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Comprehensive geriatric assessment and drug burden in elderly chronic kidney disease patients

  • Neziha Erken ORCID logo EMAIL logo and Ertugrul Erken ORCID logo
Published/Copyright: September 25, 2023
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Turkish Journal of Biochemistry
From the journal Turkish Journal of Biochemistry Volume 48 Issue 5

Abstract

Objectives

Chronic kidney disease (CKD) is a condition characterized by atherosclerosis, cognitive impairment, physical limitations, biochemical abnormalities, and vascular aging. The proportion of those with a diagnosis of CKD in the older is increasing. With comprehensive geriatric assessment, it could be possible to detect the disorders that are related to biological aging. The aim is to evaluate geriatric syndromes like frailty, cognitive dysfunction, malnutrition, and polypharmacy in an aged population with pre-dialytic CKD (stages 3a–5), and to investigate possible relations with biochemical features and anticholinergic drug burden (ADB).

Methods

One hundred and fifty-six CKD patients aged 60 and older and 164 healthy controls were included in the study. Geriatric parameters that were used for the evaluation of the groups were, Clinical Frailty Index; Charlson Comorbidity Index; Montreal Cognitive Assessment and Mini Nutritional Assessment Short-Form. Besides, biochemical parameters and ADB defined with 3 scales Anticholinergic Burden Classification (ABC), Chew’s scale, and Drug Burden Index were recorded.

Results

Despite being younger, CKD patients had higher comorbidity and frailty scores than the controls. Patients and controls had similar nutritional status, and cognitive function test results. Frailty was an important predictor for geriatric parameters and eGFR. ABC score was higher in the CKD group in ADB scale.

Conclusions

Frailty and polypharmacy are more prevalent than expected in older with CKD. In addition, anticholinergic burden and polypharmacy may form causal links with one and other and lead to increased mortality rates especially with frailty. Therefore, geriatric assessment and appropriate ADB evaluation may be recommended in CKD patients.

Keywords: chronic kidney disease; geriatric syndromes; frailty; anticholinergic burden; polypharmacy; drug interaction

Introduction

The incidence of chronic kidney disease (CKD) increases with aging. CKD, is a condition associated with atherosclerosis, inflammation, biochemical abnormalities, cognitive dysfunction, physical limitations, and Klotho deficiency. Renal hemodynamic deterioration, tubular fibrosis, and loss of filtration capacity begin in the fourth decade of life and continue into old age. In the presence of chronic kidney disease, however, there is a much faster nephron loss and vascular aging [1]. This progressive loss can result in a variety of negative consequences, such as anemia, mineral bone disorder, metabolic issues, sleep disturbances, uremia, and oliguria. More than that, there various health issues may emerge simply due to aging. These problems that increase with aging such as cognitive impairment, incontinence, delirium, dementia, falls, and frailty are defined as geriatric syndromes. With the addition of inflammation and vascular burden caused by CKD, the frequency of geriatric syndromes increases even more [2, 3].

Although polypharmacy, a geriatric syndrome commonly observed in the elderly with CKD, is defined as taking five or more drugs, recent studies have shown that drug burden, in addition to the number of drugs, is also important [2]. It has been reported that evaluating anticholinergic side effects indicating evaluation of drug burden can decrease the rates of falls, cognitive impairment, hospitalization, and mortality in the elderly [3], [4], [5]. Polypharmacy with anticholinergic drug burden, combined with metabolic disturbances, puts the elderly CKD patient at greater risk [6]. As a result, biochemical evaluation of anticholinergic drug burden combined with comprehensive geriatric assessment (CGA) could be useful, particularly in elderly CKD patients [2]. In the evaluation of the anticholinergic drug burden, potential geriatric syndromes, comorbid conditions, and biochemical parameters of the subject must be evaluated together.

CGA includes multidisciplinary diagnostic processes centered on the needs of the elderly, such as assessing biochemical, functional, and psychological capacities and allowing for the development of long-term follow-up and treatment plans. In addition to routine biochemical assessments, evaluation of physical capacity, cognitive capacity, nutritional status, and drug interactions in elderly CKD patients may help to identify overlooked problems and develop more comprehensive treatment programs. Therefore, the data obtained by CGA may reduce the risk factors for physical frailty, cognitive impairment and malnutrition in CKD patients. The aim of the present study was to evaluate geriatric syndromes in elderly individuals with CKD, and investigate possible associations with clinical features, and drug burden.

Materials and methods

The study included 156 patients over 60 years of age with stage 3a–5 CKD who were independent or partially dependent in activities of daily living and who presented to Kahramanmaraş Sütçü İmam University Nephrology clinic as outpatients. Elderly CKD patients on maintenance dialysis were excluded. In addition, subjects with recent cerebrovascular or cardiovascular disease, heart failure, severe anemia (<8 g/dL), active malignant disease, dementia, major depression, patients with active infections, and those with abnormal thyroid function tests were excluded. A total of 164 individuals over 60 years of age with an estimated glomerular filtration rate (eGFR) greater than 60 mL/min and independent in activities of daily living were included as the control group. The study was approved by Kahramanmaraş Sütçü İmam University Medical Research Ethics Committee (local ethics committee) with decision number 12 on 25/01/2022. Comorbid features and laboratory findings of the patient group were recorded. The CKD-EPI formula was employed to calculate the eGFR [7].

Detailed geriatric assessment was performed on the patient and control groups. Comorbidity, cognitive status, frailty, and nutrition were assessed on patients and controls. Comorbidities in the patient group were identified with the International Statistical Classification of Diseases (ICD) and scored with the Charlson Comorbidity Index (CCI) [8]. Cognitive assessment of patients and controls was performed with the Montreal Cognitive Assessment (MoCA) test version 7.1. The test in question was preferred because it is a test that emphasizes executive cognitive functions. MoCA includes a maximum of 30 cognitive subgroup assessments of spatial skills/execution (tracing, shape copying, clock drawing), naming, memory (short and long-term memory), attention (number repetition, letter capture and subtraction), language skills, abstraction, and orientation. If the person being tested has less than 12 years of education, 1 point is added to the MoCA global score after the test. The present study set the MoCA cut-off value for detecting cognitive impairment as ≤25 [9], [10], [11]. Cognitive tests were conducted in a separate room, and a physician with experience accompanied the test subjects.

Clinical Frailtty Index (CFI) was used to measure frailty [12]. Patients were scored from 1 to 9 based on their independence in activities of daily living. Based on the scoring system, patients with a score of 1–3 were considered to be in good general condition, those with a score of 4 were considered susceptible to frailty, and those with a score of 5–7 were considered frail. Although severely ill patients who are not expected to recover and individuals at the end of life would score 8–9 points in this analysis, such patients were not included in the study due to the exclusion criteria. Nutritional status was assessed using the Mini Nutritional Assessment Short-Form (MNA-sf) [13]. The test was calculated on a total of 14 points and patients were evaluated as malnutrition (0–7 points), risk of malnutrition (8–11 points) and normal (12–14 points). We considered advanced CKD patients with a total score of 11 or less as a malnutrition subgroup in our study [14].

The diagnosis of polypharmacy was defined as the use of 5 or more drugs [15]. Drug Burden Index (DBI), Chew score and Anticholinergic Burden Classification (ABC) scores were used for anticholinergic burden calculation [16], [17], [18]. Anticholinergic burden scales are lists of drugs that classify medicines according to their intensity of anticholinergic action. Although each scale serves the same purpose, there are differences between the medication lists of the scales. DBI is a tool that defines the anticholinergic burden of anticholinergic and sedative drugs with a calculation using the ratios between the minimum effective dose and the prescribed dose. Chew’s list of anticholinergic drugs includes 107 drugs with in vitro analysis of anticholinergic activity using a radioreceptor assay. The ABC is based on a review of the serum anticholinergic activity of 27 drugs and the scale scores from 0 to 3. Anticholinergic burden calculation tool was employed for scoring (http://www.anticholinergicscales.es/calculate).

In this study, the eGFR of elderly CKD patients were calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulation. CKD staging was done according to the eGFR levels defined by The National Kidney Foundation [19]. For laboratory analysis, ten to twelve hours fasting venous blood samples were blood drawn from the patients’ antecubital vein. Collecting tubes including EDTA and, evacuated serum separator tubes (Vacutainer SST, Becton-Dickinson) were used for blood specimens. After a blood clot has formed, the tubes were centrifuged for 10 min at 1000 g, and then stored at −70 °C before analysis. Hemoglobin, platelet, white blood cell, alanine aminotransferase, creatinine, albumin, calcium, phosphorous, parathyroid hormone (PTH), vitamin B12, 25 (OH) vitamin D3, ferritin, low density lipoprotein and triglyceride were individually assessed on the same day. Sysmex XN 3000 hematology analyzer was used for total blood count analyses in the central laboratory of our hospital. Creatinine, albumin, serum electrolyte and lipid profile were studied using the Advia 1800 Chemistry System (Siemens, Germany). Total 25 (OH) vitamin D3 levels, PTH and serum vitamin B12 were analysed with the fully automatic Advia Centaur XP immunoassay system (Siemens, Germany).

Laboratory data, comorbidity status and geriatric parameters of patients and controls were compared. Subsequently, the associations of geriatric parameter scores such as CCI, MoCA, CFI, MNA-sf, DBI, Chew and ABC with clinical characteristics were investigated. Correlation analysis was performed between clinical laboratory data and patient age and eGFR.

IBM SPSS Statistics for Windows, Version 24.0 (Amork, NY: IBM Corp.) was used for statistical analysis of the data. The data were recorded as mean±SD or %. Shapiro-Wilk method was employed to evaluate the normal distribution of continuous data. Chi-square and Fischer’s exact tests were utilized for the interpretation of categorical variables. Student’s t-test and Pearson’s test were used for the comparison of continuous data for those with normal distribution and for correlation analysis, respectively. Mann-Whitney-U test and Spearman tests were employed for those who did not show normal distribution. CGA scores and anticholinergic burden test scores that were analysis with the linear regression model.

Results

A total of 321 people were included in the study. The mean age of the total sample was 73.15±7.71 years (60–91) and 49.5 % were male. The mean estimated GFR (eGFR) was 55.63±25.61. When the stages of the patients in the CKD group were analyzed, 38 (24.4) patients were found in stage 3a, 56 (35.9) in stage 3b, 44 (28.2) in stage 4 and 18 (11.5) in stage 5. There was no statistical difference between the elderly CKD and control groups in terms of sex. However, despite being relatively younger than the control group, patients in the CKD group were frailer (p<0.001). The mean comorbidity score of the CKD group was higher than the control group, while there was no difference between the two groups in terms of cognitive scores. The number of drugs used was higher in the CKD group (p<0.01). When anticholinergic drug burden was analyzed, it was observed that only ABC burden was higher in the CKD group among the three scoring scales (<0.001). Statistical comparison of biochemical results and detailed geriatric assessment parameters of CKD patients with the control group are provided in Table 1.

Table 1:

Comparison of elderly CKD patients and healthy controls for clinical features and geriatric syndromes.

Variable CKD group (n=156) Control group (n=164) p-Value
Age, years 69.11±7.36 76.91±5.88 <0.001
Gender, M/W, n (%) 75 (48.1)/81 (51.9) 84 (51.2)/80 (48.8) 0.502
BMI, kg/m2 29.19±4.93 27.91±4.87 0.031
eGFR, mL/min/1.73 m2 34.44±13.82 76.29±15.63 <0.001
DN, n (%) 88 (56.4) 40 (24.7) <0.001
CVDs, n (%) 65 (41.7) 24 (14.8) <0.001
HT, n (%) 136 (87.2) 103 (63.6) <0.001
WBC, ×103/mm 8.18±2.55 7.59±7.96 <0.001
Hemoglobin, g/dL 12.10±1.77 13.33±1.57 <0.001
Platelet account, ×103/mm3 252.41±84.07 238.49±69.95 0.112
Creatinine, mg/dL 2.08±1.10 0.89±0.23 <0.001
ALT, U/L 15.70±9.74 20.23±9.08 <0.001
Albumin, g/dL 4.06±0.36 4.23±0.30 <0.001
Ca, mg/dL 9.08±0.69 9.50±0.43 <0.001
P, mg/dL 3.82±2.19 3.41±0.60 0.027
PTH, pg/mL 117.25±46.41 97.13±30.04 <0.001
B12 vitamin, ng/L 360.20±199.31 469.56±377.76 0.001
23 (OH) vitamin D3, ng/mL 12.71±10.72 21.28±12.21 <0.001
Albumin, g/dL 4.06±0.36 4.23±0.30 <0.001
Ferritin, μg/L 121.72±121.46 62.73±66.02 <0.001
LDL, mg/dL 108.70±37.74 130.63±35.61 <0.001
Triglyceride, mg/dL 163.67±78.89 151.66±86.97 0.214
SBP, mmHg 135.62±15.30 137.25±19.47 0.411
DBP, mmHg 77.62±9.70 75.44±12.11 0.082
CCI score 5.99±1.51 4±0.96 <0.001
CFI 3.38±1.57 2.01±1.06 <0.001
MoCA score 23.38±3.25 22.85±4.60 0.258
MNA – sf 12.03±2.21 12.13±2.63 0.757
4 m walking speed 1.30±0.63 0.51±0.39 <0.001
Drug count 6.42±2.88 5.09±3.31 <0.001
Polifarmasi, n (%) 116 (74.4) 76 (46.9) <0.001
DBI 0.26±0.39 0.32±0.40 0.151
ABC score 1.15±1.50 0.07±0.46 <0.001
Chew’s scale 0.48±0.65 0.63±1 0.092

  1. ALT, alanine aminotransferase; ABC, Anticholinergic Burden Classification; BMI, body mass index; Ca, calcium; CCI, Charlson Comorbidity Index; CFI, Clinical Frailty Index; CVDs, cardiovascular diseases; DBI, Drug Burden Index; DBP, diastolic blood pressure; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; LDL, low density lipoprotein; HT, hypertension; MoCA, montreal cognitive assessment; MNA-sf, Mini Nutritional Assessment-Short Form; P, phosphorous; SBP, systolic blood pressure; WBC, white blood cell. The parametric values were analyzed with T-test. The non-parametric values were analyzed with Mann-Whitney U test.

Univariate correlation analyses were performed for CFI score and ABC anticholinergic drug burden in elderly CKD patients. There was a positive correlation between CFI and ABC scores. Additionally, CFI and ABC scores were positively correlated with comorbidity score and number of medications used and negatively correlated with eGFR. CFI and ABC were not correlated with patient age (Table 2).

Table 2:

Univariate associates of CFI and ABC in elderly CKD patients.

CFI ABC
Variable r p-Value r p-Value
CFI 1 0.442 <0.001
MNA-sf −0.332 <0.001 −0.087 0.121
CCI score 0.647 <0.001 0.454 <0.001
Age, years 0.085 0.128 −0.105 0.061
eGFR, mL/min/1.73 m2 −0.464 <0.001 −0.382 <0.001
Drug count 0.411 <0.001 0.277 <0.001
ABC score 0.442 <0.001 1

  1. ABC, Anticholinergic Burden Classification; CCI, Charlson Comorbidity Index; CFI, Clinical Frailty Index; DBI, Drug Burden Index; eGFR, estimated glomerular filtration rate; MNA-sf, Mini Nutritional Assessment-Short Form. Normally distributed data was analyzed with the Pearson’s correlation test. Non-normally distributed data was analyzed with the Spearmen’s correlation test.

Linear regression models based on correlation analysis were performed on the data of elderly CKD patients. Advanced age, number of medications, comorbidity burden and higher ABC score were associated with high frailty scores. Decreased eGFR was also associated with increased frailty (Table 3). Anticholinergic drug burden score was found to increase with comorbidity score and frailty controlled for patient age, renal function and nutrition (Table 4).

Table 3:

Potential influences on frailty score in elderly CKD patients; linear regression model.

Dependent variable; CFI
Variable B p-Value %95 G.A.
Age, years 0.022 0.010 0.005/0.039
eGFR, mL/min/1.73 m2 −0.008 0.020 −0.014/−0.001
Drug count 0.055 0.008 0.014/0.096
MNA-sf −0.141 <0.001 −0.190/−0.093
CCI score 0.354 <0.001 0.253/0.456
ABC score 0.202 <0.001 0.096/0.309

  1. ABC, Anticholinergic Burden Classification; CCI, Charlson Comorbidity Index; CFI, Clinical Frailty Index; DBI, Drug Burden Index; eGFR, estimated glomerular filtration rate; MNA-sf, Mini Nutritional Assessment-Short Form. The liner regression analysis was performed.

Table 4:

Potential influences on ABC score in elderly CKD patients; linear regression model.

Dependent variable; ABC
Variable B p-Value %95 G.A.
Age, years −0.015 0.083 −0.033/0.002
eGFR, mL/min/1.73 m2 −0.004 0.262 −0.011/0.003
Drug count 0.027 0.204 −0.015/0.070
MNA-sf 0.013 0.622 −0.039/0.066
CCI score 0.147 0.009 0.036/0.257
CFI score 0.213 <0.001 0.101/0.325

  1. ABC, Anticholinergic Burden Classification; CCI, Charlson Comorbidity Index; CFI, Clinical Frailty Index; DBI, Drug Burden Index; eGFR, estimated glomerular filtration rate; MNA-sf: Mini Nutritional Assessment-Short Form. The liner regression analysis was performed.

Discussion

In this study we evaluated geriatric syndromes and drug burden in elderly CKD patients. We found a strong association between low eGFR and frailty. More than that, comorbidities, polypharmacy, and anticholinergic drug burden were increased elderly patients with CKD.

Aging is a natural and inevitable biological process that results in structural and functional changes in many organ systems. The diagnosis of CKD is observed in approximately half of the elderly over the age of 70 [20]. In the elderly population, mortality and morbidity rates are significantly higher in the presence of comorbid conditions such as CKD and/or diabetes mellitus [21, 22]. Physical frailty also increases in older CKD patients. In fact, it has been found that each 1-s decrease in walking speed increases mortality by 8 % in elderly CKD patients [23]. The present study evaluated geriatric syndromes, comorbidities, and drug burden in elderly with and without CKD and found that the burden of comorbidities, frailty and polypharmacy were higher in the presence of CKD. When anticholinergic drug burden was assessed, we observed that among 3 different scales, only the ABC score was higher in CKD patients.

We observed that frailty increased as eGFR decreased in elderly CKD patients. Moreover, this association was independent of patient age and comorbidities. We hypothesized that this inverse relationship between eGFR and frailty in CKD patients may be a clinical reflection of silent ischemia and biological aging. The cut-off value for the diagnosis of CKD is an eGFR below 60 mL/min/1.73 m2. With aging, muscle mass and nephron number decrease, and measured or estimated GFR levels decrease relatively. GFR measurements by methods such as cystatin C and creatinine clearance in 24-h urine are also difficult to apply in the elderly population. The margin of error of these methods increases in the presence of conditions such as atherosclerosis, inflammation, and obesity. The CKD-EPI formula, which we utilized to estimate GFR in the present study, has a high sensitivity even in the elderly population [7, 24, 25].

Frailty is a clinical condition defined in older people and refers to susceptibility to disease-related problems. It is established that there is a predisposition to frailty in the elderly with CKD [26]. The frailty scores in the CKD patient group aged 60 years and older were higher than those in the control group in the present study. The fact that the mean age of the CKD patient group was lower than that of the control group makes this result even more significant. In a previous study, we observed that frailty rates were high even in young CKD patients [5]. We suggest that CKD may be considered as the equivalent of vascular aging and physical frailty.

Besides frailty, sarcopenia, malnutrition, and cognitive impairment are geriatric syndromes that may be frequently observed in CKD patients [27]. The intersection of all these disorders includes malnutrition, anemia, hormonal imbalances, and chronic inflammation [28]. The present study showed that albumin, hemoglobin, and 25 (OH) vitamin D3 levels were lower in the elderly with CKD than in the control group. Although the serum albumin levels measured in our patients were lower than in the control group, the MNA-sf test, which was validated for nutrition prediction in the elderly, demonstrated no difference between the two groups. This discordance between albumin levels and MNA-sf results may be due to neuropsychological and gastrointestinal effects in CKD patients. Neurocognitive impairment, and anticholinergic drug burden due to polypharmacy may affect these results especially in advanced CKD patients. If patient compliance can be achieved, we suggest that the use of a more detailed nutritional scale, the MNA-long form, may make a difference.

Impairments in basic cognitive functions such as learning, memory and speech in the elderly negatively affect quality of life and lead to increased mortality [29]. Silent ischemia in CKD increases the risk of cognitive impairment. Cognitive impairment starts early in the course of CKD and may increase in parallel with the decline in kidney function. Moreover, it has also been reported that decreased renal function in the elderly increases the risk of stroke-unrelated dementia [30]. Various cognitive tests were proposed to evaluate the cognitive functions of patients with CKD. As one of these tests, MoCA is a test that specifically evaluates executive functions and can reveal cognitive impairments related to vascular disease burden [5]. However, the present study revealed no difference between elderly CKD patients and the control group in terms of cognitive capacity scores assessed by MoCA test. The similar results may be related to the lower mean age of the patient group and the fact that hemodialysis recipients were not included in this group.

Elderly CKD patients are a patient population that experiences polypharmacy and related anticholinergic drug interactions the most. The inclusion of anticholinergic load in polypharmacy further increases mortality rates [2]. Anticholinergic side effects of the drugs in particular cause peripheral and central nervous system disorders such as dry mouth, taste changes, memory loss, dizziness, and delirium. Decreased basal cholinergic levels, increased blood brain barrier permeability, decreased receptor sensitivity and changes in drug pharmacokinetics make the elderly more susceptible. Conversely, decreased drug clearance and increased uremic toxins increase the potential for side effects in the presence of CKD. There are different scales in the literature that define anticholinergic side effects. The differences between these scales have been associated with the measurement methods and the number of drugs they cover [31]. The ABC and Chew scales utilized in the present study use in vitro anticholinergic activity, whereas DBI is a mathematical formula using the number and doses of drugs. The anticholinergic burden found by the ABC scale in our CKD patients was higher than in the control group. The reason for this difference was that CKD patients were more likely to use diuretics and beta blockers. Therefore, the ABC method may be more appropriate when assessing anticholinergic drug burden in CKD patients.

The present study employed comprehensive exclusion criteria and a geriatric assessment as detailed as possible. Despite the high annual mortality of CKD in the elderly and the general reluctance of patients to participate in these and similar studies, we were able to achieve a satisfactory sample size. Nevertheless, the present study has some limitations. The possible limitations of the study include the difference in mean age between our groups, the possible presence of undiagnosed CKD cases in the control group and the variable daily doses of the drugs used by the patients in the evaluation of anticholinergic load. Another possible limitation to our study is the lack of evaluations for daily living activities. Even if we excluded CKD patients with limited daily living activities, it would have been better to implement a test for this domain. In addition, sarcopenia; a common geriatric syndrome in older CKD patients was not evaluated in this study. Even if, we did not have suitable devices to measure muscle mass and strength we implemented a 4 m walking speed test in order to gain insight about muscle strength and gait speed.

Conclusions

Frailty and polypharmacy are common geriatric syndromes in the elderly with CKD. In the presence of frailty and low GFR, biochemical side effects of anticholinergic drugs could be severe. It is essential to consider the number of drugs as well as the profile of anticholinergic side effects in the management of polypharmacy. ABC scoring may be a useful scale in this regard, because it gives weight to agents that are frequently used in CKD patients. Further studies, preferably in patients with advanced CKD, are needed to obtain more definitive results.

Corresponding author: Neziha Erken, MD, Department of Geriatric, Kahranmaraş Necip Fazıl City Hospital, Kahramanmaraş, Türkiye, Phone: 05331687139, E-mail:

  1. Research ethics: The research was conducted in accordance with the declaration of Helsinki.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: Neziha Erken: Data collection, data interpretation, statistical analysis, literature search, writing. Ertugrul Erken: Data collection, supervision, linguistic revision, writing.

  4. Competing interests: Authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: None declared.

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Received: 2023-08-21
Accepted: 2023-09-05
Published Online: 2023-09-25

© 2023 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/tjb-2023-0189
Keywords for this article
chronic kidney disease; geriatric syndromes; frailty; anticholinergic burden; polypharmacy; drug interaction
Creative Commons
BY 4.0

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Exploring nanotechnology-based approaches using miRNAs to treat neurodegenerative disorders
  4. Research Articles
  5. Rhesus factor is a stronger predictor for the risk of Sars-CoV-2 and mortality than ABO blood types
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  7. New data for endemic Phlomis brevibracteata Turrill from North Cyprus: biological activities and chemical composition
  8. Inhibitory effect of organic acids on human neutrophil myeloperoxidase’s peroxidation, chlorination, and nitration activities
  9. Prevalence and association of sIgA in saliva and Pseudomonas aeruginosa infection in TB patients: a cross-sectional study
  10. Within- and between-subject biological variation of hemostasis parameters in a study of 26 healthy individuals
  11. Nasal fluid sample as a reliable matrix for determination of cytokine levels in childhood asthma
  12. Evaluation of the monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) as diagnostic biomarkers in different lung diseases, especially for SCLC
  13. The association between plasma concentration of pigment epithelium-derived factor and diabetic retinopathy
  14. Can preoperative neopterin levels predict acute kidney injury in patients undergoing on-pump cardiac surgery?
  15. Exosomal prognostic biomarkers predict metastatic progression and survival in breast cancer patients
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