Effect of antibiotic therapy on the prognosis of ventilator-associated pneumonia caused by Stenotrophomonas maltophilia

Abstract Background Ventilator-associated pneumonia (VAP) caused by Stenotrophomonas maltophilia is poorly described in the literature. However, it has been shown to be associated with increased morbidity and mortality. Probabilistic antibiotic therapy against S. maltophilia is often ineffective as this pathogen is resistant to many antibiotics. There is no consensus at present on the best therapeutic strategy to adopt (class of antibiotics, antibiotic combination, dosage, treatment duration). The aim of this study was to evaluate the effect of antibiotic therapy strategy on the prognosis of patients with VAP caused by S. maltophilia. Results This retrospective study evaluated all consecutive patients who developed VAP caused by S. maltophilia between 2010 and 2018 while hospitalized in the intensive care unit (ICU) of a French university hospital in Reunion Island, in the Indian Ocean region. A total of 130 patients with a median Simplified Acute Physiology Score II of 58 [43–73] had VAP caused by S. maltophilia after a median duration of mechanical ventilation of 12 [5–18] days. Ventilator-associated pneumonia was polymicrobial in 44.6% of cases, and ICU mortality was 50.0%. After multivariate Cox regression analysis, the factors associated with increased ICU mortality were older age (hazard ratio (HR): 1.03; 95% CI 1.01–1.04, p = 0.001) and high Sequential Organ Failure Assessment score on the day of VAP onset (HR: 1.08; 95% CI 1.03–1.14, p = 0.002). Appropriate antibiotic therapy, and in particular trimethoprim–sulfamethoxazole, was associated with decreased ICU mortality (HR: 0.42; 95% CI 0.24–0.74, p = 0.003) and decreased hospital mortality (HR: 0.47; 95% CI 0.28–0.79, p = 0.04). Time to start of appropriate antibiotic therapy, combination therapy, and duration of appropriate antibiotic therapy had no effect on ICU mortality (p > 0.5). Conclusion In our study, appropriate antibiotic therapy, and in particular trimethoprim–sulfamethoxazole, was associated with decreased ICU and hospital mortality in patients with VAP caused by S. maltophilia.

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Staphylococcus Aureus Bacteriuria as a Predictor of In-Hospital Mortality in Patients with Staphylococcus Aureus Bacteremia. Results of a Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm9020508 ◽

2020 ◽

Vol 9 (2) ◽

pp. 508 ◽

Cited By ~ 1

Author(s):

Tobias Siegfried Kramer ◽

Beate Schlosser ◽

Désirée Gruhl ◽

Michael Behnke ◽

Frank Schwab ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Cohort Study ◽

Hospital Mortality ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cox Regression ◽

University Hospital ◽

Hospital Death ◽

Cox Regression Analysis

Staphylococcus aureus bloodstream infection (SA-BSI) is an infection with increasing morbidity and mortality. Concomitant Staphylococcus aureus bacteriuria (SABU) frequently occurs in patients with SA-BSI. It is considered as either a sign of exacerbation of SA-BSI or a primary source in terms of urosepsis. The clinical implications are still under investigation. In this study, we investigated the role of SABU in patients with SA-BSI and its effect on the patients’ mortality. We performed a retrospective cohort study that included all patients in our university hospital (Charité Universitätsmedizin Berlin) between 1 January 2014 and 31 March 2017. We included all patients with positive blood cultures for Staphylococcus aureus who had a urine culture 48 h before or after the first positive blood culture. We identified cases while using the microbiology database and collected additional demographic and clinical parameters, retrospectively, from patient files and charts. We conducted univariate analyses and multivariable Cox regression analysis to evaluate the risk factors for in-hospital mortality. 202 patients met the eligibility criteria. Overall, 55 patients (27.5%) died during their hospital stay. Cox regression showed SABU (OR 2.3), Pitt Bacteremia Score (OR 1.2), as well as moderate to severe liver disease (OR 2.1) to be independent risk factors for in-hospital mortality. Our data indicates that SABU in patients with concurrent SA-BSI is a prognostic marker for in-hospital death. Further studies are needed for evaluating implications for therapeutic optimization.

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Acute Kidney Injury Is Associated With In-hospital Mortality in Older Patients With COVID-19

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa181 ◽

2020 ◽

Cited By ~ 2

Author(s):

Qi Yan ◽

Peiyuan Zuo ◽

Ling Cheng ◽

Yuanyuan Li ◽

Kaixin Song ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hospital Mortality ◽

Older Patients ◽

Cox Regression ◽

Demographic Data ◽

Tertiary Care ◽

Kidney Injury ◽

University Hospital ◽

Cox Regression Analysis ◽

Risk Of Death

Abstract Background The epidemic of COVID-19 presents a special threat to older adults. However, information on kidney damage in older patients with COVID-19 is limited. Acute kidney injury (AKI) is common in hospitalized adults and associated with poor prognosis. We sought to explore the association between AKI and mortality in older patients with COVID-19. Methods We conducted a retrospective, observational cohort study in a large tertiary care university hospital in Wuhan, China. All consecutive inpatients older than 65 years with COVID-19 were enrolled in this cohort. Demographic data, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between patients with AKI and without AKI. The association between AKI and mortality was analyzed. Results Of 1764 in-hospital patients, 882 older adult cases were included in this cohort. The median age was 71 years (interquartile range: 68–77), 440 (49.9%) were men. The most presented comorbidity was cardiovascular diseases (58.2%), followed by diabetes (31.4%). Of 882 older patients, 115 (13%) developed AKI and 128 (14.5%) died. Patients with AKI had higher mortality than those without AKI (68 [59.1%] vs 60 [7.8%]; p < .001). Multivariable Cox regression analysis showed that increasing odds of in-hospital mortality are associated with higher interleukin-6 on admission, myocardial injury, and AKI. Conclusions Acute kidney injury is not an uncommon complication in older patients with COVID-19 but is associated with a high risk of death. Physicians should be aware of the risk of AKI in older patients with COVID-19.

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Impact of Cardiovascular Failure in Intensive CareUnit-Acquired Pneumonia: A Single-Center, Prospective Study

Antibiotics ◽

10.3390/antibiotics10070798 ◽

2021 ◽

Vol 10 (7) ◽

pp. 798

Author(s):

Ignacio Martin-Loeches ◽

Adrian Ceccato ◽

Marco Carbonara ◽

Gianluigi li Bassi ◽

Pierluigi di Natale ◽

...

Keyword(s):

Cox Regression ◽

University Hospital ◽

Single Center ◽

Cox Regression Analysis ◽

Cardiovascular Failure ◽

Icu Length Of Stay ◽

Patients At Risk ◽

Surgical Icus ◽

Pulmonary Superinfection ◽

The Impact

Background: Cardiovascular failure (CVF) may complicate intensive care unit-acquired pneumonia (ICUAP) and radically alters the empirical treatment of this condition. The aim of this study was to determine the impact of CVF on outcome in patients with ICUAP. Methods: A prospective, single-center, observational study was conducted in six medical and surgical ICUs at a University Hospital. CVS was defined as a score of 3 or more on the cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score. At the onset of ICUAP, CVF was reported as absent, transient (if lasting ≤ 3 days) or persistent (>3 days). The primary outcome was 90-day mortality modelled through a Cox regression analysis. Secondary outcomes were 28-day mortality, hospital mortality, ICU length of stay (LOS) and hospital LOS. Results: 358 patients were enrolled: 203 (57%) without CVF, 82 (23%) with transient CVF, and 73 (20%) with persistent CVF. Patients with transient and persistent CVF were more severely ill and presented higher inflammatory response than those without CVF. Despite having similar severity and aetiology, the persistent CVF group more frequently received inadequate initial antibiotic treatment and presented more treatment failures than the transient CVF group. In the persistent CVF group, at day 3, a bacterial superinfection was more frequently detected. The 90-day mortality was significantly higher in the persistent CVF group (62%). The 28-day mortality rates for patients without CVF, with transient and with persistent CVF were 19, 35 and 41% respectively and ICU mortality was 60, 38 and 19% respectively. In the multivariate analysis chronic pulmonary conditions, lack of Pa02/FiO2 improvement at day 3, pulmonary superinfection at day 3 and persistent CVF were independently associated with 90-day mortality in ICUAP patients. Conclusions: Persistent CVF has a significant impact on the outcome of patients with ICUAP. Patients at risk from persistent CVF should be promptly recognized to optimize treatment and outcomes.

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Evaluation of independent predictors of in-hospital mortality in patients with severe trauma

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh190313057m ◽

2019 ◽

Vol 147 (7-8) ◽

pp. 455-460

Author(s):

Marija Milenkovic ◽

Zaneta Terzioski ◽

Adi Hadzibegovic ◽

Jovana Stanisavljevic ◽

Ksenija Petrovic ◽

...

Keyword(s):

Hospital Mortality ◽

Cox Regression ◽

Arterial Oxygen Saturation ◽

Area Under The Curve ◽

Case Fatality ◽

Scoring Systems ◽

Severe Trauma ◽

Arterial Oxygen ◽

Emergency Center ◽

Cox Regression Analysis

Introduction/Objective. The aim of this study was to determine independent predictors and the best trauma scoring system (REMS, RTS, GSC, SOFA, APPACHE II) of in-hospital mortality in patients with severe trauma at the Department of Emergency, Emergency Center, Clinical Center of Serbia, Belgrade. Methods. Longitudinal study included 208 consecutive patients with severe trauma. In order to determine independent survival contributors, univariate and multivariate Cox regression analyses were performed. The power of above-mentioned scoring systems (measured at admission to the Emergency center) to predict mortality was compared using the area under the curve (AUC). Results. There were 208 patients (159 male, 49 female), with the average age of 47.3 ? 20.7 years. Majority of patients were initially intubated (86.1%) on admission to the emergency department, and 59.6% patients were sedated before intubation. After finishing of diagnostic procedures, 17 patients were additionally intubated, and, at that time, 94.2% patients were on mechanic ventilation. The majority of patients was traumatized in a car crash (33.2%), followed by falls from height (26.4%) and as pedestrians (22.6%). Patients had an average of 24.7 ? 21.2 days spent in intensive care unit. The overall case-fatality ratio was 17/208 (8.2%). In Cox regression analysis only elevated heart rate (HR = 1.03, p = 0.012) and decreased arterial oxygen saturation (SpO2) (HR = 0.91, p = 0.033) singled out as independent contributors to in-hospital mortality of patients with severe trauma. REMS (AUC 0.72 ? 0.64) and SOFA (AUC 0.716 ? 0.067) scores were found fair and similar predictor of in-hospital mortality, while APACHE II (AUC 0.614 ? 0.062) and RTS (0.396 ? 0.068) were poor predictors. Conclusion. Results of this study showed an important role of REMS, which appears to provide balance between the predictive ability and the practical application, and components of REMS in prediction of outcome in patients with severe trauma and that HR and SpO2 are independent predictors of in-hospital mortality.

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Prognostic Significance of Chest Imaging by LUS and CT in COVID-19 Inpatients: The ECOVID Multicenter Study

Respiration ◽

10.1159/000518516 ◽

2021 ◽

pp. 1-10

Author(s):

Claudio Tana ◽

Fabrizio Ricci ◽

Maria Gabriella Coppola ◽

Cesare Mantini ◽

Fulvio Lauretani ◽

...

Keyword(s):

Hospital Mortality ◽

Cox Regression ◽

Pearson Correlation ◽

Prognostic Significance ◽

Chest Ct ◽

Lung Damage ◽

Chest Imaging ◽

Gold Standard Method ◽

Cox Regression Analysis ◽

Total Score Range

Background: Point-of-care lung ultrasound (LUS) score is a semiquantitative score of lung damage severity. High-resolution computed tomography (HRCT) is the gold standard method to evaluate the severity of lung involvement from the novel coronavirus disease (COVID-19). Few studies have investigated the clinical significance of LUS and HRCT scores in patients with COVID-19. Therefore, the aim of this study was to evaluate the prognostic yield of LUS and of HRCT in COVID-19 patients. Methods: We carried out a multicenter, retrospective study aimed at evaluating the prognostic yield of LUS and HRCT by exploring the survival curve of COVID-19 inpatients. LUS and chest CT scores were calculated retrospectively by 2 radiologists with >10 years of experience in chest imaging, and the decisions were reached in consensus. LUS score was calculated on the basis of the presence or not of pleural line abnormalities, B-lines, and lung consolidations. The total score (range 0–36) was obtained from the sum of the highest scores obtained in each region. CT score was calculated for each of the 5 lobes considering the anatomical extension according to the percentage parenchymal involvement. The resulting overall global semiquantitative CT score was the sum of each single lobar score and ranged from 0 (no involvement) to 25 (maximum involvement). Results: One hundred fifty-three COVID-19 inpatients (mean age 65 ± 15 years; 65% M), including 23 (15%) in-hospital deaths for any cause over a mean follow-up of 14 days were included. Mean LUS and CT scores were 19 ± 12 and 10 ± 7, respectively. A strong positive linear correlation between LUS and CT scores (Pearson correlation r = 0.754; R2 = 0.568; p < 0.001) was observed. By ROC curve analysis, the optimal cut-point for mortality prediction was 20 for LUS score and 4.5 for chest CT score. According to Kaplan-Meier survival analysis, in-hospital mortality significantly increased among COVID-19 patients presenting with an LUS score ≥20 (log-rank 0.003; HR 9.87, 95% CI: 2.22–43.83) or a chest CT score ≥4.5 (HR 4.34, 95% CI: 0.97–19.41). At multivariate Cox regression analysis, LUS score was the sole independent predictor of in-hospital mortality yielding an adjusted HR of 7.42 (95% CI: 1.59–34.5). Conclusion: LUS score is useful to stratify the risk in COVID-19 patients, predicting those that are at high risk of mortality.

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Prognostic Value of Metabolic Activity of the Psoas Muscle Evaluated By Preoperative 18 F- FDG PET-CT in Breast Cancer: A Retrospective Cross-Sectional Study

10.21203/rs.3.rs-561129/v1 ◽

2021 ◽

Author(s):

Keunyoung Kim ◽

In-Ju Kim ◽

Kyoungjune Pak ◽

Taewoo Kang ◽

Young Mi Seol ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Activity ◽

Cox Regression ◽

Surrogate Marker ◽

Psoas Muscle ◽

University Hospital ◽

Cox Regression Analysis ◽

Standardized Uptake Values ◽

The Mean ◽

Receptor Negativity

Abstract Background: This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer.Methods: The medical records of 288 patients who had undergone surgical resection for stages I–III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the averaged bilateral psoas muscle to the mean SUV of the liver.Results: Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for progression-free survival (PFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter PFS.Conclusions: A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.

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Intra-Abdominal Hypertension is a Risk Factor for Increased VAP Incidence: A Prospective Cohort Study in the ICU of a Tertiary Hospital

Journal of Intensive Care Medicine ◽

10.1177/0885066618779369 ◽

2018 ◽

Vol 35 (7) ◽

pp. 700-707 ◽

Cited By ~ 1

Author(s):

Eleni Papakrivou ◽

Demosthenes Makris ◽

Efstratios Manoulakas ◽

Marios Karvouniaris ◽

Epaminondas Zakynthinos

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Tertiary Hospital ◽

University Hospital ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cox Regression Analysis ◽

Abdominal Hypertension

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period. Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P = .053), while there was an indication for an independent association between VAP and abdominal surgery (1.62 [0.87-3.03]; P = .11] and chronic obstructive pulmonary disease (1.79 [0.96-3.37]; P = .06). Conclusions: Intra-abdominal hypertension is an independent risk factor for increased VAP incidence in critically ill patients who present risk factors for IAH at admission to the ICU.

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Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage

Journal of Clinical Medicine ◽

10.3390/jcm9041236 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1236 ◽

Cited By ~ 2

Author(s):

Michael Bender ◽

Kristin Haferkorn ◽

Michaela Friedrich ◽

Eberhard Uhl ◽

Marco Stein

Keyword(s):

Regression Analysis ◽

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Cox Regression ◽

Spontaneous Intracerebral Hemorrhage ◽

C Reactive Protein ◽

Albumin Ratio ◽

Cox Regression Analysis ◽

Reactive Protein ◽

The Impact

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. Patients and Methods: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients’ demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. Results: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193–2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005–1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden’s Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). Conclusions: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients.

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Effect of Dynamic Potassium Change on In-Hospital Mortality, Ventricular Arrhythmias, and Long-Term Mortality in STEMI

Angiology ◽

10.1177/0003319718784127 ◽

2018 ◽

Vol 70 (1) ◽

pp. 69-77 ◽

Cited By ~ 6

Author(s):

Adnan Kaya ◽

Muhammed Keskin ◽

Mustafa Adem Tatlisu ◽

Osman Kayapinar

Keyword(s):

Regression Analysis ◽

Ventricular Arrhythmia ◽

Hospital Mortality ◽

Mortality Risk ◽

Ventricular Arrhythmias ◽

Cox Regression ◽

Cox Regression Analysis ◽

Normal Ranges ◽

Long Term Mortality

We evaluated the effect of serum potassium (K) deviation on in-hospital and long-term clinical outcomes in patients with ST-segment elevation myocardial infarction who were normokalemic at admission. A total of 2773 patients with an admission serum K level of 3.5 to 4.5 mEq/L were retrospectively analyzed. The patients were categorized into 3 groups according to their K deviation: normokalemia-to-hypokalemia, normokalemia-to-normokalemia, and normokalemia-to-hyperkalemia. In-hospital mortality, long-term mortality, and ventricular arrhythmias rates were compared among the groups. In a hierarchical multivariable regression analysis, the in-hospital mortality risk was higher in normokalemia-to-hypokalemia (odds ratio [OR] 3.03; 95% confidence interval [CI], 1.72-6.82) and normokalemia-to-hyperkalemia groups (OR 2.81; 95% CI, 1.93-4.48) compared with the normokalemia-to-normokalemia group. In a Cox regression analysis, long-term mortality risk was also higher in normokalemia-to-hypokalemia (hazard ratio [HR] 3.78; 95% CI, 2.07-7.17) and normokalemia-to-hyperkalemia groups (HR, 2.97; 95% CI, 2.10-4.19) compared with the normokalemia-to-normokalemia group. Ventricular arrhythmia risk was also higher in normokalemia-to-hypokalemia group (OR 2.98; 95% CI, 1.41-5.75) compared with normokalemia-to-normokalemia group. The current study showed an increased in-hospital ventricular arrhythmia and mortality and long-term mortality rates with the deviation of serum K levels from normal ranges.

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Multifactorial individualised programme for hamstring muscle injury risk reduction in professional football: protocol for a prospective cohort study

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2020-000758 ◽

2020 ◽

Vol 6 (1) ◽

pp. e000758

Author(s):

Johan Lahti ◽

Jurdan Mendiguchia ◽

Juha Ahtiainen ◽

Luis Anula ◽

Tuomas Kononen ◽

...

Keyword(s):

Cohort Study ◽

Risk Reduction ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Injury Risk ◽

Cox Regression ◽

University Hospital ◽

Professional Football ◽

Hamstring Muscle ◽

Cox Regression Analysis

IntroductionHamstring muscle injuries (HMI) continue to plague professional football. Several scientific publications have encouraged a multifactorial approach; however, no multifactorial HMI risk reduction studies have been conducted in professional football. Furthermore, individualisation of HMI management programmes has only been researched in a rehabilitation setting. Therefore, this study aims to determine if a specific multifactorial and individualised programme can reduce HMI occurrence in professional football.Methods and analysisWe conducted a prospective cohort study over two seasons within the Finnish Premier League and compare the amount of HMI sustained during a control season to an intervention season. Injury data and sport exposure were collected during the two seasons (2019–2020), and a multifactorial and individualised HMI risk reduction programme will be implemented during intervention season (2020). After a hamstring screening protocol is completed, individual training will be defined for each player within several categories: lumbo-pelvic control, range of motion, posterior chain strength, sprint mechanical output and an additional non-individualised ‘training for all players’ category. Screening and respective updates to training programmes were conducted three times during the season. The outcome will be to compare if there is a significant effect of the intervention on the HMI occurrence using Cox regression analysis.Ethics and disseminationApproval for the injury and sport exposure data collection was obtained by the Saint-Etienne University Hospital Ethics Committee (request number: IORG0007394; record number IRBN322016/CHUSTE). Approval for the intervention season was obtained from the Central Finland healthcare District (request and record number: U6/2019).

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