Stem Cell Clinic

Reference intervals of haematological parameters | IJGM – Dove Medical Press

By Adult Stem Cells

Introduction

Clinical laboratory reference intervals are necessary resources for proper test result interpretation.1,2 They can be used for health status evaluation, disease progression tracking, and reporting of potential toxicity and adverse events in clinical treatment and clinical trials. International recommendations encourage the use of reference intervals pertinent to the population of interest for which a particular test will be applied for the correct and trustworthy interpretation of laboratory test findings.35

The most crucial components for health assessment, diagnosis, staging, prognostication, and event monitoring are hematology reference intervals. Most African countries now use reference intervals for these characteristics that are primarily derived from Western populations.6 Research has shown that there are discrepancies between the reference intervals for hematological parameters used in Western populations and those applicable to Africans. Consequently, this disparity leads to the incorrect classification and misdiagnosis of healthy individuals of African descent.713 Age, gender, race or ethnic origin, nutrition, geographic location, ambient altitude, seasonal patterns, pathogen exposure, and analytical methods or instruments utilized are some examples of the variables that affect the reference values of hematological parameters.1419 It is of utmost importance for laboratories across African nations to establish and adhere to their own reference intervals for these parameters. This becomes even more critical considering the expected substantial growth in the number of clinical trials and patients receiving clinical services in sub-Saharan Africa.6,14

Presently employed reference intervals in Ethiopia are derived from diverse sources such as published literature and manufacturer studies, which predominantly rely on samples obtained from Western populations. Nevertheless, there exists a significant lack of information concerning locally generated, reliable reference intervals.20 According to the few investigations that have been done, hematology reference values differ from Western-based values.13,2124 These discrepancies have the potential to complicate the interpretation of laboratory test results and impact clinical decision-making. Hence, to ensure precise evaluation of patient well-being and to facilitate safe execution of medical studies, it is imperative to establish population-specific hematological reference intervals in Ethiopia. The objective of this research was to determine reference intervals for commonly observed hematological parameters specifically tailored to the adult population in Northeast Ethiopia.

Between April 2019 and January 2021, a community-based cross-sectional study was carried out in Dessie town and the surrounding communities of Tita, Gerado, and Borumeda in the South Wollo Zone of Northeast Ethiopia. Dessie, positioned approximately 401 kilometers northeast of Addis Ababa, the capital city of Ethiopia, is a city situated within the Amhara Regional State. Geographically, it is located at 118 N and 3938 E, with an elevation ranging from 2470 to 2550 meters above sea level. Dessie experiences a subtropical highland climate, characterized by an average annual temperature of 22.26C, resembling a temperate oceanic climate. Tita, Gerado, and Borumeda are rural communities within the South Wollo Zone of Northeast Ethiopia, encompassing the hospitals catchment area.

The sample size for this study was determined based on the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI). According to the CLSI recommendation, in order to establish a reliable reference interval, a minimum of 120 individuals who are deemed to be in good health should be included in each subgroup (such as based on sex). The analysis employed a non-parametric method with a statistical power of 90%.25 However, prior extensive study conducted in other African nations26 found that approximately 30% of the participants did not meet the inclusion criteria for reference interval determination for a variety of reasons. Consequently, a comprehensive group of 344 individuals who were presumed to be in good health were enlisted to ensure the attainment of the recommended sample size of 240, as suggested by the CLSI for determining the reference intervals. The study population was selected utilizing a convenient sampling technique based on predetermined criteria from the community residing in Dessie town and the neighboring areas of the South Wollo Zone.

Dessie town and Tita, representing urban communities, along with Gerado and Borumeda, representing rural communities, were intentionally chosen from the study area based on differences in altitude and residence. The sample size was determined in a manner that proportionally reflected the population size of each selected community. Within these communities, sub-communities were further selected based on their accessibility and suitability for safely transporting blood samples to the hospital laboratory. Ultimately, individuals from each community who met the eligibility criteria of the study were included until the desired sample size was achieved.

Participants for the study were meticulously selected and included based on stringent inclusion and exclusion criteria. Each participant underwent a comprehensive evaluation that included a review of their medical history, a thorough physical examination, and tests to assess pregnancy (for females), C-reactive protein (CRP), HIV, hepatitis, syphilis, hemoparasites, intestinal parasites, and other relevant conditions. Ultimately, apparently healthy adults aged 18 years and above, who had resided in the designated areas for at least 5 years, were included in the study. The reference group, however, excluded individuals with the following conditions: known chronic diseases (such as diabetes mellitus, hypertension, chronic renal failure, ischemic heart disease, anemia, thyroid disorders, and liver diseases), high blood pressure (140/90mmHg or higher), obesity (body mass index 30 kg/m2 or higher), a recent history of blood donation within the past six months, blood transfusion within the past year, the use of pharmacologically active substances or prescription drugs, and positive screening test results (including CRP, HIV, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, syphilis, hemoparasite, intestinal parasite infection, and pregnancy).

The study participants were invited to visit a nearby healthcare facility, where they underwent individual consenting, screening, and blood collection procedures. After being informed about the studys objectives and the associated risks, individuals who willingly provided written consent underwent comprehensive medical history assessments and physical examinations conducted by trained nurses. Socio-demographic and medical history data were collected using a carefully designed questionnaire that had been pre-tested for accuracy and relevance. The physical examinations were conducted on-site using calibrated equipment and standardized techniques.

Under sterile conditions, aseptically, between 8:00 and 11:00 am in the morning, eligible study participants underwent the collection of venous blood from the antecubital vein, with a volume of five milliliters. This procedure took place following an overnight fast of at least eight hours. Two milliliters of the whole blood were carefully dispensed into an Ethylene Diamine Tetra Acetic acid (EDTA) Vacutainer tube (manufactured by Becton Dickinson, USA) for hematologic analysis. The remaining three milliliters were dispensed into a plain tube, left to clot for 60 minutes at room temperature, and then centrifuged for five minutes at 2500 revolutions per minute (rpm) to facilitate serologic tests. Stool specimens were collected using a clean container for the detection of intestinal parasites, while urine samples were collected from female participants using a sterile plastic container, and on-site HCG testing was conducted.

The whole blood samples were analysed within two hours after blood collection using Dirui BF-6500 automated hematology analyzer (Dirui Industrial Company, China), which performs 24 hematologic parameters, for in vitro diagnosis use in clinical laboratories. The measured hematology parameters for full blood count and differential cell count were white blood cells (WBC), neutrophil (NEU#), lymphocyte (LYM#), monocyte (MON#), eosinophil (EOS#), basophil (BAS#), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width-coefficient of variation (RDW-CV) and platelets.

The quality of the data was assured by using a carefully designed semi-structured questionnaire, and then it was translated into the local language (Amharic), and re-translated into the English version to check the accuracy and consistency. It was pre-tested on 5% of participants in Kombolcha town. Appropriate modifications were made based on information obtained from thepre-testing questionnaire. In addition, data collectors were trained before beginning data collection to reduce technical and observer bias.

All stages of pre-analysis, analysis, and post-analysis adhered to the principles of Good Clinical Laboratory Practices (GCLP) and followed standardized operating procedures. Prior to sample analysis, the instrument underwent thorough calibration using calibrators and internal controls to ensure accurate results. Internal quality control (QC) measures were implemented utilizing three levels (low, normal, and high) of commercial QC materials, and the analyzer was calibrated in accordance with the manufacturers recommendations. Daily QC runs were recorded on Levy Jennings charts, and the results for all hematologic parameters fell within 2 standard deviations from their target values. Additionally, the hospital laboratory actively participates in the External Quality Assessment (EQA) program facilitated by the Ethiopian Public Health Association (EPHI).

The collected data were meticulously reviewed for completeness, thoroughly checked, and subsequently entered into EpiData version 3.1 software, developed by the Epidata Association based in Odense, Denmark. Data analyses were carried out using SPSS version 25 software, developed by SPSS Inc. located in Chicago, IL, USA, as well as MedCalc version 20.027 software from Ostend, Belgium. To assess the normal distribution of the data, the KolmogorovSmirnov test was employed. Any extreme values deemed outliers were identified and eliminated using the Dixon method.27 The study performed comprehensive calculations for each hematological parameter, including the determination of the mean, median, and non-parametric reference intervals at the 2.5th and 97.5th percentiles. Furthermore, to establish the boundaries of the reference intervals with a 90% confidence level, the study also determined the corresponding confidence intervals (CI), aligning with the guidelines prescribed by the CLSI.25 The MannWhitney U-test was employed to examine potential disparities in reference values based on gender. A significance level of less than 0.05 (P < 0.05) was deemed statistically significant.

The Declaration of Helsinkis ethical guidelines were followed to conduct the study. The study received ethical approval from the Institutional Review Board of the College of Medicine and Health Sciences at Wollo University, under reference number CMHS130/13/2019. Before participating in the study, each participant provided written informed consent. Participants who were diagnosed with any illness were referred to appropriate healthcare facilities for proper treatment. Throughout the study, all collected information was handled with strict confidentiality to ensure privacy and data security.

Out of the initial sample of 344 apparently healthy adults selected using a convenient sampling technique, a total of 16 participants were excluded from the study due to positive serological test results. Consequently, the final analysis included test values from 328 participants (164 males and 164 females) to establish reference intervals for common hematological parameters. The study participants had a mean age of 29.2 8.2 years, with males having a mean age of 29.8 8.1 years and females having a mean age of 28.6 8.2 years. The age range of the participants varied from 18 to 57 years.

Table 1 present the mean, median, 95% reference intervals, and the corresponding 90% confidence intervals (CI) for the lower and upper limits of the hematological parameters. The combined median and reference intervals for both males and females were as follows: 6.49 (3.4911.3 109/L) for WBC, 3.63 (1.227.04 109/L) for neutrophil count, 2.16 (1.074.23 109/L) for lymphocyte count, 0.52 (0.11.01 109/L) for monocyte count, 0.08 (0.021.05 109/L) for eosinophil count, 0.03 (0.00.09 109/L) for basophil count, 4.95 (3.986.12 1012/L) for RBC, 14.3 (11.217.5 g/dL) for hemoglobin, 43.4 (35.452.0%) for hematocrit, 86.7 (77.993.8 fl) for MCV, 28.6 (24.732.0 pg) for MCH, 328 (306349 g/L) for MCHC, 269 (131391 109/L) for platelet and 12.9 (12.113.8%) for RDW-CV. Significantly higher median values were observed in males compared to females for monocytes, eosinophils, RBC (red blood cell) count, hemoglobin level, hematocrit level, and RDW-CV (red cell distribution width coefficient of variation) (P < 0.05). Conversely, females exhibited significantly higher platelet counts compared to males.

Table 1 The Mean, Median, and 95% Reference Intervals for Hematological Parameters in Healthy Adults from Northeast Ethiopia

Tables 2 and 3 provide a comparison of the hematological reference intervals established for healthy adults in this study with reference intervals reported in previous studies conducted in Ethiopia, other African countries, and the United States (US) populations. The findings reveal notable differences between the reference intervals derived in this study and those reported in previous studies within Ethiopia and other African countries. Specifically, in Table 2, there are significant differences (10%) observed in the lower and/or upper limits of the reference intervals for WBC (white blood cell), RBC (red blood cell), and platelet counts when compared to the currently employed laboratory reference ranges in the area. Comparing the reference intervals obtained in this study with those from US populations, it is evident that the lower limits of the intervals for WBC counts, hemoglobin, hematocrit, and platelet counts were significantly lower (<10%). Moreover, the upper reference limits for RBC and platelet counts in this study were significantly higher (>10%) than the limits observed in the US ranges (Table 3).

Table 2 Comparison of the Hematological Reference Intervals Obtained from This Study with the Currently Employed Reference Intervals and Other Ethiopian Studies

Table 3 Comparison of the Hematological Reference Intervals Obtained from This Study with Reference Intervals from Other Selected Studies Conducted in Africa, as Well as Reference Intervals from the United States

Table 4 shows the proportion of apparently healthy individuals whose haematology test results would have been described as abnormal when the reference intervals produced by the laboratory reports in the study area and those the US-based ranges28 are used. By use of the reference ranges supplied by the laboratory reports in the study area, up to 31.0% of the RBC values in males and 23.9% of the platelet values in females were out of range. When applying the US-based ranges to the total study population, 17.7% of males and 33.3% of females had abnormal RBC values. These proportions are: platelet count, 20.3% in males and 23.9% in females; hemoglobin, 18.4% in males and 8.2% in females; and 19.9% for WBC values.

Table 4 Out of the Values Obtained, a Certain Proportion Fell Outside the Range When Compared to the Reference Values Currently in Use and Those from the United States

The absence of precise and dependable reference intervals for the Ethiopian population has led numerous clinical laboratories to rely on reference values provided by in-vitro diagnostic company kit inserts, textbooks, or published literature. This practice can potentially lead to erroneous interpretation of laboratory test results, resulting in misdiagnosis, patient safety concerns, and unnecessary exclusions during participant screening. Recognizing the significance of addressing these crucial gaps, this study was conducted to establish reference intervals for commonly utilized hematological parameters in healthy adult populations from Northeast Ethiopia.

The lower limit of the WBC reference interval in this study was comparable to reports from Gojjam, Northwest Ethiopia22 and Ghana.10 On the other hand, it was higher than reports from Amhara Regional State,13 Gondar, Northwest Ethiopia,21 Uganda,29 Tanzania11 and Kenya,30 and lower than from USA.28 The upper limit of WBC count in this study was comparable to reports from previous studies in Ethiopia,13,22 but higher than reports from other African settings10,11,21,29,30 and the USA.28 In this study, there was no significant difference between males and females in the WBC count, which is consistent with previous reports from different parts of Ethiopia,13,2123 Nigeria12 and USA.28 The upper limits of the intervals for neutrophil and lymphocyte counts in this study are comparable with reports from Amhara Regional State;13 but higher than those from other African countries10,11,21,29,30 and lower than those from USA.28 These variations could be due to differences in population genetics, environmental altitude, seasonal patterns, pathogen exposure and dietary factors or the use of different methods/instruments.14,18,31,32 No significant sex differences were found in neutrophil and lymphocyte counts across our study populations as supported by previous studies in Ethiopia,13,2123 Ghana,10 Nigeria12 and USA.28

Regarding eosinophil, monocyte and basophil counts, our reference values were higher than those reported from the US population; this finding is consistent with previous studies in other African regions.10,12,29,30,33 These differences have been largely attributed to socio-economic status, genetic factors and/or the geographic distribution of parasites including helminths, schistosomiasis and malaria.14,34 However, future region-specific research is needed as there is some evidence to suggest a lower eosinophil and monocyte counts for African adults compared with Caucasians populations.35 The significant sex-differences in eosinophil and monocyte counts in this study are consistent with other studies in Africa.10,29,30 The reasons for these differences are still unclear, but there is evidence indicating that this is attributed to sex differences in immune system and the pathogenesis of inflammatory and immune diseases due to the effects of sex hormones.36

The lower reference limits for RBC count in this study are comparable with those reported from Ethiopian studies;13,22 but lower than reports from Kenya,30 Tanzania11 and USA,28 and higher than those from Gondar, Ethiopia,21 Ghana10 and Uganda.29 The upper reference limit of RBC count in this study was comparable with reports from Gojjam, Ethiopia,22 Kenya,30 Uganda29 and Tanzania,11 but lower than those from Gondar, Ethiopia,21 and higher than those from Amhara Regional State,13 Ghana10 and USA.28 The difference observed in RBC counts is possibly related to genetic factors, environmental altitude, seasonal, nutritional, chronic exposure to parasites and/or analytical variations.14,16,33 Significant sex-difference in RBC count was observed in this study, with males having higher values than females. This was consistent with previous reports from studies in Ethiopia,13,2123 Tanzania,11 Uganda29 and Kenya,30 Nigeria12 and USA.28 The sex-related difference in RBC count could be due to the effects of androgens on erythropoiesis and to menstrual blood loss in females.14,37

The lower limits of the intervals for hemoglobin and hematocrit in this study are lower than those reported from Gojjam,22 Amhara Regional State,13 Southwest Ethiopia,23 Tanzania11 and USA,28 but higher than those from Gondar, Ethiopia,21 Uganda,29 Ghana,10 Kenya.30 The upper limits of hemoglobin and hematocrit in this study are comparable with those reported from Uganda,29 Tanzania11 and USA,28 but lower than those from other studies in Ethiopia13,2123 and higher than those from Ghana10 and Kenya.30 The differing reference intervals may be explained by genetic variation, dietary role, altitude, sessional variation and exposure to parasites or due to the analytical variability.14,16,17,33 The significant sex differences observed in the RBC parameters is a well-established fact that females have lower hemoglobin and hematocrit levels than males and has been similarly reported in studies from Ethiopia,13,2123 Africa1012,29,30 and USA.28 These sex-related differences in hemoglobin and hematocrit levels are attributed to a direct effect of the sex hormones on erythropoiesis, gender-based hormonal effects on the erythropoietin gene, or to the menstrual bleeding, which can lead iron loss in females.3740

The reference intervals for the red cell indices (MCV, MCH and MCHC) in this study showed obvious differences compared with those reported from previous studies in Ethiopia,13,2123 other African countries10,11,29,30 and USA,28 probably due to genetic, racial/ethnic, nutritional, environmental factors and/or method and instrument variations.14,17 Sex-dependent differences in the reference values of MCV, MCH and MCHC were not observed in this study, consistent with previous reports from Ethiopia13,21,23 and other African country studies.10,12,29 However, significant sex-differences were reported in African populations for the reference values of MCH and MCHC.11,22,30 The reference interval for RDW-CV in this study was lower than reports from Northwest Ethiopia21 and Ghana,10 but higher than those from Uganda29 and USA.28 RDW values vary based on race/ethnic origin, instrumentation and method of calculation.17,41 RDW-CV reference values were significantly higher in males as compared to females as supported by previous reports that RDW values differ by sex.23,42

Our platelet count reference intervals are comparable to those reported from Amhara Regional State,13 Uganda29 and Tanzania,11 but lower than those from Northwest Ethiopia21 and Kenya30 and higher than those from Ghana10 and USA.28 Differences observed in the platelet counts could be attributed to variations in sex, age, race/ethnicity, genetic factors and/or biological variations such as geographical, seasonal, and lipid variations.18,4346 We have found median platelet counts to be significantly higher in females than in males, which may be related to different hormonal profiles or a compensatory mechanism associated with menstrual blood loss.47,48 The observed sex-dependent differences in platelet count reference values align with previous reports in African populations,1012,22,23,29,30 highlighting the need for separate reference intervals to be employed for males and females.

Reference intervals provided in clinical laboratory reports play a crucial role in assisting clinicians with test result interpretation, patient health assessment, and clinical decision-making. However, it is important to note that clinical laboratories commonly rely on reference ranges proposed by test manufacturers, which are often derived from non-Ethiopian populations. Our findings indicate that a significant proportion of hematological test results, specifically 31.0% of RBCs in males and 23.9% of platelets in females, fall outside the currently employed reference ranges. This highlights the crucial role of the local reference population in establishing normal hematology reference values and emphasizes the necessity of utilizing laboratory-specific ranges. The absence or improper use of reference intervals can lead to detrimental consequences, including misdiagnosis, inappropriate treatments, and increased patient risks, all of which significantly impact the quality of patient care. Hence, it aligns with the recommendations of international regulatory bodies that emphasize the importance of clinical laboratories establishing their own reference intervals tailored to the specific local population they serve.4,5,25

Comparing the reference values obtained with the US reference range data, used in most medical research studies, also revealed significant variations for most of the parameters. Indeed, up to 20.3% of male and 33.3% of female healthy participants would have demonstrated abnormalities and require further monitor and investigation, if the US-based values are used as the standards for interpretations of normality of laboratory test results. This finding is consistent with other studies in the region, suggesting that Western derived laboratory reference values used during participant screening for study enrollment may not be applicable to Africans.10,11,29,30,49 In one of these studies; for example, using the US derived hematological reference values, up to 53% of potential study participants would have been declared as having abnormal laboratory parameters and would be excluded.10 Locally established population-specific reference intervals are therefore critical in the assessment of participant health and in decision-making. This becomes even more critical considering the anticipated significant increase in the number of clinical trials in sub-Saharan Africa.6,14 The present study has limitations in that it did not evaluate the participants for their iron profile, haemoglobinopathies, or benign ethnic neutropenia to determine whether these factors should have led to their exclusion.

In conclusion, this study successfully established reference intervals for commonly used hematological parameters in apparently healthy adults from Ethiopia. The findings revealed significant differences between males and females in monocytes, eosinophils, RBC, hemoglobin, hematocrit, RDW-CV, and platelet counts. These results support previous studies indicating that hematology reference values derived from Western populations may not be suitable for African populations in routine clinical care and medical studies. While further research is warranted, the reference intervals established in this study hold promise in facilitating the interpretation of laboratory test results and aiding decision-making processes within this specific population.

HBsAg, Hepatitis B surface antigen; HBV, hepatitis B virus; CRP, C-reactive protein; HCV, hepatitis C virus; HIV, human immune deficiency virus; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; NA, not available; QC, quality control; RBC, red blood cells, RDW-CV, red cell distribution width-coefficient of variation; WBC, white blood cells.

The data analyzed in this study are available from the manuscript.

The authors acknowledge the community members who took part in this study and the health staff at the Dessie Specialized Referral Hospital for their assistance in gathering the data.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

The authors report no conflicts of interest in this work.

1. Ozarda Y. Reference intervals: current status, recent developments and future considerations. Biochem Med Zagreb. 2016;26(1):516.

2. Horowitz GL. Reference Intervals: practical Aspects. EJIFCC. 2008;19(2):95105.

3. Aytekin M, Emerk K. Accurate reference intervals are required for accurate diagnosis and monitoring of patients. EJIFCC. 2008;19(2):137141.

4. International Organization for Standardisation. Medical Laboratories Particular Requirements for Quality and Competency. ISO 15189. Geneva: ISO; 2007.

5. Solberg HE. International Federation of Clinical Chemistry (IFCC), Scientific Committee, Clinical Section, Expert Panel on Theory of Reference Values, and International Committee for Standardization in Haematology (ICSH), Standing Committee on Reference Values. Approved Recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. J Clin Chem Clin Biochem. 1987;25(5):337342.

6. De Baetselier I, Taylor D, Mandala J, et al. Verification of chemistry reference ranges using a simple method in sub-Saharan Africa. Afr J Lab Med. 2016;5(1):404. doi:10.4102/ajlm.v5i1.404

7. Odhiambo C, Oyaro B, Odipo R, et al. Evaluation of Locally Established Reference Intervals for Hematology and Biochemistry Parameters in Western Kenya. PLoS One. 2015;10(4):e0123140. doi:10.1371/journal.pone.0123140

8. Karita E, Ketter N, Price MA, et al. CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa. PLoS One. 2009;4(2):e4401. doi:10.1371/journal.pone.0004401

9. Beutler E, West C. Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood. 2005;106(2):740745. doi:10.1182/blood-2005-02-0713

10. Dosoo DK, Kayan K, Adu-Gyasi D, et al. Haematological and Biochemical Reference Values for Healthy Adults in the Middle Belt of Ghana. PLoS One. 2012;7(4):e36308. doi:10.1371/journal.pone.0036308

11. Saathoff E, Schneider P, Kleinfeldt V, et al. Laboratory reference values for healthy adults from southern Tanzania. Trop Med Int Health. 2008;13(5):612625. doi:10.1111/j.1365-3156.2008.02047.x

12. Miri-Dashe T, Osawe S, Tokdung M, et al. Comprehensive Reference Ranges for Hematology and Clinical Chemistry Laboratory Parameters Derived from Normal Nigerian Adults. PLoS One. 2014;9(5):e93919. doi:10.1371/journal.pone.0093919

13. Enawgaw B, Birhan W, Abebe M, et al. Haematological and immunological reference intervals for adult population in the state of Amhara, Ethiopia. Trop Med Int Health. 2018;23(7):765773. doi:10.1111/tmi.13071

14. Zeh CE, Odhiambo CO, Mills LA. Laboratory reference intervals in Africa. In: Blood Cell-An Overview of Studies in Hematology. London, UK: IntechOpen; 2012:303320.

15. Rodger RS, Fletcher K, Fail BJ, Rahman H, Sviland L, Hamilton PJ. Factors influencing haematological measurements in healthy adults. J Chronic Dis. 1987;40(10):943947. doi:10.1016/0021-9681(87)90144-5

16. Al-Sweedan SA, Alhaj M. The effect of low altitude on blood count parameters. Hematol Oncol Stem Cell Ther. 2012;5(3):158161. doi:10.5144/1658-3876.2012.158

17. Saxena S, Wong E. Heterogeneity of common hematologic parameters among racial, ethnic, and gender subgroups. Arch Pathol Lab Med. 1990;114(7):715719.

18. Bain BJ. Ethnic and sex differences in the total and differential white cell count and platelet count. J Clin Pathol. 1996;49(8):664666. doi:10.1136/jcp.49.8.664

19. Liu B, Taioli E. Seasonal Variations of Complete Blood Count and Inflammatory Biomarkers in the US Population - Analysis of NHANES Data. PLoS One. 2015;10(11):67.

20. Abebe M, Enawgaw B. Clinical Laboratory Reference Intervals in Ethiopia: current Status and Future Considerations: review. Clin Lab. 2018;64(11). doi:10.7754/Clin.Lab.2018.180544

21. Yalew A, Terefe B, Alem M, Enawgaw B. Hematological reference intervals determination in adults at Gondar university hospital, Northwest Ethiopia. BMC Res Notes. 2016;9(1):483. doi:10.1186/s13104-016-2288-8

22. Mulu W, Abera B, Mekonnen Z, et al. Haematological and CD4+ T cells reference ranges in healthy adult populations in Gojjam zones in Amhara region, Ethiopia. PLoS One. 2017;12(7):e0181268. doi:10.1371/journal.pone.0181268

23. Bimerew LG, Demie T, Eskinder K, et al. Reference intervals for hematology test parameters from apparently healthy individuals in southwest Ethiopia. SAGE Open Med. 2018;6:2050312118807626. doi:10.1177/2050312118807626

24. Gelaye B, Bekele T, Khali A, et al. Laboratory reference values of complete blood count for apparently healthy adults in Ethiopia. Clin Lab. 2011;57(78):635640.

25. CLSI. Defining, Establishing, and Verifing Reference Intervals in the Clinical Laboratory. 2008. Approved Guideline-third edition.

26. Stevens W, Kamali A, Karita E, et al. Baseline morbidity in 2990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials. PLoS One. 2008;3(4):e2043. doi:10.1371/journal.pone.0002043

27. Dixon WJ. Processing data for outliers. Biometrics. 1983;9(1):7489. doi:10.2307/3001634

28. Kratz A, Ferraro M, Sluss P, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med. 2004;351(15):15481563. doi:10.1056/NEJMcpc049016

29. Eller LA, Eller MA, Ouma B, et al. Reference Intervals in Healthy Adult Ugandan Blood Donors and Their Impact on Conducting International Vaccine Trials. PLoS One. 2008;3(12):e3919. doi:10.1371/journal.pone.0003919

30. Kibaya RS, Bautista CT, Sawe FK, et al. Reference Ranges for the Clinical Laboratory Derived from a Rural Population in Kericho, Kenya. PLoS One. 2008;3(10):e3327. doi:10.1371/journal.pone.0003327

31. Bain B, Seed M, Godsland I. Normal values for peripheral blood white cell counts in women of four different ethnic origins. J Clin Pathol. 1984;37(2):188193. doi:10.1136/jcp.37.2.188

32. Lim E, Cembrowski G, Cembrowski M, Clarke G. Race-specific WBC and neutrophil count reference intervals. Int J Lab Hematol. 2010;32(6p2):590597. doi:10.1111/j.1751-553X.2010.01223.x

33. Aneke C, Nduka N, Maxwell-Owhochuku S. Comparison of some haematological indices of Africans and Caucasions resident in the Nigerian environment. Haematol Budap. 1988;21(1):5763.

34. Tandeter H, Glick K, Moser A. Neutropenia and eosinophilia among Ethiopian immigrants to Israel: familial or environmental? Eur J Gen Pr. 2016;22(4):213218. doi:10.1080/13814788.2016.1206071

35. Valeria S, Eleonora C, Alessandra B, et al. Baseline haematological and biochemical reference values for healthy male adults from Mali. Pan Afr Med J. 2019;32:5. doi:10.11604/pamj.2019.32.5.12797

36. Chen Y, Zhang Y, Zhao G, et al. Difference in Leukocyte Composition between Women before and after Menopausal Age, and Distinct Sexual Dimorphism. PLoS One. 2016;11(9):46.

37. Rushton DH, Dover R, Sainsbury AW, Norris MJ, Gilkes JJH, Ramsay ID. Why should women have lower reference limits for haemoglobin and ferritin concentrations than men? BMJ. 2001;322(7298):13551357. doi:10.1136/bmj.322.7298.1355

38. Murphy WG. The sex difference in haemoglobin levels in adults mechanisms, causes, and consequences. Blood Rev. 2014;28(2):4147. doi:10.1016/j.blre.2013.12.003

39. Rushton DH, Barth JH. What is the evidence for gender differences in ferritin and haemoglobin? Crit Rev Oncol Hematol. 2010;73(1):19. doi:10.1016/j.critrevonc.2009.03.010

40. Zeng SM, Yankowitz J, Widness JA, Strauss RG. Etiology of differences in hematocrit between males and females: sequence-based polymorphisms in erythropoietin and its receptor. J Gend Specif Med. 2001;4(1):3540.

41. Lippi G, Pavesi F, Bardi M, Pipitone S. Lack of harmonization of red blood cell distribution width (RDW): evaluation of four hematological analyzers. Clin Biochem. 2014;47(12):11001103. doi:10.1016/j.clinbiochem.2014.06.003

42. Alis R, Fuster O, Rivera L, Romagnoli M, Vaya A. Influence of age and gender on red blood cell distribution width. Clin Chem Lab Med. 2015;53(2):e258. doi:10.1515/cclm-2014-0756

43. Segal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. Ann Epidemiol. 2006;16(2):123130. doi:10.1016/j.annepidem.2005.06.052

44. Peng L, Yang J, Lu X, et al. Effects of biological variations on platelet count in healthy subjects in China. Thromb Haemost. 2004;91(2):367372. doi:10.1160/TH03-05-0276

45. Hartmann S, Krafft A, Huch R, Breymann C. Effect of altitude on thrombopoietin and the platelet count in healthy volunteers. Thromb Haemost. 2005;93(1):115117. doi:10.1160/TH04-02-0086

46. Buckley MF, James JW, Brown DE, et al. A novel approach to the assessment of variations in the human platelet count. Thromb Haemost. 2000;3(3):480484.

47. Butkiewicz AM, Kemona H, Dymicka-Piekarska V, Matowicka-Karna J, Radziwon P, Lipska A. Platelet count, mean platelet volume and thrombocytopoietic indices in healthy women and men. Thromb Res. 2006;118(2):199204. doi:10.1016/j.thromres.2005.06.021

48. Kemona H, Prokopowicz J, Woyosowicz N. The count of blood platelets and sex in humans. Experientia. 1978;34(2):257. doi:10.1007/BF01944712

49. Zeh C, Pn A, Inzaule S, et al. Population-Based Biochemistry, Immunologic and Hematological Reference Values for Adolescents and Young Adults in a Rural Population in Western Kenya. PLoS One. 2011;6(6):e21040. doi:10.1371/journal.pone.0021040

Read more from the original source:
Reference intervals of haematological parameters | IJGM - Dove Medical Press

Precision Medicine Market Global Forecast to 2028: Increasing … – GlobeNewswire

By Gene Therapy Clinics

Dublin, Nov. 17, 2023 (GLOBE NEWSWIRE) -- The "Precision Medicine Market by Type (Inhibitors, Monoclonal Antibodies, Cell & Gene Therapy, Antivirals, Antiretroviral), Indication (Oncology, Rare diseases, Hematology, Infectious), End user (Hospitals & Clinics, Home care) & Region - Global Forecast to 2028" report has been added to ResearchAndMarkets.com's offering.

The precision medicine market is expected to reach USD 50.2 billion by 2028 from USD 29.1 billion in 2023, at a CAGR of 11.5% during the forecast period. The key factors driving the growth of the precision medicine market include growing initiatives related to genomic research, and the increasing number of regulatory approvals for personalized therapeutics. Moreover, rising demand for cell and gene therapies is an opportunity area for this market.

The precision medicine market has been segmented based on type, indication, end user and region.

By type, the monoclonal antibodies segment accounted for the second largest share of the precision medicine market

Based on type, the precision medicine market is categorized into inhibitor drugs, monoclonal, cell & gene therapy, antiviral & antiretroviral drugs, and other therapeutic products. In 2022, monoclonal antibodies accounted for the highest growth rate owing to factors such as the benefits offered by monoclonal antibodies over traditional medicines. These advantages have led to shifting focus of the clinical pipeline dominantly on monoclonal antibodies.

By end user, the hospitals and clinics segment accounted for the largest share in the precision medicine market

Based on end user, the precision medicine market is segmented into hospitals and clinics and home care settings. In 2022, the hospitals and clinics segment accounted for the largest share of the precision medicine market. Growth in this market segment can be attributed to the availability of services such as genetic testing, diagnostics and counselling in hospital setups. Besides, hospitals have easy accessibility to therapeutic products which are made available for patients opting for precision medicine regimes.

North America: the largest share of the precision medicine market

North America accounted for the largest share of the precision medicine market. The large share of the North America region can be attributed to major factors such presence of technologically advanced infrastructure in healthcare settings offering precision medicines, and easy accessibility to advanced therapeutics among others. Besides, the region has a well established healthcare system which further supports the growth of this market.

Europe: The fastest-growing region in the precision medicine market.

The European precision medicine market is projected to grow at the highest CAGR during the forecast period. This is attributed to one of the major factors including the growing initiatives for precision medicine advancements with the presence of some of the key players in the market. Some examples of these players include F. Hoffmann-La Roche Ltd. (Switzerland), Novartis AG (Switzerland), AstraZeneca (UK), and GlaxoSmithKline plc (UK) among others.

Key Attributes:

Key Topics Covered:

Executive Summary

Premium Insights

Market Dynamics

Drivers

Restraints

Opportunities

Challenges

Company Profiles:

For more information about this report visit https://www.researchandmarkets.com/r/uookmb

About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Read this article:
Precision Medicine Market Global Forecast to 2028: Increasing ... - GlobeNewswire

EU Approval of AAV5 DetectCDx Provides Access to Companion … – PR Newswire

By Gene Therapy Clinics

SALT LAKE CITY, Nov. 10, 2023 /PRNewswire/ -- ARUP Laboratories today announced that it has gained the Conformit Europenne (CE) mark for AAV5 DetectCDx single-site use under the European Union's In Vitro Diagnostic Medical Devices Regulation (IVDR). AAV5 DetectCDx is a companion diagnostic developed in partnership with BioMarin Pharmaceutical Inc. to aid in the selection of adult patients eligible for BioMarin's new gene therapy for severe hemophilia A, valoctocogene roxaparvovec-rvox (ROCTAVIAN).

The new EU regulation requires that emerging medical devices meet rigorous standards for quality management and patient safety. Although AAV5 DetectCDx had already received a CE mark under the previous In Vitro Diagnostic Medical Devices Directive (IVDD) in August 2020, achieving the more stringent IVDR approval will enable ARUP to continue to provide patients access to testing in the EU after May 2026, when all medical devices will require IVDR approval. With EU approval, samples from those living in the EU and other countries that follow EU regulations can be tested at ARUP's centralized lab in Salt Lake City.

We are proud to be involved in this effort to support the needs of patients with severe hemophilia A.

"We are proud to be involved in this effort to support the needs of patients with severe hemophilia A," said Jay Patel, MD, MBA, vice president of Clinical Trials and PharmaDx at ARUP. "We've demonstrated by our ability to execute on these stringent regulatory requirements that we're committed to patient safety and access to testing."

Hemophilia A is a rare, X-linked genetic bleeding disorder caused by a deficiency in coagulation factor VIII (FVIII). People living with hemophilia A may experience painful and/or potentially life-threatening bleeding from even modest injuries because they lack sufficient clotting protein.

BioMarin's new gene therapy uses adeno-associated virus serotype 5 (AAV5) as a vector to deliver a functional copy of the gene for FVIII in a one-time infusion, with the goal of reducing or eliminating the need for chronic prophylactic treatment. AAV5 DetectCDx will be used to detect the presence of preexisting anti-AAV5 antibodies that can inhibit the efficacy of the treatment. Only individuals without anti-AAV5 antibodies will be eligible.

The approval of AAV5 DetectCDx is the result of a close collaboration between ARUP and BioMarin.

"We are gratified to see the results of this colossal effort from both teams and to fulfill an unmet need for patients with rare diseases such as hemophilia A," said Jennifer Granger, PhD, group manager of the PharmaDx Companion Diagnostics team at ARUP, who has played a key role in the pursuit of IVDR approval.

European regulators based their authorization on data from clinical trials for which ARUP's test was used to determine patient eligibility.

As a national reference laboratory closely aligned with an academic medical center, ARUP has a unique ability to support the development of companion diagnostics for emerging medical treatments. In addition to its College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) certifications, ARUP also has an International Organization for Standardization (ISO) 15189 certification, an internationally recognized quality standard, and meets the quality management requirements for medical devices, including title 21, Code of Federal Regulations (CFR), part 820.

"Very few clinical labs have the quality management system and competencies in place to execute on a new companion diagnostic at this regulatory level," Patel said. "We are proud of our ability to deliver at the highest levels for patients and for our partners."

AAV5 DetectCDx also received FDA approval on June 29, 2023, becoming the first FDA- approved companion diagnostic immunoassay for a gene therapy.

About ARUP Laboratories

Founded in 1984, ARUP Laboratories is a leading national reference laboratory and a nonprofit enterprise of the University of Utah and its Department of Pathology. ARUP offers more than 3,000 tests and test combinations, ranging from routine screening tests to esoteric molecular and genetic assays. ARUP serves clients across the United States, including many of the nation's top university teaching hospitals and children's hospitals, as well as multihospital groups, major commercial laboratories, group purchasing organizations, military and other government facilities, and major clinics. In addition, ARUP is a worldwide leader in innovative laboratory research and development, led by the efforts of the ARUP Institute for Clinical and Experimental Pathology. ARUP is ISO 15189 CAP accredited.

ARUP Media Contact

Lisa Carricaburu, [emailprotected], 801-583-2787 ext. 3842

SOURCE ARUP Laboratories

Originally posted here:
EU Approval of AAV5 DetectCDx Provides Access to Companion ... - PR Newswire

Experts’ Perspectives: Top News in Cardiology for 2023 – MD Magazine

By Gene Therapy Clinics

As the last meeting of the 3 flagship professional societies in cardiology, the American Heart Association Scientific Sessions serves as a yearly send-off for the community and, by extension, a celebration of the advances that defined the past year in medicine. This years meeting was no exception, with a wealth of breakthroughs showcased at AHA 2023.

With an interest in capturing the perspective of leading experts in the field as the cardiology community looks ahead to the close of 2023, the editorial team of HCPLive Cardiology asked 12 leading experts in cardiology what they will remember as the defining piece of news or advancement within the field from the past year.

Expert opinions spotlighted in this feature include those of Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at Cleveland Clinic, Michelle Albert, MD, MPH, immediate-past president of the AHA and the Walter A. Haas-Lucie Stern Endowed Chair in Cardiology and Professor in Medicine at the University of California at San Francisco, Marc Bonaca, MD, MPH, director of Vascular Research at the University of Colorado Anschutz Medical Campus and executive director of CPC Clinical Research, Sadiya S. Khan, MD, assistant professor of cardiology and epidemiology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician, James E. Ip, MD, an associate professor of clinical medicine at Weill Cornell Medicine at New York-Presbyterian Hospital, Rahul Aggarwal, MD, cardiology fellow at Brigham and Womens Hospital, Viet T. Le, DMSc, PA-C, researcher and physician associate at the Intermountain Health, Ahmad Masri, MD, director of the Hypertrophic Cardiomyopathy Center atOregon Health & Science University, Mandeep Mehra, MD, medical director of the Heart and Vascular Center at Brigham and Womens Hospital, Christian T. Ruff, MD, MPH, director of general cardiology at Brigham and Womens Hospital and senior investigator for the TIMI Group, Paul Ridker, MD, MPH, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital, Deepak Bhatt, MD, MPH, director of Mount Sinai Heart and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai, and Ty Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Research, and Data Science at the Providence Health.

Top Row (L to R): Deepak Bhatt, MD, MPH; Sadiya Khan, MD; Ahmad Masri, MD, MS; Michelle Albert, MD; Viet Le, DMSc, PA-C; Mandeep Mehra, MD Bottom Row (L to R): Marc Bonaca, MD; James Ip, MD; Paul Ridker, MD, MPH; Rahul Aggarwal, MD; Ty Gluckman, MD; Christian Ruff, MD, MPH; Steve Nissen, MD

Included below the responses of the aforementioned experts is a behind-the-scenes clip from the AHA 2023 episode of Dont Miss a Beat, where hosts Muthiah Vaduganathan, MD, MPH, codirector of the Center for Implementation Science at Brigham and Womens Hospital, and Steve Greene, MD, advanced heart failure specialist at the Duke Clinical Research Institute, discuss the same question.

Editors Note: These transcripts have been edited for grammar and clarity.

Nissen: I think that 2023 is the year that we get began the pivot from what the old way of developing drugs, which was small molecules given with the hope that the favorable effects would exceed the unfavorable, to the directed therapies involving these short-interfering RNAs and antisense oligonucleotides. We're in that pivot. As you know inclisiran was approved, it was the first short-interfering RNA in the cardiovascular space and now, there are others for amyloidosis. It is an explosion of new approaches to drug development, and this is the year when that transition really began to accelerate.

Albert: Well, I think the trial that we saw about semaglutide, weight reduction, and perhaps this tie to cardiovascular risk reduction. Although, right now, we do not know that the weight reduction is what was tied to cardiovascular risk reductioIt could be the drug itself and how it's working on other mechanisms.

I think the other thing is the big news in the heart failure field. Whether you have heart failure with reduced ejection fraction or heart failure with preserved ejection fractionwhether you have diabetes or don't have diabetes the SGLT2 inhibitors are extremely beneficial. I think those are the two big things I think about so far.

I would also add, as it relates to the last year, when we think about late breaking science, we a lot of times do not include social factors and social determinants of health. I think the growing recognition among all scientists and clinicians of the importance of social determinants of health is an advance, honestly. I would say 5 years ago, it was tougher to bring clinicians and researchers over that hump.

Bonaca: That's a great question. I haven't had a lot of time to think through this, but off the top of my head, I would say the focus on cardiometabolic disease. I think at ESC, STEP-HFpEF reminded us that you do not need a big trial to have a big impact. There has been a notion of "healthy obesity," and I believe it dispels, at least in part, the idea that treating individuals who are obese with a GLP-1 receptor agonist might benefit those with heart failure with preserved ejection fraction.

Now, everybody asking the question, "Is it the weight loss or the heart failure?". And the answer is yes, because these things are linked, right? They're not independent. Then SELECT is going to be presented at AHA. So, I think this story of cardiometabolic disease and weight loss is really what I think is the story of 2023. Where the field is moving, I think brings big challenges, though. Patients cannot access these drugs. They are super expensive, and you can't come off. So, I think that the future is going to play out as: How we use these agents? Are there better agents? How do we sustain the benefits without lifelong treatment with it being a very expensive therapy?

There's a big, what I would say is a corollary story, is the first digital therapeutic for treating diabetes was approved by the FDA. This approach utilizes cognitive behavioral therapy and nutritional cognitive behavioral therapy to genuinely educate individuals on lifestyle modification. To me, it prompts the question of how we conceptualize cardiometabolic disease. Should we consider these potent new drugs, such as semaglutide and others in the pipeline, as inducers for rapid weight loss? Then, can we view digital cognitive behavioral therapy and other strategies as maintenance tools that could potentially facilitate individuals coming off these interventions? I think this is a big part of 2023.

Khan: I think it is going to be the GLP-1 receptor agonists for 2023. I think in 2022 it was the SGLT2 inhibitors. Now, 2023 is the GLP-1 receptor agonists. I would say, from a trial perspective, that's true. But I would caution by saying, I actually don't want to say that's the story of 2023.

I think they are amazing therapies and it's wonderful that we are at this point, but I think the story should be: How do we get the right therapies to the right patients? So, maybe that's 2024, because it's wonderful that there are wonderful drugs that are very helpful and effective, but we need to make sure that the right patients are getting them at the right time.

Ip: As an electrophysiologist, I am very excited. I'm involved in various aspects of EP, but the one that I was most excited about, especially this week because it's so fresh in my mind, is dual chamber lead list pacing. We now have technology that can have two devices, separately, one placed in the right atrium and one in the right ventricle that can speak wirelessly. That has opened up the world of leaderless pacing for patients who need pacemaker therapywhere their sinus node dysfunction, or atrial ventricular block where they need two systems before we only had one on the bottom. Now, we have that. It was FDA approved earlier this year and we did our first commercial implants this week. So, that that was certainly a highlight of my year and my week. But I would also highlight the results of ReVeRa, because etripamil is also very exciting. I mean with the NODE studies and this study, I think that there are a lot of new exciting things, at least within EPthere are also other technologies that are being explored, but those are the ones that come to my mind.

Aggarwal: I think this year the major kind of changes, there's a lot of emphasis not just on what therapies work, but on ensuring that patients get the therapy, and the therapy is prescribed. So, for me, I think what's going to really stand out is that we're really focusing on how can we initiate therapy early? How can we get patients on therapy who may not reach their follow up or who may not see their follow up provider very quickly? So, I think the emphasis is shifting a little bit from just finding therapies that work to also how do we get the therapies to reach our patients. I think that's been a major shift in focus within a lot of the population health-based studies this year.

Le: It's a little unfair to pick one, because there are 3 things that I think about that have kind of come the confluence of things that have happened in 2023.

First of all, I think as we look back to 2023, what we'll recognize is the power of nucleic acid therapies. So, these are the antisense oligonucleotides and the siRNA. We're seeing it across lipids. We're seeing it not just in LDL-C, but were seeing it in Lp(a) now. Also in the hypertension space, where it's one injection for three or six months of therapeutic benefit, at least in terms of reduction of blood pressure. We'll see if that translates otherwise.

Here, the American Heart Association just presented what we all kind had been dancing around, which is CKM or cardiovascular-kidney-metabolic. This confluence of we need to work together upstream. These are the patients that we see in our cardiovascular clinics, but we need to be working on all of the organs and certainly the constellation of what diseases do to lead to cardiovascular outcomes and morbidities.

Lastly, this is the year obesity has really come to the forefront with this idea that it is not just an inability to choose lifestyle or right things. We're recognizing this is much deeper than that. It is social determinants, and it is deeper in our biology, in terms of obesity. We have therapies that touch upon and can help really relieve the burden as well as stigma that a lot of our patients face when they go to their provider and are told, "You probably are just eating too much or not exercising enough". My heart is just sick when I get referrals for patients and that is what they've heard. So, this is the year that we have awakened the reality to obesity management and that it is a diseasenot just willful ignorance or choice to feel poorly. I think those are the main 3 takeaways from to 2023.

Masri: It's been a very, very busy year for us in 2023. So, I honestly cannot take a single item to talk about as the biggest one,but I'll allude to some advancements in the cardiomyopathy space. The first one is that we presented data from aficamten and nonobstructive HCM from the REDWOOD-HCM cohort 4 study, which allowed us to progress to a large phase three trial in this space.

The second one is related to amyloidosis. We received the first chunk of data from a phase 1 trial for anti-ATTR antibody. That was published in the New England Journal of Medicine and showed that there is a strong rationale behind this and some more data is coming out. From the National Amyloidosis Centre in the UK, we also saw the autoantibodies that naturally develop in amyloidosis. That was also important.

The first patient with MYBPC3 hypertrophic cardiomyopathy was dosed in the Tenaya gene therapy program. This is the first patient ever to be loaded with gene therapy specifically for MYBPC3 hypertrophic cardiomyopathy. We're also seeing a lot of the data coming out from the phase one gene editing in transthyretin amyloidosis. We know that the FDA also just gave the go-ahead to proceed with the phase 3 global trial for CRISPR-Cas9 in ATTR cardiomyopathy. Last but not least, we have also seen proof of concept for gene editing in preclinical hypertrophic cardiomyopathythere are two Nature papers on this. So, it's been really, really busy, but a lot of good things are happening in our space. We're very excited to see how these progress over time.

Mehra: The big story of 2023 is that we now have great medications to undo the problems of our own personal lifestyles, but, with this, we have created an opportunity that will expose healthcare disparities in a much more magnified way. I think that's terrible and I think we're going to have to all attend to that, you know, as a community.

Ruff: I think it really has to be, and we have seen it even in the lay press, the role of the GLP-1 receptor agonists broadly in health, but particularly in cardiovascular health the impact could be just enormous. Obviously, these drugs were initially developed to lower blood glucose and people with diabetes and then, many years ago, we learned they have cardiovascular benefit in diabetes and then they have cardiovascular benefit in non-diabetics.

The fact that they cause tremendous amounts of weight loss, will, even in patients with no known heart disease, reduce their risk of heart disease. There may be no other drug in clinical practice that has such an enormous effect on health across such a broad population of patients who have diabetes or preexisting cardiovascular disease as well as the effects on the epidemic of obesity. I think that's really going to be one of the landmark findings of this year that will have a lasting impact on the way we treat patients in cardiology and really in all medicine.

Ridker: It has been a remarkable year for cardiovascular advances. For my interest, I put them in three categories. The first is the remarkable ability of the SGLT2is to actually change outcomes in our patients who have heart failure and to see this data extend out into other settings, like chronic kidney disease has been quite remarkable. The second has to obviously be the success of the GLP-1 receptor agonist. We're seeing multiple different drugs coming on market very fast, with multiple different ways of addressing these issues. We're seeing not just weight loss, but event reduction in patients with diabetes. As we're all looking forward to the data from the AHA on event reduction in patients who don't have diabetes and realizing that this is going to change how medicine is practiced. The challenges for us will be to figure out how, where, and why, but that'll be interesting.

Third is my own arena. I think it's been exciting to see the US FDA, pretty much on its own, decide that it was time to label a drug, low-dose colchicine, for anti-inflammatory therapy. That's a big issue for the vascular biology world to say, "Yes, the regulators, as well as the vascular biologists, now believe that the data are rock solid that we should be targeting inflammation, as well as hyperlipidemia".

I think a fourth area is the novel therapeutics we're seeing. Without going into specifics, we're seeing new types of drugs where maybe we can actually change the underlying biology of cells in the liver on a lifetime basis, to alter Lp(a) or to alter ApoB production or to alter various different proteins. To watch many different scientists working with industry to figure out a whole new way of addressing whether we can modify disease on a lifelong basis. Particularly for extremely high riskI think of a patient with homozygous FH or maybe very severe heterozygous FHis there a way to change their underlying hepatic biology?

We don't know whether it's completely safe yet, but the preliminary data look like it might be. I recognize we have to wait 10 to 15 years perhaps to know about safety, but it's a very exciting direction to think about: Can we actually alter the biology, rather than just simply giving drugs on a chronic basis? So, all those things to me are very exciting and, again, it's a real reminder of how science moves forward and how we as clinicians have new options for our patients.

Bhatt: The year 2023 was a really good year for cardiology, cardiometabolic disease, and cardiorenal disease. There are a lot of advances, there were a ton of stuff that just came out of the AHA, at the ESC before that, and at the ACC before that. So, it has been a good year. There have been a lot of important practice-changing trials. If you force me to just pick one thing, I think what Verve Therapeutics announced here, in terms of data that they've produced in a relatively small number of patients, was amazingthe first use of human gene-editing to lower cholesterol levels.

They were targeting PCSK9 and, at the higher doses, saw about a 50% percent reduction in LDL cholesterol that was durable out to 6 months of data. To me, that concept of editing genes in humans in a way that will hopefully be safe and durablewe will need more patients followed for longerso far looks like a really promising approach and opens the door for that approach for a variety of cardiovascular disease conditions and risk factors, including things like Lp(a). So, to me, that's really exciting for that particular approach and could be an opening-the-door strategy to a variety of approaches in the future.

To me, genetics and AI are really two exciting areas that have been hyped for years, at least with respect to cardiovascular applications, where there really was not anything, but now we have FDA-approved AI algorithms for ECGs for echocardiograms, among other things, and now we have gene editing in humans that actually seems to be really effective. It's a whole new world out there. Again, to me, those are some really exciting developments.

I was also excited to announce to the American Heart Association from the podium the TRANSFORM trial. This is going to be a randomized clinical trial of about 7500 patients or so followed for a while in the primary prevention universe.

So, we are taking primary prevention patients and then getting a CT scan on them, which will use an AI-enabled algorithm to determine the staging of the coronary plaque. Stage 0, for example, means you don't have any plaques, or you probably don't need to be on a bunch of meds. Then the successive stages 1, 2, and 3sort of like staging cancerwith staging plaque based on plaque volume, plaque burden across all the different coronary arteries, and plaque composition. So, incorporating all that in a pretty sophisticated AI-enabled algorithm to take the risk of that individual patient, based on their stage of plaque, and then, using that information, to counsel the patient on lifestyle, but also to titrate, very intensive medical therapy beyond what the guidelines currently recommend, including things like colchicine, SGLT1/2 inhibitors, or bempedoic acid, where all these agents have outcome data in different sorts of settings. We want to see, can you use plaque to add agents, these and others, to really refine how we treat patients with respect to cardiovascular risk reduction. Patients will be randomized to that approach or a guideline-based approach following current guidelines where they also get a CT at baseline and also at 2 years. That arm will be blinded until the end of the trial, but we will know the answers in the investigation arm.

So, this will give us 3 different opportunities within TRANSFORM. TRANSFORM-Classify will see if this approach is better than conventional risk scores. TRANSFORM-Plaque will look at CT at baseline and a repeat CT at 2 years to see if there is plaque progression and whether we can impact that with intense medical therapy versus standard guideline-directed therapy as it currently stands as well as whether those changes in plaque that may occur from baseline and 2 years do or don't predict subsequent cardiovascular events. Then, in TRANSFORM-Outcomes, we are actually going to look at major adverse cardiovascular events to see if the strategy using AI-enabled imaging and then incorporating that information to intensify medical therapy is better than just doing what the guidelines would tell us to do. So, that's the cardiovascular outcome part of the trial.

This is something that will take a few years to reach the end, but when it's done, whatever it shows, I think it will be informative about whether imaging should be part of how we stratify patients in terms of their risk in the primary prevention world and whether we can or should not use that information to them titrate their medical therapies.

Gluckman: I would say 2023 has been a year and maybe several years leading up to it that has really reinforced the importance of targeted therapies for cardiovascular, metabolic, and kidney disease. Maybe that's all ensconced in the fact that a therapy that can help facilitate weight reduction as a GLP-1 receptor agonist and that translates into blood pressure improvement, cholesterol improvement, anti-inflammatory properties improvement, and glycemic control can improve cardiovascular outcomes at-risk individuals, but I think the intersection of high cholesterol, diabetes, high blood pressure, obesity, chronic kidney disease, nonalcoholic fatty liver disease really reinforces the importance from a public health standpoint, from a cardiovascular prevention standpoint, when close to 70-plus percent of the US population is overweight or obese. When we have rising rates of diabetes and unacceptably, high rates of lack of control for high blood pressure and high cholesterol. We need to do better. So, I hope that this is a furthering of acceleration in terms of therapeutic approaches that can wind that back.

Click here for the full AHA 2023 episode of Dont Miss a Beat, which focuses on SELECT results and DAPA-MI.

Continue reading here:
Experts' Perspectives: Top News in Cardiology for 2023 - MD Magazine

Catalyst Pharmaceuticals To Participate in Piper Sandler 35th Annual Healthcare Conference

By Global News Feed

CORAL GABLES, Fla., Nov. 16, 2023 (GLOBE NEWSWIRE) -- Catalyst Pharmaceuticals, Inc. ("Catalyst") (Nasdaq: CPRX), a commercial-stage biopharmaceutical company focused on in-licensing, developing, and commercializing novel medicines for patients living with rare diseases, today announced that Patrick J. McEnany, Chairman and CEO of Catalyst, along with other members of the management team, will participate at the upcoming Piper Sandler 35th Annual Healthcare Conference taking place at the Lotte New York Palace hotel.

See more here:
Catalyst Pharmaceuticals To Participate in Piper Sandler 35th Annual Healthcare Conference

Biomea Fusion Abstract “BMF-219: A Novel Therapeutic Agent to Reestablish Functional Beta Cells and Provide Long-term Glycemic Control"…

By Global News Feed

BMF-219 is an investigational novel covalent menin inhibitor designed to regenerate insulin-producing beta cells with the aim to cure diabetes BMF-219 is an investigational novel covalent menin inhibitor designed to regenerate insulin-producing beta cells with the aim to cure diabetes

Original post:
Biomea Fusion Abstract “BMF-219: A Novel Therapeutic Agent to Reestablish Functional Beta Cells and Provide Long-term Glycemic Control"...

Bright Green Corporation announces exclusive partnership with Asia Capital Pioneers Group to present new EB-5 offering

By Global News Feed

GRANT, N.M., Nov. 16, 2023 (GLOBE NEWSWIRE) -- Bright Green Corporation (BGXX) (“BGXX”, “Bright Green” or the “Company”) today announced the Company’s new alliance with Asia Capital Pioneers Group Inc. (“ACPG”), an Asia-based investment firm with global investments within high growth industries. ACPG will be BGXX’s exclusive Asia partner, connecting the Company with investors that fulfill the requirements for permanent U.S. residency via an EB-5 Investment Visa in the Asia-Pacific region.

Read the rest here:
Bright Green Corporation announces exclusive partnership with Asia Capital Pioneers Group to present new EB-5 offering

→←