key: cord-0820667-gea12cd6 authors: Bernabeu-Wittel, M; Ternero-Vega, J E; Nieto-Martín, M D; Moreno-Gaviño, L; Conde-Guzmán, C; Delgado-Cuesta, J; Rincón-Gómez, M; Díaz-Jiménez, P; Giménez-Miranda, L; Lomas-Cabezas, J M; Muñoz-García, M M; Calzón-Fernández, S; Ollero-Baturone, M title: Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks date: 2020-08-01 journal: J Gerontol A Biol Sci Med Sci DOI: 10.1093/gerona/glaa192 sha: b63694b854acb74e3d133b331b98d4d5bbfab171 doc_id: 820667 cord_uid: gea12cd6 BACKGROUND: Nursing homes are highly vulnerable to the occurrence of COVID-19 outbreaks, which result in high lethality rates. Most of them are not prepared to SARS-CoV-2 pandemic. METHODS: A coordinated on-site medicalization program (MP) in response to a sizeable COVID-19 outbreak in four nursing homes was organized, with the objectives of improving survival, offering humanistic palliative care to residents in their natural environment, and reducing hospital referrals. Ten key processes and interventions were established (provision of informatics infrastructure, medical equipment, and human resources, universal testing, separation of 'clean' and 'contaminated' areas, epidemiological surveys, and unified protocols stratifying for active or palliative care approach, among others). Main outcomes were a composite endpoint of survival or optimal palliative care (SOPC), survival, and referral to hospital. RESULTS: 272 out of 457 (59.5%) residents and 85 out of 320 (26.5%) staff members were affected. The SOPC, survival, and referrals to hospital, occurred in 77%, 72.5%, and 29% of patients diagnosed before MP start, with respect to 97%, 83.7% and 17% of those diagnosed during the program, respectively. The SOPC was independently associated to MP (OR=15 [3-81]); and survival in patients stratified to active approach, to the use of any antiviral treatment (OR=28 [5-160]). All outbreaks were controlled in 39 [37-42] days. CONCLUSIONS: A coordinated on-site medicalization program of nursing homes with COVID-19 outbreaks achieved a higher survival or optimal palliative care rate, and a reduction in referrals to hospital, thus ensuring rigorous but also humanistic and gentle care to residents. The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is beating most countries. Europe, and particularly Spain are one of the most affected areas with accumulated cases and a mortality rates of 504.6 and 61.5 per 100.000 population, respectively in the latter (1, 2) . The disease affects more frequently and more severely aged people; as a matter of fact they make up around 30% of all cases, 45-50% of all hospitalizations, and 80% of all deaths (2) (3) (4) . In these age strata SARS-CoV-2 disease (COVID-19) lethality rate can reach up to 20-40% (3, 4) . There are various reasons to explain an increased mortality rate in this age group. There are already known risk factors (immunosenescence, frailty, infection acting as a trigger to decompensate other chronic conditions, and development of geriatric syndromes' cascade) (5) ; but in the actual pandemic context, there are other evident or subtle reasons, like health-care systems collapse, lack of material and human resources, and disaster situations involving ethical issues, which are contributing to this poor results (6) (7) (8) (9) (10) . Additionally, one of the most critical and helpless environments for the expansion of SARS-CoV-2 are nursing homes (11) . In these facilities, the impact of COVID-19 on human health by affecting the most vulnerable population, and therefore conditioning the subsequent health-care system saturation, is a real danger that can be devastating (11, 12) . Data are scarce, but affected nursing home populations may be a significant proportion of all COVID-19 cases in some countries (11) (12) (13) . Another consequence of this fact is the potential transmission to community, and hence, the persistence of SARS-CoV-2 circulation. As a matter of fact nursing homes are integrated in the community, and their facilities are opened to residents' families, friends and different community resources. Unfortunately, most of them lack structure and work-flows to face an epidemic of this magnitude; many of them are poorly connected with the health-care system, count with lower staff ratio (adjusted to attend A c c e p t e d M a n u s c r i p t 4 'stable' residents); and have suboptimal staff training and expertise in managing patients with COVID-19 (11) (12) (13) . Therefore, many COVID-19 outbreaks affecting nursing home residents, staff members and residents' families have occurred (14) (15) (16) . In the present work we detail an innovative coordinated on-site medicalization program (MP), which was carried out in response to a sizeable COVID-19 outbreak declared in last days of March 2020, in four nursing homes of Seville province (Southern Spain, 1.942.389 inhabitants, 688.592 of them living in the city) with the aim of offering medically rigorous but also humanistic care to residents with COVID-19 in their natural environment, avoiding the community widespread of SARS-CoV-2 thorough specific and forthright measures, and minimizing hospital saturation, helping therefore to achieve a better and proper use of these resources. Specifically we will describe all details of the MP and its achievements in terms of survival or optimal palliation of treated residents, as well as hospital referral reductions. On March 17th, 2020 a 98 year-old patient coming from a nursing home was admitted to Hospital Universitario Virgen del Rocío (tertiary teaching center of Seville with a reference population of 557.576 citizens), and diagnosed with COVID-19. The following days up to 27 new cases coming from this and other 3 similar facilities located in the city of Seville, within the hospital's reference area, were also transferred and diagnosed with the disease. Under these circumstances a Primary Care and Hospital coordinated MP was quickly built. This program contained informatics, medical equipment and material, pharmacy, and human resources to fully attend the outbreaks in the 4 nursing homes on-site. The MP was initiated among 1st and 6th of April, 2020 in all these residential centers. Reference population and inclusion criteria: The total population was 777 people, 457 of them were residents (86 years-old [Quartile1-Quartile3 (Q1-Q3)=79-91], 75% women), and A c c e p t e d M a n u s c r i p t 5 320 were staff-members. A description of the magnitude of the outbreak is detailed in Table 1 . All residents diagnosed with COVID-19 were included in the MP. All staff-members were treated and followed-up with the hospital current management protocols, but were excluded from the present study. MP characterization: The program contained the following critical processes and interventions carried out on-site in all 4 nursing homes: 1. Locating a 'clean room' for informatics equipment, clinical work, consulting and writing in electronic clinical charts, and administrative tasks. Full connection with health-care electronic information systems. 2. Locating a secure locker room for health care workers' dressing and undressing. Ensuring personal protective equipment supplies to all MP team members. Clinical algorithm and treatment protocols: The main clinical algorithm is detailed in Figure 1 . After a thorough clinical evaluation, based on the 6-month adapted 'surprise question' ('would I be surprised if this patient dies in the next six months?'), patients' and families' preferences, and after consulting patient's advance directives for life-support, all residents with COVID-19 were offered either active standard care or advanced palliative care. All patients were daily assessed for early mobilization, sitting and starting physical therapy. Clinical cure was defined after three days of being asymptomatic, and microbiological cure when the patient tested a control negative nasopharyngeal swab PCR after clinical cure. All patients were isolated in the 'contaminated area' for 14 days after being asymptomatic; then, were performed a control nasopharyngeal swab PCR before discharging and transferring them to the 'clean area'. Active standard care: Patients in this group were actively treated with hydroxycloroquine (HCQ) with or without lopinavir/ritonavir (LPV/RTV) (under judgement of clinician in charge) with the addition of adjuvant and antimicrobial treatments in the circumstances detailed in Supplementary Appendix, Table S1 . Daily measurement of vital signs, clinical follow-up until 3 days after being asymptomatic, and at least during the whole antiviral treatment were carried out. Blood sample extraction to assess biological parameters was available. Point of care ultrasonography (POCUS) (Vscan Extend Dual Probe®, GE Healthcare, Little Chalfont, UK) was performed if oxygen saturation fell below 94% or 5 or more points from patient's baseline saturation. Any clinical, biological, or ultrasound data of macrophage activation syndrome-like disease were monitored to implement first-line antiinflammatory treatment. A c c e p t e d M a n u s c r i p t 8 Advanced palliative care: All patients in this group were offered a single room, ensuring comfort, personalized care, and spiritual support. A global multidimensional evaluation was performed with symptomatic focus and medications were daily adjusted. Oxygen therapy and antimicrobials were used when dyspnea/hypoxemia or bacterial co-infection were present, respectively. In some patients corticosteroids were also used, but never before the 5th day of symptoms beginning. Clinicians were proactively aware of end-of-life/agony symptoms and signs occurrence; in this situation, palliative sedation as well as the accompaniment of one family member were offered; the accompanying family member was offered a personal protective equipment with specific instructions on its use. An optimal palliative care was defined when the complete process (offering, acceptance, and materialization of all the above mentioned issues, including the offering of palliative sedation and accompaniment if indicated) was accomplished. Treatment protocols included antiviral treatment, adjuvant treatments, and antimicrobials are detailed in Supplementary Appendix, Table S1 . Mann-Whitney U test in the case of quantitative variables that were not normally distributed. We included the factors which showed statistical differences in unadjusted analysis, in a multivariable backward stepwise logistic regression model in order to obtain those independently associated to SOPC. With respect to survival in patients stratified to receive active standard care we also included the factors which showed statistical differences in unadjusted analysis, in a multivariable Cox proportional hazards model for time to death, in order to obtain those independently associated to survival. In this group of patients we also performed Kaplan-Meier curves (and log-rank test), considering death as a time-dependent variable, to assess differences in survival trajectories of those diagnosed before or during the implementation of the MP. In total 357 people out of 777 (46%) were infected by SARS-CoV-2; of them 272 out of 457 (59.5%) were residents, and 85 out of 320 (26.5%) staff members ( Table 1 ). The median number of days since first resident was diagnosed with COVID-19 until the start of MP were 12 [11] [12] [13] [14] , and the median duration of MP was 39 [37-41] days. The main differential clinical and biological features of all residents affected are detailed in Table 2 . Briefly, they were mostly aged women, suffering of multiple chronic conditions, with functional decline and polypharmacy. The most frequent symptoms were fatigue and global deterioration, followed by low-grade fever, dyspnea, cough, anorexia, diarrhea and delirium. Sixty-six residents (24%) developed no symptoms, or these were mild. All staff-members developed mild to moderate symptoms or stayed asymptomatic. Residents affected were diagnosed with a positive nasopharyngeal swab PCR test Table S1 ), antiviral treatment was administered to 139 (73.5%) patients; the most frequent scheme was hydroxycholoroquine (114 patients, 60%) followed by hydroxychloroquine plus lopinavir/ritonavir (18, 10%), and hydroxychloroquine plus azythromycin (7, 5%). Low molecular weight heparin was administered to 119 patients (44%), antimicrobials to 62 (23%), and systemic corticosteroids to 57 (21%). All patients proposed for advanced palliative care were treated with supportive care. Additionally they were treated with low molecular weight heparin (36, 43%), antimicrobials (33, 39.8%), antiviral drugs (30, 36%), and corticosteroids (21, 25%). The most frequent complications and main outcomes are detailed in Table 3 . A 13% (n=24) and a 45% (n=37) of patients proposed for active standard-or for optimal palliative care died, respectively. In multivariate analysis the main outcome SOPC was independently In the epidemiologic survey it was stated, that in all nursing homes, the symptoms onset dates of the first affected staff members preceded in 5.5 (Q1-Q3=2-9.7) days to those symptoms onset dates of the first affected residents (Supplementary Appendix, Figure S1 ). The incorporation of a coordinated MP in the management and control of four sizeable COVID-19 outbreaks in nursing homes, resulted in significant better outcomes of the composite end point of survival or optimal palliative care, as well as reductions in hospital referral rates. This MP virtuously gathered substantial hospital and primary care resources as well as internal medicine, primary care, and epidemiology professionals during an intense but short time-period. Specifically the reduction of COVID-19 mortality during MP to nearly 16% was notably lower if compared to other reported outbreaks in long-term care facilities (27-33%) (11, 14, 15) ; and also when compared to rates of in-patients of our hospital (54% in those over 80 years, data not published) or to patients of same ages in Spain (globally 22%, and 48.5% in those needing hospital care) (2) . The MP also achieved as additional benefits, the development of fewer medical complications, and a more comfortable and peaceful care process in those with a previous poor life expectancy. We think, that the clues to explain benefits of the MP are three: First of all, it enabled an earlier symptoms recognition by well-trained professionals, which led to earlier treatments and support measures; this is an evident fact common to all diseases; in this sense, our data show, that stratifying and treating very old patients with potentially acceptable life expectancy, is safe and of probable benefit; otherwise we could fall in a somehow nihilist deviation of clinical practice (19, 20, 21) . Second, it allowed the on-site care in the natural environment of patients, which led to fewer complications, mainly due to less geriatric syndromes occurrence; early mobilization, rehabilitation, and use of common spaces and rooms in the contaminated area for the continuity of activities, prevented the highly frequent complications of hospital care; as a matter of fact rooms of hospital wards dedicated to COVID-19 are isolated, and interactions with patients generally restricted to the strictly A c c e p t e d M a n u s c r i p t 15 necessary (19) . Third, it incorporated humanistic and gentle attention to the most frail and terminally ill residents, enabling a personalized care according to preferences of patients and families; the rush of a pandemic situation should not make palliative care invisible, on the contrary an exquisite stratification and subsequent optimal palliative care has to be offered to this selected population in order to avoid futility and unnecessary iatrogenia (20, 21) ; in this sense it is important to remark, that optimal palliative care does not mean death; as a matter of fact 55% of patients stratified to optimal palliative care survived COVID-19. Epidemiological surveys, showed that SARS-CoV-2 could have entered nursing homes either by staff members or by visitors in preceding days to the declaration of national alarm state by the Government of Spain on March 14th, 2020 (22). Then, the virus spread fast, probably because of the same reasons as those already detailed in similar outbreaks (14, 15, 23) . The city epidemic curve ran parallel but preceded a few days those observed in the nursing homes outbreaks, which supports the previously commented hypothesis. No impact of the delayed incidental case peak of nursing homes outbreaks was observed in the global epidemic curve of the city; nevertheless we can extract no definitive conclusions because this could reflect the absence of transmission from nursing homes to community due to the MP, the effects of national lockdown measures, or both. One of the leading results of this study is the complete clinical picture of COVID-19, that we obtained in a large sample of frail elderly people. We observed the typical patterns of COVID-19 less frequently, whereas more subtle and unspecific symptoms and presentations were more prevalent. This has also been observed by other authors and follows the pattern of getting sick in geriatric populations, which is well known with respect to other diseases (24, 25) . Of notable remark is the absence of prognostic influence of any comorbidities taken them individually; only their combination in the PROFUND index showed prognostic ability. In contrast, some COVID-19 symptoms and biological parameters like dyspnea, fatigue and A c c e p t e d M a n u s c r i p t 16 general deterioration, C-reactive protein and ferritin levels, showed a strong independent association with death. The presence of any of these symptoms in old patients with COVID-19, has to put us on alert. Another remarkable finding was the strong independent association of antiviral treatments with survival. This fact is both concordant as well as contradictory to previous reports and puts in the front line the urgent needs of counting with evidence to optimally treat COVID-19 patients (26) (27) (28) (29) (30) (31) . In the absence of this evidence, we are of the opinion, that best available choices (those safest drugs with best previous results) should be offered to patients. In this sense we opted to use hydroxychloroquine with or without lopinavir/ritonavir, because of their extensive use in many protocols (29, 30) . The MP was a huge effort on many levels, but the effectiveness shown proved this effort to be worth it. Many voices and societies have emphasized, that nursing homes and other long term care facilities are the most vulnerable environments to the effects of SARS-CoV-2 pandemic (11), urging all actors (community leaders, governments, health and social care authorities) to prioritize them in their strategies (32) (33) (34) . In some countries like Spain, this fact is even more critical due to its high life expectancy and the significant number of elderly citizens living in these facilities (35). But beyond statements and guidelines, reality also needs pragmatic actions and interventions, because these extraordinary times need our help with unprecedented solutions (36). The main lessons we have learned after the MP task are also three: First of all we learned, that nursing homes are key elements and one of the main targets in the fight against possible future SARS-CoV-2 pandemic waves; many have considered them in the border of health care and social services, and because of that their connections and boundaries to both systems are somehow imprecise, as many countries have painfully witnessed; it is time to globally rethink the role and place of nursing homes in our societies, and to really work in a A c c e p t e d M a n u s c r i p t 17 deeper integration of health and social care (11, 23, 33) . Second, we learned, that health care resources re-allocation is an effective strategy to manage this pandemic, and that decisive and anticipated actions save lives and prevent unfortunate consequences; one may think, that this mobilization was exaggerated and expensive, but otherwise at least two hundred of these residents would have needed hospital care, so in this scenario the same health care resources would have been used, but in a overcrowded and saturated hospital. And at last we learned, that a true synergistic coordination between Primary and Hospital Care is possible and it works. We all have read a lot about this issue, and know, however, the daily difficulties in its implementation (37). In these extraordinary circumstances integration worked wonderfully, because it emerged from professionalism values: willingness to serve people, altruism, generosity, and mutual respect. This study has some limitations, that should be remarked. First, the retrospective collection of the cohort's data, which could introduce some biases, as it is already known for this kind of approaches. Second, the confidence intervals for some of the findings are wide, reflecting limits in study power for some analyses. And third, the possible regression to the mean, which is present in most health care initiatives directed towards high-risk populations, could have played a role in the results; however, we think that this effect is not at all present in the obtained data, because when MP started, obviously all patients (included those who were diagnosed previously) were attended; so, these last patients also received the benefits of the program, but were treated in the analysis of end-points as if they had not. In conclusion our work show, that a coordinated on-site medicalization program of nursing homes with COVID-19 outbreaks achieved better outcomes of survival and optimal palliative care, as well as a reduction in referrals to hospital, thus ensuring rigorous but also humanistic and gentle care to residents. M a n u s c r i p t 29 TABLE TITLES AND FIGURE CAPTIONS Table 1 . Global data of the four nursing homes' COVID-19 outbreaks in the city of Seville, Spain. Table 3 . Unadjusted differential complications and outcomes of affected residents during the medicalization program of four nursing homes with COVID-19 outbreaks in Seville, Spain. European Centre for Disease Control and Prevention. 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The PROFUND index Functional evaluation: The Barthel Index Assessment and Treatment of Older Individuals With COVID 19 Multi-System Disease: Clinical and Ethical Implications COVID-19 pandemic: palliative care for elderly and frail patients at home and in residential and nursing homes For The Covid-Task Force Of Palliative Ch COVID-19: decision making and palliative care declaring the state of alarm for the management of the health crisis situation caused by COVID-19 Covid-19: the precarious position of Spain's nursing homes Atypical Presentation of COVID-19 in a Frail Older Person Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly Epub ahead of print Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019 A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19 Compounds with Therapeutic Potential against Novel Respiratory Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 COVID-19 diagnosis and management: a comprehensive review American Geriatrics Society Policy Brief: COVID-19 and Nursing Homes Susana Padrones (Manager and Medical Director of Primary Care District of Seville) SD= standard deviation; Q1-Q3=quartile1-quartile3; Nº= number; %=percentage MP=medicalization program; OR=odds ratio; CI= confidence interval * Composite end -point of survival or optimal end-of-life care Our support and affection to all residents, their families and the nursing homes' staff members for their collaboration, patience and resilience. Special thanks to all members of Primary Care and Hospital COVID teams listed below, and health managers who have worked so hard to heal and alleviate patients and their families. A c c e p t e d M a n u s c r i p t 18 A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 26 A c c e p t e d M a n u s c r i p t 28