Application and utility of boosting machine learning model based on laboratory test in the differential diagnosis of non-COVID-19 pneumonia and COVID-19.

BACKGROUND: Non-Coronavirus disease 2019 (COVID-19) pneumonia and COVID-19 have similar clinical features but last for different periods, and consequently, require different treatment protocols. Therefore, they must be differentially diagnosed. This study uses artificial intelligence (AI) to classify the two forms of pneumonia using mainly laboratory test data. METHODS: Various AI models are applied, including boosting models known for deftly solving classification problems. In addition, important features that affect the classification prediction performance are identified using the feature importance technique and SHapley Additive exPlanations method. Despite the data imbalance, the developed model exhibits robust performance. RESULTS: eXtreme gradient boosting, category boosting, and light gradient boosted machine yield an area under the receiver operating characteristic of 0.99 or more, accuracy of 0.96-0.97, and F1-score of 0.96-0.97. In addition, D-dimer, eosinophil, glucose, aspartate aminotransferase, and basophil, which are rather nonspecific laboratory test results, are demonstrated to be important features in differentiating the two disease groups. CONCLUSIONS: The boosting model, which excels in producing classification models using categorical data, excels in developing classification models using linear numerical data, such as laboratory tests. Finally, the proposed model can be applied in various fields to solve classification problems.

Temporary suspension of visiting as experienced by non-covid-19 patients undergoing orthopaedic surgery, their relatives, and health professionals, a multimethod study

Background: Hospitals worldwide implemented visitor restrictions policies due to the SARS-CoV-2 pandemic. Aim: To investigate the impact of visitor restrictions experienced by non-Covid-19 orthopaedic patients, their relatives, and health professionals from a person-centred practice (PCP) perspective. Methods: Seventy-eight patients/relatives completed a self-reported survey. Template Analysis was conducted on twenty-five telephone interviews and one focus group interview. Findings: Despite accepting the restrictions for the country's good, we found a profound need for visits among the relatives. However, one-fifth of the patients were content, and one-third got more rest than earlier admissions. We uncovered a current readiness to develop an organisational PCP culture focused on the good of the patient. All stakeholders were attentive to the importance of the relatives' role, and the need for the involvement of relatives as team players became evident. Conclusion: The study emphasised the need for PCP strategies to involve relatives when visitor restrictions are necessary.

On-scene time delays for epileptic seizures in emergencies during a social pandemic: A population-based study.

OBJECTIVES: The on-scene time of Emergency Medical Services (EMS), including time for hospital selection, is critical for people in an emergency. However, the outbreak of the novel coronavirus disease 2019 (COVID-19) led to longer delays in providing immediate care for individuals with non-COVID-19-related emergencies, such as epileptic seizures. This study aimed to examine factors associated with on-scene time delays for people with epilepsy (PWE) with seizures needing immediate amelioration. MATERIALS & METHODS: We conducted a population-based retrospective cohort study for PWE transported by EMS between 2016 and 2021. We used data from the Hiroshima City Fire Service Bureau database, divided into three study periods: "Pre period", the period before the COVID pandemic (2016-2019); "Early period", the early period of the COVID pandemic (2020); and "Middle period", the middle period of the COVID pandemic (2021). We performed linear regression modeling to identify factors associated with changes in EMS on-scene time for PWE during each period. In addition, we estimated the rate of total EMS call volume required to maintain the same on-scene time for PWE transported by EMS during the pandemic expansion. RESULTS: Among 2,205 PWE transported by EMS, significant differences in mean age and prevalence of impaired consciousness were found between pandemic periods. Total EMS call volume per month for all causes during the same month <5,000 (-0.55 min, 95% confidence interval [CI] -1.02 - -0.08, p = 0.022) and transport during the Early period (-1.88 min, 95%CI -2.75 - -1.00, p < 0.001) decreased on-scene time, whereas transport during the Middle period (1.58 min, 95%CI 0.70 - 2.46, p < 0.001) increased on-scene time for PWE transported by EMS. The rate of total EMS call volume was estimated as 0.81 (95%CI -0.04 - 1.07) during the expansion phase of the pandemic to maintain the same degree of on-scene time for PWE transported by EMS before the pandemic. CONCLUSIONS: On-scene time delays on PWE in critical care settings were observed during the Middle period. When the pandemic expanded, the EMS system required resource allocation to maintain EMS for time-sensitive illnesses such as epileptic seizures. Timely system changes are critical to meet dramatic social changes.

Examination of Gender Difference in Heart Disease-Related Excess Deaths during COVID-19 Pandemic Era: Findings from the United States

Background/Objective: Heart disease is the leading cause of death among women in the United States, and women are experiencing more strokes at younger ages than men. Despite accumulating evidence of increased burden of heart disease among women, there is little data on gender difference in heart disease-related mortality during the COVID-19 pandemic. Method(s): This study extracted the data of weekly number of deaths between January 2017 and December 2020 from the United States Center for Disease and Control and Prevention (CDC) mortality and morbidity data, modified to a monthly scale. Stratified by gender, the study applied the Farrington method on monthly data to calculate excess number of deaths. Excess heart disease-related deaths were observed in March and July 2020 for both males and females. Result(s): While the overall number of heart disease-related deaths was higher in men than women among US population <75 years old, a greater rate increase of heart disease-related deaths in 2020 from 2019 was observed among women than men. This increased burden was more pronounced among young women <25 years old. A similar pattern of excess deaths caused by underlying heart disease condition was observed for both genders during COVID-19 pandemic. On the other hand, increase in heart disease-related death burden in 2020 from 2019 was greater amongst females than males. This may be partially accounted for by deferred cardiovascular care and prevention amongst women during the pandemic. Conclusion(s): While no gender difference was observed in excess deaths caused by underlying heart disease condition, females faced a greater increase in heart disease-related death burden during the pandemic compared to pre-pandemic than males. Copyright: Copyright © 2022 The Author(s).

Forging clinical collaborations and cooperation in overcoming challenges for non-COVID-19 patients during COVID-19 times: Surgical case studies requiring a multidisciplinary and inter-agency approach in Malaysia

The COVID-19 pandemic has brought global health services to a standstill. National healthcare systems and medical staffing in many countries have reached crisis levels due to the phenomenal outbreak. Healthcare resources have been strained to meet the unprecedented numbers of patient admissions with a significant amount of funding and manpower being channelled towards tackling this global pandemic. Despite the rollout of vaccinations, the development of new viral strains has now presented a new challenge. With the inevitable conversion of tertiary public hospitals to specialized COVID-19 centres with 'Full Covid Status' and the mobilization of its doctors from all specialities to care for these patients, the non-COVID-19 patients are becoming more neglected. The lack of elective surgeries performed and non-emergent admissions due to the unavailability of beds and personnel to care for this group of patients are concerning. As most of the focus and resources are now aimed at COVID-19 patients, the need to forge collaborations and cooperation between hospitals, agencies and healthcare systems are pertinent to ensure the provision of quality treatment for those suffering from non-COVID-19 diseases. To highlight this effort in Malaysia, we would like to present 2 case studies of non-COVID-19 patients undergoing elective surgeries through intergovernmental ministerial collaborations and a public-private partnership.Copyright © The Author(s) 2022.

An Analysis of Image Features Extracted by CNNs to Design Classification Models for COVID-19 and Non-COVID-19.

The SARS-CoV-2 virus causes a respiratory disease in humans, known as COVID-19. The confirmatory diagnostic of this disease occurs through the real-time reverse transcription and polymerase chain reaction test (RT-qPCR). However, the period of obtaining the results limits the application of the mass test. Thus, chest X-ray computed tomography (CT) images are analyzed to help diagnose the disease. However, during an outbreak of a disease that causes respiratory problems, radiologists may be overwhelmed with analyzing medical images. In the literature, some studies used feature extraction techniques based on CNNs, with classification models to identify COVID-19 and non-COVID-19. This work compare the performance of applying pre-trained CNNs in conjunction with classification methods based on machine learning algorithms. The main objective is to analyze the impact of the features extracted by CNNs, in the construction of models to classify COVID-19 and non-COVID-19. A SARS-CoV-2 CT data-set is used in experimental tests. The CNNs implemented are visual geometry group (VGG-16 and VGG-19), inception V3 (IV3), and EfficientNet-B0 (EB0). The classification methods were k-nearest neighbor (KNN), support vector machine (SVM), and explainable deep neural networks (xDNN). In the experiments, the best results were obtained by the EfficientNet model used to extract data and the SVM with an RBF kernel. This approach achieved an average performance of 0.9856 in the precision macro, 0.9853 in the sensitivity macro, 0.9853 in the specificity macro, and 0.9853 in the F1 score macro.

Burden of Influenza and Respiratory Syncytial Viruses in Suspected COVID-19 Patients: A Cross-Sectional and Meta-Analysis Study.

Non-SARS-CoV-2 respiratory viral infections, such as influenza virus (FluV) and human respiratory syncytial virus (RSV), have contributed considerably to the burden of infectious diseases in the non-COVID-19 era. While the rates of co-infection in SARS-CoV-2-positive group (SCPG) patients have been determined, the burden of other respiratory viruses in the SARS-CoV-2-negative group (SCNG) remains unclear. Here, we conducted a cross-sectional study (São José do Rio Preto county, Brazil), and we collected our data using a meta-analysis to evaluate the pooled prevalence of FluV and RSV among SCNG patients. Out of the 901 patients suspected of COVID-19, our molecular results showed positivity of FluV and RSV in the SCNG was 2% (15/733) and 0.27% (2/733), respectively. Co-infection with SARS-CoV-2 and FluV, or RSV, was identified in 1.7% of the patients (3/168). Following our meta-analysis, 28 studies were selected (n = 114,318 suspected COVID-19 patients), with a pooled prevalence of 4% (95% CI: 3-6) for FluV and 2% (95% CI: 1-3) for RSV among SCNG patients were observed. Interestingly, FluV positivity in the SCNG was four times higher (OR = 4, 95% CI: 3.6-5.4, p < 0.01) than in the SCPG. Similarly, RSV positivity was significantly associated with SCNG patients (OR = 2.9, 95% CI: 2-4, p < 0.01). For subgroup analysis, cold-like symptoms, including fever, cough, sore throat, headache, myalgia, diarrhea, and nausea/vomiting, were positively associated (p < 0.05) with the SCPG. In conclusion, these results show that the pooled prevalence of FluV and RSV were significantly higher in the SCNG than in the SCPG during the early phase of the COVID-19 pandemic.

The impact of the COVID-19 pandemic and related policy responses on non-COVID-19 healthcare utilization in China.

We investigate the impact of the COVID-19 pandemic and related policy responses on non-COVID-19 healthcare utilization (i.e., different types of outpatient care) up to October 2020 in China. Using an administrative database from a large prefecture-level city, we find that both direct exposure to the COVID-19 pandemic and the strict containment policy responses led to reductions in outpatient care utilization. The largest decline during the lockdown was observed in preventive care visits, which nevertheless recovered to pre-pandemic levels 2 months after the lockdown. The disruptions in prenatal care visits could not be offset by the recovery later on. Chronic care and emergency department visits had not returned to pre-pandemic levels as of October 2020, which may be driven by extended days' supply of prescription medication, increased use of telemedicine, and improved health-protective behaviors. In the reopening period, there were increases in visits for mental and sleep disorders, especially among children, and for medical abortion. Among health facilities at all levels, primary care facilities saw the least reductions in total outpatient visits. Our results emphasize the need for strategies to ensure access to urgent or essential care services when managing the current epidemiologic transition and future crises.

The Pattern of Non-Covid-19 Paediatric Admissions in Malaysia Teaching Hospitals: Before and during the Covid-19 Pandemic with Movement Control Order

To study the characteristics of paediatric patients admitted to two non-COVID-19 teaching hospitals before and during the implementation of the Movement Control Order (MCO) in Malaysia. The retrospective study was performed in two phases (before MCO between February to March 2020, and during MCO lockdown between March to April 2020) in two teaching hospitals on the East Coast of Peninsular Malaysia. Hospitalized children <18 years were included and those coming for elective procedures or oncology treatment were excluded. The clinical data were retrieved from both hospitals' admission records. There was a total of 496 and 191 admissions to two teaching hospitals on the East Coast of Peninsular Malaysia, respectively. A significant reduction in the number of non-COVID-19 hospital admissions was seen in both hospitals. For Hospital Universiti Sains Malaysia, the daily hospital admissions were reduced with a mean of 10 (before MCO) to 7 (during MCO) admissions/day (95% CI 1.54,7.54, p=0.001). In Sultan Ahmad Shah Medical Centre, a reduction in hospital admission was seen from 5 (before MCO) to 3 (during MCO) admissions/day (95% CI 0.61, 3.15, p=0.005). Our study observed a general drop in non-COVID-related respiratory illnesses and infectious disease cases during the MCO period. There were significant differences in neurological (p=0.029) and accident (p = 0.001) cases admissions observed between the two periods. Copyright © 2022, Faculty of Medicine, University of Malaya. All rights reserved.

COVID-19: Salt in the Wound of Health Care Inequality and the Cause of a New Health Care Disparity.

The year 2020 will forever be associated with a new chapter in the history of global health, COVID-19. However, this new chapter would have a similar message because many other chapters were written before it. The COVID-19 pandemic would disproportionately affect minorities, those of low socioeconomic class, and those with limited access to health care. However, COVID-19 would also bring about a new health care disparity, limiting access to medical care for those with non COVID-19 related medical needs.

Coronavirus disease 2019 (COVID-19) excess mortality outcomes associated with pandemic effects study (COPES): A systematic review and meta-analysis.

Background and aim: With the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times. Methods: We searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Of 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons (n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06-0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38-1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07-1.30, p < 0.00001). There was "very low" certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain. Interpretation: The COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain. Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256].

Randomized placebo-controlled trial of oral tannin supplementation on COVID-19 symptoms, gut dysbiosis and cytokine response.

The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction in the inflammatory state was evident and significantly correlated with microbiota modulation. Among cytokines measured, MIP-1α was significantly decreased with tannin treatment (p=0.03) where it correlated positively with IL-1ß and TNF- α, and negatively with stool Bifidobacterium abundance.

Non-COVID-19 deaths in times of pandemic.

BACKGROUND AND OBJECTIVE: To investigate the effect of the COVID-19 pandemic on non-COVID-19 deaths in Mexico. METHODS: This study analyzes monthly administrative data on 15 different causes of death in Mexico from 2017 to 2020. The effects of the COVID-19 pandemic on non-COVID-19 deaths are conducted using a difference-in-differences methodology and an event study. RESULTS: The evidence shows mixed results. There is an increase in six causes of death: diabetes (36.8%), hypertension (25.8%), heart attacks (40.9%), bronchitis- asthma (24.2%), anemia (28.6%) and prostate cancer (21.4%). There is a decrease in two causes of death: traffic accidents (8.8%) and HIV (13.8%). There are null effects for seven causes of death: breast cancer, cerebrovascular disease, malnutrition, alcohol-related liver disease, renal insufficiency, homicides and suicides. CONCLUSIONS: The COVID-19 pandemic affected non-COVID-19 deaths caused by diseases that require intensive healthcare services. Conversely, this pandemic reduced social interactions, which contributed to a decrease on deaths such as traffic accidents.

Plasma Metabolome Alterations Discriminate between COVID-19 and Non-COVID-19 Pneumonia.

Pneumonia is a common cause of morbidity and mortality and is most often caused by bacterial pathogens. COVID-19 is characterized by lung infection with potential progressive organ failure. The systemic consequences of both disease on the systemic blood metabolome are not fully understood. The aim of this study was to compare the blood metabolome of both diseases and we hypothesize that plasma metabolomics may help to identify the systemic effects of these diseases. Therefore, we profiled the plasma metabolome of 43 cases of COVID-19 pneumonia, 23 cases of non-COVID-19 pneumonia, and 26 controls using a non-targeted approach. Metabolic alterations differentiating the three groups were detected, with specific metabolic changes distinguishing the two types of pneumonia groups. A comparison of venous and arterial blood plasma samples from the same subjects revealed the distinct metabolic effects of pulmonary pneumonia. In addition, a machine learning signature of four metabolites was predictive of the disease outcome of COVID-19 subjects with an area under the curve (AUC) of 86 ± 10 %. Overall, the results of this study uncover systemic metabolic changes that could be linked to the etiology of COVID-19 pneumonia and non-COVID-19 pneumonia.

A Glance Into Healthcare Delivery During COVID-19 Pandemic: A Survey Among Turkish Medical Doctors.

The coronavirus 2019 (COVID-19) pandemic had an enormous impact on healthcare delivery globally. We conducted a cross-sectional online survey in Turkey to evaluate the impact of COVID-19 on healthcare services in Turkey. A 35-item anonymized online survey was completed by HCPs (medical doctors, MD) who continued their clinical practice during the COVID-19 pandemic in Turkey, regardless of their specialties or degrees. Overall, 209 HCPs participated in the study. Forty-two percent of the participants stated that their current workload intensity has been increased compared with the pre-pandemic era. More than half of the participants (54.6%) were using telemedicine services during their clinical practice, however, the effectiveness of telemedicine for first-time patients and follow-up patients was rated as low. The majority of participants (59.3%) reported that during the peak period of the pandemic, they encountered only a small variety of cases, other than COVID-19. Fifty-two percent of the participants agreed that they occasionally had patients who received misdiagnosis in the first admission due to the suspicion of a possible COVID-19 infection predominating the diagnostic process (eg., not excluding COVID-19 even though the PCR test is negative). For the distribution of possible late-diagnosed diseases, 25.8% of HCPs selected chest diseases, followed by infectious diseases, heart diseases, and cancer. In general, participants agreed that there was an increase in the negligence in the follow-up of various diseases and/or complication rates due to COVID-19 pandemic. Sixty percent of the HCPs agreed that HCPs are being much more rigorous to diagnose/treating COVID-19 than other important diseases. Fifty-seven percent of the participants stated that the diagnosis and follow-up of chronic diseases are affected, while 57.9% of the HCPs stated that some diseases that show similar signs and symptoms as COVID-19 are not diagnosed correctly during COVID-19 pandemic. Findings from this study emphasize that COVID-19 pandemic has significantly caused delayed diagnoses and interruption in the management of chronic diseases, and also increased the risk of missing out the diagnosis of non-COVID-19 diseases. The study genuinely aims to yield the floor to a permanent improvement in post-pandemic clinical management and it also shows the need for a focused approach in distinct areas of medical care. Policymaking is required to drive changes to better support HCPs in Turkey.

Pathological Findings in COVID-19 and Non-COVID-19 Vaccine-Associated Lymphadenopathy: A Systematic Review.

COVID-19 vaccine-associated lymphadenopathy (C19-VAL) is increasingly encountered with the widespread use of the vaccine in controlling the outbreak. We aim to characterize the pathological findings of COVID-19 and non-COVID-19 vaccine-associated lymphadenopathy (NC19-VAL). A search for studies that reported pathological findings in vaccine-associated lymphadenopathy on PubMed and Google Scholar was performed on 11 December 2021. C19-VAL studies were pooled for analysis. These studies were split into clinical lymphadenopathy (CL) and subclinical lymphadenopathy detected on imaging (SLDI) for subgroup analysis. A total of 25 studies were related to COVID-19 vaccines, and 21 studies were included in the pooled analysis. The pooled analysis included 37 patients with a mean age of 47.8 ± 19.1 years old, and 62.2% were females. The mean duration from last vaccination to development of CL/SLDI was 14.5 ± 11.0 days. Most were diagnosed as reactive or negative for malignancy (28/37, 75.5%), followed by Kikuchi-Fujimoto disease (KFD) (3/37, 8.1%), florid lymphoid hyperplasia (2/37, 5.4%), and granulomatous inflammation (2/37, 5.4%). Metastases were reported in two patients with a history of malignancy (2/37, 5.4%). Cases with florid lymphoid hyperplasia and KFD were younger than those with reactive changes. A total of 14 studies were related to non-COVID-19 vaccines. Caseating granulomatous inflammation was reported in BCG vaccine-associated lymphadenopathy, while other vaccines were associated with reactive lymphoid hyperplasia, florid post-vaccinal reactions, and KFD. Although most C19-VAL cases were reported as reactive or negative for malignancy, other diagnoses included florid lymphoid hyperplasia, KFD, and granulomatous inflammation. Metastases were reported in lymphadenopathy of patients with a history of malignancy, who had been incidentally vaccinated. In conclusion, C19-VAL can yield different histopathological diagnoses when sampled, most of which require clinical and radiological correlation for optimal patient management.

Excess deaths from non-COVID-19-related causes in Japan and 47 prefectures from January 2020 through May 2021 by place of death.

Excess deaths, including all-causes mortality, were confirmed for the first time in Japan in April 2021. However, little is known about the indirect effects of COVID-19 on the number of non-COVID-19-related deaths. We then estimated the excess deaths from non-COVID-19-related causes in Japan and its 47 prefectures from January 2020 through May 2021 by place of death. Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare. Using quasi-Poisson regression models, we estimated the expected weekly number of deaths due to all-causes excluding COVID-19 (non-COVID-19) and due to respiratory disease, circulatory disease, malignant neoplasms, and senility. Estimates were made separately for deaths in all locations, as well as for deaths in hospitals and clinics, in nursing homes and elderly care facilities, and at home. We defined a week with excess deaths as one in which the observed number of deaths exceeded the upper bound of the two-sided 95% prediction interval. Excess death was expressed as a range of differences between the observed and expected number of deaths and the 95% upper bound of the two-sided predictive interval. The excess percentage was calculated as the number of excess deaths divided by the expected number of deaths. At the national level, excess deaths from non-COVID-19-related all-causes were observed during April 19 to May 16, 2021. The largest excess percentage was 2.73-8.58% (excess deaths 689-2161) in the week of May 3-9. Similar trends were observed for all four cause categories. The cause-of-death categories which contributed to the excesses showed heterogeneity among prefectures. When stratified by place of death, excess mortality tended to be observed in nursing homes and elderly care facilities for all categories, in hospitals and clinics for circulatory disease, and at home for respiratory disease, malignant neoplasms, and senility. A caution is necessary that for the lastest three months (March-May 2021), adjusted data were used to account for possible reporting delays.

Prevalence, Causes, and Adverse Clinical Impact of Delayed Presentation of Non-COVID-19-Related Emergencies during the COVID-19 Pandemic: Findings from a Multicenter Observational Study.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic has disrupted healthcare systems worldwide, resulting in decreased and delayed hospital visits of patients with non-COVID-19-related acute emergencies. We evaluated the impact of the COVID-19 pandemic on the presentation and outcomes of patients with non-COVID-19-related medical and surgical emergencies. METHOD: All non-COVID-19-related patients hospitalized through emergency departments in three tertiary care hospitals in Saudi Arabia and Bahrain in June and July 2020 were enrolled and categorized into delayed and non-delayed groups (presentation ≥/=24 or <24 h after onset of symptom). Primary outcome was the prevalence and cause of delayed presentation; secondary outcomes included comparative 28-day clinical outcomes (i.e., 28-day mortality, intensive care unit (ICU) admission, invasive mechanical ventilation, and acute surgical interventions). Mean, median, and IQR were used to calculate the primary outcomes and inferential statistics including chi-square/Fisher exact test, t-test where appropriate were used for comparisons. Stepwise multivariate regression analysis was performed to identify the factors associated with delay in seeking medical attention. RESULTS: In total, 24,129 patients visited emergency departments during the study period, compared to 48,734 patients in the year 2019. Of the 256 hospitalized patients with non-COVID-19-related diagnoses, 134 (52%) had delayed presentation. Fear of COVID-19 and curfew-related restrictions represented 46 (34%) and 25 (19%) of the reasons for delay. The 28-day mortality rates were significantly higher among delayed patients vs. non-delayed patients (n = 14, 10.4% vs. n = 3, 2.5%, OR: 4.628 (CI: 1.296-16.520), p = 0.038). CONCLUSION: More than half of hospitalized patients with non-COVID-19-related diagnoses had delayed presentation to the ED where mortality was found to be significantly higher in this group. Fear of COVID-19 and curfew restrictions were the main reasons for delaying hospital visit.

COVID-19 Pandemic and Trends in Clinical Trials: A Multi-Region and Global Perspective.

To evaluate the effect of the COVID-19 pandemic on clinical development, the number of newly started clinical trials in each geographical region between January 2018 and December 2020 were calculated based on data from the ClinicalTrials.gov database. Data regarding new drug applications were obtained from European Medicines Agency monthly reports, pharmaceutical company press releases, and the archives of the Drugs.com database. The mean percentage change in newly started clinical trials for diseases other than COVID-19 between each month in 2019 and the corresponding month in 2020 was -7.5%, with the maximum of -57.3% observed between April 2019 and April 2020. Similarly, the mean percentage change of reported results for each month in 2019 and 2020 was -5.1%, with the maximum of -27.4% observed in July 2020. The activity of clinical trials was decreased as the number of COVID-19 patients was increased, and a statistically negative correlation was observed between the prevalence of COVID-19 and the percentage decrease in the number of clinical trials stared or reported results. As for new drug submissions, decreases were observed in the latter half of 2020 compared with the same period during the previous year, for each indicator. A considerable decline in non-COVID-19 activity for all indicators regarding clinical developments was suggested during the first wave of the COVID-19 pandemic. It is important to recognize the situation and continue to make efforts to conduct clinical trials for both COVID-19 and no-COVID-19 for new medical developments in the future.

A retrospective analysis of metabolic control in children with PKU in the COVID-19 era.

Background: Patients with phenylketonuria (PKU) must maintain a lifelong natural protein-restricted diet to prevent neuro-cognitive damage. Early diagnosis is established with newborn screening, with diet subsequently controlled by regular phenylalanine (Phe) monitoring. During the COVID-19 pandemic, significant lockdown measures were introduced that may have influenced the above. Aim of our study: To establish whether the diagnosis was delayed in neonates during the pandemic. In addition, metabolic control was further assessed during the COVID-19 pandemic era (CE) compared to the same period a year prior (non-COVID-19 era, NCE). The lockdown periods (LD) were also compared with unrestricted periods (URP). Patients methods: Six neonates born during the CE and eight neonates born during NCE were included in the newborn screening analysis. Seventy-two classical PKU patients aged 2-18 years and categorized as children (2-12 years; 51 patients) and adolescents (>13 years; 21 patients) were included in the metabolic control analysis. The frequency of dried blood spot (DBS) sampling and Phe levels were assessed according to the different periods. Results: There was no diagnostic or therapeutic delay in reaching the recommended Phe range in neonates born during CE compared to those born in NCE (median [interquartile range, IQR]: 23.5 [22.5-24] vs. 22 [18.0-27] days, p = NS). The cumulative DBS sampling frequency in children increased by 9.9% in the CE while no change was noted in the adolescent group. The median Phe level increased significantly in both age groups in the CE, but remained within the recommended target range. During CE, changes in Phe levels differed in the two age groups: children had the highest median Phe in the second lockdown period (LD2), while the adolescents had an increased Phe in URP.There were significant negative correlations between DBS sampling frequencies and Phe levels in both age groups in NCE (children: r - 0.43, p = 0.002; adolescents r = -0.37, p = 0.012), and in adolescents in CE (r = -0.62, p = 0.006). Conclusion: The pandemic did not impact newborn metabolic screening. The increased frequency of DBS sampling in CE and good target Phe levels suggest a better compliance in a very sensitive period. Since many factors may impact metabolic control in the different age groups, further studies are needed to analyse their respective role.