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Research Article
Revised

Association of intradialytic hypertension and antihypertensive medication use in patients undergoing maintenance hemodialysis: a prospective observational study

[version 2; peer review: 1 approved with reservations, 1 not approved]
PUBLISHED 06 Jan 2025
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Abstract

Background

In patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis, intradialytic hypertension and intradialytic hypotension are the common complications. The study aimed to collect and assess intradialytic Blood Pressure (BP) complications and their association with BP medications.

Methods

This was a prospective observational study, conducted at the hemodialysis center in a teaching hospital in the UAE, that provide a specialist’s care for the patients receiving ongoing hemodialysis. Patient demographics, medications used, lab data and the peridialytic BP (pre-, intra-, and post-) dialytic BP were collected for a period of 6 months. SPSS Version 29, Armonk, NY was used for statistical analysis. Pearson Chi-square test and Fischer’s Exact test were used to compare the association between categorical variables to intradialytic hypertension and hypotension. Binary logistic regression was used to find the effect of predictive variables to the presence or absence of intradialytic complications.

Results

Blood pressure data was collected from 47 hemodialysis patients for a total of 2616 hemodialysis sessions during the 6 months study period. Non-dialysable antihypertensives were predominantly used. Beta-blockers (68%) and calcium channel blockers (66%) were the commonly used drug classes. Intradialytic hypertension events were diagnosed in 49 (1.9%) hemodialysis sessions and intradialytic hypotension was diagnosed in 23 (0.9%) hemodialysis sessions. Chi-square test showed association of antihypertensive medication use to the occurrence of intradialytic hypertension; especially ARBs, and alpha-1 blockers. Beta-blockers and calcium channel blockers use were associated with decreased number of intradialytic hypertension events (p-value <0.05). Regression showed broad confidence intervals. On the other hand, antihypertensive medication use showed no association with intradialytic hypotension.

Conclusions

Even though antihypertensive medications showed varying occurance of intradialytic hypertension, the results are inconclusive due to large confidence intervals that could be due to the presence of colliniarity between the variables. Future studies are required in larger populations.

Keywords

Hypertension, comorbidities, intradialytic hypertension, intradialytic hypotension, factors, dialysis patients

Revised Amendments from Version 1

Following are the changes made in version 2.
No changes in the title, and authors.
The abstract is modified to include the regression analysis and its results.
The introduction is rephrased to increase clarity. Two references are replaced.
The method is modified by adding more details about the study setting and data collection procedure. Also, binary logistic regression is used to find the odds ratio and 95% confidence interval. 
In the results, the new results from binary regression are added as a new table, and elaborated the results.
Reorganized the discussion part.
The conclusion is modified including the results from binary regression.

See the authors' detailed response to the review by Carmine Zoccali
See the authors' detailed response to the review by Peter K Uduagbamen

Introduction

Although hypertension is prevalent in more than 80% of chronic maintenance hemodialysis patients, there is no consensus about the BP threshold, BP target, and the effect of BP reduction on cardiovascular outcomes. Hypertension in the hemodialysis population is multifactorial and is different from other patient populations.15 Patients undergoing hemodialysis may experience several complications in their treatment journey that affect their quality of life. Many patients have varying adherence to therapy and struggle to achieve optimal blood pressure outcomes.610

Although the drug treatment is effective, the number of patients who achieved adequate BP control is limited. BP obtained in dialysis centers poorly represents the actual blood pressure status of the hemodialysis patients, makes the management of hypertension particularly challenging. Despite calculating the fluid removal during hemodialysis, many patients experience intradialytic BP complications.1113 Intradialytic hypertension (IDHTN) and hypotension (IDH) are common complications during hemodialysis. Their prevalence range 20.2–33.4% and 10-12% respectively. These complications occur due to multiple factors including volume overload, endothelial dysfunction, electrolyte alterations, and/or overactive sympathetic nervous system and renin angiotensin aldosterone system (RAAS). These BP complications are associated with increased risk of mortality.14,15

Beta-blockers, (dihydropyridine) calcium channel blockers, and renin-angiotensin system (RAS) inhibitors are commonly used in the hemodialysis patients followed by central α agonists, peripheral α antagonists, and direct vasodilators, and diuretics. The choice of antihypertensives depends on factors including comorbidity, residual renal function, dialyzability, and cardiovascular benefits. Compared to dialyzable beta blockers, nondialyzable beta blockers are associated with reduced frequency of intradialytic hypertension. A single center study showed that intradialytic hypertension is high with highly dialysable antihypertensive use. CCB use is associated with a lower risk of hypotension during dialysis, independent of predialysis systolic BP and other antihypertensives use. ACE inhibitors or ARBs, and diuretics had increased risk of hemodialysis hypotension compared with CCBs, β and αβ blockers.1119

Aim

The aim of the study was to investigate the association of intradialytic hyper or hypotension and the antihypertensive medications use in patients undergoing dialysis.

Methods

Research design & setting

This prospective observational study was conducted in the hemodialysis unit of a 350 bedded tertiary care teaching hospital in the UAE. This is one of the largest hemodialysis units among the private sector hospitals in the UAE. The center had dialysis sessions starting from 7 AM to 11 PM and was working in 3 shifts (morning, noon and evening). Most patients were on weekly 3 times dialysis sessions. The center was functioning under the supervision of a nephrologist. For the research, patient information was mostly collected from electronic medical records and the physician’s register of patient’s medications. The data collection process began on November 1, 2022, and continued until the end of April 2023.

Study population

Fifty-six patients with end-stage kidney disease and hypertension and were undergoing regular maintenance hemodialysis at the study site. After removing patients who had been on dialysis for less than three months, the total number of participants was 47.

Ethical concerns

Patient confidentiality was maintained, and consent was obtained from the patients for the study. Ethical approval for the study was granted by the institutional review board of Gulf Medical University (IRB approval date: 19 November 2020; Ref No. IRB/COP/STD/07/Nov-2020). The principles of the Declaration of Helsinki were used in this research.

Data collection

All the data were collected using a standard data collection from the electronic medical records and the dialysis register maintained by the dialysis unit staff. Ambulatory or home BP measurements were not feasible and were not used in the study. For every patient, a trained dialysis nurse measured and recorded BP at the start of dialysis (Pre dialysis BP), BP during dialysis (measured and recorded every 30 minutes, using the automatic cuff attached to the HD machine, an average of 6-8 BP reading is taken by the researcher (intra dialytic BP) and BP after the dialysis session ends (post dialytic BP). Generally, each hemodialysis session was for 4 hours unless complications led to an early finish. Data collection continued for six months to identify the patterns of blood pressure, as well as complications of intradialytic hypertension, and hypotension that occurred during each dialysis session. All patients had same type dialyzer and dialysate solution and none were on low sodium dialysate. The events of IDHTN and IDH were based on the clinicians’ diagnosis of the same which was based on the patient’s symptoms.

Data analysis

Descriptive statistics was used to summarize the data. Pearson Chi-square test and Fischer’s Exact test were used to compare the association between categorical variables to intradialytic hypertension and hypotension. Whereever association was found significant, Mantel-Haenszel test and b inary logistic regression was used to estimate the odds ratios. SPSS Version 29, Armonk, NY (https://www.ibm.com/support/pages/downloading-ibm-spss-statistics-29011) was used for statistical analysis.

Results

A total of 2616 hemodialysis sessions occurred during the 6 months period for 47 maintenance hemodialysis patients. Patients were of age 55 (±13) years. 55.3% of patients were less than 60 years old and 74.5% of patients were males. Health insurance was present for 85% patients. Three times per week dialysis was for 62% patients. An overview of the sociodemographic and health status characteristics of the 47 study participants is given in Table 1.30

Table 1. Patient demographics at baseline.

Characteristics Mean (±SD) or n (%)
Age in years, Mean (±SD)55 (±13)
 Less than 60 years, n (%)26 (55.3%)
 60 years or above, n (%)21 (44.7%)
Gender
 Male35 (74.5%)
 Female12 (25.5%)
Ethnicity
 Arab21 (44.7%)
 Non-Arab 26 (55.4%)
Marital status
 Married42 (89.4%)
 Not married5 (10.6%)
Employment status: Employed27 (57.4%)
Health insurance active40 (85.1%)
Smoking status:
 Current smoker1 (2.1%)
 Ex-smoker 04 (8.5%)
 Never smoker42 (89.3%)
BMI in kg/m2, Mean (±SD)28.12 (±5.77)
Dialysis vintage in months, mean (±SD)26.89 (16.74)
Number of dialysis sessions per week
 Two times per week18 (38)
 Three times per week29 (62)
Comorbidities
 Diabetes27 (57.4)
 Hypertension40 (85.1)
 Dyslipidemia9 (19.1)
 Cerebrovascular accident (CVA)14 (29.8)
 Ischemic heart disease6 (12.8)
 Anemia27 (57.4)
 Asthma1 (2.1)
 Depression1 (2.1)
 Obstructive sleep apnea (OSA)1 (2.1)

Average institutional blood pressure recordings before, during, and after dialysis of the study population were provided in Table 2. Elevated SBP was more commonly seen compared to elevated DBP in the pre-, intra- and post dialysis periods.

Table 2. Average peri-dialytic values of 6 months study period (n=47).

Blood pressureMean (±SD)
Pre dialytic SBP (mmHg)153.614.5
Pre dialytic DBP (mmHg)82.19.3
Intra dialytic SBP (mmHg)149.614.7
Intra dialytic DBP (mmHg)81.27.1
Post dialytic SBP (mmHg)149.217.1
Post dialytic DBP (mmHg)81.07.6
Pre dialytic weight (kg)77.216.8
Post dialytic weight (kg)74.816.4
Ultrafiltration (L)2.40.7

Calcium channel blockers and beta blockers were the commonly used antihypertensive medications ( Figure 1). Non dialyzable antihypertensives were mostly used. Amlodipine (61.7%), bisoprolol (44.7%), furosemide (20%), doxazosin (29.8%), moxonidine (21.3%), hydralazine (12.8%), nebivolol (10.6%), and carvedilol (8.5%) were the commonly used ones. Other antihypertensive use was less than 25%. A combination of four or more antihypertensives was used by 16 (34%) patients, indicating the presence of resistant hypertension.

407db30e-0a9e-4199-8667-803c9c80fc09_figure1.gif

Figure 1. Antihypertensive use among the study population (n=47).

X-axis shows percentage of patients on antihypertensives, and Y-axis shows antihypertensive drug class.

Out of the 2616 hemodialysis sessions, 49 (1.9%) sessions had intradialytic hypertension and 23 (0.9%) dialysis sessions had intradialytic hypotension. This include intradialytic hypertension in 16 (34%) patients and Intradialytic hypotension in 11(23%). Both events occurred in 3 (6%) patients. Twenty-three (49%) patients had no interdialytic BP complications.

Association between antihypertensive medication and IDHTN is provided in Table 3. The association was statistically significant for Angiotensin Receptor Blocker (ARB), Beta Blockers, Calcium Channel Blockers, Alpha-1 Blockers and diuretics. Centrally acting drugs and vasodilators did not show statistically significant association to IDHTN.

Table 3. Association of antihypertensives to intradialytic Blood Pressure Complications.

Antihypertensive classAntihypertensive useNo Intra-dialytic HypertensionIntra-dialytic Hypertension P-value#
Angiotensin Receptor Blocker (ARB)Nonuser27 (57.4%)9 (19.1%)0.02*
User4 (8.5%)7 (14.9%)
Beta BlockersNonuser15 (31.9%)2 (4.3%)0.02*
User16 (34.0%)14 (29.8%)
Calcium Channel BlockersNonuser13 (27.7%)1 (2.1%)0.01*
User18 (38.3%)15 (31.9%)
Alpha-1 BlockersNonuser24 (51.1%)7 (14.9%)0.02*
User7 (14.9%)9 (19.1%)
DiureticsNonuser21 (44.7%)5 (10.6%)0.02*
User10 (21.3%)11 (23.4%)
Central acting agentsNonuser26 (55.3%)10 (21.3%)0.10
User5 (10.6%)6 (12.8%)
VasodilatorsNonuser28 (59.6%)13 (27.7%)0.38
User3 (6.4%)3 (6.4%)

* P value <0.05.

# Pearson Chi-Square test or Fischer exact test.

Age (<60 years or more), gender (male or female), ethnicity (Arab or Non-Arab), frequency of dialysis per week (twice or thrice), polypharmacy (≥5 medications), Hemoglobin level (moderate-severe anemia), and presence of comorbidities diabetes or hypertension did not show any association to IDHTN. Dialysis vintage (>1year vs < 1year), resistant hypertension with the use of 4 or more antihypertensive drugs, showed association to IDHTN.

None of the antihypertensive drug classes showed association to intradialytic hypotension.

Patients using ARBs or alpha-1 blockers had higher intradialytic hypertension events. Beta-blocker and calcium channel users had lower intradialytic hypertension. Other antihypertensive use did not show any association with intradialytic hypertension. Antihypertensive medication use showed no association with intradialytic hypotension.

A binary logistic regression analysis was performed to examine the relation between antihypertensive use and IDHTN. Results are shown in the Table 4.

Table 4. Effect of Antihypertensives on incidence of Intradialytic hypertension.

VariableCategoryNo IDHTN
(n=31)
IDHTN
(n=16)
Odds ratio (OR)P value95% Confidence interval
Lower Upper
ARBNonuser2795.25.0241.2422.19
User47
BBNonuser1526.56.0251.2733.85
User1614
CCBNonuser13110.83.0301.2792.66
User1815
A1BNonuser2474.41.0251.2016.14
User79
DiureticNonuser2154.62.0211.2616.92
User1011
Resistant HTNNo2566.94.0051.8026.75
Yes610
Dialysis vintage >1 yearNo890.27.0440.080.97
Yes237

The crude odds ratio indicated a statistically significant association. However, the adjusted multinomial regression analysis showed no significant odds ratios. It could be due to the multiple instances of collinearity among the variables that was revealed in the correlation analysis.

Discussion

Hemodialysis helps manage hypertension in patients with end-stage kidney disease (ESKD) alongside the use of antihypertensive medications. The association between antihypertensive use and intradialytic blood pressure complications was a new study from the Middle East region. Thrice-weekly sessions are the most common approach for maintenance hemodialysis. Frequent dialysis sessions are crucial for effectively removing waste products and excess fluid from the body, helping to maintain overall stability in ESKD patients. Antihypertensive medications are essential for controlling blood pressure in dialysis patients, as hypertension is a common comorbidity in this population and is linked to increased cardiovascular risks. Effective fluid removal is critical to prevent complications associated with fluid overload, such as congestive heart failure and pulmonary edema in ESKD. Some antihypertensive medications were more likely to be associated with intradialytic hypertension than others.1115

Hemodialysis helps in managing hypertension in ESKD patients along with antihypertensive medications. The antihypertensive use and its association with intradialytic BP complications was novel finding from the Middle East region. Some antihypertensive medications were associated with intradialytic hypertension compared to others. Thrice-weekly sessions were the most common approach for maintenance hemodialysis. Frequent dialysis sessions are crucial for effectively removing waste products and excess fluid from the body to maintain proper kidney function. Antihypertensive medications are essential for controlling blood pressure in dialysis patients, as hypertension is a common comorbidity in this population and is associated with increased cardiovascular risks. Effective fluid removal is critical to prevent complications associated with fluid overload, such as congestive heart failure and pulmonary edema in ESKD.20,21

The most common intradialytic complication in our study was IDHTN experienced by 34% of patients and accounted for 1.9% of total dialysis sessions. IDH occurred in 23% patients and accounted for 0.9% of total dialysis sessions. Age, gender, ethnicity, dialysis frequency, and polypharmacy did not show any association to IDHTN. Dialysis wintage less than 1 year and use of 4 or more antihypertensive drugs were found to increase the risk of IDHTN.

Beta-blockers were the most frequently prescribed cardiovascular medications among dialysis patients in this study. These agents are well-established for their efficacy in lowering heart rate and blood pressure, making them essential in managing hypertension and reducing cardiac workload. Loop diuretics, such as furosemide, play a critical role in managing fluid overload and congestive heart failure, common complications in dialysis patients resulting from impaired renal function. These agents facilitate diuresis and contribute to maintaining fluid balance and hemodynamic stability in this high-risk population. Furthermore, beta-blockers have demonstrated benefits in improving cardiovascular outcomes and reducing mortality in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Their use in this population is consistent with current clinical guidelines and reflects a proactive approach to mitigating cardiovascular risk.2224

In this study population, both beta-blockers and calcium channel blockers (CCBs) were associated with a higher incidence of intradialytic hypertension. CCBs are also effective in lowering blood pressure and have been shown to improve outcomes in CKD, particularly by slowing the progression of renal disease. Due to their favorable safety profile and tolerability in patients with compromised kidney function, CCBs are considered an appropriate therapeutic option for dialysis patients, many of whom present with pre-existing cardiovascular conditions.2224

Beta-blockers were the most commonly prescribed cardiovascular medication among dialysis patients. Beta-blockers are well-known for their ability to lower heart rate and blood pressure, making them valuable in managing hypertension and reducing the workload on the heart. Additionally, they have been shown to be beneficial in improving overall cardiovascular outcomes and reducing mortality rates in patients with CKD and ESKD. The use of beta-blockers in this population aligns with current guidelines and represents a proactive approach to cardiovascular risk reduction. Beta-blockers calcium channel blockers (CCBs) were associated with more frequent intradialytic hypertension in our study population. CCBs are also effective in reducing blood pressure and have been shown to improve outcomes in CKD patients, particularly in terms of slowing the progression of kidney disease. CCBs are considered safe and well-tolerated in patients with impaired kidney function, making them a suitable choice for dialysis patients who often have pre-existing cardiovascular complications. Loop diuretics, such as furosemide, are crucial for managing fluid overload and congestive heart failure, common complications in dialysis patients due to impaired kidney function. These medications promote diuresis and help maintain fluid balance and hemodynamic stability in this vulnerable population.14,22,23

The low utilization of ACE inhibitors in this study may be attributed to individual patient characteristics, contraindications, or specific preferences of healthcare providers. Similarly, thiazide diuretics are often used as add-on therapy to manage hypertension in CKD patients. Thiazide diuretics are effective in promoting diuresis and blood pressure control, but their usage may be limited in patients with advanced kidney disease due to decreased renal excretion and potential electrolyte disturbances. Vasodilators, such as hydralazine and Nifedipine, were also relatively underutilized. Vasodilators act to relax blood vessels, thus reducing blood pressure and improving cardiac function. Their low usage in this study could be attributed to various factors, including the presence of alternative medications or individual patient responses.13,15,22,24

Hypertension is a significant concern among dialysis patients due to impaired kidney function and fluid balance. Our study observed that a substantial proportion of patients were prescribed antihypertensive medications. Intradialytic BP complications are reported in many studies, but not their association with antihypertensive medications, making our study unique. Intradialytic hypertension is a concern that needs to be addressed more effectively.2530

Conclusion

Intradialytic hypertension was the most common BP complication among our study population, contrary to the common belief that intradialytic hypotension is the most common complication among patients undergoing hemodialysis. Beta-blockers and calcium channel blockers were the most prescribed antihypertensives in the study population. Patients using ARBs or alpha-1 blockers had higher intradialytic hypertension events. Beta-blocker and calcium channel users had lower intradialytic hypertension events. Other antihypertensive were not showing a significant difference. Regression analysis showed wide confidence intervals for all such relationships demanding further research.

Strengths and limitations

The study was conducted in one of the biggest private healthcare settings in the United Arab Emirates. Most of the patients were on antihypertensive medications for their hypertension management. This study focused on assessing relationship of antihypertensive medication on intradialytic blood pressure complications and the study being conducted in a single site produces a cohort effect as all patients receive same standard of care during the study period.

Though number of study population was limited, it was enough to find statistically significant association. Medication adherence was not collected in detail in this study. Patients were asked about medication adherence and found they were generally adherent to their antihypertensive medications, as there were clinical pharmacy interventions prior to this study to improve medication adherence. Reinforcement advice was provided to the study participants on the importance of medication adherence.

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Sherif M, Zachariah S and Jagdale R. Association of intradialytic hypertension and antihypertensive medication use in patients undergoing maintenance hemodialysis: a prospective observational study [version 2; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2025, 13:634 (https://doi.org/10.12688/f1000research.144153.2)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 14 Jun 2024
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Reviewer Report 01 Aug 2024
Peter K Uduagbamen, Bowen University / Bowen University Teaching Hospital, Ogbomosho, Nigeria 
Approved with Reservations
VIEWS 10
Authors should mention specific timings for BP measurements. How were the necessary precautions in BP measurement effected? 
What about the dialyzable and the non-dialyzable anti-hypertensive drugs and their effects.
Food taken within 30 minutes to an hour prior ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Uduagbamen PK. Reviewer Report For: Association of intradialytic hypertension and antihypertensive medication use in patients undergoing maintenance hemodialysis: a prospective observational study [version 2; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2025, 13:634 (https://doi.org/10.5256/f1000research.157907.r302267)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 06 Jan 2025
    Seeba Zachariah, College of Pharmacy, Gulf Medical University, Al Jurf, 4184, United Arab Emirates
    06 Jan 2025
    Author Response
    1. Authors should mention specific timings for BP measurements. How were the necessary precautions in BP measurement effected?
    Author Response: The dialysis center was functioning from 7 AM to 11 AM ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 06 Jan 2025
    Seeba Zachariah, College of Pharmacy, Gulf Medical University, Al Jurf, 4184, United Arab Emirates
    06 Jan 2025
    Author Response
    1. Authors should mention specific timings for BP measurements. How were the necessary precautions in BP measurement effected?
    Author Response: The dialysis center was functioning from 7 AM to 11 AM ... Continue reading
Views
9
Cite
Reviewer Report 23 Jul 2024
Carmine Zoccali, Renal Research Institute, New York, New York, USA;  Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy;  Associazione Ipertensione Nefrologia Trapianto Renale (IPNET), Reggio Calabria, Italy 
Not Approved
VIEWS 9
The study aimed to assess intradialytic blood pressure (BP) complications and their association with various factors, including BP medication, in patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis. It was a prospective observational study conducted at a hemodialysis center ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Zoccali C. Reviewer Report For: Association of intradialytic hypertension and antihypertensive medication use in patients undergoing maintenance hemodialysis: a prospective observational study [version 2; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2025, 13:634 (https://doi.org/10.5256/f1000research.157907.r302273)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 24 Jul 2024
    Seeba Zachariah, College of Pharmacy, Gulf Medical University, Al Jurf, 4184, United Arab Emirates
    24 Jul 2024
    Author Response
    Philosophical underpinning of this research is real-world observational, but the reviewer comments are from an experimental interventional research viewpoint. The mix up of research paradigms creates confusion. Causal relationship is ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 24 Jul 2024
    Seeba Zachariah, College of Pharmacy, Gulf Medical University, Al Jurf, 4184, United Arab Emirates
    24 Jul 2024
    Author Response
    Philosophical underpinning of this research is real-world observational, but the reviewer comments are from an experimental interventional research viewpoint. The mix up of research paradigms creates confusion. Causal relationship is ... Continue reading

Comments on this article Comments (0)

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Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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