Establishment of reference intervals for complete blood count in times of COVID-19 and vaccination.

Introduction: COVID-19 and vaccination may affect some parameters of the complete blood count (CBC). The aim of this study was to determine reference intervals (RI) of CBC in healthy population with different COVID-19 and vaccination backgrounds and compare them with those established previously. Materials and methods: A cross-sectional study was conducted in donors who attended the Traumatology Hospital "Dr. Victorio de la Fuente Narváez" (HTVFN) from June to September 2021. Reference intervals were established using the non-parametric method on Sysmex XN-1000. For differences between groups with different COVID-19 and vaccination backgrounds, non-parametric tests were used. Results: The RI were established in 156 men and 128 women. Haemoglobin (Hb), haematocrit (Hct), red blood cells (RBC), platelets (Plt), mean platelets volume (MPV), monocytes and relative neutrophils were higher in men than women (P < 0.001). The percentiles of Hb, Hct, RBC, MPV and relative monocytes showed higher values; Plt, white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils and absolute basophils, the 2.5th was higher and the 97.5th was lower; for lymphocytes and relative neutrophils, both percentiles had a trend toward lower values, compared to previous RI. Differences between groups with different COVID-19 and vaccination backgrounds, in lymphocytes (P = 0.038), neutrophils (P = 0.017) and eosinophils (P = 0.018) in men; Hct (P = 0.014), RDW (P = 0.023) in women and MPV (P = 0.001) in both, were not considered pathological. Conclusions: The RI for the CBC were established in a Mestizo-Mexican population with different COVID-19 and vaccination backgrounds, so should be updated and validated in different hospitals close to the HTVFN that use the same analyser.

Multiparameter mobile blood analysis for complete blood count using contrast-enhanced defocusing imaging and machine vision.

Blood analysis through complete blood count is the most basic medical test for disease diagnosis. Conventional blood analysis requires bulky and expensive laboratory facilities and skilled technicians, limiting the universal medical use of blood analysis outside well-equipped laboratory environments. Here, we propose a multiparameter mobile blood analyzer combined with label-free contrast-enhanced defocusing imaging (CEDI) and machine vision for instant and on-site diagnostic applications. We designed a low-cost and high-resolution miniature microscope (size: 105 mm × 77 mm × 64 mm, weight: 314 g) that comprises a pair of miniature aspheric lenses and a 415 nm LED for blood image acquisition. The analyzer, adopting CEDI, can obtain both the refractive index distributions of the white blood cell (WBC) and hemoglobin spectrophotometric information, enabling the analyzer to supply rich blood parameters, including the five-part WBC differential count, red blood cell (RBC) count, and mean corpuscular hemoglobin (MCH) quantification with machine vision algorithms and the Lambert-Beer law. We have shown that our assay can analyze a blood sample within 10 minutes without complex staining, and measurements (30 samples) from the analyzer have a strong linear correlation with clinical reference values (significance level of 0.0001). This study provides a miniature, light weight, low-cost, and easy-to-use blood analysis technique that overcomes the challenge of simultaneously realizing FWD count, RBC count, and MCH analysis using a mobile device and has great potential for integrated surveillance of various epidemic diseases, including coronavirus infection, invermination, and anemia, especially in low- and middle-income countries.

Safety and Feasibility of Ultra-Restrictive Transfusion Protocol as a Blood-Preservation Strategy During Shortage Crises.

BACKGROUND: We hypothesized that implementation of new ultra-restrictive transfusion protocol in adult surgical intensive care units (SICU) was safe and feasible during pandemic-associated shortage crises. METHODS: Retrospective analysis two months pre- and post-implementation of ultra-restrictive transfusion protocol in March 2020 with hemoglobin cutoff of 6 g/dL (6.5 g/dL if ≥ 65 years old) for patients without COVID, active bleeding, or myocardial ischemia. RESULTS: We identified 16/93 and 27/168 patients PRE and POST meeting standard transfusion threshold (7 g/dL); within POST, 12 patients met ultra-restrictive cutoffs. There was no significant difference between PRE and POST in the rate of mortality, ischemic complications, or the number of transfusions per patient, however, the overall incidence of transfusion was lower in the POST group (7.1 vs 17.2%, p = 0.02). Patients received a mean (SD) of 4(3.8) and 2.4(1.5) PRBC transfusions pre- and post-implementation. Odds ratio of mortality in POST group was 0.62 (95%CI: 0.08-5.12) adjusted for age, sex, and SOFA score. CONCLUSIONS: Implementation of an ultra-restrictive transfusion protocol was feasible and effective as a blood- preservation strategy.

Is biomass fuel smoke exposure associated with anemia in non-pregnant reproductive-aged women?

OBJECTIVES: Sri Lanka is a developing country where the majority of households still rely on firewood for cooking. Furthermore, the prevalence of anemia among reproductive-aged women is of moderate public health importance, according the classification of World Health Organization. Despite the researchers' ongoing efforts to investigate a link between solid fuel smoke exposure and anemia, the veracity of their findings remains uncertain. As a result, the purpose of this study was to examine the relationship between biomass fuel smoke exposure and anemia in non-pregnant reproductive-aged women in Sri Lanka. METHODS: A descriptive cross-sectional study was conducted among 382 non-pregnant reproductive-aged (15 to 49 years) women in Central Province, Sri Lanka. Data was collected using a standardized interviewer-administered questionnaire, and exposure was assessed using a breath carbon monoxide monitor. Drabkin's cynomethhemoglobin technique was used to determine blood hemoglobin concentration. RESULTS: The overall prevalence of anemia was 36.1%. The logistic regression model revealed no effect of cooking fuel type on anemic or non-anemic status after adjusting for potential confounding factors (p > 0.05). The multivariate regression analysis also discovered that cooking fuel type had no effect on women's blood hemoglobin concentration. CONCLUSIONS: The study results suggest no impact of solid fuel smoke exposure on anemia among non-pregnant, reproductive-aged women. Larger scale prospective cohort studies are recommended. The reasons behind the high prevalence of anemia among reproductive-aged women should be further investigated, and corrective measures should be implemented urgently.

Cost-effectiveness of alternative minimum recall intervals between whole blood donations.

BACKGROUND: The INTERVAL trial showed shorter inter-donation intervals could safely increase the frequency of whole-blood donation. We extended the INTERVAL trial to consider the relative cost-effectiveness of reduced inter-donation intervals. METHODS: Our within-trial cost-effectiveness analysis (CEA) used data from 44,863 whole-blood donors randomly assigned to 12, 10 or 8 week (males), and 16, 14 or 12 week inter-donation intervals (females). The CEA analysed the number of whole-blood donations, deferrals including low- haemoglobin deferrals, and donors' health-related quality of life (QoL) to report costs and cost-effectiveness over two years. FINDINGS: The mean number of blood donation visits over two years was higher for the reduced interval strategies, for males (7.76, 6.60 and 5.68 average donations in the 8-, 10- and 12- week arms) and for females (5.10, 4.60 and 4.01 donations in the 12-, 14- and 16- week arms). For males, the average rate of deferral for low haemoglobin per session attended, was 5.71% (8- week arm), 3.73% (10- week), and 2.55% (12- week), and for females the rates were: 7.92% (12-week), 6.63% (14- week), and 5.05% (16- week). Donors' QoL was similar across strategies, although self-reported symptoms were increased with shorter donation intervals. The shorter interval strategies increased average cost, with incremental cost-effectiveness ratios of £9.51 (95% CI 9.33 to 9.69) per additional whole-blood donation for the 8- versus 12- week interval for males, and £10.17 (95% CI 9.80 to 10.54) for the 12- versus 16- week interval arm for females. CONCLUSIONS: Over two years, reducing the minimum donation interval could provide additional units of whole-blood at a small additional cost, including for those donor subgroups whose blood type is in relatively high demand. However, the significance of self-reported symptoms needs to be investigated further before these policies are expanded.

Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study.

INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. METHODS: We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold. RESULTS: Current 2-yearly screening with a f-Hb threshold of 120 µg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 µg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs. CONCLUSION: Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

Passive order auditing associated with reductions in red blood cell utilization: National blood shortage experience.

BACKGROUND: Decreased blood collection during the Coronavirus Disease 2019 (COVID-19) pandemic resulted in long-term red blood cell (RBC) shortages in the United States. In an effort to conserve RBCs, the existing passive alert system for auditing inpatient transfusions was modified to activate at a lower hemoglobin threshold (6.5 g/dL instead of 7.0 g/dL for stable, nonbleeding inpatients) during a 9-month shortage at an academic medical center. Hemoglobin levels prior to RBC transfusions were compared for inpatients receiving RBC transfusions to determine whether RBC utilization changed during the intervention. STUDY DESIGN AND METHODS: This retrospective study compared the number of single-unit RBC transfusions and hemoglobin levels prior to RBC transfusion among inpatients during the 9 months of the intervention (Period 2, 06/01/2021-2/28/2022) to the same period of the previous year (Period 1, 06/01/2020-2/28/2021). RESULTS: Overall full unit RBC transfusions to inpatients decreased by 15% from 5182 to 4421. Of all transfusions, 50.3% and 49.8% were single-unit RBC transfusions in Period 1 and Period 2, respectively. The incidence rate difference and incidence rate ratio of single RBC units transfused per 1000 patient days were significantly decreased (p = 0.0007). The average pre-transfusion hemoglobin level significantly decreased from 7.18 g/dL to 7.05 g/dL (p = 0.0002), largely due to significant decreases in hemoglobin transfusion triggers for adult inpatient ward transfusions. DISCUSSION: Modification of the passive alert system was associated with significantly decreased RBC utilization during a long-term RBC shortage. Modification of transfusion criteria recommended by passive alerts may be a feasible option to decrease RBC utilization at centers during long-term RBC shortages.

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity.

BACKGROUND: Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. METHODS: The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. RESULTS: Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019-30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081-5108.103)). CONCLUSIONS: For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.

Influence of Coronavirus Disease 2019 on some Physiological Blood Parameters in Patients with Kidney Failure in Iraq.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2), which is related to the SARS-CoV-2 and the Middle East Respiratory Syndrome Coronavirus, which caused serious outbreaks in 2003 and 2012. This study aimed to determine if there is an association between ABO blood types/renal failure and infection with COVID-19. Furthermore, the effects of COVID-19 infection on some blood parameters and electrolyte levels were investigated in this study. In the current study, 90 samples were obtained from males and females aged between 21-68 years old. The data were collected from September to February 2021 in a Kidney Center of Alsaader Teaching Hospital. The participants were divided into three groups (n=30) of A) kidney failure, B) kidney failure with COVID-19, and C) kidney failure with COVID-19 recovery after one month. The variables of this study included blood group types, blood electrolytes, and some blood biochemical parameters. According to the results, regarding the frequency of blood groups, in the control group, 34, 20, 14, and 36 participants belonged to the A , B, AB, and O blood groups, respectively. The recorded data showed that participants who had suffered from kidney failure and were infected with COVID-19 belonged to the A, B, AB, and O blood groups (25%, 10%, 27%, and 45%), respectively, while kidney failure patients who had recovered after one month from COVID-19 had blood groups of A, B, AB, and O (25%, 22%, 105%, and 45%, respectively). The recorded data showed a significant decrease (P<0.05) in the levels of Potassium (K), Sodium (Na), and Calcium (Ca) in the B group, compared to the A group, while the levels of K, Na, and Ca had significantly improved in group C (P<0.05), compared to group B. The Chloride level showed no significant differences among the groups. Furthermore, non-significant differences (P>0.05) were observed in the red blood cells (RBC), hemoglobin (Hb), and white blood cell count (WBC) in the COVID-19 group (Group B), compared to group A; however, there was a significant raise (P<0.05) in WBC and platelet (PLT), as well as a significant decrease (P<0.05) in lymphocyte (LYM), RBC, Hb, and hematocrit (HCT) in group C, compared to groups A and B. In conclusion, blood group O obtained the lowest level of resistance to COVID-19, compared to blood group A which had the highest response to recovery. The COVID-19 patients with kidney failure showed a significant decrease in blood parameters, such as RBCs, Hb, LYM, PLT, HCT, and electrolytes.

A cohort study of duplicate faecal immunochemical testing in patients at risk of colorectal cancer from North-West England.

OBJECTIVES: We sought to investigate if duplicate faecal immunochemical testing (FIT) sampling improves the negative and positive predictive value of patients thought to be at risk of colorectal cancer (CRC). Specifically, we aimed to investigate whether the proportion of FIT-negative CRC missed by a single FIT test in symptomatic patients could be reduced by duplicate FIT testing. DESIGN: A retrospective service evaluation cohort study of the diagnostic accuracy of duplicate FIT testing. SETTING: Patients referred from primary care with suspected CRC to four secondary care trusts in North-West England. PARTICIPANTS: 28 622 patients over 18-years-old with lower gastrointestinal symptoms suggestive of CRC who completed two FIT samples. PRIMARY AND SECONDARY OUTCOME MEASURES: The performance of duplicate FIT for detecting CRC at a threshold of 10 µgHb/g. RESULTS: The sensitivity if either test was >10 µgHb/g was 0.978 (0.955-0.989), specificity was 0.662 (0.657-0.668), positive predictive value 0.031 (0.028-0.035) and negative predictive value 1.00 (0.999-1.00). Despite two-thirds of patients (18952) being negative following two tests, at this threshold only seven CRC were missed over a 26-month period. All seven patients had other high-risk features which should have prompted investigation. CONCLUSIONS: This study suggests that in routine NHS practice, a duplicate FIT sample strategy together with clinical evaluation for evidence of anaemia and weight loss is superior to a single FIT sample alone and would allow symptomatic patients to be managed in primary care without the need for urgent referral to secondary care for urgent colonic imaging.

Faecal immunochemical tests safely enhance rational use of resources during the assessment of suspected symptomatic colorectal cancer in primary care: systematic review and meta-analysis.

OBJECTIVE: Implementation of faecal immunochemical tests (FIT) as a triage test in primary healthcare may improve the efficiency of referrals without missing cases of colorectal cancer (CRC). We aim to summarise the performance characteristics of FITs for CRC in symptomatic patients presenting to primary healthcare. DESIGN: We performed a systematic literature review of Medline and EMBASE databases from May 2018 to November 2020. Previous related systematic searches were also adapted to this aim and completed with reference screening. We identified studies performed on adult patients consulting for abdominal symptoms in primary care which reported data such that the FIT diagnostic performance parameters for CRC could be obtained. Bivariate models were used to synthesise available evidence. Meta-regression analysis was performed to evaluate the causes of heterogeneity. RESULTS: Twenty-three studies (69 536 participants) were included (CRC prevalence 0.3%-6.2%). Six studies (n=34 691) assessed FIT as rule in test (threshold of ≥150 µg Hb/g faeces) showing a sensitivity of 64.1% (95% CI 57.8% to 69.9%) and a specificity of 95.0% (95% CI 91.2% to 97.2%). A threshold of 10 µg/g (15 studies; n=48 872) resulted in a sensitivity of 87.2% (95% CI 81.0% to 91.6%) and a specificity of 84.4% (95% CI 79.4% to 88.3%) for CRC. At a 20 µg Hb/g faeces threshold (five studies; n=24 187) less than one additional CRC would be missed per 1000 patients investigated compared with 10 µg Hb/g faeces threshold (CRC prevalence 2%). CONCLUSION: FIT is the test of choice to evaluate patients with new-onset lower gastrointestinal symptoms in primary healthcare.

The use of the faecal immunochemical test during the COVID-19 pandemic to triage urgent colorectal cancer referrals.

AIM: During the first wave of the COVID-19 pandemic in 2020, elective gastrointestinal endoscopy services were abbreviated for fear of viral transmission. However, urgent suspected colorectal cancer (CRC) referrals continued. Serendipitously, a national study suggested that a new faecal immunochemical test (FIT) might be helpful in triaging patients with colorectal alarm symptoms. METHODS: This was a single centre observational study of patients referred using NG12 criteria between March and August 2020. Patients were triaged to the urgent cancer pathway for FIT ≥ 10 µg/g and investigated using the latest National Health Service England guidance. Demographic data, method of investigations, cancer and polyp detection rates were compared to patients referred in the 6 months prior to the use of FIT as a triage tool. RESULTS: In all, 1192 patients (median age 70) were referred using NG12 guidelines during the pandemic period, compared with 1592 patients (median age 72) in the previous 6 months. CRC detection was similar in both groups (n = 45, 2.8% vs. n = 38, 3.5%; P = 0.248). Two patients with a negative FIT (0.36%) had CRC. Using FIT as a triage tool resulted in a significant reduction in the use of endoscopy (n = 477, 43.6% vs. n = 1186, 74.5%; P > 0.001) with a significant increase in CT scanning (n = 696, 63.6% vs. n = 750, 47.1%; P < 0.001). CONCLUSION: The use of FIT in NG12 patients triaged during the first wave of the COVID-19 pandemic reduced endoscopy but not CT scanning and did not compromise CRC detection rates. It is a safe method that aids in reducing the burden on services greatly. A negative FIT test does not absolutely exclude CRC.

Finding of the factors affecting the severity of COVID-19 based on mathematical models.

Since 2019, a large number of people worldwide have been infected with severe acute respiratory syndrome coronavirus 2. Among those infected, a limited number develop severe coronavirus disease 2019 (COVID-19), which generally has an acute onset. The treatment of patients with severe COVID-19 is challenging. To optimize disease prognosis and effectively utilize medical resources, proactive measures must be adopted for patients at risk of developing severe COVID-19. We analyzed the data of COVID-19 patients from seven medical institutions in Tokyo and used mathematical modeling of patient blood test results to quantify and compare the predictive ability of multiple prognostic indicators for the development of severe COVID-19. A machine learning logistic regression model was used to analyze the blood test results of 300 patients. Due to the limited data set, the size of the training group was constantly adjusted to ensure that the results of machine learning were effective (e.g., recognition rate of disease severity > 80%). Lymphocyte count, hemoglobin, and ferritin levels were the best prognostic indicators of severe COVID-19. The mathematical model developed in this study enables prediction and classification of COVID-19 severity.

Faecal calprotectin is not necessarily required as a screen for significant bowel disease in primary care.

OBJECTIVE: NICE recommends measurement of faecal haemoglobin (f-Hb) using faecal immunochemical test (FIT) when colorectal cancer is suspected and calprotectin (f-Cal) in the context of inflammatory bowel disease, though neither is disease specific. During the COVID-19 pandemic, f-Hb has been a requirement prior to referral for endoscopy in England; f-Cal is often performed simultaneously. The aim of this study was to investigate test performance of both tests for significant bowel disease in those patients referred. DESIGN: All adult patients with simultaneous measurements of f-Hb and f-Cal between April 2019 and September 2020 were included. For those referred, outcomes were determined from clinical records. RESULTS: 650 patients with simultaneous samples for f-Hb an f-Cal were managed in Primary Care; 319 patients were referred to hospital; SBD was found in 32 (10.0%) (CRC 5, high risk adenomas 5, IBD 22). At a cut-off of 10 µg/g for f-Hb and 200 µg/g for f-Cal, the sensitivity, specificity and negative predictive value for diagnosis of SBD were 84.4%, 58.2% and 96.7% and 68.8%, 89.6% and 95.7%, respectively. Performance of both tests would have enabled diagnosis of two more cases of significant, but non-malignant, bowel disease but required over 4% more referrals for investigation. CONCLUSION: Use of FIT has become established to assist prioritisation of patients for referral from Primary Care. Whilst introduced specifically for CRC, FIT performs well as a rule out for IBD in Primary Care and the use of f-Cal is not required.

Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.

BACKGROUND: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).

Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.

BACKGROUND: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. METHODS: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).

The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial.

In this study, the therapeutic efficacy of quercetin in combination with remdesivir and favipiravir, were evaluated in severe hospitalized COVID-19 patients. Our main objective was to assess the ability of quercetin for preventing the progression of the disease into critical phase, and reducing the levels of inflammatory markers related to SARS-Cov-2 pathogenesis. Through an open-label clinical trial, 60 severe cases were randomly divided into control and intervention groups. During a 7-day period, patients in the control group received antivirals, i.e., remdesivir or favipiravir, while the intervention group was treated with 1000 mg of quercetin daily in addition to the antiviral drugs. According to the results, taking quercetin was significantly associated with partial earlier discharge and reduced serum levels of ALP, q-CRP, and LDH in the intervention group. Furthermore, although the values were in normal range, the statistical outputs showed significant increase in hemoglobin level and respiratory rate in patients who were taking quercetin. Based on our observations, quercetin is safe and effective in lowering the serum levels of ALP, q-CRP, and LDH as critical markers involved in COVID-19 severity. However, according to the non-significant borderline results in comparing the mortality, the ICU-admission rate, and the duration of ICU-admission, further studies can be helpful to compensate the limitations of our study and clarify the therapeutic potential of quercetin in COVID-19 treatments.

Mortality prediction with CHA2DS2-VASc, CHA2DS2-VASc-HS and R2CHA2DS2-VASc score in patients hospitalized due to COVID-19.

OBJECTIVE: We aimed to test the efficiency of CHA2DS2-VASc, CHA2DS2-VASc-HS, R2CHA2DS2-VASc score systems on the prediction of mortality in the patients with COVID-19. PATIENTS AND METHODS: The data were collected from 508 hospitalized patients with COVID-19. Comorbidity features including coronary artery disease, peripheral arterial disease, congestive heart failure, hypertension, atrial fibrillation, diabetes mellitus, hyperlipidemia, smoking, chronic obstructive pulmonary disease, cerebrovascular event, cancer status, and renal disease were recorded. The patients were divided as surviving group (n=440) and non-survivors (n=68). RESULTS: The in-hospital mortality rate of the patients with COVID-19 was 13.4%. Factors found to be associated with mortality in univariate analysis were CHA2DS2-VASc, CHA2DS2-VASc-HS, R2CHA2DS2-VASc, cancer state, atrial fibrillation, hemoglobin, lymphocyte count, CRP, albumin and ferritin. Model 1 multivariate cox regression analysis revealed CHA2DS2-VASc, hemoglobin, CRP and ferritin levels to be independently associated with mortality. Factors that were found to be independently associated with in-hospital mortality in Model 2 analysis were CHA2DS2-VASc-HS, R2CHA2DS2-VASc, hemoglobin, CRP and ferritin whereas except hemoglobin in Model 3 analysis, the other variables had been the same. Predictive power of R2CHA2DS2-VASc was better than of both CHA2DS2-VASc (p=0.002) and CHA2DS2-VASc-HS (p=0.034) in determining the in-hospital mortality. Patients with higher R2CHA2DS2-VASc (> 3 points), CHA2DS2-VASc-HS (> 3 points) and CHA2DS2-VASc (> 2 points) scores exhibited the highest mortality rate in survival analysis by using Kaplan-Meier and long-rank tests. CONCLUSIONS: CHA2DS2-VASc, CHA2DS2-VASc-HS, and R2CHA2DS2-VASc were found to be independent predictors of mortality in hospitalized COVID-19 patients. The current study revealed that the predictive ability of R2CHA2DS2-VASc was better than the both of CHA2DS2-VASc and CHA2DS2-VASc-HS score.

Faecal immunochemical test outside colorectal cancer screening?

Faecal immunochemical tests (FITs) are the most widely colorectal cancer (CRC) diagnostic biomarker available. Many population screening programmes are based on this biomarker, with the goal of reducing CRC mortality. Moreover, in recent years, a large amount of evidence has been produced on the use of FIT to detect CRC in patients with abdominal symptoms in primary healthcare as well as in surveillance after adenoma resection. The aim of this review is to highlight the available evidence on these two topics. We will summarize the evidence on diagnostic yield in symptomatic patients with CRC and significant colonic lesion and the different options to use this (thresholds, brands, number of determinations, prediction models and combinations). We will include recommendations on FIT strategies in primary healthcare proposed by regulatory bodies and scientific societies and their potential effects on healthcare resources and CRC prognosis. Finally, we will show information regarding FIT-based surveillance as an alternative to endoscopic surveillance after high-risk polyp resection. To conclude, due to the coronavirus disease 2019 pandemic, FIT-based strategies have become extremely relevant since they enable a reduction of colonoscopy demand and access to the healthcare system by selecting individuals with the highest risk of CRC.