key: cord-0739543-ym1ylx2a
authors: Driver, Vickie R.; Couch, Kara S.; Eckert, Kristen A.; Gibbons, Gary; Henderson, Lorena; Lantis, John; Lullove, Eric; Michael, Paul; Neville, Richard F.; Ruotsi, Lee C.; Snyder, Robert J.; Saab, Fadi; Carter, Marissa J.
title: The impact of the SARS‐CoV‐2 pandemic on the management of chronic limb‐threatening ischemia and wound care
date: 2021-10-29
journal: Wound Repair Regen
DOI: 10.1111/wrr.12975
sha: 7752136a6d0a1afcd1f3fdcfc30f79ea9fb10695
doc_id: 739543
cord_uid: ym1ylx2a

In the wake of the coronavirus pandemic, the critical limb ischemia (CLI) Global Society aims to develop improved clinical guidance that will inform better care standards to reduce tissue loss and amputations during and following the new SARS‐CoV‐2 era. This will include developing standards of practice, improve gaps in care, and design improved research protocols to study new chronic limb‐threatening ischemia treatment and diagnostic options. Following a round table discussion that identified hypotheses and suppositions the wound care community had during the SARS‐CoV‐2 pandemic, the CLI Global Society undertook a critical review of literature using PubMed to confirm or rebut these hypotheses, identify knowledge gaps, and analyse the findings in terms of what in wound care has changed due to the pandemic and what wound care providers need to do differently as a result of these changes. Evidence was graded using the Oxford Centre for Evidence‐Based Medicine scheme. The majority of hypotheses and related suppositions were confirmed, but there is noticeable heterogeneity, so the experiences reported herein are not universal for wound care providers and centres. Moreover, the effects of the dynamic pandemic vary over time in geographic areas. Wound care will unlikely return to prepandemic practices. Importantly, Levels 2–5 evidence reveals a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in‐person visits at clinics and hospitalizations, with the exception of severe cases such as chronic limb‐threatening ischemia. The use of telemedicine and home care will likely continue and improve in the postpandemic era.

Revascularization is required to restore blood flow to the limb, and up to 75% of patients are indicated for endovascular therapy, but amputation rates remain unsettlingly high, with as many as 20% of patients requiring an amputation at 1 year. 1, 2, 11 The mortality risk following diagnosis is 24% at 1 year and 60% at 5 years. 12 Poor outcomes compound the reduced quality of life and high pain experienced by patients with CLTI, with 25% dead at 1 year and more than 60% dead at 5 years. 6, 13, 14 Among European patients, male sex, obesity, the 65-67 year age group, and having high cholesterol and triglycerides have been found to be associated with a CLTI diagnosis. 15 Amputation rates due to CLTI are disproportionately higher among racial and ethnic minorities. A univariate model was developed based on data collected from 88,346 White patients (7.2% of whom had a below-knee amputation [BKA] ) and 23,115 Black patients (12.3% of whom had a BKA). 16 Among both racial groups, 6465 patients also identified as Hispanic. Univariate analysis revealed that black race (odds ratio 1.93, 95% CI 1.84-2.03) and Hispanic ethnicity (odds ratio 1.62, 95% CI 1.51-1.73) had a significantly higher risk of having a BKA compared to the White reference group (p < 0.001). 16 The financial costs of CLTI may be as high as $12 billion a year among Medicare patients. 9, 17 Under normal circumstances, managing CLTI and preventing limb loss is extremely challenging. In addition to CLTI management, a multidisciplinary team approach can offer an intensive prevention strategy (that includes patient education, foot care, and therapeutic footwear) to avoid a significant number of amputations. 18 The multidisciplinary team is part of the global transition from clinic-centred to patientcentric health care in chronic diseases that require involvement of multiple specialties. 19 At the end of the 20th century, collaboration between vascular surgery and podiatry demonstrated economic benefit. 20 Since March 2020, health systems have been overburdened by the SARS-CoV-2 pandemic, with wound care sometimes being a casualty of lockdowns that deemed these potentially limb-preserving services to be 'nonessential'. 21 As of 21 October 2021, there have been more than 242 million confirmed global diagnoses of coronavirus and at least 4.9 million known global deaths. Yet the uncalculated toll of the SARS-CoV-2 pandemic on wound care may not be known for years to come, and a 'pandemic within a pandemic' is foreboding, with healthcare providers worried over future increases in mortality rates and amputations as a result of wound care centres closing, services being disrupted, and patients staying home and avoiding medical attention (and risk of SARS-CoV-2 infection). [21] [22] [23] Given the uncertainty over when the pandemic will end, the CLI Global Society Wound Care Committee began an important dialogue to understand the impact of SARS-CoV-2 pandemic on the CLTI population, especially with tissue loss, and analyse the available evidence regarding impact of the pandemic. Since health care will likely never return to prepandemic practices, the CLI Global Society aims to develop improved clinical guidance that will both inform better care standards to reduce tis- We screened article abstracts for their relevance to CLTI, tissue loss, and/or wound care, and we included general articles about changes made to health care or other areas of medicine during the pandemic that could still be applicable to CLTI and wound care. Few articles were returned from our initial search that were relevant to the impact of COVID on home healthcare; therefore, we did a separate, more generalized search using the terms: home AND healthcare, for articles published since 2020, which then returned articles relevant to the pandemic.

We chose studies or papers mainly on content related to a hypothesis or supposition. Where there were choices, we focused on higher level of evidence studies (e.g., a full-length published crosssectional study versus published correspondence or a research letter, or editorial). Pre-print articles not indexed on PubMed were not included. Each paper or study was rated according to the Oxford Centre for Evidence-Based Medicine scheme (https://www.cebm.ox.ac. uk/resources/levels-of-evidence/ocebm-levels-of-evidence) but was not assessed further. Table 1 summarizes the overall graded evidence we found in relation to hypotheses and suppositions.

3.1.1 | Hypotheses 1. No universal approaches in regard to testing of patients or staff 2. Many staff members and providers (facilities) are very concerned that they will become infected by patients 3. Some facilities assume that patients are virus positive (especially for high risk or emergent procedures) 4. Polymerase chain reaction testing is the most widely used form of testing; rapid testing is not being widely used due to accuracy concerns • Early in the pandemic, healthcare facilities in the hardest-hit areas of the world developed procedures to protect their healthcare workers from SARS-CoV-2 infection. In Italy, for example, patients wishing to access an outpatient facility, such as the angiology unit, were not allowed to enter until the reception nurse, equipped with personal protective equipment (PPE), had taken their temperature and provided them with a mask and hand sanitizing gel. 24 The patients were then given a questionnaire on their health condition, particularly focused on signs and symptoms typical of SARS-CoV-2 as part of their flowchart procedures. Once admitted, patients had to socially distance from one another (1 m). Patients possibly infected with SARS-CoV-2 were sent to the Infectious and Tropical Diseases Unit for further evaluation, whereas patients with a fever but not suspected of infection were sent home and invited to call their general practitioner/primary care practitioner or paediatrician or the regional toll-free number, if their symptoms worsened. Only 1 person accompanying each patient was allowed in the facility and only when absolutely necessary. If overcrowding happened, patients were asked to wait outside the facility until called. Once admitted, patients underwent the scheduled examination during which they were asked to keep their heads turned away from the operator, when possible, to avoid close face-to-face contact. At the end of the visit, patients were invited to wait for the report in T A B L E 1 Summary of evidence-based status of each hypothesis and supposition on the impact of the SARS-CoV-2 pandemic on the population with chronic limb-threatening ischemia and wound care In ambulatory surgical centres in the United States, procedures were similar, except patients were additionally asked health questions and had their temperatures tested at the facility entrance. 25 It was assumed that a proportion of patients were infected asymptomatically. Most operating rooms (ORs) were dedicated to procedures that were not airway-aerosol-producing and could be performed without general anaesthesia. Throughput was increased by performing nerve blocks before patients entered ORs. The phase I postanaesthesia care unit was bypassed whenever possible by appropriate choices of anaesthetic approach and drugs. For cases in which the surgical procedure did not cause aerosol production, but general anaesthesia was used, initial (phase I) postanaesthesia recovery was recommended to occur in the OR where the surgery was done. Anaesthetic practices that achieved fast initial recovery of the brief ambulatory cases were also done. When surgical procedures caused aerosol production (e.g., bronchoscopy), phase I recovery was conducted in the OR, and multimodal environmental decontamination effected after each case.

Finally, anaesthesia and nursing teams staggered cases in more than 1 room, so that they were doing one surgical case while the other room was being cleaned. • Issues with amputations also seem to reflect lack of access to the operating room (OR) to prevent more serious situations from developing (example: sepsis is not being treated as a priority or being treated as a Level 1 access)

• Lack of interoperability (providers cannot easily access patient medical records outside of their healthcare system)

The changes in amputation trends are an important indicator of the impact of the SARS-CoV-2 pandemic on the population with CLTI.

There is considerable Level 3 evidence both for an overall increase in amputations, as well as an increase in the major to minor amputation ratio. For example, a United States study (Ohio) found odds ratios of 10.8 for any amputation compared to prepandemic years 28 ; several other studies noted amputation rates more than doubled or tripled to as high as 60%. 29, 30 Major amputation odds ratios were as high as 12.5, 28 and the major to minor amputation ratio was reported to increase from 0.3 to 0.7. 31 In India, researchers commented that the severity of diabetic foot ulcers (DFUs) ranged from Wagner grade III to grade V, and if patients had come in earlier, more lower extremities could have been salvaged. 32 In the United States, the higher proportions of patients with diabetic foot had more severe cases of infection during the pandemic compared to prepandemic times (15% vs. 10% of patients). 28 In the Netherlands, higher proportions of Rutherford 5 and 6 classifications were presenting among patients with CLTI. 33 Most of these studies took place early on during the pandemic in the spring or early summer of 2020; therefore, we do not know if the situation still holds.

In the Campania region of Italy, among the hardest hit areas in the spring of 2020, the rate of CLTI-related hospitalization decreased from 74 cases/100,000 residents/year to 25 cases/100,000 residents/year, with physicians again reporting higher grades (Fontaine stage IV) during lockdown of 72.4 vs. 57.0 for prepandemic times. 30 There was also a considerable reduction in the rate of urgent revascularization, a finding echoed by researchers reporting from three New

York City hospitals about the same time, with a decrease of 74%. 34 One prospective international cohort study (1103 vascular interventions, 19 countries) indicated a lower limb revascularization mortality of 9.8% and that acute limb ischemia was seen in 18.5% of patient presentations for lower limb, with a documented mortality of 20.4%;

all of these numbers are high compared to prepandemic years. 35 In India, an extremely robust, predictive model using glycemic data from previous disasters (taken as similar in impact to the acute lockdown period) and HbA1c/diabetes-related complications from national databases predicted outcomes for periods of lockdown up to 90 days. 36 Lockdowns of 30 and 45 days, respectively, increased HbA1c by 2.3% and 3.7%, respectively, with an annual predicted percentage increase in lower extremity amputation rates at the end of just a 30-day lockdown of 10.5%.

Several groups reported on strategies adopted during the pandemic. The STRIDE approach used a triage protocol of virtual care, electronic medical record data mining, and tracing for rapid risk stratification to derive optimal care delivery methods. 37 After implementation, 98% of face-to-face visits were due to DFUs, with the overall outpatient rate dropping by 82%, and minor amputation rates dropping by 56% (major amputation rates were not reported The main variable associated with an increased risk of PIs was the total number of days under pronation cycles, and 24 hr was a significant breakpoint.

In regard to prone positioning in a biomechanical study, multilayered silicone foam dressings applied as tissue protectors at the forehead and chin resulted in considerable reductions in soft tissue exposures to effective stresses and strain energy densities, respectively. 46 While proning engendered a three times higher risk of DRPIs The levels of the evidence of the majority of studies investigating PIs were 4 or 5. The evidence confirms that PI incidence increased in 2020 due to proning hospitalized patients with SARS-CoV-2 and due to extensive use of PPE. In a study of dermatology services in the United Kingdom, patient-related factors include patient anxiety surrounding the risk of contracting SARS-CoV-2 when attending general practitioners or hospitals and socioeconomic or age-related barriers to using virtual systems. 55 Patients may have been reluctant to seek help due to restrictions on face-to-face consultations. In primary and secondary care, some healthcare professionals were also absent due to sickness, self-isolation, shielding or redeployment to different departments.

Some dermatology facilities were reallocated to other purposes relating to the pandemic. These factors may all have disproportionately affected minority groups and elderly patients, who are at greatest risk from SARS-CoV-2. An Italian study of CLTI patients also found that patients may be gun-shy in reporting symptoms for fear of SARS-CoV-2 exposure at hospital admission-also confirmed for patients with acute coronary syndromes. 30 Thus, patients' fear is very real.

That said, analysis of patient's responses in another Italian survey demonstrated that, for many patients, fear of the consequences of a DFU were higher than fear of contracting SARS-CoV-2, the more so if the patient had had prior diabetic wounds or an amputation. 58 We can think of this as two competing risks: SARS-CoV-2 and the consequences of not managing wounds; when wounds and/or comorbidities are severe, the sequiturs of not managing the situation outweigh the sequiturs of SARS-CoV-2 infection.

Telemedicine plays a large role in all the different assessment systems that have come into play worldwide, but not without limitations.

For example, in a study of clinical decision support (CDS) assessment for an intrapandemic ambulatory setting, clinically significant CDS malfunctions highlighted the importance of reassessing ambulatory CDS performance after telemedicine expansion. 59 In other words, after introduction of such services, reassessment should be con- Patients are very satisfied with telemedicine, which they perceive as improved care, and it is much more convenient to them as a timesavings alternative to in-person visits and (in many areas) more affordable. They prefer remote care and monitoring due to the major benefit that they do not have to risk exposure to SARS-CoV-2 at a hospital or health centre. Among 3962 patients receiving telemedicine in a large, private academic health network in Santiago, Chile, they reported even greater access to care compared to in-person visits in 2019 (p < 0.001), although access was similar to in-person visits in 2020. 73 In Tuscany, Italy, patients with diabetic foot reported on a scale from 0 to 5 that telephone monitoring was useful (mean 4.35), including for the future (mean 4.34). 58 In Saudi Arabia, only 6.9% of patients with diabetes thought the quality of telemedicine was less than in-person care. 74 Privacy concerns was a major factor in accepting telemedicine in Korea p < 0.001), and data protection must be ensured. 67 The coverage and reimbursement of telemedicine visits by CMS, national health systems in the United Kingdom, France, China, and Chile, and private insurers across the globe has greatly facilitated the increased use of telemedicine. 21, 73, [75] [76] [77] In March 2020, CMS announced that 'telehealth visits' are reimbursed at the same rate as in-person visits to further incentivize provider use. 21 The principal barrier to adopting telemedicine among providers is physician unwillingness. In the American Academy of Facial Plastic and

Reconstructive Surgery survey, 69.2% of providers identified physical examination as the main difficulty to using telemedicine. 63 In wound care, where the physical examination is particularly crucial, providers are concerned that it is very challenging to comprehensively assess the wound using telemedicine if they cannot smell the wound or touch the wound for temperature differences. 21, 60 Assessing the wound for edema, depth, undermining, and tunnelling is also difficult using telemedicine.

Patients who live alone need assistance with photographing wounds in difficult locations, such as the sacrum. 21, 60, 78 It has been suggested that initial wound assessment and complex, ischemia, and/or deteriorating wounds should be seen in-person. However, the evidence supports that assessment via videos and photographs are comparable to in-person assessments and can be used successfully to detect infection and produce good outcomes. 21 A removable offloading device is recommended to be used whenever possible in a patient that is highly compliant, 57 although total contact casts can be applied by wound care specialists during home visits to ensure optimal offloading. 21, 80 F I G U R E 1 A wound care physician provides a remote wound care consultation to a home healthcare nurse. On the computer screen on the right, a digital photograph of the wound was sent by the nurse to the physician to assess. On the computer screen on the left, the nurse, wearing personal protective equipment (a N95 mask) is seen in the patient's bedroom dressing the patient's wound, while the physician guides her through the standard of care process High-risk, unstable wounds, including those with ischemia, moderate-to-severe infection, and increasing wound size and pain (especially in patients with diabetes), should be treated in-person by a wound care specialist. 21, 37, 38, [56] [57] [58] 60, [80] [81] [82] Limb-or life-threatening infection, especially with diabetes, must be attended to as a surgical emergency. Patients with PAD can participate in telemedicine, but should they develop CLTI, they must be referred to a vascular specialist for in-person care. 27, 33 Urgent intervention is required for CLTI;

procedures may be postponed for a short time, in patients with peripheral vascular disease with rest pain or tissue loss. Patient hospitalized for wound infections and/or other complications should be discharged as soon as their wound is stable. 21, 37, 38, [56] [57] [58] 60, [80] [81] [82] Because patients with CLTI and/or diabetes are at greater risk of hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this hybrid model also introduces a new opportunity for wound care to be provided via remote consultation between a wound care specialist and the patient's provider to ensure the continuity of wound care during SARS-CoV-2 infection. 21, 37, 60, 68 Providers also face ongoing risk of SARS-CoV-2 infection, and so, organizing teams of providers that rotate between in-person contact and remote care is recommended. 37 Given the risk providers have to be quarantined at home, the coordination of teams needs to also be fluid.

Those who are quarantined without suspected SARS-CoV-2 could still provide remote care from their homes.

For telemedicine to be successful, it is imperative that all patient data are documented in the electronic medical record (EMR) system. 37, 68, 72, 74, 76 This will be a challenge where EMRs are not used; more increased coordination between all providers and caregivers will be necessary. Protection of patient data must be guaranteed, and before any remote consultation begins, it is necessary to first confirm the patient's identity and obtain patient (or their caregiver's) consent. 37 Thus, the drastic increase in telemedicine is confirmed by Home healthcare visits were also reduced during the pandemic as a result of skilled nursing facilities and assisted and independent living facilities prohibiting all visitors, including providers, to mitigate the risk of SARS-CoV-2 exposure and infection. 84 The lack of access to care in nursing homes is a particular concern for the population with CLTI, with a considerable proportion living in nursing homes. In the Netherlands, among 449 elderly patients with CLTI who underwent surgical/endovascular treatment, 15.1% (n = 68) lived in a nursing home before their procedure. 87 Among 1472 surgical cases, 45.8% were discharged to rehabilitation or a nursing home for the first time. 88 The lack of care available to these patients in nursing homes could cause an increase in amputations and mortality. Primary careled outbreak mitigation was implemented among 1794 residents in 101 assisted living facilities. 89 Practitioners visited once or twice per

week, first undergoing diagnostic testing for SARS-CoV-2 prior to each visit, and employees used a secure, cloud-based smartphone app to self-screen for SARS-CoV-2 symptoms and isolate at home, as necessary. Only 7 residents (0.4%) tested positive for SARS-CoV-2, 1 of whom died, demonstrating that it was safe to continue to offer primary care at assisted living facilities.

There was no evidence in the literature that home healthcare providers went out of business or had their programmes discontinued. 92, 94 In addition, booster shots aimed at increasing immunity to later strains of the virus will almost certainly be necessary. 93 Consequently, many patients with CLTI in many regions of the world will be at higher risk for adverse events for several years, and wound care will still have to operate using pandemic models.

Research trials are another casualty of the pandemic. In general, many sites of existing trials were shut down for long periods, thus delaying their completion and creating outcome issues, while the launch of new trials, including those involving oncology, has been delayed. 95, 96 The United States Food and Drug Administration issued new guidelines for conducting such trials and waivers for certain kinds of events during the pandemic. 97 As far as trials of new devices, drugs, or biologics involving patients with PAD and CLTI, this means their completion will be delayed for up to a year or more depending on where the sites are geographically, prolonging access to potentially limb-saving therapies.

As a group, we set out to answer many questions that we formulated based on our own observations of wound care during the pandemic. In the vast majority of cases, these were confirmed through a review of the literature (Table 1) . However, there were several instances in which this was not true. For example, there is no published evidence in wound care operations that many staff members and providers (facilities) are very concerned that they will become infected by patients. That does not mean a significant percentage of staff members do not have this fear, as it has been common among healthcare workers and home health aides. 84, 98, 99 Likewise, we did not discover what kind of testing was apparent, because SARS-CoV-2 testing at healthcare facilities is widely disparate and country-and facility-dependent. In the case of amputations, we could find no evidence that the increase was due to lack of OR access or lack of priority for those with sepsis, but again absence of evidence is not equal to evidence of absence. This might equally apply to amputation metrics in particular countries or regions, or even cities. Finally, we saw no reports that many home healthcare providers had discontinued programmes or gone out of business, although it was clear that reduced services were common in many areas for a variety of reasons. 84, 86 Among hypotheses and suppositions that were supported by the evidence, the evidence base was generally weak (Levels 4 and 5), with the exception of trends in amputations during the pandemic, which had moderate levels of evidence (Level 3) (Table 1) . This is not surprising, given the short timeframe during which the evidence was quickly published after the pandemic was declared, the waiving of open access fees by journals during the pandemic in a push to make related medical information more accessible to all, and the negative impact of lockdowns on implementing clinical trials. A limitation of undertaking a critical review is that we did not include all the possible evidence published since the onset of the pandemic, so there may be some publication bias in our findings, particularly when considering the speed and volume at which pandemic-related articles have been produced. Any Epublications (ahead of print) indexed on PubMed were considered for inclusion, but we did not search for preprint publications beyond those indexed on PubMed.

One main limitation of this study methodology is that we did not review what we did not originally discuss during the roundtable. A good example of this is the effect of racial disparities, socioeconomic strata, and rural versus urban settings for patients. These fault lines existed long before the pandemic, but they have been highlighted in terms of testing and treatment for SARS-CoV-2 and technological barriers to accessing telemedicine. 60, 65, [67] [68] [69] [70] [71] [72] 100, 101 These factors should be considered, as many patients with CLTI fall into these categories, and they are significantly likely to have worse outcomes (and undergo amputations). 16 There are likely other examples that we must bear in mind as we go forward.

Our search of the literature tells us that there are several tools we can employ to mitigate risks for the global CLTI population while the pandemic is ongoing, including better patient education, telemedicine visits, employment of camera systems to study wounds during those visits, and keeping in contact. Most importantly, we need to better triage our patients so that those at highest risk for severe events can be identified, seen quickly, and a plan of care instituted.

Many patients in wound care can be managed remotely and/or at home, but it must be emphasized that patients whose wounds are increasing in size, ischemic, and/or have moderate-to-severe infection must have in-person care by a wound care specialist. 21, 37, 38, [56] [57] [58] 60, [80] [81] [82] Limb-or life-threatening infection must be emergently drained or debrided no matter what the circulation is, but vascular evaluation begins immediately once sepsis is controlled. Furthermore, a vascular specialist must treat in-person all patients with CLTI. 27, 33 Some patients will be vaccinated this year, but some will not for various reasons, and so a significant proportion of patients with CLTI could still have limited access to care.

If there is a silver lining to the pandemic, it is that we have the potential to permanently take better care of our patients based on what we have learned over the last year. Importantly, during the pandemic, there has been a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in-person visits at clinics and hospitalizations, with the exception of severe cases such as CLTI. Our patients generally prefer remote care, and it is unlikely that they will want to return to traditional ways of accessing care in the postpandemic era. While PPE and SARS-CoV-2 protocols may not be a long-term issue, if herd immunity and efficient global vaccine distribution is eventually achieved, the majority of the recommendations that have emerged during the pandemic will likely continue in practice, such as PI prevention protocols for proned patients. It is likely the hybrid telemedicine model of care will continue to be offered by wound care providers to low-risk patients, with the aim to avoid unnecessary visits while improving communication, contact, and coordination that will translate to better patient/caregiver engagement and, hopefully, outcomes. Having these models in place will make healthcare systems better equipped to manage and adapt to future pandemic threats, as well as any other crises that may risk patient and provider safety and possibly overburden health systems.

The long-term benefits of these new, adaptive models in the postpandemic era will be that they will ensure continuity of wound care when the patient is unable to visit the wound care centre, is hospitalized for another condition, and/or is in a nursing home.

Ultimately, improved wound care could be a viable outcome in the postpandemic future.

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A mortality prediction model for elderly patients with critical limb ischemia

Risk score for nonhome discharge after lower extremity bypass

Home-based primary care led-outbreak mitigation in assisted living facilities in the first 100 days of coronavirus disease 2019

Medical home visit programs during COVID-19 state of emergency

Effectiveness of a nurse-led tele-homecare program for patients with multiple chronic illnesses and a high risk for readmission: a randomized controlled trial

COVID-19 vaccine challenges: what have we learned so far and what remains to be done

Antibody evasion by the P.1 strain of SARS-CoV-2

Uneven power dynamics must be levelled in COVID-19 vaccines access and distribution. Public Health Pract (Oxf)

Trends in oncology clinical trials launched before and during the COVID-19 pandemic

Assessing the impact of COVID-19 on the clinical trial objective and analysis of oncology clinical trials-application of the estimand framework

FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency

Correction to: fear of COVID-19 scale for hospital staff in regional hospitals in Mexico: a brief report

Fighting fear in healthcare workers during the COVID-19 pandemic

Location matters: geographic disparities and impact of coronavirus disease 2019

Black-white risk differentials in COVID-19 (SARS-COV2) transmission, mortality and case fatality in the United States: translational epidemiologic perspective and challenges

The impact of the SARS-CoV-2 pandemic on the management of chronic limb-threatening ischemia and wound care