Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

Association between Covid-19 and Pulmonary Embolism (AC-19-PE study)

The lifestyles change of children and adolescents during the COVID-19 pandemic due to antipandemic measures can affect their sleep health. Existing studies have used convenient samples and focused on the initial months of the pandemic, leaving a knowledge gap on changes in young people's sleep patterns under the "new normal" under COVID-19. As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. Sleep parameters were collected using the structured diagnostic interview for sleep patterns and disorders. We investigated the pandemic's effects on sleep parameters by comparing data of participants recruited pre-COVID and those recruited during COVID using multivariate regression, adjusting for age, sex, household income, seasonality, and presence of mental disorders, and the moderators and mediators of the effects. Between September 1, 2019 and June 2, 2021, 791 primary and 442 secondary school students were recruited and analyzed. Primary school and secondary school participants assessed before COVID had a longer sleep latency on school days (95% confidence interval [CI] = 1.0-5.2 minutes, adjusted P-value = .010; and 95% CI= 3.9-13.0 minutes, adjusted P-value = .004, respectively) and nonschool days (95% CI = 1.7-7.2 minutes, adjusted P-value = .005; 95% CI = 3.4-13.7 minutes, adjusted P-value = .014, respectively). Low household income was a moderator for later bedtime (adjusted P-value = .032) and later sleep onset (adjusted P-value = .043) during nonschool days among secondary school students. Changes associated with COVID have a widespread and enduring effect on the sleep health of school-aged students in Hong Kong. Household income plays a role in adolescent sleep health resilience, and the impact of antiepidemic measures on the health gaps of the youth should be considered. Chau SWH, Hussain S, Chan SSM, etal. A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic. J Clin Sleep Med. 2023;19(4):749-757.

Small-animal positron emission tomography as a tool for neuropharmacology

The COVID-19 pandemic and public health response to the pandemic has caused huge setbacks in the management of other infectious diseases. In the present study, we aimed to (i) assess the trends in numbers of samples from patients with influenza-like illness and severe acute respiratory syndrome tested for influenza and the number and proportion of cases detected from 2015–2021 and (ii) examine if there were changes during the COVID-19 period (2020–2021) compared to the pre-COVID-19 period (2015–2019) in three states of India. The median (IQR) number of samples tested per month during the pre-COVID-19 period was 653 (395–1245), compared to 27 (11–98) during the COVID-19 period (p value < 0.001). The median (IQR) number of influenza cases detected per month during the pre-COVID-19 period was 190 (113–372), compared to 29 (27–30) during the COVID-19 period (p value < 0.001). Interrupted time series analysis (adjusting for seasonality and testing charges) confirmed a significant reduction in the total number of samples tested and influenza cases detected during the COVID-19 period. However, there was no change in the influenza positivity rate between pre-COVID-19 (29%) and COVID-19 (30%) period. These findings suggest that COVID-19-related disruptions, poor health-seeking behavior, and overburdened health systems might have led to a reduction in reported influenza cases rather than a true reduction in disease transmission.

Context The COVID-19 pandemic caused mandated restrictions on movements and distancing of people with implications for meat supply chains. Despite the COVID restrictions, agricultural activities were permitted to continue as essential services in Australia. However, there were reported shortages of meat on the shelves of supermarkets and a general increase in the price of meat in Australia during the COVID period. Hence, there is a need to establish whether the restrictions affected upstream activities in Australia’s beef supply chain. Aim This study aims to examine the impact of the COVID-19 pandemic and confounding factors including rainfall and export bans on beef cattle trade and movement in Australia. Methods Using annual data on beef cattle sold, purchased, transferred off-farm and transferred onto farms sourced from the database of the Australian Bureau of Agricultural and Resource Economics and Sciences, a t-test analysis was conducted to establish the significant changes in cattle movement and trade for the pre-COVID (2014–2019) and COVID (2020–2022) periods. Additionally, a flexible least squares model augmented with a flexible generalised least squares model was used to assess the impact of confounding factors on cattle trade and movement. Key results The results indicate no significant change in the proportion of beef cattle sold nationwide. Tasmania, New South Wales, and Western Australia (WA) recorded significant changes (1.4% increase, 3.6% increase, and 3.8% decrease, respectively) in the proportion of beef cattle purchased. For WA, these changes were localised to changes that occurred in WA Central and Southern Wheat Belt and WA Southwest Coastal regions. Moreover, rainfall did not significantly impact cattle trade but did affect cattle movements. The export ban only significantly impacted beef cattle sold in Queensland. Conclusions Overall, the findings suggest that most regions in Australia did not experience significant changes in farm-level decisions regarding beef cattle movement and trade during the COVID period. Instead, minor adjustments were made to address the demand changes. Implications The findings imply that adopted policies that facilitated the implementation of biosecurity bubbles and the movements of animal transport workers for breeding facilities and abattoirs during the COVID period were effective in normalising farm-level operations.

The COVID-19 pandemic has disrupted cancer care. An audit at a major Paediatric Oncology Department in Turkey was performed to determine its impact on paediatric cancer care. A comparison was made among the number of daily paediatric cancer patients, diagnostic and treatment procedures. The data for the ‘COVID-19 period’ (10 March to 31 October 2020) were compared with the corresponding ‘prior year control period’ (10 March to 31 October 2019). Moreover, presentation delay (duration between first symptoms to healthcare visit) was calculated for new cases. The findings indicate that the mean 34.7 outpatients per day during ‘COVID-19 period’ was significantly lower than the ‘prior year control period’ (52.2). There were 17.7 inpatients per day during the ‘COVID-19 period’ which was significantly lower than 23.8 inpatients per day during the ‘prior year control period’. Significant reduction in the daily mean number of patients undergoing chemotherapy, radiotherapy, surgery and imaging studies during the ‘COVID-19 period’ was also evident. A negative trend in the diagnosis of new paediatric cancers was evident with 128 new cancer cases during the ‘COVID-19 period’, whereas the corresponding number was 212 for the ‘prior year control period’. The presentation delay (median 31 days) remain unchanged during the ‘COVID-19 period’. The findings suggest significant damage to paediatric cancer care during the COVID-19 pandemic. Appropriate obligatory actions by oncology societies and policymakers can minimise longer term negative impacts.

Objective: To investigate the impact of the COVID-19 pandemic on the diagnosis and treatment processes of ectopic pregnancies (EP) at a tertiary hospital in Turkey. Methods: This retrospective study compared 221 cases of tubal EP diagnosed after March 15, 2020, with 217 cases diagnosed before this date. Patient demographics, clinical characteristics, and treatment modalities were analyzed. Statistical analyses, including independent t-tests, Chi-square tests, and multinomial logistic regression, were conducted to assess differences between the COVID and pre-COVID periods. Results: The study found no significant differences in maternal age, gravidity, parity, or gestational weeks between the COVID and pre-COVID periods. However, there was a notable increase in patients presenting with abdominal pain (52.5% vs. 37.8%) and intraperitoneal hemorrhage (26.7% vs. 7.4%) during the COVID period. Despite the higher frequency of abdominal pain, vaginal bleeding was less common during the pandemic. Treatment approaches also shifted, with a significant increase in medical management (41.2% vs. 29.0%) and a slight decrease in surgical interventions during the COVID period. Multinomial logistic regression revealed that parity, gestational week, presence of Douglas fluid, and the period of diagnosis (COVID vs. pre-COVID) were significant predictors of treatment modality. Conclusion: The COVID-19 pandemic influenced the clinical presentation and management of ectopic pregnancies in our hospital. While there were no significant differences in key demographic or laboratory parameters, the increased presence of abdominal fluid and a shift towards medical management during the pandemic period suggest changes in patient presentation and treatment preferences. This study underscores the importance of maintaining vigilant diagnostic and therapeutic approaches for EP, even during global health crises.

Natural hazards combined with the COVID-19 pandemic have had significant global impacts to the community and the environment. This study explores the impact of the Australian 2019/20 bushfires followed by the COVID-19 pandemic on unintentional coastal drowning fatalities. Fatality data were collated using triangulation methodology. Percentage change in coastal drowning fatalities between 2019/20 financial year (FY) and the 15FY annual average (2004/5–2018/19) were calculated for the dominant bushfire period (August 2019–February 2020 inclusive) and COVID-19 restrictions in place for 2019/20FY (March–June 2020 inclusive). Relative risk (RR; with 95% confidence intervals [CI]) of coastal drowning was calculated against the average for overall, bushfire and COVID-19 periods, using coastal participation data as the denominator, weighted for the predicted decrease in the use of outdoor coastal areas due to these widespread events. Coastal drowning fatalities increased in 2019/20FY by 9% overall (bushfires: 6%; COVID-19: 9%). Swimming/wading drowning fatalities increased during the bushfire period (RR = 2.02; 95% CI: 1.13–3.63), while boating and personal watercraft (PWC)-related fatalities increased during both the bushfire (RR = 2.92; 95% CI: 1.41–6.05) and COVID-19 period (RR = 3.86; 95% CI: 1.64–9.11). Rock fishing fatalities also increased across both the bushfire (RR = 4.19; 95% CI: 1.45–12.07; p = 0.008) and COVID-19 (RR = 3.8;95% CI: 1.24–11.62; p = 0.027) periods. Findings indicate the activity patterns leading to coastal drowning fatalities changed despite significant public health events impacting freedom of movement and thus opportunity for coastal participation. Understanding, and preparing for, the impacts of natural hazards on drowning risk is vital for future preventive efforts.

For the development of the next generation of polymeric nanomedicines, it is crucial to gain a fundamental understanding of their behaviour and interactions with and within biological systems. Moving beyond in vitro models, into in vivo models, earlier in the development process will greatly aid in the advancement of the next generation of nanomedicines. By moving to whole animal models, our understanding of these systems progresses beyond cell targeting and uptake, to developing mechanisms for how these materials will distribute through tissues and their pharmacokinetic profile. This information is important for truly assessing the performance of a nanomedicine. One possible set of tools for obtaining this information is molecular imaging. Molecular imaging is a field of research dedicated to the real time monitoring of biological processes in vivo, without the use of invasive techniques such as biopsies and dissections. Molecular imaging has been used extensively to follow the in vivo behaviour of a labelled material. This is advantageous because the performance of a single material in one subject can be monitored and mapped against the progression of disease. It can help to provide the pharmacokinetic information necessary for preclinical development of nanomedicines. Nanomedicines can be designed to combine molecular imaging with targeting molecules and therapeutic agents to create a theranostic, which can be used for simultaneous imaging and treatment of disease. This thesis aims to synthesise novel multimodal molecular imaging agents based on a hyperbranched polymer architecture, and to gain a deeper understanding of how these materials behave in vivo. To achieve this, biocompatible hyperbranched polymers with defined architectures were synthesised using RAFT polymerisation techniques. These materials were extensively characterised using a wide range of spectroscopic techniques to thoroughly understand their physical and chemical properties. A variety of synthetic strategies were investigated for functionalising both the α- and ω-chain ends of these polymers with multiple imaging ligands to form multimodal imaging agents. Far-red and near-infrared fluorophores provided for fluorescence imaging and radiometal chelators allowed for positron emission tomography (PET) imaging. These hyperbranched polymer systems were first evaluated as molecular imaging agents in C57 BL/6J mice using whole animal fluorescence and PET-CT imaging. It was shown that the rate of excretion was dependent on the size and level of branching of the hyperbranched polymer cores. The larger more highly branched material showed extended circulation times, making it suitable for use as a passive targeting agent for cancer. It was demonstrated in a murine model for melanoma, that the material showed significant uptake within the tumour after 24 hours and that the material was not cleared from the tissue within 72 hours. To gain a deeper understanding of the behaviour of these materials in vivo, PET imaging was combined with gadolinium contrast enhanced MRI, in order to gain both molecular and physiological information. Using this technique, we were able to show that while a folic acid targeted hyperbranched polymer did accumulate in the tumour tissue, its distribution was concentrated in highly vascularised areas of the tumour. This is the first time that this phenomenon has been demonstrated at a macroscopic level, in a living animal. This has important implications for using these materials as theranostics, because heterogeneous distribution of the nanomaterial, and therefore delivery of a therapeutic, can lead to ineffective treatment of the cancer and thus lead to tumour recurrence. In further development of these imaging agents into theranostics, targeting of the hyperbranched polymers by conjugating single chain fragment antibodies (scFv) was explored. Two potential routes to improve efficiency of conjugation were investigated. Both approaches used novel bifunctional oligoethylene glycol (OEG) linkers to introduce the required chemical functionality to either the hyperbranched polymer or scFv. The first approach utilised a heterobifunctional OEG which was synthesised with a pentafluorophenol ester at one end for coupling with amines and an ω-azide group at the other end to allow for the copper catalysed Huigsen 1,3-dipolar cycloaddition reactions. This linker was first attached to the scFv via activated ester chemistry, to provide the necessary azide functionality for coupling of the scFv to the alkyne end groups of the hyperbranched polymer. The second route used an enzymatic cross coupling approach using the sortase enzyme. In order to achieve this, a triglycine functionalised OEG ligand was synthesised and attached to the hyperbranched polymer. The triglycine could then be used as a substrate for enzymatic cross coupling to scFv bioengineered to possess the required recognition sequence (LPETG). Despite both OEG linkers being demonstrated to be able to undergo conjugation to both the hyperbranched polymers and scFv independently, further optimisation is required to achieve conjugation of the two macromolecules.

BackgroundOut-of-hospital cardiac arrest (OHCA) remains one of the leading causes of death worldwide, and bystander CPR with public-access defibrillation improves OHCA survival outcomes. The COVID-19 pandemic has posed many challenges for emergency medical services (EMS), including the suggestion of compression-only resuscitation and recommendations for complete personal protective equipment, which have created operational difficulties and prolonged response time. However, the risk factors affecting OHCA outcomes during the pandemic are poorly defined. This study aimed to assess the characteristics and outcomes of OHCA patients before and during the COVID-19 pandemic in Thailand.MethodsThis single-center, retrospective cohort study used data from electronic medical records and EMS paper records. All OHCA patients who visited Ramathibodi Hospital’s emergency department before COVID-19 (March 2018 to December 2019) and during COVID-19 (March 2020-December 2021) were identified, and the number of emergency department returns of spontaneous circulation (ED-ROSC) and characteristics in OHCA patients before and during the COVID-19 pandemic in Thailand were collected.ResultsA total of 136 patients were included (78 men [59.1%]; mean [SD] age, 67.9 [18] years); 60 of these were during the COVID-19 period (beginning March 2020), and 76 were before the COVID-19 period. The overall baseline characteristics that differed significantly between the two groups were bystander witness and mode of chest compression (p-values < 0.001 and < 0.001, respectively). The ED ROSC during the COVID-19 period was significantly lower than before the COVID-19 period (26.67% vs. 46.05%, adjusted OR 0.21, p-value < 0.001). There were significant differences in survival to admission between the COVID-19 period and before (25.00% and 40.79%, adjusted OR 0.26, p-value 0.005). However, 30-day survivals were not significantly different (3.3% during the COVID-19 period and 10.53% before the COVID-19 period).ConclusionsDuring the COVID-19 pandemic in Thailand, ED ROSC and survival to admission in out-of-hospital cardiac arrest patients were significantly reduced. Additionally, the witness responses and mode of chest compression were very different between the two groups.Trial registrationThis trial was retrospectively registered on 7 December 2021 in the Thai Clinical Trial Registry, identification number TCTR20211207006.

To investigate the epidemiological changes in emergency department (ED), including changes in toxic substances and ED outcomes in pediatric and adolescent patients who visited the EDs before and during the COVID-19 pandemic. This cross-sectional observational study used data from the ED-based Injury In-depth Surveillance from 2017 to 2021 in South Korea (SK). The study population comprised patients aged <19 years who visited 23 EDs because of poisoning before and during the COVID-19 outbreak. We divided the study period into pre-COVID-19 (January 2017 to February 2020) and COVID-19 periods (March 2020 to December 2021). In total, 5862 patients were included in the final analysis, with 3863 and 1999 in the pre-COVID-19 and COVID-19 periods, respectively. The patients' mean age increased from 8.3 ± 7.1 to 11.2 ± 6.9 years between the pre-COVID-19 and COVID-19 periods (P < 0.001), and the number of adolescents (aged 13-18 years) significantly increased during the COVID-19 period (1653 [42.8%] vs. 1252 [62.6%]; P < 0.001). The number of intentional poisoning cases increased from 1332 (34.5%) before COVID-19 to 1174 (58.7%) during COVID-19 (P < 0.001). Specifically, pharmaceutical poisoning significantly increased during the COVID-19 period (2242 [58.0%] vs. 1443 [72.2%]; P < 0.001), with central nervous system (CNS) drug poisoning being the most common type (780 [34.8%] vs. 747 [51.8%]; P < 0.001). Among the intentional poisoning cases, pharmaceutical substance use significantly increased during the COVID-19 period (1207 [90.6%] vs. 1102 [93.9%]; P = 0.007). We used Bayesian structural time series (BSTS) forecasting models to forecast the number of ED visits during COVID-19. The total number of pediatric patients with poisoning decreased during the COVID-19 pandemic. However, when using the BSTS forecasting model, the decrease in the number of patients was not significant. Furthermore, the forecasting models showed no statistically significant increase in the number of intentional pediatric poisoning cases. The previous studies suggested a decrease in the total number of patients with poisoning but an increase in intentional poisoning cases during the COVID-19 pandemic. By using similar methods to those of previous studies, our results also reached the same conclusion. However, the BSTS model, which predicts real-world time series patterns, seasonal effects, and cumulative effects, shows no significant change in pediatric poisoning patterns during the COVID-19 pandemic.

Breast Cancer Survivorship Care During the COVID-19 Pandemic Within an Urban New York Hospital System

BackgroundDuring the Covid-19 pandemic, non‐operative management for acute appendicitis (AA) was implemented in the UK. Aim of this study was to determine the efficacy and outcomes of conservative versus surgical management of AA during the pandemic.Materials & MethodsWe conducted an observational study in a tertiary referral centre. Data was collected from patients (≥16 years) with a diagnosis of AA between 1st November 2019 to 10th March 2020 (pre-COVID period) and 10th March 2020 to 5th July 2020 (COVID period).ResultsA total of 116 patients in the pre-COVID period were included versus 91 in the COVID period. 43.1% (n = 50) of patients pre-COVID were classified as ASA 2 compared to 26.4% (n = 24) during the COVID period (p-value=0.042). 72.5% (n = 66) of the patients during the COVID period scored as high risk using the Alvarado score compared to 24.1% (n = 28) in the pre-COVID period (p-value<0.001). We observed a significant increase in radiological evaluation, 69.8% versus 87.5% of patients had a CT in the pre-COVID and COVID periods respectively (p-value=0.008). 94.9% of patients were managed operatively in the pre-COVID period compared to 60.4% in the COVID period (p-value<0.001). We observed more open appendicectomies (37.3% versus 0.9%; p-value<0.001) during the COVID period compared to the pre-COVID period. More abscess formation and free fluid were found intraoperatively in the COVID period (p-value= 0.021 and 0.023 respectively). Re-attendance rate due to appendicitis-related issues was significantly higher in the COVID period (p = 0.027).ConclusionRadiological diagnosis of AA was more frequent during the COVID period. More conservative management for AA was employed during the COVID-19 pandemic, and for those managed operatively an open approach was preferred. Intra-operative findings were suggestive of delayed presentation during the COVID period without this affecting the length of hospital stay.

Acute appendicitis management during the COVID-19 pandemic: A prospective cohort study from a large UK centre

Objectives: Thousands of designated COVID-19 hospitals have been set up in China to fight the ongoing COVID-19 pandemic. Anecdotal reports indicate a falling rate of acute stroke diagnoses in these hospitals during the COVID-19 period. We conducted an exploratory single-center analysis to estimate the change in acute stroke presentation at the designated COVID-19 hospitals.Methods: This retrospective observational study included all patients admitted to Yongchuan Hospital Affiliated to Chongqing Medical University with acute stroke between January 24 and March 10, 2020. Patient demographics, characteristics of the stroke, treatment details, and clinical outcomes were compared with those of patients admitted in the corresponding period in the year before (2019, “the pre-COVID-19 period”). Subgroup analysis was performed in the ischemic and hemorrhagic stroke groups.Results: A total of 110 patients presented with acute stroke symptoms during the COVID-19 pandemic, compared with 173 patients in the pre-COVID-19 period. A higher proportion of stroke patients presented to the hospital via emergency medical services during the pandemic (48.2 vs. 31.8%, p = 0.006). There was a lower proportion of ischemic stroke patients (50.9 vs. 65.3%, p = 0.016) than in the preceding year. There were significantly fewer patients with 90-day modified Rankin Scale score ≥3 in the COVID-19 period compared with the pre-COVID-19 period (17.3 vs. 30.6%, p = 0.012). Among patients with ischemic stroke, the mean time from patient arrival to vessel puncture for emergency endovascular therapy in the COVID-19 period was shorter than that in the pre-COVID-19 period (109.18 ± 71.39 vs. 270.50 ± 161.51 min, p = 0.002). Among patients with hemorrhagic stroke, the rate of emergency surgical operation in the COVID-19 period was higher than that in the pre-COVID-19 period (48.1 vs. 30.0%, p = 0.047). The mean time from patient arrival to emergency surgical operation (15.31 ± 22.89 vs. 51.72 ± 40.47 min, p = 0.002) was shorter in the COVID-19 period than in the pre-COVID-19 period.Conclusions: Although fewer acute stroke patients sought medical care in this designated COVID-19 hospital during the COVID-19 pandemic, this type of hospital was more efficient for timely treatment of acute stroke. Recognizing how acute strokes presented in designated COVID-19 hospitals will contribute to appropriate adjustments in strategy for dealing with acute stroke during COVID-19 and future pandemics.