remdesivir, Dexamethasone, Convalescent Plasma, and insight into newer agents. The systemic manifestations of COVID-19 requiring ICU care such as acute respiratory distress syndrome, myocardial injury, arrhythmias, hypercoagulable state, and acute renal dysfunction have been highlighted. The need of updating records with research protocols cannot be disregarded. The care of patients should not compromise the health-care personnel requirements. Conclusion: The evidence-based preparedness strategy can curtail the critical care crunch in COVID-19 management; however, institutional specific approach should be formulated.
Keywords: COVID-19 current treatment, COVID-19 pandemic, intensive care unit preparedness, personal protective equipment, reverse-transcriptase polymerase chain reaction
|How to cite this article:|
Sahu MK, Vaswani P. Critical care preparedness and conduct in COVID-2019 crisis. J Pract Cardiovasc Sci 2021;7:16-23
| Introduction|| |
The 3rd pandemic of coronavirus in this century, the severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) is highly contagious. Although less fatal than the previous two of its kind (SARS-2002 and MERS-Middle East Respiratory Syndrome 2012),, COVID-19 is spreading like wildfire throughout the globe with overwhelming effects on health care which has led to a crisis situation. The preservation of critical care resources without denying the level of care in COVID-19 patients has been the strategy globally adopted. The intensive care unit (ICU) management protocols revolve around preparing, early identifying, and provision of supportive care with an expectant management till a vaccine or herd immunity are developed. There is also a need to watch the newer treatment modalities and their upcoming researches in order for an effective management of COVID-19 situation. Here, we discuss the care of severe COVID-19 infection with preparedness of ICU, management of complications, and an insight into the newer modalities against COVID-19.
| Methods|| |
The English medical literature in MeSh database was searched utilizing keywords such as “COVID-19 pandemic,” “ICU preparedness,” “COVID-19 management,” “COVID-19 therapy,” and “COVID-19 systemic effects,” and the relevant studies were included for the formulation of the effective critical care conduct. The multidisciplinary meetings also contributed to the formulation of ICU care strategy.
| Results and Recommendations|| |
Intensive care unit preparedness
The policy for ICU admission should be in liaison with advice from epidemiological experts studying the local and national viral trends. The false-negative rates of 30%–50% with reverse-transcriptase polymerase chain reaction (RTPCR) test should be borne in mind during patient evaluation; however, testing should be mandatory before receiving in the ICU. The maintenance of adequate distance between beds (6 feet) and provision of appropriate donning and doffing areas in the ICU premises should be given utmost regard. Regular drills in intubating COVID-19 patients, identification of skilled member of the team as team leader, availability of video-laryngoscope for intubation which is being performed by the most skilled team member who is identified at commencement of the shift, limited yet adequate number of health personnel in every shift, use of N-95 or equivalent masks, availability of personal protective equipment kit, negative ventilation rooms if feasible/or well-ventilated single rooms, enhanced record keeping, minimizing transfer for radiological investigations with increasing reliance on portable point of care ultrasonography, and coherence with the development of team approach should be the ICU norms.
Proper training on how to don and doff the protective gear emphasizing more on appropriate doffing, strict prohibition on personal mobiles or other accessories use in the ICU with emphasis on regular disinfection of contact areas, waste disposal strategy, and restricted visitor entry with use of teleconferencing between patients and their family members should be considered. The ICU staff must have expert working personnel too who are well versed with proning maneuvers. The provision of mental boost should not be neglected both for patients and health care personnel in optimizing their mental health in such crisis times.
The discharge from the ICU should be based on at least two negative RTPCR assays performed at 24–48 h' interval as dispersion of virus continues till 2 weeks' time.
The ICU awareness regarding the spectrum of clinical manifestations for ready identification, the various organ systems involved during disease course, the grading of severity [Figure 1], associated comorbidities potentiating further risk of mortality (including cardiovascular, diabetes, hypertension, preexisting chronic pulmonary conditions, malignancy, chronic renal dysfunction, obesity, smoking, etc.,), enlisting serum investigations in monitoring the course, discharge policy [Institutionalized, [Figure 1], and finally, the record keeping for mortality trends in the ICU. The altering mortality trends may give indirect evidence of the ICU preparedness and management strategy.
|Figure 1: Grading of coronavirus disease 2019 with institutional discharge policy. RA–Room air, SpO2-Oxygen saturation, Room air, PaO2/FiO2-Partial pressure of oxygen to Fraction of oxygen in inspired air. *Recommended, but may vary based on institutional feasibility|
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Drug therapy requiring special mention
It is now recommended in cases of severe COVID-19 infection. Remdesivir is prepared in a cyclodextrin vehicle that interferes in glomerular filtration which may add to nephrotoxicity; however, the short duration therapeutic strategy of 7–10 days, discontinuation before discharge from the hospital and minimal amount of cyclodextrin being bound seldom amounts to grave kidney damage. Therefore, it has been considered safe in both acute and chronic renal disease states., In addition, in cases of hepatic dysfunction, it must be judiciously used. There are in vitro studies that have established its activity in suppressing coronavirus as an analogous nucleotide in the viral agent. The recommended dosage in adults in 200 mg intravenously (I/V) on the 1st day followed by 100 mg I/V for 5–10 days depending on individual response. It also interferes and interacts with hydroxychloroquine. Beigel et al. in their double blinded, randomized trial which concluded the superiority of Remdesivir over placebo in the reduction of duration of recovery in patients with pulmonary involvement as observed in 1062 patients where the median duration was reduced from 15 to 10 days (95% confidence interval [CI] 1.12–1.49, odds ratio = 1.32, P < 0.001). There was also a statistically insignificant benefit over placebo group in terms of 1-month survival. Its benefit, however, could not be established in mortality reduction over a 2-week period. The study also did not reveal co-therapeutic agents being used. The results of this study could not be confirmed in a multicentric randomized trial by Wang et al. The overall results from various randomized studies, however, do not depict a substantial advantage with the use of Remdesivir.,,,,,
In a meta-analysis of 85 trials enrolling 41,669 study subsets by Siemieniuk et al., Remdesivir failed to illustrate an advantage on reduction of mortality, mechanical ventilatory support, duration of institutional admission, or symptom duration. The WHO funded SOLIDARITY trial involving patients from multiple nations, in an interim report failed to demonstrate a difference in a 1-month mortality between Remdesivir and placebo group. However, the meta-analysis also included patients from SOLIDARITY trial, the trend showed in favor of Remdesivir which could not reach statistical significance. There is also a debate regarding the duration of use of Remdesivir for 5 days versus 10 days of administration as studied in 397 patients having severe COVID 19 revealing no difference among the two durations; however, these patients did not require any ventilatory support. Therefore, the duration should vary based on ICU protocols and individualized to different clinical scenarios. The adverse effects observed with Remdesivir have been primarily gastrointestinal with others being drop in hemoglobin, acute onset renal insult, hyperpyrexia, altered blood sugar profile, and raised transaminases. A study by Beigel et al. revealed no difference in the incidence of these adverse events in placebo versus Remdesivir. Wang et al., however, reported discontinuation of Remdesivir due to worsening cardiopulmonary profile in addition to other adverse effects.
The combination with Janus kinase inhibitor Baricitirib seems to potentiate antiviral effects with Remdesivir. In a double-blind randomized study by Kalil et al. comparing combination therapy of the two versus placebo in 1033 COVID-19 afflicted patients showed earlier symptomatic relief with improved clinical profile, especially in those requiring higher flow rates of oxygen or on ventilator support without potentiation of adverse effects. The median duration of recovery was 18 days in placebo group versus 10 days on combination group among 216 patients with higher oxygen requirements (respiratory rate 1.51, 95% CI 1.10–2.08).
The early results of RECOVERY trial, which is a randomized study administering low dose dexamethasone (oral or I/V route), have revealed significant reductions in a 4-week mortality in admitted patients in comparison with home care. The entire study population had 17% decline in mortality; however, those who required ventilator support or extracorporeal membrane oxygenation (ECMO), there was an even higher benefit with 35% decline in mortality. The ones requiring noninvasive support modes had 20% reduction in mortality. Similar benefit was not observed in patients not requiring any support for oxygenation. The theoretical risks of altered blood sugar profile and elevated incidence of infections were not observed in any of the subgroups., This portends the use of steroids in ICU as part of critical care.
This is still under trial; however, early evidence has propagated its use in special situations.
Ideally, plasma from convalescent individuals obtained should consist of:-
- Optimum concentration of antibodies devoid of microorganisms
- Proven efficiency and safety profile for the relevant condition.,
The neutralizing antibodies binding to viral particles reduce cellular entry of the virus simultaneously enhancing their clearance through phagocytosis or cellular toxicity response. These are produced against spike protein and nucleo-capsid protein.,, The various randomized trials, however, did not demonstrate superiority in clinical improvement and mortality reduction.,,, Simonovich et al. in their study of 333 patients, in which 228 received plasma versus 105 receiving placebo found no difference among the two in clinical benefit or survival.
In a Chinese study, 103 patients with severe COVID 19 disease were enrolled and random allocation to standard versus plasma therapy was done. These patients received plasma with elevated levels of neutralizing antibodies, although a major proportion of patients were administered only a single dose. The median duration from the symptom onset to treatment with convalescent plasma was 30 days, quite late in the disease course. This study revealed that although, the RTPCR tests (detecting virus) done over a 3-day interval became negative earlier in plasma therapy group (87% vs. 38% in standard therapy group), there was no significant difference in the rate of clinical improvement or improved overall survival. The mere clearance of virus did not lead to mortality reduction signifying the cytokine storm being stirred by viral epitopes as a significant contributor for the disease severity. The late administration of plasma also could have been a significant factor. Joyner et al. demonstrated the safety and toleration profile of plasma in individuals in their report in Mayo Clinic of 20,000 patients. In a report by Wang et al., monoclonal antibody targeting viral epitope has been documented which may have a significant therapeutic impact. This has not yet been corroborated in other studies and continues to be under trial.
A study by Li et al. from China enrolling 103 patients demonstrated that although, rate of clearance of viral RNA was quicker in the plasma group, however was not translated into clinically appreciable benefit or mortality reduction.  The trend was toward reduced mortality but could not reach statistical significance in those with life-threatening COVID-19. Similarly, PLACID trial from India by Agarwal et al. which enrolled 464 adults over 39 health-care institutions demonstrated suboptimal results showing no superiority over optional standardized institutional care. In this study, however, no titer measurement was provided before and after the institution of plasma.
Interleukin 6 pathway inhibitors
The elevations in the markers of inflammation, for example, D-Dimer, Ferritin, and interleukin 6 (IL-6) have been observed in the initial stages of COVID 19, setting up a cytokine storm contributing to mortality. A pilot study by Sciascia et al. has evaluated the use of Tocilizumab as an IL-6 antagonist in 63 patients with severe disease. There was significant improvement in PaO2/FiO2 (partial pressure of oxygen to fraction of inspired oxygen) and laboratory marker profile with a reduced overall rate of demise. The mortality benefit was observed when Tocilizumab was administered within 6 days of hospitalization. Therefore, we advocate the serial levels of biomarkers to guide the administration of this agent early in course of the disease.
It acts against RNA polymerase and has been used for influenza; however, its use has not been advocated in severe category patients. There has been observed radiological improvement and faster clearance of virus in mild-to-moderate cases in comparison with lopinavir-ritonavir combination, although the nondisclosure of co-therapeutic confounder agents is a matter of concern while interpreting the results of this study. However, further studies ongoing may reveal its use in critical care support of COVID-19 patients.
The growing interest in this agent stems its roots in the animal-based study by Chan et al. owing to similarity between COVID 19 and MERS virus. The beneficial effects of this agent versus lopinavir-ritonavir have been established in a single-center study by Hung et al., however, not for severe patient subset and improved clinical profile was observed when interferon IFN-beta was administered within 1 week of illness. Other immune-modulatory agents are being evaluated, however, in small case series with multiple confounders. Anakinra (IL-1 inhibitor), similarly, has been studied in severe patients maintained on noninvasive ventilatory support in a retrospective study by Cavalli et al.; however, since the group receiving hydroxychloroquine/lopinavir-ritonavir was older in age in comparison and the presence of confounding variables which could not be measured, it has raised questions about the results of this study. These immunemodulators may have role, however, currently are far from being established. In addition, there have been the reports of some traditional Chinese medications such as XueBiljing and others being employed for the management of COVID-19; however, no peer reviewed safety and efficacy data are available regarding them. These are being further evaluated in a study by Chan et al.
It has been postulated to enhance the innate immunity responding against COVID-19 disease. In addition, critical illness is usually associated with reduced serum concentration. In a pilot study from Spain by Entrenas Castillo et al. enrolling 50 patients who received Vitamin D metabolite and 26 patients who didn't, demonstrated that there was a statistically significant reduction in ICU admission (2% vs. 50%, P < 0.001) and reduced disease severity; however, they stressed on the need of larger studies in this regard. There were various confounding factors such as hypertension and diabetes by being more predominant in the control arm, jeopardizing their results. The randomized trial by Murai et al. from the Brazilian population constituting 237 randomizes patients failed to the establishment of Vitamin D in severe or moderate COVID-19 infection. There was no statistically significant difference in duration of hospital stay, survival (7.6% vs. 5.1%), ICU admission (16% vs. 21.2%), and ventilatory support (7.61% vs. 14.4%). However, Vitamin D role in COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and still being researched.
Management of special situations
Acute respiratory distress syndrome
The discussion of ARDS associated with COVID-19 would be incomplete without emphasizing on the types of pneumonitis induced by the viral progression. It has been described in the study by Gattinoni et al. into two time-related processes, namely the “L” type and “H” type. The “L” type which is characterized by lower elasticity depicting near normal lung compliance, lower ventilation-perfusion mismatch, lower lung weight associated with the radiological features of ground-glass opacities predominantly without additional appreciable sequelae and lower amounts of nonaerated areas in lung parenchyma, thereby less reliance on pulmonary recruitment maneuvers. However, the advanced progressive form seen later in the disease course known as the 'H' type is characterized by higher lung elasticity owing to edematous tissues, higher ventilation-perfusion mismatch attributed to left-to-right shunt wherein gravity-dependent pulmonary areas receiving higher proportion of circulation without corresponding aeration, substantially increased lung weight quantifying severe respiratory distress syndrome in the ranges of more than 1.5 kg and higher need for pulmonary recruitment manoeuvres in order to recruit the higher amount of nonaerated pulmonary segments. The phenomenon of patient induced self-inflicted lung injury described by Barach and Mascheroni et al. forms the basis of progression of one type of pneumonia to other., The synergy of negative intra-thoracic pressure while inhalation in the background of ongoing inflammatory process associated pulmonary permeability potentiates this transition and culminates in disastrous sequelae. This clinical picture reveals worsening nature of shortness of breath with increasing inspired fraction of oxygen requirement leading to adoption of ventilatory support both noninvasive and invasive type depending on clinical profile. The reversal of hypoxia at the earliest may prevent progression to 'H' type. This can be achieved through adoption of high flow nasal cannulas, positive pressure support or noninvasive ventilatory support in selected cases with dyspnea. The pleural pressure changes measured indirectly through central venous pressure tracings may guide toward invasive ventilation conversion as delaying this may aggravate self-inflicted lung injury. The “H” type pneumonitis may respond to prone positioning with ventilatory support, higher end expiratory pressures, and finally, resorting to mechanical circulatory support in subsets with hemodynamic compromise. This understanding of pathophysiological process marks an indispensable tool for adoption of appropriate therapeutic strategy averting clinical decline.
The strategy in managing ARDS is based on supportive care keeping a close watch for involvement of the liver, kidney, and heart. The routine estimations of renal and liver function tests should be considered at specified intervals (at least on alternate days) as a part of the ICU strategy. The super-added infections and preexisting comorbid conditions must be managed appropriately. This involves exchange of ideas among the specialist in critical care, pulmonary medicine, and cardiologist together as an expert team. Close eye should be kept on serum levels of biomarkers-(IL-6, D-dimer, Ferritin, C-reactive protein, and lactate dehydrogenase). The placement of central venous line for guiding fluid therapy, checking blood gases at regular intervals with invasive vital monitoring by arterial lines, supervised undertaking of these procedures, using inotropes whenever unresponsive to fluid boluses or in cases with myocardial injury, avoiding frequent nebulization, use of metered dose inhalation devices even in those on ventilator support minimizing the aerosol dispersion or use of separate rooms for patients with exacerbation of chronic pulmonary illness, targeting SpO2 above 90% with frequent reassessment of those on high flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) support are a few essential steps to be catered to while managing these patients. There is a risk of spread of aerosols in NIV and HFNO, however, they may have a role in avoiding invasive mechanical ventilation which has poorer prognosis. HFNO is preferred over NIV whenever used for such patients with moderate to severe COVID 19 illness, however, NIV has established role in management of COPD exacerbations., The use of appropriate fitting masks is mandatory for an adequate seal. The enlistment of intubation criteria with use of a rapid sequence technique while avoiding bag-mask ventilation and using special viral or double bacterial filters in the breathing circuit effectively reducing aerosol generation. The utilization of lung protective ventilation with prone positioning, alveolar recruitment maneuvers, inhalational pulmonary vasodilatation agents like inhaled nitric oxide, paralytic agents in patients with unresponsive hypoxemia with use of Veno-venous or Veno-arterial ECMO as a last rescue therapy should be laid out clearly in ICU protocols. ECMO device with circuit accessories including cannulae, tubing kit, oxygenator, etc., should be ready for disposal in case need arises with special laid down criteria for ECMO institution. Cardiologists, intensivists, pulmonologists and cardiac surgeons should be involved in formulation of comprehensive ECMO use algorithm. The adoption of prone position in conjunction with mechanical ventilation should be the institutional practice. In a retrospective study by Sartini et al., 12 of 15 patients afflicted with COVID-19 were subjected to prone position alternating with NIV. These patients showed improved peripheral oxygen levels compound with the rest. In a prospective cohort study (PRON-COVID) done by Coppo et al. including 56 patients, feasibility for prone position was found in 84% patients. There was statistically significant elevation of PaO2/Fio2 (180.5 ± 76.6 in supine to 285.5 ± 112.9, P < 0.0001). This improvement persisted in 50% of the patients. Prone ventilation has been adopted as standard of care in patients develops COVID-19 ARDS where there is failure of oxygenation.,
The start of empirical broad antibiotics based on ICU cultures and in-hospital trend with early tracing of the culture reports to convert into narrow spectrum, bed sore prevention with air mattress use and regular position changes, ulcer prophylaxis with proton pump inhibitors, early institution of nutritional support is essential. Additionally, systemic administration of steroids and other agents should be evidence based as highlighted above. The use of investigational agents should be considered in individualized situations as these therapeutic agents continue to evolve.
Managing arrhythmias and myocardial insult
Sinus tachycardia manifests in majority of COVID 19 patients, however, atrial fibrillation, atrial flutter and mono or polymorphic ventricular tachycardia have been reported. The QT interval should be monitored in serial 12 lead electrocardiographic (ECG's). QT interval values more than 500 msonds have been observed in 6.1% cases in a study of 4250 patients. In another study involving 393 patients, it was found that atrial rhythm abnormalities were more frequent among patients on ventilatory support (17.7% vs. 1.9% of those not on ventilator) with additional need for inotropic support (95.4% vs. 1.5%) and evidence of new onset kidney dysfunction with requirement of dialysis (13.3% vs. 0.4%) in those on mechanical ventilation support. The management ensues on ambient temperature monitoring, avoiding hyper or hypothermic situations, controlling electrolyte imbalances especially potassium levels, administration of intravenous magnesium whenever necessary, anti-arrhythmic agents and utilization of pharmacological or electrical cardioversion in cases with hemodynamic alterations with cardiologist consultation.
Myocardial insult has been reported in rates varying from 7% to 28%.,, Prevalence of heart failure has been seen as high as 49% in patients who succumbed (113 patients) versus only 3% in those who recovered (161 patients) in a retrospective study by Chen et al. involving 799 patients. The levels of Troponin are estimated at baseline on ICU admission as a marker for myocardial insult with ECG monitoring for ST segment changes and bedside echocardiography for abnormalities in regional wall motion. Levels of B-type natriuretic peptide can be corroborated closely with heart failure, although, elevated levels are often observed in early periods of severe COVID-19. The appropriate management entails quick diagnosis and supportive care with inotropes, vasodilator agents and inclusion of mechanical assist devices whenever deemed necessary in consultation with cardiac team. The indications for ECMO use in such patients should be discussed.
Management of hypercoagulable state
There have been noted complications related to development of a hypercoagulable state in COVID 19 such as deep vein thrombosis, pulmonary thrombo-embolism, stroke, acute limb ischemia and microvascular thrombosis. The ICU protocol devised must entail the conduct of complete blood profile with thrombocyte count, prothrombin time, activated partial thromboplastin time, fibrinogen and D-dimer levels with further evaluation by thromboelastographic tests whenever available for a timely intervention.,, All admitted patients in moderate category must receive prophylactic dose of low molecular weight heparin with escalation to therapeutic dose in ICU admissions.,,,, Limb physiotherapy with use of sequential intermittent pneumatic compression devices can be considered in synergism. Thrombolysis must be reserved for cases with limb threatening scenario, hemodynamically significant pulmonary embolus, acute ischemic stroke and acute myocardial infarction after consult with stroke and cardiac team., The thrombo-prophylaxis should be continued in patients with higher risk of thrombosis based on clinical judgment for the entire convalescent phase till they resume the routine activities with the use of compression stockings. The anticoagulation must be strived at a higher level due to the hypercoagulable state induced by COVID-19 infection.
Management of acute renal dysfunction
Acute kidney injury (AKI) has been observed in 37% of 5449 COVID-19 patients in a study by Hirsch et al. with severe grade AKI in 31% of them. Hematuria and proteinuria have been associated with higher predisposition to mortality when present in association with AKI. The pathophysiology behind AKI either due to poor hemodynamics or cytokine storm, is yet unclear. The patients requiring renal replacement therapy can be grouped together or kept in the separate isolation rooms if feasible with provision of bedside dialysis avoiding transfer-related adverse scenarios, preference being given to continuous renal replacement therapy over intermittent hemodialysis, expert nephrology staff at bedside and audio or video surveillance of these rooms preventing the need for continuous monitoring with reduction in the exposure of personnel involved. The circuit tubing's should be thoroughly anticoagulated considering the hypercoagulable pathological state created by COVID-19. The presence of COVID-19 or other viruses has not been revealed in the dialysis effluent; hence, no special provisions for disposing this are required.
Intensive care unit research
The evolving pandemic situation requires the conduct of research with strenuous record keeping, collaboration with multiple centers both national and worldwide for optimal networking platform. This also requires patiently and cautiously analyzing the study results with emphasis on methodology for the provision of a comprehensive care policy.
| Conclusion|| |
The pandemic has stirred a turmoil in the critical care management while jeopardizing routine hospital functioning. The preservation of critical care resources is mandatory in crisis times with judicious allocation to those in dire need. Strict monitoring, supportive care provision, early diagnosis of the sequelae of COVID-19, vigilant surveillance of newer therapeutic agents with a holistic care of the patients, and staff would comprehensively address this situation. The herculean task of conducting research with a global collaboration is imperative for a successful critical care program.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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