REVIEW | doi:10.20944/preprints202009.0067.v1
Online: 3 September 2020 (09:29:32 CEST)
Background: The reported associations between time to first antibiotic dose after hospital arrival and short-term mortality have varied in prior studies of CAP. It is unclear the benefit of early antibiotics in all patients given the risks of antibiotic overuse and misdiagnosis; Methods: A PubMed and Google Scholar search was performed to identify articles detailing the epidemiology, prognosis, diagnosis, and preliminary management of CAP; Results: In sepsis, antibiotics should not be delayed, and should be administered as soon as possible after recognition. For moderate or severe CAP patients without sepsis, antibiotics should be administered as soon as the diagnosis of CAP is highly likely. For stable, non–critically ill patients with CAP, the timing of antibiotics is not as clear and available evidence does not recommend strict requirements. Antibiotic timing – both rapid and delayed could be used as indicators of quality care in differing clinical scenarios; Results: The dogma of starting antibiotics quickly, within a rigid timeframe of expectations and guidelines has not improved outcomes in pneumonia patients, and has led to an increase in antibiotic treatment in uninfected patients. Severity of illness is the key factor associated with poor outcomes and should more significantly guide the timing of antibiotic initiation.
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Treatment outcome; Data Collection; Pharmaceutical Preparations; Outcome Assessment; Health Care
Online: 4 September 2020 (10:12:02 CEST)
Human infection caused by the SARS-CoV-2 virus, called COVID-19, is a new pandemic with devastating effects worldwide. Science seeks the rational and systematic explanation of phenomena. In pandemics, decisions on prevention and treatment of people should be consistently taken, supported by scientific knowledge and ethical principles to produce more good than harm. At first, prospective observational studies to systematically collect patient data, correlating protective or therapeutic interventions with outcomes to assess effectiveness and safety, should be prioritized as the most appropriate type of study. The proposed protocol in this article aims to provide doctors with information on the reduction of harm in early COVID-19 patients by applying individualized interventionist or expectant therapeutic strategies, respecting the autonomy and preferences of physicians and patients in clinical decision-making. The evaluation of the clinical status, besides laboratory confirmation of COVID-19, comprises an individualized symptom score for each patient, a global self-perception scale of the severity of the disease, a clinical progression scale developed by the WHO for clinical studies in COVID-19 and, at the first consultation, doctors´ overall impression on the clinical prognosis. The analysis of anonymized data should preferably use descriptive and inferential statistical resources. The case report form is available for free use in the protocol, along with examples of patient informed consent forms for the prescription of off-label medications and authorization to use the data. Their results may be useful to indicate interventions that are candidates for efficacy trials, in randomized controlled trials, with a higher chance of success. It respects the autonomy and preferences of doctors and patients to decide the best options for treatment in uncertain situations. It also allows the gathering of useful information for future more rigorous clinical trials, trying to link science, ethics, and personal clinical experience.
ARTICLE | doi:10.20944/preprints202004.0092.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Acute coronary syndrome; inflammation; neutrophil; outcome
Online: 7 April 2020 (11:18:03 CEST)
Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.
ARTICLE | doi:10.20944/preprints201608.0087.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: natriuretic peptides; heart failure; congestion; outcome
Online: 9 August 2016 (11:33:03 CEST)
Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.
ARTICLE | doi:10.20944/preprints202107.0680.v1
Subject: Medicine & Pharmacology, Allergology Keywords: NEC; Surgical; Medical; Risk factor; Outcome; Neonate
Online: 30 July 2021 (09:11:09 CEST)
Background: Necrotizing enterocolitis (NEC) is one of the leading causes of death in newborns, however, little is understood of which patients can be treated medically or require surgery. The purpose of our study is to analyze the associated factors of surgically treated patients compared to patients requiring only medical treatment. Methods: Patients diagnosed with necrotizing enterocolitis over a period of 14 years in a single children’s hospital were retrospectively enrolled. Demographics and clinical data patients were collected and analyzed. Results: A total of 189 patients with NEC were included. Surgically treated patients had a lower gestational age (P = .018), body weight at birth (P = .034), and percentage of exclusive breast milk feeding (P= .001). They had increased comorbidity with respiratory distress syndrome (RDS) (P = .005), number of days of antibiotic use (P = .014), and length of hospital stay (P = .000). In multivariate logistic analysis, a lower percentage of exclusive breast milk feeding (OR = 0.366, 95% CI: 0.164-0.817) and a longer hospital stay (OR = 1.010, 95% CI: 1.001- 1.019) was associated with surgical NEC. Conclusion: Comparing medical and surgical NEC, a significantly lower percentage of surgical NEC patients were exclusively fed breast milk and their hospital stays were longer.
ARTICLE | doi:10.20944/preprints202011.0717.v1
Subject: Medicine & Pharmacology, Allergology Keywords: OYST; molecular characteristics; targetable mutation; patients’ outcome
Online: 30 November 2020 (11:06:47 CET)
Most malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and can be cured by chemotherapy, with yolk sac tumors (OYSTs) having the worse prognosis among MOGCTs. These tumors are rare and can benefit in the next future from specific therapeutic strategies after failure of platinum-based first-line and salvage regimens. In collaboration with EORTC SPECTA, we have developed a project to explore the molecular characteristics of OYST. The pilot part of the project was performed using retrospective samples and ten OYST patients including relapsed and disease free patients. The molecular analysis was performed using FoundationOne CDx. For each patient, the following variables are described in the molecular report provided by FMI (Fondation Medicine Incorporation): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (patient's tumor type and other tumor types), tumor mutational burden (TMB) and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 were analyzed. Four patients (40%) had a molecular alteration, according to the FMI test. A subset of three patients (33.3% of all patient) harbored targetable (KRAS, KIT, ARID1A) oncogenic mutations. Two patients at relapse harbored a targetable mutation. In this retrospective study, we were able to identify clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate if they could benefit from specific therapeutic strategies after failure of platinum-based first-line and salvage regimens and if the presence of a molecular alteration could be linked to patients’ outcome.
ARTICLE | doi:10.20944/preprints202010.0021.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Pioglitazone; DPP4-inhibitor; ESRD; Cardiovascular outcome; Mortality
Online: 1 October 2020 (15:41:50 CEST)
While pioglitazone reduces insulin resistance and hepatic gluconeogenesis effectively in patients with T2DM, these benefits remained controversial in patients with ESRD. We compared MACCEs and mortality (overall, infection-related, and MACCE-related) of pioglitazone to that of DPP4-inhibitors in patients with T2DM and ESRD. From Taiwan’s national health insurance database, 647 pioglitazone users and 6080 DPP4-inhibitors users between April 1st, 2006 and December 31th, 2016 were followed from the 91th date after the ESRD certification till study outcomes, independently; withdraw from the NHI program, death, or Dec. 31th, 2017. After weighting, risks of MACCEs (10.48% vs 12.62% per person-years, [HR]: 0.85, 95% [CI]: 0.729–0.985) and all-cause mortality (12.86% vs 13.22% per person-years, [HR]: 0.88, 95% [CI]: 0.771–0.995) are significantly lower in pioglitazone group. Subgroup analysis found lower MACCEs risk in the pioglitazone users without insulin therapy (6.44% vs 10.04% [HR]: 0.59, 95% [CI]: 0.42–0.82) and lower MACCEs related death (2.76% vs 3.84% [HR]: 0.61, 95% [CI]: 0.40–0.95) in the pioglitazone group with dyslipidemia, when comparing with DPP4-inhibitors users. Pioglitazone is associated with lower all-cause mortality and MACCEs in diabetic patients with ESRD, compared to DPP4-inhibitors. These benefits were further significant in the non-insulin users and patients with dyslipidemia.
ARTICLE | doi:10.20944/preprints202006.0261.v1
Subject: Life Sciences, Molecular Biology Keywords: adverse outcome pathway; toxicity pathway; computational toxicology
Online: 21 June 2020 (11:10:34 CEST)
Background: Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked. Objectives: To identify molecular mechanisms sensitive to chemical exposures in an unbiased manner. Methods: We used data on 641,516 unique chemical-gene interactions from the Comparative Toxicogenomic Database. Only data from high-throughput gene expression experiments with human, rat or mouse cells/tissues were extracted. The total number of chemical-gene interactions was calculated for every gene, and used as a measure of gene sensitivity to chemical exposures. These values were further used in enrichment analyses to identify molecular mechanisms sensitive to chemical exposures. Results: Remarkably, use of different input subsets with non-overlapping lists of chemical compounds identified largely the same genes and molecular pathways as most sensitive to chemical exposures, indicative of an unbiased nature of our analysis. One of the most important findings of this study is that almost every known molecular mechanism may be affected by chemical exposures. Predictably, xenobiotic metabolism pathways and mechanisms of cellular response to stress and damage were among the most sensitive. Additionally, our analysis identified a range of highly sensitive molecular pathways, which are not widely recognized by modern toxicology as major targets of toxicants, including lipid metabolism pathways, longevity regulation cascade and cytokine mediated signaling. Discussion: Molecular mechanisms identified as the most sensitive to chemical exposures are relevant for significant public health problems, such as aging, cancer, metabolic and autoimmune disease. Thus, public health system will likely benefit from future research focus on these sensitive molecular mechanisms. Additionally, approach used in this study may guide identification of priority adverse outcome pathways (AOP) for in-vitro and in-silico toxicity testing methods.
ARTICLE | doi:10.20944/preprints202107.0057.v1
Subject: Engineering, Automotive Engineering Keywords: cross-curricular learning outcome; ethical responsibility; environmental responsibility
Online: 2 July 2021 (14:13:00 CEST)
This paper presents a study on the development of the cross-curricular learning outcome (CCLO) "Ethical, environmental and professional responsibility" by the students of different Bache-lor’sDegrees taught at Universitat Politècnica de València. The work and development of this learning outcome entails great complexity, given the double dimension of responsibility that it involves. At the end of their training at the university, students are expected to show ethical, en-vironmental, and professional responsibility towards themselves and others. Interviews have been conducted with lecturers who work and assess this outcome in their subjects, most/all of them related to science and engineering. The objective was to identify the learning approach used at the different subjects to guarantee the acquisition of this CCLO by the students. A focus group has also been carried out with students to determine the importance they give to this learning outcome, and to know their degree of satisfaction with the training received. The methodology used to obtain the data from lecturers and students and to process the information to get a precise diagnosis is fully described in the paper. Results are satisfactory to some extent: most of the lecturers carry out appropriate activities and most of students achieve the expected proficiency level. Finally, recommendations are given to improve the development of this cross-curricular learning outcome.
Subject: Medicine & Pharmacology, Allergology Keywords: femur fracture; orthopedic; trauma; management and outcome; Qatar
Online: 15 April 2021 (12:11:23 CEST)
Background: We aimed to describe the patterns, management, and outcome of traumatic femoral shaft fractures. Methods: An observational descriptive retrospective study was conducted for all trauma patients admitted with femoral shaft fractures between January 2012 and December 2015 at the only level 1 trauma center and tertiary hospital in the country. Data were analyzed and compared according to the time to intramedullary nailing, mechanisms of injury and age groups. Main outcomes included in-hospital complications and mortality Results: A total of 605 cases were analyzed, with mean age of 30.7±16.2 years. The majority of fractures were unilateral (96.7%) and 91% were closed fractures. Three-fourth of fractures were treated by reamed intramedullary nailing (rIMN); antegrade in 80%. The pyriform fossa nails were used in 71.6% while trochanteric entry nails were used in 28.4%. Forty-five (8.9%) of fractures were treated with external fixator, 37 (6.1%) had conservative management. Traffic-related injuries occurred more in patients aged 14-30 years whereas; injuries related to fall were significantly higher in patients aged 31-59 years. Thirty-one patients (7.8%) had rIMN < 6 h post-injury, 106 (25.5%) had rIMN < 6-12 h and 267 (66.8%) had rIMN > 12 h. The implant type, duration of surgery, DVT prophylaxis, in-hospital complications and mortality were comparable among the three treatment groups. Conclusion: In our center, the frequency of femoral fracture is 11% which mainly affects severely injured young males due to traffic-related collisions or falls. Further multicenter studies are needed to reach a consensus for the appropriate management based on the location and timing of injury
COMMUNICATION | doi:10.20944/preprints202005.0253.v1
Subject: Life Sciences, Genetics Keywords: Cas9; Cas12a; Cpf1; zebrafish; gene knockout; repair outcome
Online: 15 May 2020 (10:16:55 CEST)
CRISPR/Cas genome editing is a widely used research technology. Its simplest variant is gene knockout resulting from reparation errors after introduction of dsDNA breaks by Cas nuclease. We compared the outcomes of the break repair by two commonly used nucleases (SpCas9 and LbCas12a) in zebrafish embryos to reveal if application of one nuclease is advantageous in comparison to the other. To address this question, we injected ribonucleoprotein complexes of nucleases and corresponding guide RNAs in zebrafish zygotes and three days later sequenced the target gene regions. We found that LbCas12a breaks resulted in longer deletions and more rare inserts, in comparison to those generated by SpCas9, while the editing efficiencies of both nucleases were the same. On the other hand, overlapping protospacers were shown to lead to similarities in repair outcome, although they were cut by two different nucleases. Thus, our results indicate that the repair outcome depends both on the nuclease mode of action and on protospacer sequence.
COMMUNICATION | doi:10.20944/preprints202101.0065.v1
Subject: Life Sciences, Biochemistry Keywords: COVID-19; Angiotensin Converting Enzyme 2 (ACE2); Adverse outcome pathway(AOP); Molecular initiation Event (MIE); Key event (KE); Adverse Outcome (AO)
Online: 4 January 2021 (16:37:08 CET)
Increasing global concern over COVID-19 has recently brought greater attention to studies due to the ease of person-to-person transmission and the current lack of effective antiviral therapy. Here, we proposed the application of the adverse outcome pathway (AOP) framework to support re-search on the pathogenesis of viral disease. We first constructed adverse outcome pathways (AOPs) applicable to COVID-19 management to understand whether the infection causes severe acute respiratory distress. Based on the AOP framework where mechanistic elucidation of the pathway from the interaction of chemicals (or viruses) to apical endpoints is represented, our COVID-19 AOP indicated that the molecular initiating event (MIE) was angiotensin-converting enzyme 2 (ACE2) interaction, and the key events (KEs) were the increased pro-inflammatory cytokines in immune cells, with increased mortality as an apical adverse outcome (AO). However, there is still limited information on the toxicity mechanisms of AOPs in COVID-19; therefore, detailed KEs and AOs on toxicity mechanisms will be required to fill these gaps in the data. This study demonstrated that the COVID-19 AOP framework is a suitable tool to design new drugs and to integrate crowded-sourced information for the battle against the COVID-19 pandemic.
REVIEW | doi:10.20944/preprints202208.0316.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: ANCA-associated vasculitis; Proteinase 3; Myeloperoxidase; Clinical Phenotype; Outcome
Online: 17 August 2022 (09:58:51 CEST)
The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.
ARTICLE | doi:10.20944/preprints202108.0223.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: nephroblastoma; clinical malformations; cancer predisposition syndromes; tumor surveillance; outcome
Online: 10 August 2021 (09:55:14 CEST)
Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.
ARTICLE | doi:10.20944/preprints202105.0167.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Heart arrest; optic nerve sheath diameter; Patient outcome assessment
Online: 10 May 2021 (10:51:42 CEST)
Optic nerve sheath diameter (ONSD) can help predict the neurologic outcome of patients with post-cardiac arrest (CA) return of spontaneous circulation (ROSC). We aimed to investigate the effect of ONSD changes before and after CA on neurologic outcomes in patients with ROSC after CA using brain computed tomography (CT). The study included patients hospitalized after CA, who had undergone pre- and post-CA brain CT from January 2001 to September 2020. The patients were divided into good and poor neurologic outcome (GNO and PNO, respectively) groups based on the neurologic outcome at hospital discharge. We performed between-group comparisons of the amount and rate of ONSD changes on brain CT and calculated the area under the curve (AUC) to determine their predictive value for neurologic outcomes. Among the 96 enrolled patients, 25 had GNO. Compared to the GNO group, the PNO group showed significantly higher amount (0.30 vs. 0.63 mm; p=0.030) and rate of change (5.26 vs. 12.29 %; p=0.041). The AUC for predicting PNO was 0.64 (95% CI=0.53–0.73; p=0.04) and patients with a rate of ONSD change >27.2% had PNO with 100% specificity and positive predictive value. Hence, ONSD changes may predict neurologic outcomes in patients with post-CA ROSC.
COMMUNICATION | doi:10.20944/preprints202101.0573.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Adverse Outcome Pathways; COVID-19; mechanisms; systematic organization; interdisciplinary
Online: 27 January 2021 (17:01:44 CET)
Adverse Outcome Pathways (AOP) provide structured frameworks for systematic organization of research data and knowledge. The AOP framework follows a set of key principles that allow for broad application across diverse disciplines related to human health, including toxicology, pharmacology, virology and medical research. The COVID-19 pandemic engages a great number of scientists world-wide and data is increasing with exponential speed. Diligent data management strategies are employed but approaches for systematically organizing the data-derived information and knowledge are lacking. We believe AOPs can play an important role in improving interpretation and efficient application of scientific understanding of COVID-19. Here, we outline a newly initiated effort to streamline collaboration between scientists across the world towards development of AOPs for COVID-19, and describe the overarching aims of the effort, as well as the expected outcomes and research support that they will provide.
REVIEW | doi:10.20944/preprints202005.0392.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: RAAS inhibitors; COVID-19; coronavirus; angiotensin; clinical outcome; antihypertensive
Online: 24 May 2020 (17:48:42 CEST)
Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-May 5, 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). A total of 6,997 hypertensive patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.
ARTICLE | doi:10.20944/preprints202005.0269.v1
Online: 16 May 2020 (16:41:27 CEST)
The prevalence and case fatality rates of Pediatric Lassa fever disease (LFD) are not well documented. This study was aimed at determining the prevalence, pattern and outcome of Pediatric LFD. It was a prospective observational study. A total of 183 subjects that met the criteria for LFD suspects were recruited consecutively and subjected to Lassa virus PCR test. Structured questionnaire was used to collect information. Of the 183 children recruited, 24 tested positive to Lassa virus PCR, giving a positivity rate of 13.1%. Mean duration of illness at presentation was 8.54 ± 3.83 days. Fever, abdominal pain and vomiting were the three highest presenting complaints. Seven out of 24 children died giving a case fatality rate (CFR) of 29.2%. Subjects with bleeding, poor urine output, convulsions and unconsciousness were more likely to die of LFD. Positivity and CFR of LFD are high. Improved case finding and prompt treatment is advocated.
CASE REPORT | doi:10.20944/preprints201909.0081.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: mercury; prenatal exposure; postnatal outcome; environmental health; epidemiological monitoring
Online: 7 September 2019 (01:06:51 CEST)
Background: It is well known the adverse effect of mercury exposure on pregnant women and newborns. Interactions between environmental factors and individual genetic susceptibility have been identified, particularly polymorphisms of codifying genes for the Glutathione S-transferase family (GSTs). Herein, we report a case series of patients with high Hg levels in biosamples. Case Series: Fourteen cases with high Hg levels were identified. Non-occupational or home exposure risk factors were identified. All mothers reported fish consumption during pregnancy. Almost 60% of the individuals were null for either one GSTs gene. To date, in the subsequent mother-child pairs toxicology controls no signs or symptoms of poisoning were identified and most of the mercury levels decreased and are below the accepted limit. Discussion: In this case series we found some similarities with the literature; among them, the relation of Hg ratio in maternal blood and umbilical cord, a possible exposure factor is the consumption of fish during pregnancy and, the high levels of Hg may be related with susceptibility biomarkers such as GSTs gene polymorphisms. This case series highlights the need to develop studies that evaluate the interactions between environmental factors and individual genetic susceptibility. Additionally, the importance of evaluating which Colombian fish species present the highest levels of Hg.
ARTICLE | doi:10.20944/preprints201904.0089.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: Fook intake; pizza; pasta; vegetables; pregnancy; adverse perinatal outcome
Online: 8 April 2019 (11:35:16 CEST)
Growing body of evidence endorse the hypothesis of a protective role played by the in-utero environment on a suitable fetal programming, mainly sustained by fitting maternal diet. Our purpose was to assess the linkage between maternal food intake and poor obstetric results, with a special focus on typical Italian food. A cross sectional study including delivering women was designed. A self-reported questionnaire about socio-demographic data, obstetric history, and food frequency intake during pregnancy was administrated. A composite of adverse perinatal outcomes (APO) was constructed. Statistically significant differences were found between APO and control group in smoking habit (9.7 vs. 3.2%, p=0.045) and BMI at delivery (27.9±4.9 vs. 26.9±3.9, p=0.003). Women complicated by any or more APOs reported increased rates of pasta (5.3± 3.6 vs.4.4±1.9 times per week, p<0.001) and pizza (1.9±3.4 vs. 1.1±0.6, p<0.001) intake, with lower consumption of vegetables (5.4±3.9 vs. 7.1±2.9, p<0.001). By logistic regression analysis and after adjustments for maternal age, ethnicity, SES, maternal BMI at delivery, excessive ingestion of pizza (aOR 1.676, 95%CI 1.199-2.343, p=0.033), but not pasta (aOR 1.077, 95%CI 0.950-1.211, p=0.244), was found associated with APO. Vegetable consumption showed a protective role in reducing APOs (aOR 0.897, 95%CI 0.818-0.985, p=0.022). Nutrition in pregnancy should minimalize pizza intakes.
ARTICLE | doi:10.20944/preprints202109.0108.v1
Subject: Medicine & Pharmacology, Urology Keywords: Acute Cystitis Symptom Score; cystitis; patient-reported outcome; questionnaire; women
Online: 6 September 2021 (17:02:05 CEST)
The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) was the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed after ethical approval by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different time points after the start of treatment was demonstrated as well. The age (mean±SD) of the 53 patients (44.7±17.0) and 39 controls (49.3±15.9) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p<0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patient’s self-diagnosis of AC and as a PRO measure tool.
ARTICLE | doi:10.20944/preprints202007.0491.v1
Subject: Behavioral Sciences, Clinical Psychology Keywords: FoMO; Social Cognitive Theory; Social Influence; Self-efficacy; Positive Outcome Expectancy
Online: 21 July 2020 (12:57:49 CEST)
Objectives: This study proposes a model that integrates three determinants of social cognitive theory (SCT) to explain the impact of FoMO on SNS usage. Design: A cross-sectional study is conducted using data for 259 participants recruited from a website. Main Outcome Measures: The analysis focuses on FoMO, social influence, positive outcome expectancy, refusal self-efficacy, and SNS-related behavior cloud-based sites. Data are examined using descriptive analysis and structural equation modeling. Results: The proposed model reported proper goodness of fit. FoMO does not directly or indirectly impact SNS usage through the determinants of SCT. However, social influence and refusal self-efficacy have a direct effect. Conclusions: The roles of the three determinants of SCT vary by stage of SNS usage. FoMO and refusal self-efficacy are more strongly related with SNS addiction. Further research, particularly longitudinal and intervention studies, is needed to examine the effects of specific factors on SNS addiction.
ARTICLE | doi:10.20944/preprints202005.0113.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS-CoV-2; COVID-19; inflammation; smoking; nicotine; hospitalization; adverse outcome
Online: 7 May 2020 (08:52:04 CEST)
Background: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. Methods: We performed a systematic review of the literature (PubMed) for studies published until April 25. Studies were included into the analysis if they satisfied all of the following criteria: 1. To present hospitalized patients with COVID-19. 2. To classify patients into less and more severe disease, irrespective of the severity definition (defined as “adverse ourtcome”). 3. To present data on the smoking status, separately for each severity classification. We identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted, population-based expected prevalence by calculating Prevalence Odds Ratio (POR). The association between current, compared to non-current and former, smoking and adverse outcome was examined by calculating Odds Ratio (OR). All analyses were performed using random-effects meta-analysis. Results: Among 6515 patients, 440 of whom were current smokers, the pooled prevalence of current smoking was 6.8% (95%CI: 4.8-9.1%) and the POR was 0.21 (95%CI: 0.16-0.26, P < 0.001). In Chinese studies only, the POR was 0.22 (95%CI: 0.17-0.27, P < 0.001). Current smokers were more likely to have an adverse outcome compared to non-current smokers (OR: 1.53, 95%CI: 1.06-2.20, P = 0.022). However, they were less likely to have an adverse outcome compared to former smokers (OR: 0.42, 95%CI: 0.27-0.74, P = 0.003). Conclusion: An unexpectedly low prevalence of current smoking was observed among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared to non-current smokers but lower odds compared to former smokers for an adverse outcome. The possibility that nicotine may have a protective effect in COVID-19 which may be masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored.
REVIEW | doi:10.20944/preprints201811.0506.v2
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: circadian rhythm; sleep disorders; socioeconomic status; stress; allostatic load; health outcome
Online: 10 December 2018 (14:18:30 CET)
The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. This theoretical review explores some theories linking environment of people with occurrence of SD, with different patterns associated to SES. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.
ARTICLE | doi:10.20944/preprints201810.0678.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: post-operative death; unstructured data; logistic regression; text mining; surgery outcome
Online: 29 October 2018 (11:46:18 CET)
Text fields in electronic medical records (EMR) contain information on important factors that influence health outcomes, however, they are underutilized in clinical decision making due to their unstructured nature. We analyzed 6,497 inpatient surgical cases with 719,308 free text notes from Le Bonheur Children’s Hospital EMR. We used a text mining approach on preoperative notes to obtain the text-based risk score algorithm as predictive of death within 30 days of surgery. We studied the additional performance obtained by including text-based risk score as a predictor of death along with other structured data based clinical risk factors. The C-statistic of a logistic regression model with 5-fold cross-validation significantly improved from 0.76 to 0.92 when text-based risk scores were included in addition to structured data. We conclude that preoperative free text notes in EMR include significant information that can predict adverse surgery outcomes.
ARTICLE | doi:10.20944/preprints201808.0186.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: Gait; Pain; Back disorder; Outcome evaluations; Daily activity; Fear of pain
Online: 9 August 2018 (11:26:15 CEST)
Abstract: This study evaluates the effect of paravertebral spinal injection (PSI), utilizing both subjective and objective assessments in chronic low back pain (LBP) associated with facet joint arthrosis over a one-month duration. Subjective questionnaires included the Visual Analogue Scale (VAS) for pain, Oswestry Disability Index, Health Survey SF-12, and the short Falls Efficacy Scale International (FES-I). Objective assessments included in-clinic gait and timed-up-and-go (TUG) tests using wearable sensors, as well as 48-hour daily physical activity (DPA) monitored using a chest-worn tri-axial accelerometer. Subjective and objective measures were performed prior to treatment, immediately after the treatment, and one-month afterthe treatment. Eight LBP patients were recruited for this study (mean age = 54±13 years, body mass index = 31.41±6.52 kg/m2, 50% males). Results show significant decrease in pain (~55%, p<0.05) and disability (Oswestry scores, ~21%, p<0.05). In-clinic gait and TUG were also significantly improved (~16% and ~18% faster walking and shorter TUG, p<0.05); however, DPA (including percentage of physical activities (walking and standing) and the number of steps) showed no significant change after PSI (p>0.25; effect size≤0.44). We hypothesize that DPA may continue to be truncated by conditioned fear-avoidance, a psychological state that may prevent increase in daily physical activity to avoid pain.
ARTICLE | doi:10.20944/preprints202201.0326.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Deep hypothermic circulatory arrest time; acute type A aortic dissection; surgical outcome
Online: 21 January 2022 (13:12:22 CET)
(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p<0.001). Accordingly, cardiopulmonary bypass (p<0.001), cross-clamping (p<0.001) and DHCA times (p<0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p<0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.
ARTICLE | doi:10.20944/preprints202011.0662.v1
Subject: Medicine & Pharmacology, Allergology Keywords: maintenance cost; patient related outcome measurements; quality of life; mandibular overdentures; edentulism
Online: 26 November 2020 (10:40:14 CET)
Denture wearers often complain about jeopardized function and reduced quality of life due to lack of prosthesis’ retention. Implant retained mandibular overdentures, on 2 non-connected implants (2IOD) are well-proven solutions to overcome these issues. We prospectively assessed 69 patients and scrutinized clinical records until at least 7 years of function. Thirty-six were retained on Locator ® Abutments (LA) and thirty-tree on Ball Abutments (BA). Both systems were compared regarding the type, amount and total cost of required maintenance. One implants was lost, yielding 98.7% survival after 7 years. In total 438 technical issues occurred: 121 (27.35%) in BA and 317 (72.4%) in LA. Out of these, 343 events (78%) were solved chairside: 191 (43.6%) were replacements of retention caps, 113 (25.8%) were minor acrylic repairs, in 26 (5.9%) pressure ulcers had to be relieved and 13 (3%) related to abutments. LA required 179 insert replacements compared to 12 in the BA group. The overall initial treatment cost was 3850 euro. The average total maintenance cost in relation to the initial cost for the LA and BA groups was 19.11% (range 0% - 82.24%) and 18.91% (range 0% - 113.26%) respectively (P=0.540). Conclusions: The 7-years maintenance costs for a 2IOD is acceptable when the patient is regularly checked and professionally maintained. Most events are easily solvable chairside, but a few patients required more expensive interventions, regardless of the type of attachment used.
ARTICLE | doi:10.20944/preprints202011.0653.v1
Subject: Medicine & Pharmacology, Allergology Keywords: misoprostol; induction of labor; high-risk pregnancy; obesity; diabetes; hypertension; perinatal outcome
Online: 25 November 2020 (16:41:16 CET)
Background and objectives: Induction of labor (IOL) is an event that occurs in up to one-quarter of pregnancies; less is known about the outcomes and safety of IOL in obese pregnant woman; no data is available on misoprostol vaginal insert (MVI) IOL in high-risk pregnancy obese women. Objectives: (1) to evaluate the rate of successful IOL with 200 μg MVI in obese (Body Mass Index - BMI over 30 kg/m2) high-risk pregnant women: late-term pregnancy, hypertension or diabetes, compared to obese non-high-risk ones; (2) to evaluate the safety profile of MVI in high-risk pregnancy obese patients. Study design: We conducted a cross-sectional study in "Filantropia" Clinical Hospital, Bucharest, Romania, from June 2017 to September 2019 (28 months). From a total of 11,096 registered live births, IOL was performed in 206 obese patients; 74 obese high-risk pregnant patients matched the inclusion criteria; of these, 33.8% pregnancies (n=25) were late-term (41 – 41+6 weeks), 43.2% (n=32) had associated pathologies (hypertension and diabetes); labor induction was guided using a standardized protocol. We evaluated the maternal and gestational age, parity, fetal tachysystole, hyper-stimulation, initial cervical status, time from induction to delivery, drug side effects, mode of delivery, and neonatal outcomes. Results: (a) The overall successful labor induction rate, evaluated by the vaginal delivery rate, was 71.6% (n=53), spontaneously or instrumentally assisted; 28.4% (n=21) births were unsuccessful MVI IOL, converted into caesareans. (b) No significant differences were found regarding the maternal outcomes; in terms of perinatal outcomes of safety, four cases of high-risk pregnancies vaginally delivered were associated with neonatal intensive care unit (NICU) admissions and a one-minute Apgar score under seven (5.4%). Most cases with adverse effects of misoprostol have been managed conservatively, except for three emergency C-section cases. Conclusions: Misoprostol vaginal insert is a safe choice in IOL in obese high-risk pregnancies with good maternal and perinatal outcomes.
ARTICLE | doi:10.20944/preprints202001.0213.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: glomerular filtration rate; Brenner hypothesis; extreme low birth weight infants; renal outcome
Online: 19 January 2020 (05:12:19 CET)
Different cohort studies documented a lower glomerular filtration rate (GFR) in former extremely low birth weight (ELBW, <1000 g) neonates throughout childhood when compared to term controls. The current aim is to pool these studies to describe the GFR pattern over the pediatric age range. To do so, we conducted a systematic review on studies reporting on GFR measurements in former ELBW cases while GFR data of healthy age-matched controls included in these studies were co-collected. Based on 248 hits, 6 case-control and 3 cohort studies were identified, with 444 GFR measurements in 380 former ELBW cases (median age 5.3-20.7 years). The majority were small (17-78 cases) single center studies, with heterogeneity in GFR measurement (inulin, Cystatin C or creatinine estimated GFR formulae) tools. Despite this, the median GFR (ml/kg/1.73m2) within case-control studies was consistently lower (-13, range -8 to -25%) in cases, so that a relevant minority (15-30%) has a eGFR<90 mgl/kg/1.73m2). Consequently, this pooled analysis describes a consistent pattern of reduced eGFR in former ELBW cases throughout childhood. Research should focus on perinatal risk factors for impaired GFR and long-term outcome, but is hampered by single center cohorts, study size, and heterogeneity of GFR assessment tools.
ARTICLE | doi:10.20944/preprints201810.0228.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: cerebellar hemorrhage; intraventricular hemorrhage; preterm; MRI; neurodevelopment; outcome prediction; white matter injury
Online: 11 October 2018 (04:21:24 CEST)
Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe from normal-moderate neurodevelopmental outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation, had MR imaging at term-equivalent age, and neurodevelopmental testing at 18-24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors strongly predictive of outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean GA = 26.1±1.8 weeks, BW = 889.1±226.2 grams). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + ROP requiring surgery) had strong discriminatory power for severe disability (AUC=0.850), with a PPV of 76% and NPV of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit most from such services.
ARTICLE | doi:10.20944/preprints201701.0013.v1
Subject: Medicine & Pharmacology, Other Keywords: Rheumatoid Arthritis; thematic analysis; Outcomes assessment; Qualitative Research; Patient reported outcome measures
Online: 3 January 2017 (11:32:52 CET)
Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.
ARTICLE | doi:10.20944/preprints202208.0394.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: acute subdural hematoma; comorbidity; elderly; outcome; surgery; timing of surgery; traumatic brain injury
Online: 23 August 2022 (05:08:46 CEST)
Background: The incidence of traumatic acute subdural hematomas (ASDH) in elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays a no clear role as predictor. We investigated if the timing of surgery has a major role in influencing outcome in these patients.Methods: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 years period in 5 Italian Hospitals. Patients were divided in 3 surgical timing groups from hospital arrival: ultra-early (within 6h); early (6-24h); delayed (after 24h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed.Results: We included 136 patients. About 33% died for consequences of ASDH and among the survivors only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting GCS, which was on average lower in ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared associated neither with survival nor with functional outcome also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. Conclusions: An earlier surgery was offered to patients with worse clinical-radiological findings. Also after stratification for GCS it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.
ARTICLE | doi:10.20944/preprints202203.0073.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: focus group; patient reported outcome measures; oral health; education; COVID-19; dental problem
Online: 4 March 2022 (07:08:57 CET)
This study reports results of focus groups with school nurses and teachers from elementary, middle, and high schools to explore their perceptions of child and adolescent oral health. Participants included 14 school nurses and 15 teachers (83% Female; 31% Hispanic, 21% White, 21% Asian, 14% African American, and 13% Others). Respondents were recruited from Los Angeles County schools and scheduled by school level for six one-hour focus groups, using Zoom. Audio recordings were transcribed, reviewed, and saved with anonymization of speaker identities. NVivo software was used to facilitate content analysis and identify key themes. The nurses’ rate of “Oral Health Education” comments statistically exceeded that of teachers, while teachers had higher rates for “Parental Involvement” and “Mutual Perception” “Need for Care” was perceived to be more prevalent in immigrants to the United States based on student behaviors and complaints. “Access to Care” was seen as primarily the nurse’s role. Strong relationships between community clinics and schools were viewed by some as integral to students achieving good oral health. The results suggest dimensions and questions important to item development for oral health surveys of children and parents to address screening, management, program assessment, and policy planning.
REVIEW | doi:10.20944/preprints202102.0444.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Caesarean scar ectopic pregnancy; risk factors; clinical presentation; complication; management; outcome of CSEP
Online: 19 February 2021 (14:35:47 CET)
Caesarean scar ectopic pregnancy (CSEP) is an uncommon form of ectopic pregnancy. This review defines types of CSEP, discusses pathophysiology, clinical presentation and diagnosis and compares common treatment options and outcomes. The pathophysiology is not yet fully understood. One third of patient are asymptomatic. In symptomatic patients vaginal bleeding and pelvic pain which is usually misdiagnosed as threatened or missed abortion. The main principles of treatment for CSEP are early diagnose, quick management, and maintain reproductive function as much as possible. Up to date; no consensus or guidelines for the treatment and management of CSEP. Management of CSEP depends on the clinical presentation and gestational age. Significant controversy exists regarding management, for this reason, several factors should be considered including age of the patient, myometrial thickness, clinical symptoms, hemodynamic status, fertility preservation.
ARTICLE | doi:10.20944/preprints202011.0512.v1
Subject: Medicine & Pharmacology, Allergology Keywords: antimicrobials; meropenem; generic drug; real-life studies; product surveillance, postmarketing; treatment outcome; pharmacovigilance
Online: 19 November 2020 (13:34:26 CET)
Background. To determine the effectiveness and safety of meropenem in routine clinical practice, in terms of clinical and microbiological response. Methods. A real-world, observational, descriptive, longitudinal study with daily monitoring of clinical history records was conducted on all patients who were medically prescribed meropenem during a period between October 2015 and March 2016 at a university hospital in Bucaramanga (Colombia). Results. The study evaluated 84 patients with an average age of 63.2 years, mostly older adults with multiple comorbidities, of whom 54.8% were men. A positive clinical or microbiological response was obtained in 98.8% of the patients. At the end of the treatments, significant improvements in dysthermia (0% vs 29% at the beginning, p = 0.000), tachycardia (13% vs 47%, p = 0.049) and leukocytosis (39% vs 15% at the beginning, p = 0.008) were evidenced. The improvement in the indicator that combines all the SIRS criteria was also significant (p = 0.000). The treatment was well tolerated, although we identified some non-serious and expected adverse reactions. Conclusions. Generic meropenem proved to be effective and well tolerated for different types of infection in routine clinical practice. The results are consistent with the findings of the clinical studies with the innovator drug.
ARTICLE | doi:10.20944/preprints202109.0010.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: spinal cord stimulation; screening trial; infection; supervised learning; machine learning; predictive modeling; patient outcome
Online: 1 September 2021 (12:05:18 CEST)
Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.
ARTICLE | doi:10.20944/preprints202105.0731.v1
Subject: Life Sciences, Biochemistry Keywords: cytokine storm; COVID-19; CD169; inflammation; respiratory outcome; T-cell exhaustion; COVID-19 therapy
Online: 31 May 2021 (10:28:24 CEST)
Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.
ARTICLE | doi:10.20944/preprints202105.0596.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Atopic dermatitis; Patient Reported Outcome Measures; Dupilumab; Quality of life; Satisfaction; Efficacy; Safety; Adherence
Online: 25 May 2021 (09:15:21 CEST)
Dupilumab is used to treat atopic dermatitis patients who have proven to be refractory to previous treatments. The aim of this study was to assess evolution and patient reported outcome measures in adult patients with moderate-to-severe atopic dermatitis treated with Dupilumab in routine clinical practice. The outcomes were evaluated and registered at baseline and weeks-16, 40 and 52. The variables evaluated were: diseases severity, pruritus, stressful life events, difficulty to sleep, anxiety and depression, quality of life, satisfaction, adherence to the treatment, efficacy and safety. Eleven patients were recruited between Nov 14th 2017 and Jan 16th 2018. Demographic variables: 90% Caucasian, 82% women. Clinical variables: Mean duration of AD =17.7 (±12.8), 91% had severe disease severity. At baseline, SCORAD mean score = 61.7 (±15.5); itch was reported by 100% of patients; itch Visual Analogue Scale mean range of 8 (6-10); HADS mean total score =13.9 (±5.5); DLQI mean score =13.3 (±8.3): EQ-5D-3L mean range = 57 (30-99). At week-52 there is a significant reduction of SCORAD scores, HADS total score and improved quality of life. ¡This study confirms that Dupilumab, used for 52-weeks under routine clinical practice, maintains the improved atopic dermatitis signs and symptoms obtained at week-16, with a good safety profile.
ARTICLE | doi:10.20944/preprints201612.0033.v1
Subject: Behavioral Sciences, Other Keywords: 360-degree assessment; perceived credibility; evaluation of outcome; theory of reasoned action; attitude formation
Online: 6 December 2016 (11:09:16 CET)
This study analyzes how Perceived Credibility of a 360-degree feedback and Evaluation of Outcome impact on ratees’ attitudes towards behavioral change. The study adopts a qualitative-quantitative mixed method approach. Reasoned Action Theory was selected as the theoretical framework, and ten 360-degree assessment ratees were interviewed on their perceived credibility, evaluation of outcome and attitude toward behavioral change in the 360-degree assessment practices. The qualitative inputs were analyzed under the methodology of grounded theory. Additional 159 respondents participated in the quantitative research phase of the research to validate the findings in the qualitative research phase. It was validated that Perceived Credibility, Evaluation of Outcome has impact on Attitude Toward Behavioral Change in 360-degree assessment.
ARTICLE | doi:10.20944/preprints202011.0484.v1
Subject: Medicine & Pharmacology, Urology Keywords: Acute Cystitis Symptom Score; ACSS; cystitis; urinary tract infection; female patients; diagnosis; patient-reported outcome
Online: 18 November 2020 (16:35:23 CET)
Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following FDA guidance. At Day 1 (diagnosis) the mean(SD) sum score of the six ACSS typical symptoms reached 10.60(2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favoured ACSS criteria (sum score of typical symptoms 0.98(1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. Conclusion The American-English ACSS showed high predictive ability and responsiveness, and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice or for self-diagnosis of women with symptoms of UC.
ARTICLE | doi:10.20944/preprints201912.0411.v1
Subject: Engineering, Construction Keywords: safety; electrical contractors; construction accidents; nature and outcome of injuries; Chi-square test of independence
Online: 31 December 2019 (11:19:50 CET)
Electrical contractors have experienced a rise in occupational fatalities in recent years. In 2017, electrical contractors also had the second highest number of non-fatal injuries among specialty trade contractors. Identifying statistically significant dependencies between these catastrophic outcomes and a handful of well-defined contributing factors in construction accidents offers a first step in mitigating the risks of construction accidents in this trade. Therefore, this study used methodologies of descriptive and quantitative statistics to identify the contributing factors most affecting occupational accident outcomes among electrical contracting enterprises, given an accident occurred. Accident reports were collected from the Occupational Safety and Health Administration’s fatality and catastrophe database. To ensure the reliability of the data, the team manually codified more than 600 incidents through a comprehensive content analysis using injury-classification standards. Inclusive of both fatal and non-fatal injuries, the results showed that most accidents happened in nonresidential buildings, new construction, and small projects (i.e., $50,000 or less). The main source of injuries manifested in parts and materials (46%), followed by tools, instruments, and equipment (19%), and structure and surfaces (16%). The most frequent types of injuries were fractures (31%), electrocutions (27%), and electrical burns (14%); the main injured body parts were upper extremities (25%), head (23%), and body system (18%). Among non-fatal cases, falls (37%), exposure to electricity (36%), and contact with objects (19%) caused most injuries; among fatal cases, exposure to electricity was the leading cause of death (50%), followed by falls (28%) and contact with objects (19%). The analysis also investigated the impact of several accident factors on the degree of injuries and found significant effects from such factors such as project type, source of injury, cause of injuries, injured part of body, nature of injury, and event type. In other words, the statistical probability of a fatal accident—given an accident occurrence—changes significantly based on the degree of these factors. Beyond these outcomes, the described content-analysis methodology contributes to the accident-analysis body of knowledge by providing a framework for codifying data from accident reports to facilitate future analysis and modeling attempts (e.g., developing logistic regression models) to subsequently mitigate more injuries in other fields.
ARTICLE | doi:10.20944/preprints202112.0264.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: concussion; mild traumatic brain injury; working memory; long-term cognitive outcome; support vector machine classifier; personalized prediction
Online: 16 December 2021 (10:24:08 CET)
Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear because abnormality is often absent in structural imaging findings. The purpose of the study was to determine whether machine learning-based models using functional magnetic resonance imaging (fMRI) biomarkers and demographic or neuropsychological measures at baseline could effectively predict 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically-matched healthy controls enrolled between September 2015 to August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to the significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after concussion. Approximately half of the patients experienced prolonged cognitive impairment at 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy=87.5%), 6 months (accuracy=83.3%), 1 year (accuracy=83.3%), and performed worse at 1-year follow-up compared to baseline assessment (accuracy=83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.
ARTICLE | doi:10.20944/preprints201912.0271.v1
Subject: Medicine & Pharmacology, Other Keywords: chiropractic; physical therapy; treatment outcome; low back pain; therapy; economics; patient satisfaction; recurrence; health care costs; illness
Online: 20 December 2019 (07:41:47 CET)
Low back pain (LBP) is a pandemic and costly musculoskeletal condition in the United States. Patients with LBP may endure surgery, injections, and expensive visits to emergency departments. Some suggest that using physical therapy or chiropractic in the earlier stage of LBP reduces the utilization of expensive health services and lowers the treatment costs. Nevertheless, there is no consistent evidence to declare which one of these methods is a cost-effective treatment within a short (less than a year) period of time. The purpose of this study was to investigate the cost-effectiveness of chiropractic versus physical therapy in the United States. A decision tree analytic model was used for estimating the economic outcomes. The findings showed that in the chiropractic group, the total average cost was $48.56 lower than the physical therapy group, and daily adjusted life years (DALY) was 0.0043 higher than the physical therapy group. Chiropractic care was shown to be a cost-effective alternative compared with physical therapy for adults with at least three weeks of low back pain over six months.
ARTICLE | doi:10.20944/preprints201811.0454.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: perioperative goal-directed fluid therapy; haemodynamics monitoring; fluid management; kidney transplantation; major postoperative complications; outcome of surgery
Online: 19 November 2018 (10:57:00 CET)
Background: Kidney transplantation is considered the first-choice therapy in ESRD patients. Despite recent improvements in terms of outcomes and graft survival in recipients, postoperative complications still concern health-care providers involved in the management of those patients. Particularly challenging are cardiovascular complications. Perioperative goal-directed fluid-therapy (PGDT) and hemodynamic optimization are widely used in high-risk surgical patients, and are associated with a significant reduction in postoperative complication rates and length of stay (LOS). The aim of this work is to compare the effects of perioperative goal-directed therapy (PGDT) with conventional fluid therapy (CFT), and to determine whether there are any differences in major postoperative complications rates and delayed graft function (DGF) outcomes. Methods: Prospective study with historical controls. Two groups, a PGDT- and a CFT- group were used: the stroke volume (SV) optimization protocol was applied in PGDT group throughout the procedure. Conventional fluid therapy with fluids titration at a central venous pressure (CVP) 8-12 mmHg and mean arterial pressure (MAP) >80mmHg was applied to the control-group. Postoperative data collection including vital signs, weight, urinary output, serum creatinine, blood urea nitrogen, serum potassium, and assessement of volemic status and the signs and symptoms of major postoperative complications occurred at 24h, 72h, 7 days and 30 days after transplantation. Results: Among the 66 patients enrolled, 33 were in each group and both groups had similar physical characteristics. Good fuctional recovery was evident in the 94% of patients. The statistical analysis has showed a difference in postoperative complications as follows: significant reduction of cardiovascular complications, DGF episodes (p<0.05) and surgical complications (p<0.01). There were no significant differences in pulmonary or other complication. Conclusions: PGDT and SV optimization effectively influenced the rate of major postoperative complications, reducing the overall morbidity and thus the mortality in patients receiving kidney transplantation.
ARTICLE | doi:10.20944/preprints201710.0032.v1
Subject: Social Sciences, Geography Keywords: Environmental decision support systems; applications; outcome-based approach; adaptive management; user requirements; environmental management; participatory land planning
Online: 6 October 2017 (08:51:07 CEST)
There is increasing demand from stakeholders for tools to support outcome-based approaches in environmental management. For such tools to be useful, understanding user requirements is key. In Scotland, UK, stakeholders were engaged in the development of an Environmental Decision Support System (EDSS) to support the management of land and freshwater resources for multiple policy outcomes. A structured participatory engagement process was employed to determine stakeholder requirements, establish development principles to fulfil these requirements and road-test prototypes. The EDSS specification that emerged from this bottom-up process was spatially-explicit, free at the point of use, and touch and mobile device compatible. This application, which is under development, does not closely resemble most existing published EDSS. We suggest that there is a mismatch between the way scientists typically conceptualise EDSS and the kinds of applications that are likely to be useful to decision-makers on the ground. Interactive mobile and web-based geospatial information services have become ubiquitous in our daily lives, but their importance is not reflected in current literature on EDSS. The current focus in environmental management on adaptive, stakeholder-centred strategies based on outcomes offers an opportunity to make better use of these new technologies to aid decision-making processes.
ARTICLE | doi:10.20944/preprints201908.0269.v2
Subject: Behavioral Sciences, Applied Psychology Keywords: Exercise; Health Behavior; Attitudes; Referral; Quality of Life; Low Back Pain; Health Services; Models; Outcome Assessment (Health Care)
Online: 11 December 2020 (11:32:36 CET)
Background: Low-level physical activity (PA) among Chronic Low Back Pain (cLBP) is associated with various biopsychosocial factors. This research aimed to study the predictors of PA behavior among cLBP patients. Methods: In the present study 300 eligible patients with cLBP who referred to comprehensive health service centers in the Shahid Beheshti University of Medical Sciences (SBUMS) in Tehran, Iran were random selected.To diagnose the predictors of PA behavior, all the Theory of Reasoned Action (TRA) constructs were examined as risk factors to see if they influence on the probability of PA behavior occurrence and were interpreted through odds ratio (OR). SPSS version 19 was used to analyze the data. Results: Totally 280 cLBP patients with mean age of 57.07 ±13.09 years old participated in the study. This study showed that motivation to comply significant predictor the cLBP patients for subjective norm OR (%95CI): 2.095(0.116-2.792), p-value<0.001), intention was significant predictor for perform the PA behavior OR (%95CI): 1.431(0.138-1.538), p-value <0.001), behavior beliefs could predictor for attitude OR (%95CI): 1.276(0.106-1.355), p-value= 0.002). attitude, normative beliefs, subjective norm ,and evaluation outcome behavior could predictors the cLBP patients for intention to perform the PA behavior OR (%95CI): 1.188(0.032-1.312), p-value<0.001)., OR (%95CI): 1.158(0.076-2.208), p-value=0.003) ., OR (%95CI): 1.104(0.076-1.128), p-value<0.001) ., OR (%95CI): 0.814(0.301-1.440), p-value=0.007). Conclusions: This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm). This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm). This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm).
ARTICLE | doi:10.20944/preprints202012.0735.v1
Subject: Medicine & Pharmacology, Urology Keywords: Greek language; translation; acute cystitis symptom score; ACSS; cystitis; urinary tract infection; female pa-tients; diagnosis; patient-reported outcome
Online: 29 December 2020 (15:40:33 CET)
Objective: The Acute Cystitis Symptom Score (ACSS) was developed and validated as a self-reporting questionnaire for diagnosing and monitoring acute, uncomplicated cystitis (AC) in female patients. The study aims at the translation of the ACSS into Greek from original Russian as a source and American English as a new master version and at its linguistic validation. Material and Methods: Three independent professional native Greek translators, two of them experts in Russian and one in English, translated the ACSS from Russian and American English into Greek. The second group of three translators translated each of the three versions back into the original language to detect or correct any important discrepancies. These three Greek versions were then used for linguistic validation. Results: The English to Greek translation reflected more the spoken language, the two Russian to Greek translations more the written, formal language. A total of 60 randomly selected females and 30 healthcare professionals was asked about their preferences and to comment on each of the three translations. Considering all comments the scientific committee (SC) developed the Greek consensus version. For cognitive assessment additional 30 healthcare professionals and 30 females were asked to comment on the intelligibility of all items. Considering their comments the linguistically validated Greek study version was established by the SC. Conclusion: The linguistically validated Greek version of the ACSS can now be used for the clinical validation study.
REVIEW | doi:10.20944/preprints202011.0721.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Non-invasive direct current stimulation; Cortical, Suboccipital and Spinal stimulation; Quantitative sensory testing, Pain outcome measures, Endogenous pain modulation.
Online: 30 November 2020 (11:44:44 CET)
Background: Objectives. The objective of this study was to compare the efficacy of direct current stimulation (DCS) applied at the transcranial, suboccipital and spinal level on experimental sensory modalities and pain outcome measures in healthy subjects. The hypothesis of this study was that systematic analysis of the efficacy of DCS on modulating evoked thermal and mechanical pain modalities and mechanisms such as endogenous pain modulation in healthy individuals would reveal sensitive outcome measures help develop this technique for the control of chronic pain. Materials and Methods. Database searches were conducted up to December 2019 for randomized controlled trials that performed sham-controlled DCS of experimental sensory modalities and pain outcomes following transcranial, suboccipital and spinal locations in healthy participants. Standardized mean differences with 95% confidence intervals were calculated for sensory modalities, including random-effect metanalysis. Results: Thirty-one studies were included for analysis (647 participants). A significant decrease in pain intensity for active vs sham transcranial stimulation was identified for pain intensity (n=158; SMD=0.79; 95% CI=0.56 to 1.02), a significant increase in heat pain threshold (n=222; SMD=1.16; 95% CI=0.95 to 1.37), and a significant increase in cold pain threshold (n = 155; SMD = 0.77, 95% CI 0.53 to 1.01). No significant modulation of pressure pain threshold was identified with DCS and only a limited number of studies focused on experimental pain modulation following neuromodulation at the suboccipital or spinal level. Conclusions: These results show significant transcranial DCS neuromodulation of pain intensity and on thermal pain modalities. Future studies should focus on endogenous pain and sensory modality modulation with sham-controlled DCS applied at transcranial, suboccipital and spinal locations.
REVIEW | doi:10.20944/preprints202206.0121.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2 infection; COVID-19; modulating factors; Adverse Outcome Pathway; sex; age; co-morbidities; lifestyle; environment; pre-existing conditions
Online: 8 June 2022 (09:47:23 CEST)
Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.
REVIEW | doi:10.20944/preprints201806.0137.v1
Subject: Medicine & Pharmacology, Other Keywords: opportunity; challenge; perspective; health data; disease prediction; clinical outcome prediction; healthcare process; data quality; quantity and quality analysis; artificial intelligence
Online: 8 June 2018 (13:22:08 CEST)
Health information technology has been widely used in healthcare, which has contributed a huge amount of data. Health data has four characteristics: high volume; high velocity; high variety and high value. Thus, they can be leveraged to i) discover associations between genes, diseases and drugs to implement precision medicine; ii) predict diseases and identify their corresponding causal factors to prevent or control the diseases at an earlier time; iii) learn risk factors related to clinical outcomes (e.g., patients’ unplanned readmission), to improve care quality and reduce healthcare expenditure; and iv) discover care coordination patterns representing good practice in the implementation of collaborative patient-centered care. At the same time, there are major challenges existing in data-driven healthcare research, which include: i) inefficient health data exchanges across different sources; ii) learned knowledge is biased to specific institution; iii) inefficient strategies to evaluate plausibility of the learned patterns and v) incorrect interpretation and translation of the learned patterns. In this paper, we review various types of health data, discuss opportunities and challenges existing in the data-driven healthcare research, provide solutions to solve the challenges, and state the important role of the data-driven healthcare research in the establishment of smart healthcare system.
REVIEW | doi:10.20944/preprints202009.0254.v1
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: dental care; emotions; health personnel; health services; human needs; motivation; patient reported outcome measures; patient satisfaction; personal satisfaction; theory of satisfaction
Online: 11 September 2020 (09:44:11 CEST)
There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.
ARTICLE | doi:10.20944/preprints202102.0059.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; Critical Illness; Hospital Mortality; Intensive Care Units; Outcome Assessment, Health Care; Prognosis; Risk Adjustment; Severe acute respiratory syndrome coronavirus 2
Online: 1 February 2021 (15:51:34 CET)
Objectives To develop and validate a prediction model for 28-day in-hospital mortality among adult patients critically ill with COVID-19 in the UK. Design Observational cohort study. Setting 287 adult critical care units in England, Wales and Northern Ireland, of which 260 admitted at least one eligible patient. Participants 10,933 patients with confirmed COVID-19 of whom 10,401 were eligible (excluding 532 patients with a duration of critical care less than 24 hours and 1 patient with unknown 28-day outcome): 8,666 development (March-April 2020) and 1,735 temporal validation (May-August 2020). Main outcome measures 28-day in-hospital mortality from start of critical care. Results Two models were developed using 14 patient level predictors selected from 30 candidate predictors, with and without adjustment for calendar time. In the temporal validation data, the model discrimination was maintained (c index 0.78) but calibration was poor, particularly for the model not adjusted for calendar time (ratio of observed to predicted mortality 0.74 versus 0.88 for the model adjusted for calendar time). Conclusions We developed and validated a prediction model for 28-day in-hospital mortality for patients critically ill with COVID-19. Although absolute predictions were inaccurate due to changing outcomes, the models will support risk-adjustment in analyses and monitoring changes in risk-adjusted outcome over time.
ARTICLE | doi:10.20944/preprints201908.0059.v1
Subject: Biology, Forestry Keywords: deciduous forest; female; forest bathing; forest therapy; Positive and Negative Affect Schedule; Profile of Mood States; Restorative Outcome Scale; restoration; Shinrin-Yoku; snow covered forest; Subjective Vitality Scale; winter
Online: 5 August 2019 (08:56:32 CEST)
Forest recreation can be successfully conducted for the purpose of psychological relaxation, as has been proven in previous scientific studies. During the winter in many countries, when snow cover occurs frequently, forest recreation (walking, relaxation, photography, etc.) is common. Nevertheless, whether forest therapy conducted in a forest environment with a snow cover will also have a positive effect on psychological indicators remains unknown. Furthermore, male subjects frequently participate in forest therapy experiments, whereas females are rarely involved. Thus, in this study, the effectuality of forest recreation during winter and with snow cover was tested on 32 young females. For these reasons, the experiment involved 15-minute periods of relaxation in a forest environment or in an urban environment, in addition to a pre-test under indoor conditions. Four psychological questionnaires (POMS, PANAS, ROS, SVS) were administered to participants before and after interventions. Results showed that participants’ levels of negative mood, as measured by different aspects of the POMS questionnaire (tension-anxiety, anger-hostility, depression-dejection, confusion, fatigue), decreased after exposure to the forest environment. In contrast, both tension-anxiety and anger-hostility increased in the urban environment. The indicator of negative affect from the PANAS questionnaire also increased after exposure to the urban environment, whereas the indicator of positive affect based on PANAS was higher in the forest environment than in the urban environment. Restorativeness and subjective vitality exhibited higher values after exposure to the forest environment in comparison to those from the control and pre-test. The changes in these indicators demonstrates that forest recreation in the snow during winter can significantly increase psychological relaxation in young females, as well as showing that recreation can be successfully conducted under these winter conditions.
ARTICLE | doi:10.20944/preprints202110.0235.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Spinal Cord Stimulation; rescue therapy; salvage therapy; new waveforms; paresthesia-free waveforms; High-Frequency stimulation; Burst stimulation; spatial neural targeting; temporal neural targeting; SCS programming; adapter; mapping software; paresthesia coverage; patient outcome; salvage algorithm
Online: 18 October 2021 (10:04:52 CEST)
While paresthesia-based spinal cord stimulation (SCS) has been proven effective to treat chronic neuropathic pain, initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neu-rostimulation adapters, in patients already implanted with SCS and experienced LoE. We retro-spectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before, and at 1, 3, 6 and 12-month follow-up. Outcomes included pain intensity rating with Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N=27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and Quality of Life (p=0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompa-nied by paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conver-sion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled by spatial retargeting. In light of these results, adapters could be integrated to SCS rescue algorithms or should be considered in SCS rescue.