“Salus Populi Suprema Lex”: Considerations on the Initial Response of the United Kingdom to the SARS-CoV-2 Pandemic

In several countries worldwide, the initial response to coronavirus disease 2019 (COVID-19) has been heavily criticized by general public, media, and healthcare professionals, as well as being an acrimonious topic in the political debate. The present article elaborates on some aspects of the United Kingdom (UK) primary reaction to SARS-CoV-2 pandemic; specifically, from February to July 2020. The fact that the UK showed the highest mortality rate in Western Europe following the first wave of COVID-19 certainly has many contributing causes; each deserves an accurate analysis. We focused on three specific points that have been insofar not fully discussed in the UK and not very well known outside the British border: clinical governance, access to hospital care or intensive care unit, and implementation of non-pharmaceutical interventions. The considerations herein presented on these fundamental matters will likely contribute to a wider and positive discussion on public health, in the context of an unprecedented crisis

Evaluation of Antiproliferative Activity of Some Traditional Anticancer Herbal Remedies from Jordan

Purpose: To evaluate the in vitro antiproliferative activity of the extracts of the three plants against a panel of human tumor cell lines representing the most common types of cancer in Jordan, viz, breast and colorectal and skin cancers.Methods: The methanol extracts of the aerial parts of the three plants (Arbutus andrachne L., Chrysanthemum coronarium L., and Teucrium polium L.) were prepared and assessed for antiproliferative activity against six human tumor cell lines (A375.S2, WM1361A, CACO-2, HRT18, MCF-7, T47D) using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide MTT cell proliferation assay.Results: C. coronarium extract, at the concentration range of 25 to 400 μg/mL, significantly inhibited (10 – 50 %) the proliferation of the 6 cell lines in a dose-dependent manner, whilst the extracts of the other two plants exhibited weak antiproliferative activity (2 – 10 % inhibition). The half-maximal inhibitory concentration (IC50) values of C. coronarium extract against the six cell lines were in the range of 75.8 to 138.5 μg/mL.Conclusion: The methanol extract of the aerial parts C. coronarium possesses a relatively potent antiproliferative activity and therefore might be a potential source of natural compounds that can be developed into new antineoplastic agents.Keywords: Antiproliferative, Arbutus andrachne L., Chrysanthemum coronarium L., Teucrium polium L. Jordan flora, Medicinal plants, Cancer, Antineoplasti

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Grand Challenges in global eye health: a global prioritisation process using Delphi method

Background We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenge

Quality of life of women with breast cancer undergoing treatment and follow-up at King Salman Armed Forces Hospital in Tabuk, Saudi Arabia

Attiya Mohammed Al Zahrani,1 Yousif Alalawi,1 Umar Yagoub,2 Nooralsbah Saud,1 Kashif Siddig11Department of Surgery, King Salman Armed Forces Hospital, Northwestern Region, Tabuk 71411, Saudi Arabia; 2Research Unit, Department of Academic Affairs, King Salman Armed Forces Hospital, Northwestern Region, Tabuk 71411, Saudi ArabiaBackground: Assessment of quality of life can significantly impact the diagnosis and treatment course of breast cancer, resulting in a better prognosis among patients. However, very limited data are available regarding quality of life among breast cancer patients in Saudi Arabia.Objective: To determine the quality of life of women with breast cancer referred to the Surgery Department of King Salman Armed Forces Hospital for treatment and follow-up.Materials and methods: This cross-sectional study used a questionnaire to assess the quality of life of 96 adult Saudi female patients diagnosed with breast cancer from January 2016 to September 2017.Results: One-third of the surveyed patients (31.3%) were >48 years of age, and 29.2% were in the 18- to 27-year age group. Regarding marital status, 35.4% of the women were married and 8.3% were single. The highest score was observed for the physical well-being subscale (7.65±071), followed by the spiritual well-being subscale (7.19±0.66), psychological well-being scale (7.09±0.30) and social concerns subscale (7.02±0.41). Age, marital status and cancer stage differed remarkably (P=0.00) for the physical well-being subscale scores. Meanwhile, employed women differed significantly (P=0.01) in terms of psychological well-being compared to those who were not employed. The social well-being subscale score of single and married women was significantly higher than that of widowed and divorced women. Women who underwent radiation and immunotherapy had significantly higher scores for the spiritual well-being subscale.Conclusions: Scores were determined for the physical, spiritual, psychological and social well-being scales. Age, marital status and cancer stage significantly influenced the physical well-being scale; the occupation status of the patients significantly impacted the psychological well-being scale. Social well-being can be predicted by marital status, and chemotherapy and radiation significantly impacted the spiritual well-being scale.Keywords: cross-sectional study, QOL instrument, independent t-test, ANOVA analysis, test-retest, immunotherap

Uptake, Safety and Attitudes Towards COVID-19 Vaccination: A Cross-Sectional Study on First and Second Doses Among the General Public

Mansour A Mahmoud,1 Alnada Ibrahim,2 Fawaz Alharbi,3 Ali Mohammed Alalawi,4 Faris Alnezary,1 Ahmed Aldafiri,3 Yaser Alahmadi,1 Sultan Othman Alolayan,1 Sultan S Althaqfan,1 Mohammed M Alsultan,5 Safaa Omer,6 Musaad B Alsahly7 1Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; 2Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O.Box 84428, Riyadh, 11671, Saudi Arabia; 3AlHaram Hospital, Ministry of Health, Al-Madinah Al-Munawarah, Saudi Arabia; 4Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; 5Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 6Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia; 7College of Medicine, Department of Physiology, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Alnada Ibrahim, Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia, Email [email protected] Mansour A Mahmoud, Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, AL-Madinah Al-Munawara, Saudi Arabia, Email [email protected]: To investigate public uptake, attitudes and the safety of the first and second doses of COVID-19 vaccination.Methods: This was a cross-sectional web-based survey study. A self-administered questionnaire was prepared from a literature search and information about COVID-19 available at various resources. The developed questionnaire was validated for readability by experts and refined in light of the feedback received from the experts and the final version was prepared. The reliability of the questionnaire was 0.7 which shows an acceptable level of scale internal consistency. The data analysis was performed using IBM SPSS software (version 25).Results: A total of 513 participants completed the survey, including 311 (60.6%) women and 202 (39.4%) men. The mean age was (31.5± 12.8) years. It was found that 493 (96.1%) took the first and second doses of COVID-19 and 376 (73.3%) suffered from side effects, of these 14% (56/376) reported the side effects to the health authorities. The most common side effects were fatigue (51.5%), fever (42.3%), headache (39.5%), and injection site pain (37.6%). Half of the participants (50.5%) had a positive attitude towards COVID-19 preventive measures. Females had higher odds of experiencing side effects than males OR (95% CI); 2.002 (1.312– 3.056). Individuals living in urban areas had lower odds of experiencing side effects than those living in rural areas OR (95% CI); 0.364 (0.142– 0.933).Conclusion: Vaccine uptake was massive and side effects due to the COVID-19 vaccine were common but minor. The majority of the participants had positive attitudes towards recommended COVID-19 preventive measures. Being female and living in rural areas were associated with experiencing side effects.Keywords: COVID-19, safety, uptak

Chemokine receptors as novel targets of the oncogene Notch1 in acute lymphoblastic leukemia

Background: Malignant cells from different cancers express different profiles of chemokine receptors (CKR). Their presence may influence site-specific spread of tumor cells, by enabling them to respond to chemokine gradient, and may increase cell sensibility to chemokine mediated proliferative and anti-apoptotic stimuli. Notch ability to positively regulate CKR has been reported: stimulation of Pax5-/- pre-B cells with the Notch ligand Delta-1 results in induction of transcripts for CCR4, CCR8 and CXCR 6; the Delta-1-dependent regulation of Langerhans cell development includes induction of CCR6 expression resulting in the activation of chemotactic response to MIP-1a; Notch controls CCR7 signaling a regulator of CNS infiltration in T-acute lymphoblastic leukemia (T-ALL). Methods: This work aims to explore the correlation between the activation of the Notch oncogenic pathway in T-ALL and multiple myeloma (MM) cells and the aberrant expression CKR. Human T-ALL cell lines were treated with the Notch activation inhibitor, DAPT, or with a potent inhibitor of the Notch target, C-MYC, and evaluated the expression and functions of CCR9, CCR5, and CXCR4. Results: Treatment of human T-ALL and MM cell lines with pharmacologic inhibitors of Notch receptor activation produced a significant reduction of CCR9, CCR5 and CXCR4 expression, at both mRNA and protein levels. Results were confirmed by chemotaxis and survival assays. We identified the product of C-MYC gene as a possible mediator of Notch effect in regulating CKR networks in T-ALL and MM. Conclusions: These results suggest that Notch receptors play a previously unknown role in cancer progression and metastasis, by maintaining the expression levels of CKR. In conclusion, the identification of the potential axis Notch/CKR could have a prognostic value and provide the rationale for a tailored approach, since both Notch and CKR are targeted by emerging drugs