Skip to main content
PLOS One logoLink to PLOS One
. 2021 Mar 16;16(3):e0248575. doi: 10.1371/journal.pone.0248575

Magnitude and determinants of drug-related problems among patients admitted to medical wards of southwestern Ethiopian hospitals: A multicenter prospective observational study

Firomsa Bekele 1,*, Tesfaye Tsegaye 1, Efrem Negash 2, Ginenus Fekadu 3,4
Editor: M Mahmud Khan5
PMCID: PMC7963049  PMID: 33725022

Abstract

Background

Drug-related problem (DRP) is an event involving drugs that can impact the patient’s desired goal of therapy. In hospitalized patients, DRPs happen during the whole process of drug use such as during prescription, dispensing, administration, and follow-up of their treatment. Unrecognized and unresolved DRPs lead to significant drug-related morbidity and mortality. Several studies conducted in different hospitals and countries showed a high incidence of DRPs among hospitalized patients. Despite the available gaps, there were scanties of studies conducted on DRPs among patients admitted to medical wards in Ethiopia. Therefore, this study assessed the magnitude of drug-related problems and associated factors among patients admitted to the medical wards of selected Southwestern Ethiopian hospitals.

Patients and methods

A multicenter prospective observational study was conducted at medical wards of Mettu Karl Hospital, Bedele General Hospital and Darimu General Hospital. Adult patients greater than 18 years who were admitted to the non-intensive care unit (ICU) of medical wards and with more than 48 h of length of stay were included. Identified DRPs were recorded and classified using the pharmaceutical care network Europe foundation classification system and adverse drug reaction was assessed using the Naranjo algorithm of adverse drug reaction probability scale. Hill-Bone Compliance to High Blood Pressure Therapy Scale was used to measure medication adherence. Multivariable logistic regression was used to analyze the associations between the dependent variable and independent variables.

Result

Of the 313 study participants, 178 (56.9%) were males. The prevalence of actual or potential DRPs among study participants taking at least a single drug was 212 (67.7%). About 125 (36.63%) patients had one or more co-morbid disease and the average duration of hospital stay of 7.14 ± 4.731 days. A total of 331 DRPs were identified with an average 1.06 DRP per patient. The three-leading categories of DRPs were unnecessary prescription of drugs 92 (27.79%), non-adherence (17.22%) and dose too high (16.92%). The most common drugs associated with DRPs were ceftriaxone (28.37%), cimetidine (14.88%), and diclofenac (14.42%). The area of residence (AOR = 2.550, 95CI%: 1.238–5.253, p = 0.011), hospital stay more than 7 days (AOR = 9.785, 95CI%: 4.668–20.511, p≤0.001), poly pharmacy (AOR = 3.229, 95CI%: 1.433–7.278, p = 0.005) were predictors of drug-related problem in multivariable logistic regression analysis.

Conclusion

The magnitude of drug therapy problems among patients admitted to the medical wards of study settings was found to be high. Therefore, the clinical pharmacy services should be established in hospitals to tackle the DTPs in this area. Additionally, healthcare providers of hospitals also should create awareness for patients seeking care from health facilities of the importance of rational drug usage.

Background

Drug therapy problem (DTP) is an event occurred during disease treatment that can have the probability to affect the desired treatment outcomes of patients, such as dose too low, dose too high, adverse drug reaction, need additional drug therapy, unnecessary drug therapy, non-adherence, and ineffective drug therapy [1,2]. Despite used for disease treatment and prevention, drugs are also responsible for drug-related problems (DRPs) [3]. In hospitalized and chronic care patients, drug-related problems (DTPs) happen during the whole process of drug use such as during prescription, dispensing, administration, and follow-up of their treatment [4].

Due to several reasons, hospitalized patients are receiving more medications than those treated as outpatients [5]. The rate of hospital admission due to DTP was estimated to be 5–10%, and the magnitude of patients discharged with DRP was about 22%. Among the seven categories of DTP, non-adherence, inappropriate indication, and ADR were resulted in emergency department visits in 28% of the patients [6].

The impact of DTPs among hospitalized patients includes decreased quality of life, prolonged hospital stays, increased healthcare budget, finally leading to death [7]. More people die of inappropriate drug treatment than breast cancer, AIDS, and traffic accidents all together [8]. Due to their training, pharmacists can play a key role in identifying these DTPs in resolving actual DTPs and preventing potential DTPs through careful pharmaceutical practices [9].

In USA and Australia about$177.4 and £100707 billion was spent to manage the consequences of DTPs annually, respectively [1,9]. A study done in Lagos State University Teaching Hospital, Nigeria, reported that approximately1.83 million naira (15,466.60 USD) was spent on managing all the patients admitted due to adverse drug reactions (ADRs). Therefore, it is possible to reduce the economic impacts of DRPs on patients, general population, and health care by tackling any DRP before its occurrence [3,7].

ADRs cause patients to lose confidence toward their physicians and seek self-treatment options, which consequently precipitate additional ADRs [10]. About 17% of heart failure (HF) patients experience adverse effects of their medication and 6.7% of ADR-related hospitalizations to cardiac units [11]. Around 5% of all hospital admissions are the result of an ADR, and around 10%–20% of inpatients will have at least one ADR during their hospital stay [10]. Therefore, ADR is the most common cause of patient morbidity, mortality, and increased healthcare costs [6,7,12].

The findings from England, Uganda, Brazil, and North India showed that the prevalence of ADR among admitted patients was 6.5%, 4.5%, 11.5%, and 22.6%, respectively [1316]. The high rate of ADR is due to polypharmacy, adequate monitoring of drugs and irrational prescription of drugs by unauthorized professional [13,16]. A study conducted in Australian showed that about 1.3 million people were injured each year due to medication errors and adverse drug events (ADEs) in 16.6% of admissions, resulting in permanent disability in 13.7% and death in 4.9% patients [17].

Hospitalized patients are more likely to be exposed to poly pharmacy. Some DRPs exist at the time of admission to hospital, while others arise during hospital management. On average 2.6 DRPs occur per patient in internal medicine wards in Norway and the presence of DRPs increased approximately linearly with the number of drugs used [18]. Know a day’s more than half of hypertensive patient’s treatment was un-controlled despite different combination therapy was used. The condition is due to DRPs such as non-adherence, ADRs, ineffective drugs, under dose and overdose [19].

Therefore, several studies conducted in different hospitals and countries showed high incidence of DRPs among hospitalized patients. However, there was no DTP study conducted in medical wards of Ilubabor and Buno bedele zone and this study assessed DRPs and its predictors in medical ward of Mettu karl, Bedele, and Darimu hospitals.

Patients and methods

Study setting, design and study period

A multicenter prospective observational study was conducted in three hospitals found in the Ilu ababor and Buno bedele zones. The included hospitals are Mettu Karl Hospital (MKH), Bedele General Hospital (BGH) and Darimu General Hospital (DGH) during the study period of March 1, 2020 to June 1, 2020. Iluababor and Buno bedele zones are found in southwest Ethiopia located at 572 km and 423 km away from Addis Ababa, the capital city of Ethiopia, respectively.

Study participants and eligibility criteria

Adult patients more than 18 years who were admitted to the non-intensive care unit (ICU) of medical wards and with more than 48 h of length of stay were included. Patients who refused to participate, re-admitted during the study period, and developed ADR due to genetic factors were excluded.

Study variables and outcome endpoints

The DTP was the primary outcome. ADR was assessed using the Naranjo algorithm of the ADR probability scale [20]. Hill-Bone Compliance to High Blood Pressure Therapy Scale was used to measure medication adherence. Accordingly, the nine-item medication-taking sub-scale was employed. Each item is a four-point Likert type scale (none of the time, some of the time, most of the time and all of the time) [21,22]. The total scores on this subscale range from 9 to 36, with higher scores reflecting poorer adherence to drug therapy. The median split was used and dichotomized into two groups 1 = Adherent to the treatment and 0 = Non-adherent to the medication.

Sample size and sampling technique

The single population proportion formula was used to calculate the required sample size by considering the following assumptions: Proportion of drug-related problems was 75.51% from else report [6], 95% confidence level, and 5% margin of error (the absolute level of precision).

n=(Zα/2)2p(1p)d2
z=1.96
P=75.51%(0.7551)andd=0.05
n=(1.96)2(0.755)(0.245)(0.05)2=284.24284
Where,n=samplesize

A 10% contingency yielded a final sample size of 313. Proportional allocation was used to select study subjects based on the number of patients that the respective hospitals contained in their medical wards. From the total sample size calculated, 190 patients were from MKH, 68 patients were from BGH and 55 patients were from DGH. The subjects were chosen using a consecutive sampling technique.

Data collection process and management

Data were collected using questionnaire which was developed after reviewing different literature and checklist was prepared to verify the patient’s medical information. Four medical doctors, four nurses and four pharmacists were recruited for data collection. Additionally, three medical doctors and three pharmacists were assigned to supervise the data collection process. The supervisor and principal investigator were closely following the data collection process at the spot. The principal investigator evaluated the appropriateness of medical therapy using various references like Medscape, up to date, Lexicom and Micromedex and different guidelines. Identified DRPs were recorded and classified using the DRP registration format [2]. ADR was assessed using Naranjo algorithm of ADR probability scale. Accordingly, ADR Probability scale was categorized by taking sum the of 10 questions and grouped as definite, probable, possible, or doubtful if the total score is ≥9, 5–8, 1–4 and 0, respectively [20].

Five percent of the sample was pre-tested to check the acceptability and consistency of the data collection tool two weeks before the actual data collection.

Data processing and analysis

EPI-Info 3.5.4 software was used to enter the data. The principal investigator checked and evaluated the completeness of data before conducting the analysis. Finally, statistical software for social sciences (SPSS) 23.0 was used to analyze the data. Descriptive data were placed as frequency and percentage. Results were expressed as proportions and as means ± Standard Deviations (SD) based on the type of data. Bivariate and multivariate logistic regression were used to analyze the associations between the dependent variable and independent variables. A p-value of less than 0.05 was considered statistically significant.

Ethics approval and consent-to-participate

Ethical clearance was obtained from the Research Ethics Review Committee (RERC) of Mettu University. Permission was obtained from the medical director of the MKH, DH and BH to access medical ward patients and conduct the study. The benefits and risks of the study were explained to each participant included in the study. Written and oral informed consent were obtained from each patient involved in the study. The approval of using oral informed consent was obtained from the Research Ethics Review Committee (RERC) of Mettu University. To ensure confidentiality, name and other identifiers of patients and healthcare professionals was not recorded on the data collection tools.

Operational definitions

Drug-related problem

Includes ADR, non-adherence, inappropriate indication and dose, drug interaction and ineffective drug therapy.

Unnecessary drug therapy

If fulfilled the following criteria [2].

  • There is no valid medical indication for drug therapy at the time.

  • Multiple drug products are being used for a condition that requires a single drug therapy.

  • The medical condition is more appropriately treated with nondrug therapy.

  • Drug therapy is being taken to treat an avoidable adverse reaction associated with another medication.

  • Drug abuse, alcohol use, or smoking is causing the problem.

Hospital stay

The duration from patient’s admission to discharge.

Medication error

Any preventable event that cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer.

Pharmaceutical care

The process through which a pharmacist cooperates with a patient and other professional in designing, implementing, and monitoring a therapeutic plan that will produce specific therapeutic outcomes for the patient.

Polypharmacy

The daily consumption of 5 or more medications [7].

Co-morbidity

The presence of two or more diseases [11].

Results

Socio-demographic characteristics of study participants

Of the 313 eligible patients admitted to medical wards of MKH, BGH, and DGH about 178 (56.9%) were males and about 163 (52.1%) of them were in the age range of 18–35 years. More than 171(54.6%) were married and 179 (57.2%) were farmers by occupation (Table 1).

Table 1. Socio-demographic characteristics of patients admitted to medical wards of MKH, BGH, and DGH, 2020.

Variables Frequency (n) Percentage (%)
Sex Male 178 56.9
Female 135 43.1
Age (years) 18–35 163 52.1
36–64 124 39.6
≥ 65 26 8.3
Marital status Married 171 54.6
Single 95 30.4
Divorced 31 9.9
Widowed 16 5.1
Educational status illiterate 61 19.5
Grade 1–8 114 36.4
Grade 9–12 60 19.2
Diploma 43 13.7
Degree and above 35 11.2
Occupation Farmer 179 57.2
Merchant/trade 18 5.8
Government employee 53 16.9
Homemaker 18 5.8
Student 38 12.1
Others* 7 2.2
Residence Urban 70 22.4
Rural 243 77.6

Others*: Daily laborer, non-governmental employee.

Lifestyle and clinical characteristics of the study participants

A total of 125 (36.63%) patients had one or more co-morbid disease and 127 (59.4%) patients had a prolonged hospital stay (>7 days) with an average duration of hospital stay of 7.14 + 4.731 days. Regarding their lifestyle, 62 (19.8%) of them had habit of alcohol drink (Table 2).

Table 2. Lifestyle and clinical characteristics of patients admitted to medical wards of MKH, BGH, and DGH, 2020.

Variables Frequency (n) Percentage (%)
Drink alcohol Yes 62 19.8
No 251 80.2
Chew a chat Yes 45 14.4
No 268 85.6
Smoke a cigarette Yes 25 8
No 288 92
Presence of comorbidity Yes 125 36.63
No 188 60.1
Length of hospital stay (days) <7 186 39.9
≥7 127 59.4
Number of medications per patient <5 241 77
≥5 72 23

Incidences of DRPs and common drugs involved in DRPs

The incidence of actual or potential DTPs among subjects who were taking at least a single drug was 212 (67.7%). A total of 331 DRPs were identified on average with 1.057 DRPs per patient. The three-leading category of drug-related problems found to be a culprit was unnecessary 92 (27.79%), non-adherence 57 (17.22%) and dose too high 56 (16.92%) (Table 3). Regarding the patients that were developed ADR, about 4 (50%), 3 (37.5%),1(12.5%) were definite, probable, possible ADR.

Table 3. Types of drug therapy problems among patients admitted to the medical ward of MKRH, BH and DH.

Types of DRPs Frequency (n) Percentage (%)
Unnecessary drug therapy 92 27.79%
Non-adherence 57 17.22%
Dose too high 56 16.92%
Needs additional drug therapy 50 15.11%
Dose too low 38 11.48%
Ineffective drug therapy 30 9.06%
ADR 8 2.42%

The common drugs involved in DRPs

The most common drugs responsible for drug therapy problems were ceftriaxone 61(28.37%), cimetidine 32(14.88%), and diclofenac 31(14.42%) (Table 4).

Table 4. Common drugs associated with the occurrence of DRPs among patients admitted to the medical ward of MKRH, BGH and DGH, 2020.

Individual Drugs Frequency (n) Percentage (%)
Ceftriaxone 61 28.37
Cimetidine 32 14.88
Diclofenac 31 14.42
Furosemide 26 12.09
Doxycycline 24 11.16
Metronidazole 20 9.30
Tramadol 13 6.05
Augumentin 12 5.58
Acetyl salicylic acid 10 4.65
Spironolactone 9 4.19

Of the patients prescribed Ceftriaxone, 34(55.74%) of them were in the age range of 36–64 years. However, doxycycline was commonly given (45.83%) in the age range of 18–35 years. With regard to gender, cimetidine was commonly prescribed in females 18(56.25%) (Table 5).

Table 5. Major drugs associated with DRPs in terms of socio-demographic and morbidity characteristics among patients admitted to the medical ward of MKRH, BGH and DGH.

Variables Category Categories of Drugs
Ceftriaxone Cimetidine Diclofenac Furosemide Doxycycline
Age (years) 18–35 18(29.51) 7(21.88) 10(32.26) 9(34.62) 11(45.83)
36–64 34(55.74) 19(59.38) 16(51.61) 11(42.31) 8(33.33)
≥ 65 9(14.75) 6(18.75) 5(16.13) 6(23.08) 5(20.83)
Sex Male 34(55.74) 14(43.75) 16(51.61) 17(65.38) 16(66.67)
Female 27(44.26) 18(56.25) 15(48.39) 9(34.62) 8(33.33)
Comorbidity Yes 40(65.57) 19(59.38) 20(64.52) 15(57.69) 15(62.50)
No 21(34.43) 13(40.63) 11(35.48) 11(42.31) 9(37.50)
Residence Rural 32(52.46) 19(59.38) 13(41.94) 14(53.85) 10(41.67)
Urban 29(47.54) 13(40.63) 18(58.06) 12(46.15) 14(58.33)

Factors associated with DRPs

The results of the multivariable logistic regression showed that there is a significant association between the area of residence, length of hospital stay, and polypharmacy with the presence of DRPs. Patients living in rural areas were 2.5 times more likely to have at least one DTP than patients who live in urban areas (AOR = 2.550,95CI%: 1.238–5.253, p = 0.011). Patients whose hospital stays greater than or equal to seven days were about 10 times more likely to have DRPs than patients whose hospital stay less than seven days (AOR = 9.785,95CI%: 4.668–20.511, p≤0.001). Lastly, patients who have prescribed 5 or more drugs (polypharmacy) were about 3 times more likely to have DRPs than patients prescribed with less than 5 drugs (AOR = 3.229,95CI%: 1.433–7.278, p = 0.005) (Table 6).

Table 6. Multivariable logistic regression analysis results of factors associated with DRPs among patients admitted to Medical Wards of MKRH, BGH and DGH.

Variables Category DRPs COR (95%CI) p-value AOR (95%CI) P-value
Yes (n = 212) No (n = 101)
Sex Male 126 (59.43%) 52(51.49%) 1.38(0.857–2.22) * 0.185 1.54(0.892–2.665) 0.121
Female 86(40.57%) 49(48.51%) 1 1
Area of residence Urban 47(22.17%) 23(22.77%) 1 1 0.011
Rural 165(77.83%) 78(77.23%) 0.966 (0.548–1.703) * 0 .1905 2.550(1.238–5.253) **
Presence of comorbidity Yes 85(40.09%) 40(39.60%) 1.021 (0.629–1.66) * 0.193 1.41(0.775–2.558) 0.261
No 127(59.91%) 61(60.40%) 1 1
Poly pharmacy Yes 63(29.72%) 9(8.91%) 4.322 (2.051–9.106) * <0.001 3.229 (1.433–7.278) ** 0.005
No 149(70.28%) 92(91.09%) 1 1
Length of hospital stay (days) ≥7 113(53.30%) 14(13.86%) 7.093 (3.794–13.259) * <0.001 9.785 (4.668–20.511) ** <0.001
<7 99(46.70%) 87(86.14%) 1 1
Drink alcohol Yes 47(22.17%) 15(14.85%) 1.633(.864–3.088) * 0.131 2.218(0.959–5.128) 0.063
No 165(77.83%) 86(85.15%) 1 1
Smoke cigarette Yes 18(8.49%) 7(6.93%) 1.246(0.503–3.086) * 0.164 0.445(0.139–1.429) 0.174
No 194(91.51%) 94(93.07%) 1 1
Chew a chat Yes 25(11.79%) 20(19.80%) 0.541(0.285–1.030) * 0.062 1.714(0.775–3.793) 0.183
No 187(88.21%) 81(80.20%) 1 1

*Shows significant at p-value 0.25

**Shows statistically significant at p-value 0.05.

AOR: Adjusted odds ratio; COR: Crudes odds ratio.

Discussion

This study assessed factors associated with an increased risk of developing one or more DRP among patients admitted to medical wards in selected hospitals of South Western Ethiopia. The prevalence of DRP in the study area was 212 (67.7%), which complies with the study conducted in Gondar (66%) [7], Northern Sweden (66%) [23]. However, the magnitude of the DTP was lower than the study done in Dessie referral hospital (75.51%) [6], Kenya (93.8%) [24], Tikur Anbesa Specialized hospital (70.4%) [18], and Jimma University specialized hospital (73.5%) [11]. The magnitude was also higher than the study conducted in India in which the overall incidence of DRPs was found to be 47.66% [4].

The large variation seen on the magnitude of DRPs across studies might be due to different classification of systems used to classify DRPs and settings in which DRPs were assessed. Despite the difference seen in different areas, the magnitude of DRP is high that requires further intervention to tackle the progress and improve the patient’s quality of life. This intervention requires collaborative efforts from the different stakeholders, patients and policy makers. Furthermore, we recommend future studies to use similar DRP classification systems to generate comparable evidence.

In this study, unnecessary drug therapy 92 (27.79%), non-adherence 57 (17.22%), and dose too high 56 (16.92%) were most frequently encountered DRPs. The finding was consistent with the study of Dilla university referral hospital in which non-adherence was the most occurred types of DRP 68(29.69%), and ADR was the least type of DRP 7(3.06%) [25]. Additionally, the study at the University of Gondar reported inappropriate dose was the prevalent DRP [7] and in India, ADR was the least occurred type of DRP (1.39% [4]. However, non-adherence was the least common type of drug therapy problem in Jimma University Specialized Hospital [11]. Alternatively, ADR (18.6%) was the most occurred DRP in Adama hospital medical college [19].

In our study, the most common drugs associated with at least one of the drug therapy problems were ceftriaxone 61 (28.37%), cimetidine 32(14.88%), and diclofenac 31(14.42%). Similarly, a study conducted in Dessie referral hospital revealed that ceftriaxone (25.81%) was the most frequent specific drug for DTP and non-steroidal anti-inflammatory drugs accounts, 9 (4.84%) [6]. The study conducted in India showed that Antibiotics (33.5%), GIT drugs (29.3%) and NSAID (16.08%) were the most involved in DTPs [4]. In contrast, a study conducted at the university of Gondar showed that the most common agents associated with DTPs were omeprazole 45 (17.6%), heparin 22 (8.6%), and aspirin 21 (8.2%) [7]. A study conducted in Hong Kong revealed that Gentamicin, ranitidine and fluconazole were most frequently associated with DRPs [26]. The variety of drugs involved in DTPs was due to availability, patients and physician preferences, and different treatment guidelines within different countries.

In this study, 331 DRPs were recorded with 1.057 DRPs per patient. This finding is lower than study conducted among Hiwotfana specialized university hospital [27], Kenya [24], but comparable with the study of University of Gondar Teaching Hospital, Northwest Ethiopia [7]. The large variation seen on the magnitude of DRPs across studies might be due to a different classification system used to classify DRPs, settings in which DRPs were assessed, and differences in sample size of the study participants.

In this study, it was found the association between the risk of DRP and area of residence. Patients who live in rural areas were about 2.5 times more likely to develop drug-related problems compared to patients who were in urban area. The finding was inconsistent with the study of Spain in which, among demographic variables, only female sex was associated with a higher risk of developing at least one DRP [28]. Similarly, the area of residence was not a determinant of DRP in Jimma University specialized hospital [29]. The highest risk of DRP in rural areas was due to the lack of access to health information because of long distance to reach the health facilities.

Logistic regression analysis showed that the number of drugs prescribed per patient (≥5 prescribed drugs) was strong one predictor of the occurrence of DRP. The finding was consistent with the study in Hong Kong [26], Singapore [30], Dilla University Referral Hospital [25], and Jimma University Specialized Hospital [29]. The reason might be the potential drug-drug interaction as the results of polypharmacy.

In our study, patients who had a prolonged hospital stay were higher risk for developing at least one type of DTP. Our outcome was consistent with that of study-done university of Gondar [7]. In contrast, in Jimma’s University Specialized Hospital, the length of hospital stay did not predict the presence of drug-related problems [11]. The reason might be the patients who had prolonged hospital stay have higher probability to develop different nosocomial infections requiring complex therapeutic management.

As the strength, the study was a multicenter and prospective as well as information on different organ function tests (renal, liver), diagnostic and laboratory tests were used to assess any drug therapy problems. Our study has some limitations. First, the study was a cross-sectional study, which is difficult to determine the causal effect relationship. In addition, we only evaluate DTPs among patients admitted to the medical ward, which lacks generalizability. Finally, COVID-19 pandemic increased the stress of physicians and health workers to manage the patient’s drug therapy.

Conclusion

About two-thirds of the patients admitted to the medical ward of MKH, BGH, and DGH were experienced DRP. The three-leading category of drug-related problems found to be a culprit was unnecessary, non-adherence and dose too high. Ceftriaxone, cimetidine and diclofenac were the most common drugs involved in DTPs. The area of the residence, polypharmacy, and prolonged hospital stay were the predictors of the DTPs. Therefore, clinical pharmacy services should be established in hospitals to tackle any drug-related problems in our study area and healthcare providers of hospitals should create an awareness of patients seeking care from health facility about the importance of rational drug utilization. Policy makers and different stakeholders should also focus on the way to reduce the occurrence DTPs and improve the outcome. Future studies with large sample size at multiple hospitals for a longer period are highly warranted.

Acknowledgments

We thank Mettu University for logistic support. We are grateful to staff members and healthcare professionals of Metu karl, Bedele, and Darimu hospital, data collectors, and study participants for their cooperation in the success of this study.

Abbreviations

ADE

Adverse Drug Event

ADR

Adverse drug reaction

AIDS

AIDS: Acquired immune deficiency disease

ASA

Acetyl Salicylic Acid

AOR

Adjusted odds ratio

BGH

Bedele General Hospital

COR

crude odds ratio

DGH

Darimu General Hospital: DRP: Drug related problem

DTP

Drug therapy problem

GIT

Gastro Intestinal Drug

ICU

Intensive care unit

MKH

Mettu Karl Hospital

NSAID

Non-Steroidal Inflammatory Drug

SD

Standard Deviation

SPSS

statistical package for social sciences

USA

United States of America

USD

United State Dollar

Data Availability

Due to ethical restrictions by the research review committee of College of Health Sciences, Mettu University, the data underlying this study is available only upon request. Interested, qualified researchers can access the data by requesting research coordinator, College of Health Sciences Mettu University, Mohammedamin Hajure (sikoado340@gmail.com) and the corresponding author, Firomsa Bekele (firomsabekele21@gmail.com).

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Pharmaceutical Care Network Europe Foundation (2010) The PCNE classification scheme for drug related problems, 62. [Google Scholar]
  • 2.Cipolle R. J., Strand L. M., & Morley P. C (2012) Pharmaceutical care practice: the patient-centered approach to medication management. McGraw Hill Professional. [Google Scholar]
  • 3.Birarra M. K., Heye T. B., and Shibeshi W (2017) Assessment of drug-related problems in pediatric ward of Zewditu Memorial Referral Hospital, Addis Ababa, Ethiopia. International journal of clinical pharmacy, 39(5), 1039–1046. Int J Clin Pharm 10.1007/s11096-017-0504-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Mohammed S., Poudel S., Laloo F., Madhur A., Robert R., & Mathew B (2017) Assessment of drug-related problems in a tertiary care teaching hospital, India. Asian J Pharm Clin Res, 10, 310–3. [Google Scholar]
  • 5.Flaherty J. H., Perry H. M. III, Lynchard G. S., & Morley J. E (2000) Polypharmacy and hospitalization among older home care patients. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 55(10), M554–M559. 10.1093/gerona/55.10.m554 [DOI] [PubMed] [Google Scholar]
  • 6.Belayneh Y. M., Amberbir G., & Agalu A (2018) A prospective observational study of drug therapy problems in medical ward of a referral hospital in northeast Ethiopia. BMC health services research, 18(1), 808. 10.1186/s12913-018-3612-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Srikanth A (2017) Assessment of drug related problems and its associated factors among medical ward patients in university of gondar teaching hospital, northwest Ethiopia: a prospective cross-sectional study. Journal of Basic and Clinical Pharmacy, 8. S016–S021. [Google Scholar]
  • 8.Donaldson M. S., Corrigan J. M., & Kohn L. T. (Eds.) (2000) To err is human: building a safer health system (Vol. 6). National Academies Press. [PubMed] [Google Scholar]
  • 9.Easton K. L., Chapman C. B., & Brien J. A. E (2004) Frequency and characteristics of hospital admissions associated with drug‐related problems in paediatrics. British journal of clinical pharmacology, 57(5), 611–615. 10.1111/j.1365-2125.2003.02052.x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Schatz S., & Weber R. (2015). Adverse drug reactions. Pharmacy Practice, 1(1). [Google Scholar]
  • 11.Tigabu B. M., Daba D., & Habte B (2014) Drug-related problems among medical ward patients in Jimma university specialized hospital, Southwest Ethiopia. Journal of research in pharmacy practice, 3(1), 1. 10.4103/2279-042X.132702 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Bekele F, Fekadu G, Bekele K, Dugassa D, Sori J(2021). Drug-related problems among patients with infectious disease admitted to medical wards of Wollega University Referral Hospital: Prospective observational study.SAGE Open Medicine. Volume 9:1–8. 10.1177/2050312121989625 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Pirmohamed M., James S., Meakin S., & Green C (2004) Adverse drug reactions as cause of admission to hospital: Authors’ reply. Bmj, 329(7463), 460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Tumwikirize W. A., Ogwal-Okeng J. W., Vernby A., Anokbonggo W. W., Gustafsson L. L., & Lundborg S. C (2011) Adverse drug reactions in patients admitted on internal medicine wards in a district and regional hospital in Uganda. African health sciences, 11(1). [PMC free article] [PubMed] [Google Scholar]
  • 15.Saavedra P. A., Meiners M. M. M. D. A., Lopes L. C., Silva E. V. D., Silva D. L. M. D., Noronha E. F., et al. (2016) Adverse drug reactions among patients admitted with infectious diseases at a Brazilian hospital. Revista da Sociedade Brasileira de Medicina Tropical, 49(6), 763–767. 10.1590/0037-8682-0238-2016 [DOI] [PubMed] [Google Scholar]
  • 16.Bichave A., Aggarwal A., Shinde P. K., & Pimple S (2015) AIN-1 Study of Anti-inflammatory and Ulcerogenic Potential of some Structurally Similar 1, 3, 4-oxadiazole Analogues. Indian Journal of Pharmacology, 47(7), 57–177. [Google Scholar]
  • 17.Bosma L., Jansman F. G., Franken A. M., Harting J. W., & Van den Bemt P. M (2008) Evaluation of pharmacist clinical interventions in a Dutch hospital setting. Pharmacy World & Science, 30(1), 31–38. [DOI] [PubMed] [Google Scholar]
  • 18.Ayalew M. B., Megersa T. N., & Mengistu Y. T (2015) Drug-related problems in medical wards of Tikur Anbessa specialized hospital, Ethiopia. Journal of research in pharmacy practice, 4(4), 216. 10.4103/2279-042X.167048 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Hussein M., Lenjisa J., Woldu M., Tegegne G., Umeta G., & Dins H (2014) Assessment of drug related problems among hypertensive patients on follow up in Adama Hospital Medical College, East Ethiopia. Clinic Pharmacol Biopharmaceut, 3(122), 2. [Google Scholar]
  • 20.Naranjo C. A., Busto U., Sellers E. M., Sandor P., Ruiz I., Roberts E. A., et al. (1981) A method for estimating the probability of adverse drug reactions. Clinical Pharmacology & Therapeutics, 30(2), 239–245. 10.1038/clpt.1981.154 [DOI] [PubMed] [Google Scholar]
  • 21.Song Y., Han H. R., Song H. J., Nam S., Nguyen T., & Kim M. T (2011) Psychometric evaluation of hill-bone medication adherence subscale. Asian Nursing Research, 5(3), 183–188. 10.1016/j.anr.2011.09.007 [DOI] [PubMed] [Google Scholar]
  • 22.Kim M. T., Hill M. N., Bone L. R., & Levine D. M (2000) Development and testing of the hill-bone compliance to high blood pressure therapy scale. Progress in cardiovascular nursing, 15(3), 90–96. 10.1111/j.1751-7117.2000.tb00211.x [DOI] [PubMed] [Google Scholar]
  • 23.Peterson C., & Gustafsson M (2017) Characterisation of drug-related problems and associated factors at a clinical pharmacist service-naïve hospital in northern Sweden. Drugs-real world outcomes, 4(2), 97–107. 10.1007/s40801-017-0108-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Degu A., Njogu P., Weru I., & Karimi P (2017) Assessment of drug therapy problems among patients with cervical cancer at Kenyatta National Hospital, Kenya. Gynecologic oncology research and practice, 4(1), 15. 10.1186/s40661-017-0054-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Bekele N. A., & Hirbu J. (2020) Drug Therapy Problems and Predictors Among Patients Admitted to Medical Wards of Dilla University Referral Hospital, South Ethiopia: A Case of Antimicrobials. Infection and Drug Resistance, 13, 1743–1750. 10.2147/IDR.S247587 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Rashed A. N., Wilton L., Lo C. C., Kwong B. Y., Leung S., & Wong I. C (2014) Epidemiology and potential risk factors of drug-related problems in Hong Kong paediatric wards. British journal of clinical pharmacology, 77(5), 873–879. 10.1111/bcp.12270 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Ayele Y., Melaku K., Dechasa M., Ayalew M. B., & Horsa B. A (2018) Assessment of drug related problems among type 2 diabetes mellitus patients with hypertension in Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia. BMC research notes, 11(1), 1–5. 10.1186/s13104-017-3088-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Urbina O., Ferrández O., Luque S., Grau S., Mojal S., Pellicer, et al. (2015) Patient risk factors for developing a drug-related problem in a cardiology ward. Therapeutics and clinical risk management, 11, 9. 10.2147/TCRM.S71749 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Niriayo Y. L., Kumela K., Kassa T. D., & Angamo M. (2018) Drug therapy problems and contributing factors in the management of heart failure patients in Jimma University Specialized Hospital, Southwest Ethiopia. PloS one, 13(10), e0206120. 10.1371/journal.pone.0206120 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Koh Y., Kutty F. B. M., & Li S. C (2005) Drug-related problems in hospitalized patients on polypharmacy: the influence of age and gender. Therapeutics and clinical risk management 1(1): 39. 10.2147/tcrm.1.1.39.53597 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

M Mahmud Khan

8 Dec 2020

PONE-D-20-30167

Magnitude and Determinants of Drug Related Problems among Patients Admitted to Medical wards of Ilu Ababor and Buno bedele zonal Hospital: A Multicenter Prospective Observational Study

PLOS ONE

Dear Dr. Bekele,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 17 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

M. Mahmud Khan

Academic Editor

PLOS ONE

Additional Editor Comments:

In addition to the reviewer's report, I have reviewed the paper and my comments are below:

1. The paper should provide more information on drugs used by patient characteristics, i.e., major drugs with problems can be cross-tabulated with age, morbidity status, etc.

2. In the introduction, authors mentioned that a significant proportion of patients get admitted to hospitals due to adverse drug events. What approach did the study follow to ensure that the patient was not admitted due to adverse drug reactions?

3. Define the drug therapy problem "Unnecessary drug therapy" and since it is quite high, is there some specific patient groups that are more likely to be affected by this? Does it indicate error in physician prescription?

4. Paper needs thorough editing and revisions.

5. Methodology should be clearly presented (see the reviewer #1 comment on this as well)

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for including your ethics statement: "Ethical clearance was obtained from the ethics review board of Mettu University. Permission was obtained from medical director of the MKH, DH and BH to access medical ward patients and conducts the study."   

 a.Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study.

 b.Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

 For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research.

3. In the Methods, please state:

- Why written consent could not be obtained

- Whether the Institutional Review Board (IRB) approved use of oral consent

- How oral consent was documented

For more information, please see our guidelines for human subjects research: https://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research

4. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service.  

Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services.  If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free.

Upon resubmission, please provide the following:

  • The name of the colleague or the details of the professional service that edited your manuscript

  • A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

  • A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

5. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

6. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author.

- https://www.jbclinpharm.org/articles/assessment-of-drug-related-problems-and-its-associated-factors-among-medical-ward-patients-in-university-of-gondar-teaching-hospit.html

- https://link.springer.com/article/10.1007%2Fs11096-017-0504-9

- http://isfcppharmaspire.com/issueforpublication.aspx?Article=PHARMASPIRE_1_2017

- https://www.hindawi.com/journals/cdtp/2020/2509875/

- https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-018-3612-x

https://www.research.ed.ac.uk/portal/en/publications/the-apical-protein-apnoia-interacts-with-crumbs-to-regulate-tracheal-growth-and-inflation(70776d5d-4841-4fe5-b7f9-c614328149ee).html

- https://www.omicsonline.org/open-access/assessment-of-drug-related-problems-among-hypertensive-patients-2167-065X.1000122.php?aid=31481

The text that needs to be addressed involves the Background section of your manuscript.

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript needs proof reading. there are awkward sentences that are difficult to understand that can be easily fixed at a proof reading stage. For example the first sentence in the abstract is not correct. Also in many places through the manuscript words that shouldn’t be capitalized are capitalized.

In many instances of importance to evaluate the manuscript rigor the provided text is missing critical information.

For example the author say in the method section, it says a questionnaire was developed. But then the authors reference medical chart review. The connection between the different steps need to be further developed to allow the reader to understand what was actually done.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: PONE-D-20-30167_reviewer.pdf

PLoS One. 2021 Mar 16;16(3):e0248575. doi: 10.1371/journal.pone.0248575.r002

Author response to Decision Letter 0


6 Jan 2021

M. Mahmud Khan

Editor, PLOS ONE

Dear Editor in chief of the Manuscript PONE-D-20-30167 entitled " Magnitude and Determinants of Drug Related Problems among Patients Admitted to Medical wards of Ilu Ababor and Buno bedele zonal Hospital: A Multicenter Prospective Observational Study," submitted to PLOS ONE. Thanks for your time and consideration in editing and reviewing the manuscript. We have carefully read your comments and corrected inline of your comments and suggestions. All comments raised were edited and incorporated in the revised manuscript.

Here are the responses and elaborations for the comments from editor and reviewer!

EDITORS COMMENTS

Editor comment: The paper should provide more information on drugs used by patient characteristics, i.e., major drugs with problems can be cross-tabulated with age, morbidity status, etc.

Author response: In table 5 of revised manuscript most common drugs was cross tabulated with the variables like sex, residence, co-morbidity and age

Editor comment: In the introduction, authors mentioned that a significant proportion of patients get admitted to hospitals due to adverse drug events. What approach did the study follow to ensure that the patient was not admitted due to adverse drug reactions?

Author response: ADR was assessed by using the Naranjo algorithm of the ADR probability scale

Editor comment: Define the drug therapy problem "Unnecessary drug therapy" and since it is quite high, is there some specific patient groups that are more likely to be affected by this? Does it indicate error in physician prescription?

Author response: In operational definition we have added the definition and criteria of unnecessary drug therapy

Editor comment: Paper needs thorough editing and revisions.

Author response: The whole manuscript was edited as per your comments

Editor comment: Methodology should be clearly presented (see the reviewer #1 comment on this as well)

Author response: We carefully revised and edited the methodology part

Editor comment: Regarding o Journal Requirements

Author response: The manuscript was written as per PLOS ONE's style

Editor comment: Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study.

Author response: The full name of the ethics committee/institutional review board(s) was written in revised manuscript and Ethics Statement” field of the submission

� The written consent was be obtained

� The statements showing that the Institutional Review Board (IRB) approved use of oral consent was written in revised manuscript

Editor comment: We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar.

Author response: We have edited the English grammar throughout the manuscripts

Editor comment: Regarding the data availability statement

Author response: We have updated the data availability statement in which it is placed as supporting information.

Editor comment: Regarding to text overlap

Author response: The manuscript was paraphrased to minimize the texts overlap

REVIEWER COMMENTS

Reviewer 1

Reviewer comments: The conclusions must be drawn appropriately based on the data presented.

Author response: The conclusion was edited to relate with data presented

Reviewer comments: Regarding statistical analysis

Author response: The data was re-analyzed

Reviewer comments: Is the manuscript presented in an intelligible fashion and written in Standard English?

Author response: We have edited the English grammar throughout the manuscripts

Reviewer comments: The manuscript needs proof reading. There are awkward sentences that are difficult to understand that can be easily fixed at a proof reading stage. For example the first sentence in the abstract is not correct. Also in many places through the manuscript words that shouldn’t be capitalized are capitalized.

Author response: The manuscript was edited carefully and the first sentence in the abstract was corrected. Finally any capitalization was corrected

Reviewer comments: In many instances of importance to evaluate the manuscript rigor the provided text is missing critical information. For example the author say in the method section, it says a questionnaire was developed. But then the authors reference medical chart review. The connection between the different steps need to be further developed to allow the reader to understand what was actually done.

Author response: It was written as data was collected using questionnaire which was developed after reviewing different literature and checklist was prepared to verify the patient’s medical information in revised manuscript

Reviewer comments: Don’t capitalize the P in pharmaceutical

Author response: The capitalization was removed

Reviewer comments: Replace DTP by DRP

Author response: In abstract under result DTP was replaced by DRP

Reviewer comments: Re word A total of 331 DRPs were identified on average, 1.057 DRPs per

Patient to a total of 331 DRPs were identified, an average of 1.06 DRPs per patient.

Author response: It was written as per your comment

Reviewer comments: This sentence doesn’t make sense. Maybe something like the three-leading categories of DRPs were found to be unnecessary (not sure unnecessary what prescription of drug or consumption of drugs) with 92 cases (27.79%), non-adherence with 57 patients (17.22%) and high drug dosage with 56 cases (16.92%).

Author response: It was corrected as prescribed drugs

Reviewer comments: Is the term drug therapy problem the same as DRPs?

Author response: We have used them interchangeably

Reviewer comments: missing reference on ADR and The connection between these two sentences is not clear.Also two sentences can’t make a paragraph you need at least 5. I think the authors are trying to convey the significance of the problem and that if 5-20% patients may lose trust in the physicians treating them. But the authors never explain why that is a bad thing or make the actual connection.

Author response: The sentence regarding ADR was cited

• The two sentence was connected appropriately and many references was added to explain more about DRP

• We have discussed the reasons for high burden of ADR

Reviewer comments: What treatment that was poorly controlled? This thought is not complete

Author response: It was corrected in revised manuscript as hypertensive patient’s was poorly controlled

Reviewer comments: This time frame in of concern since the pandemic really started. Wouldn’t that impact the stress of physicians and health workers. Should be addressed in the limitaitons

Author response: The impact of COVID-19 on stress of physicians was written as limitation

Reviewer comments: You never explain ADR

Author response: ADR was assessed by using Naranjo algorithm of ADR probability scale. Accordingly, ADR Probability Scale was categorized by taking sum of 10 questions and grouped as definite, probable, possible or doubtful, if the total score is ≥9, 5-8, 1-4 and 0 respectively.

Thanks for your time and consideration,

Regards!

Attachment

Submitted filename: plose one DTP esponse letter.docx

Decision Letter 1

M Mahmud Khan

25 Jan 2021

PONE-D-20-30167R1

Magnitude and determinants of drug related problems among patients admitted to medical wards of south-western Ethiopian hospitals : A multicenter prospective observational Study

PLOS ONE

Dear Dr. Bekele,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 11 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

M. Mahmud Khan

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Unfortunately, the paper needs thorough editing, maybe by a professional English language editor. I still find many language and expression related issues in the revised version. Without thorough editing, the paper cannot be accepted for publication.

Thanks

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 Mar 16;16(3):e0248575. doi: 10.1371/journal.pone.0248575.r004

Author response to Decision Letter 1


8 Feb 2021

M. Mahmud Khan

Editor, PLOS ONE

Dear Editor in chief of the Manuscript PONE-D-20-30167 entitled " Magnitude and determinants of drug-related problems among patients admitted to medical wards of south-western Ethiopian hospitals: A multicenter prospective observational study" submitted to PLOS ONE. Thanks for your time and consideration in editing and reviewing the manuscript. We have carefully read your comments and corrected inline of your comments and suggestions. All comments raised were edited and incorporated in the revised manuscript.

Here are the responses and elaborations for the comments from editor and reviewer!

EDITORS COMMENTS

Editor comment: The paper should provide more information on drugs used by patient characteristics, i.e., major drugs with problems can be cross-tabulated with age, morbidity status, etc.

Author response: In table 5 of revised manuscript most common drugs was cross tabulated with the variables like sex, residence, co-morbidity and age

Editor comment: In the introduction, authors mentioned that a significant proportion of patients get admitted to hospitals due to adverse drug events. What approach did the study follow to ensure that the patient was not admitted due to adverse drug reactions?

Author response: ADR was assessed by using the Naranjo algorithm of the ADR probability scale

Editor comment: Define the drug therapy problem "Unnecessary drug therapy" and since it is quite high, is there some specific patient groups that are more likely to be affected by this? Does it indicate error in physician prescription?

Author response: In operational definition we have added the definition and criteria of unnecessary drug therapy. Patients presents with infectious disease were highly affected by unnecessary drug therapy because in our study are ceftriaxone was used unnecessarily. Any medication error occurred during prescribing, administration and dispensing was considered as unnecessary drug therapy

Editor comment: Paper needs thorough editing and revisions.

Author response: The whole manuscript was edited as per your comments

Editor comment: Methodology should be clearly presented (see the reviewer #1 comment on this as well)

Author response: We carefully revised and edited the methodology part

Editor comment: Regarding o Journal Requirements

Author response: The manuscript was written as per PLOS ONE's style

Editor comment: Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study.

Author response: The full name of the ethics committee/institutional review board(s) was written in revised manuscript and Ethics Statement” field of the submission

� The written consent was be obtained

� The statements showing that the Institutional Review Board (IRB) approved use of oral consent was written in revised manuscript

� The oral consents was clearly documented in separate checklists

Editor comment: We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar.

Author response: We have edited the English grammar throughout the manuscripts

Editor comment: Regarding the data availability statement

Author response: We have updated the data availability statement in which it is restricted

Editor comment: Regarding to text overlap

Author response: The manuscript was paraphrased to minimize the texts overlap

REVIEWER COMMENTS

Reviewer 1

Reviewer comments: The conclusions must be drawn appropriately based on the data presented.

Author response: The conclusion was edited to relate with data presented

Reviewer comments: Regarding statistical analysis

Author response: The data was re-analyzed

Reviewer comments: Is the manuscript presented in an intelligible fashion and written in Standard English?

Author response: We have edited the English grammar throughout the manuscripts

Reviewer comments: The manuscript needs proof reading. There are awkward sentences that are difficult to understand that can be easily fixed at a proof reading stage. For example the first sentence in the abstract is not correct. Also in many places through the manuscript words that shouldn’t be capitalized are capitalized.

Author response: The manuscript was edited carefully and the first sentence in the abstract was corrected. Finally any capitalization was corrected

Reviewer comments: In many instances of importance to evaluate the manuscript rigor the provided text is missing critical information. For example the author say in the method section, it says a questionnaire was developed. But then the authors reference medical chart review. The connection between the different steps need to be further developed to allow the reader to understand what was actually done.

Author response: It was written as data was collected using questionnaire which was developed after reviewing different literature and checklist was prepared to verify the patient’s medical information in revised manuscript

Reviewer comments: Don’t capitalize the P in pharmaceutical

Author response: The capitalization was removed

Reviewer comments: Replace DTP by DRP

Author response: In abstract under result DTP was replaced by DRP

Reviewer comments: Re word A total of 331 DRPs were identified on average, 1.057 DRPs per

Patient to a total of 331 DRPs were identified, an average of 1.06 DRPs per patient.

Author response: It was written as per your comment

Reviewer comments: This sentence doesn’t make sense. Maybe something like the three-leading categories of DRPs were found to be unnecessary (not sure unnecessary what prescription of drug or consumption of drugs) with 92 cases (27.79%), non-adherence with 57 patients (17.22%) and high drug dosage with 56 cases (16.92%).

Author response: It was corrected as prescribed drugs

Reviewer comments: Is the term drug therapy problem the same as DRPs?

Author response: We have used them interchangeably

Reviewer comments: missing reference on ADR and The connection between these two sentences is not clear.Also two sentences can’t make a paragraph you need at least 5. I think the authors are trying to convey the significance of the problem and that if 5-20% patients may lose trust in the physicians treating them. But the authors never explain why that is a bad thing or make the actual connection.

Author response: The sentence regarding ADR was cited

• The two sentence was connected appropriately and many references was added to explain more about DRP

• We have discussed the reasons for high burden of ADR

Reviewer comments: What treatment that was poorly controlled? This thought is not complete

Author response: It was corrected in revised manuscript as hypertensive patient’s was poorly controlled

Reviewer comments: This time frame in of concern since the pandemic really started. Wouldn’t that impact the stress of physicians and health workers. Should be addressed in the limitaitons

Author response: The impact of COVID-19 on stress of physicians was written as limitation

Reviewer comments: You never explain ADR

Author response: ADR was assessed by using Naranjo algorithm of ADR probability scale. Accordingly, ADR Probability Scale was categorized by taking sum of 10 questions and grouped as definite, probable, possible or doubtful, if the total score is ≥9, 5-8, 1-4 and 0 respectively.It is mentioned as ”Regarding to the patients that were developed ADR, about 4(50%), 3(37.5%),1(12.5%) were definite, probable, possible ADR’’.

Thanks for your time and consideration,

Regards!

Attachment

Submitted filename: plose one DTP esponse letter.docx

Decision Letter 2

M Mahmud Khan

2 Mar 2021

Magnitude and determinants of drug-related problems among patients admitted to medical wards of southwestern Ethiopian hospitals : A multicenter prospective observational study

PONE-D-20-30167R2

Dear Dr. Bekele,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

M. Mahmud Khan

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

M Mahmud Khan

4 Mar 2021

PONE-D-20-30167R2

Magnitude and determinants of drug-related problems among patients admitted to medical wards of southwestern Ethiopian hospitals: A multicenter prospective observational study

Dear Dr. Bekele:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. M. Mahmud Khan

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: PONE-D-20-30167_reviewer.pdf

    Attachment

    Submitted filename: plose one DTP esponse letter.docx

    Attachment

    Submitted filename: plose one DTP esponse letter.docx

    Data Availability Statement

    Due to ethical restrictions by the research review committee of College of Health Sciences, Mettu University, the data underlying this study is available only upon request. Interested, qualified researchers can access the data by requesting research coordinator, College of Health Sciences Mettu University, Mohammedamin Hajure (sikoado340@gmail.com) and the corresponding author, Firomsa Bekele (firomsabekele21@gmail.com).


    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES