A cross-sectional study on COVID-19-related changes in self-medication with antibiotics.

BACKGROUND AND AIM: Dental treatments have been limited to emergency care in many countries worldwide due to the global rapid spread of coronavirus disease-2019 (COVID-19). Fear of contracting the disease in dental clinics has also altered the pattern of dental visits and self-medication. The present study compared self-medication with antibiotics (SMA) and the pattern of dental visits before and after the emergence of COVID-19 pandemic in a referral dental clinic in the north of Iran.
MATERIALS AND METHODS: The data for the present cross-sectional study was collected from 756 patient records retrieved from the archives of the Faculty Clinic of Rasht School of Dentistry during two separate periods: before the COVID-19 pandemic from mid-November 2019 to mid-February 2020, and after the pandemic emergence from mid-April to mid-July 2020. In addition to demographic variables namely age, gender, and place of residence of patients, their smoking status, chief complaint, and SMA were also extracted from patient records. The Chi-square test and binary logistic regression models with 95% confidence interval served for statistical analysis.
RESULTS: In total, 756 patient records (412 records from the pre-pandemic period and 344 records from the post-pandemic period) were evaluated. SMA was significantly more prevalent after the pandemic compared to that before pandemic (OR = 3.39, 95% CI = 2.43-4.73, P<0.001). The number of patients who smoke significantly decreased after the pandemic by 6.6% compared to that in pre-pandemic period. Dental pain, pus discharge, and abscess as the chief complaints of patients were significantly more prevalent during the post-pandemic period; while, dental checkups, tooth hypersensitivity, and esthetic dental problems were significantly more frequent as the chief complaints of patients during the pre-pandemic period.
CONCLUSION: There is indication that during the COVID-19 pandemic, SMA and prevalence of acute dental problems in patients have increased. With regard to the consequences of SMA, there is a need to raise public awareness on this matter.

Introduction

The coronavirus disease-2019 (COVID-19) is an emerging infectious disease, rapidly evolving worldwide [1]. World Health Organization (WHO) announcement on 11th of March 2020 officially declared the spread of the COVID-19 virus as a global pandemic [2]. The disease emerged unexpectedly, and has now turned into a challenging dilemma not only for the public, but also health professionals including dental practitioners, physicians, medical and dental students worldwide [3]. The American Dental Association released the list of emergency and non-emergency dental procedures for dental practitioners and the lay people, and emphasized on limiting the provision of dental services to emergency care only [4]. Such instructions should be strictly followed for prevention and control of COVID-19 [5].

In Iran, all dental offices and clinics were shut down in the first 2 months following the announcement of COVID-19 pandemic by the order of the Iranian Ministry of Health and Medical Education, and only some certain clinics, designated by the Ministry of Health remained open to provide emergency dental services and safety protocols for dental care provision were compiled [6].

In addition to the limitations set by the Ministry of Health, patients less commonly present to dental clinics and offices due to fear of contracting COVID-19. Resultantly, the patient flow and the chief complains of patients have greatly changed since the emergence of COVID-19. A retrospective study conducted in China on 2,537 patients reported a reduction in patient referrals to dental emergency care centers by 38% following the emergence of COVID-19 [7].

According to a definition by the World Health Organization, self-medication refers to medication intake without a prescription, refilling old prescriptions, sharing medications with the family members or one’s social cycle, or using the available leftover medications [8, 9]. The reasons for self-medication may include limited access to healthcare facilities, shortage of healthcare services, illegal distribution of medications, wrong beliefs about physicians, and poor knowledge of individuals [10]. Self-medication with antibiotics (SMA) has significant adverse effects such as drug toxicity, resistance of microorganisms, prolonged hospitalization, unsuccessful treatment, high cost of treatment, and increased rate of incurable diseases [11]. In contrast to other medications and almost all other modalities, the efficacy of antibiotics is decreasing over time [12]. A cross-sectional study of self-medication patterns of adults presenting to the dental clinic of Sharjah Dental School for their oral and dental problems revealed that 70.7% of patients had tried self-medication. The most common reason for self-medication was reported to be time shortage for visiting a dentist (37.6%), and not taking oral and dental problems seriously (36.8%) [13]. According to the available statistics, the rate of medication intake in Iran is three times the mean global rate [14, 15].

Considering the increasing use of antibiotics, emergence of multi-drug resistant microorganisms is among the most important public health dilemmas [16, 17]. To the best of our knowledge, no report existed on the COVID-19-related changes among dental patients in Iran. With regard to the alarming consequences of the possible increase in SMA among dental patients during the COVID-19 pandemic, the present study aimed to compare SMA and the pattern of dental visits before and after the emergence of COVID-19 pandemic in a referral dental clinic in the north of Iran.

Materials and methods

Study design and participants

This cross-sectional study evaluated 756 records of patients older than 18 years old, referring to the Faculty Clinic of Rasht School of Dentistry during the morning shifts. The patients had been visited by a general dentist during a 6-month period, starting 3 months before the emergence of COVID-19 pandemic from mid-November 2019 to mid-February 2020, and after the emergence of COVID-19 pandemic from mid-April to mid-July 2020. The patient records were evaluated anonymously, and the extracted data were recorded in datasheets. There is a routine statement in the hospital records, requiring the patients to show if they give consent to use their data anonymously for research purposes. The patients have the option to deny. In our study, all the patients’ had shown agreement to use their data for research purposes. This was considered as written informed consent. The study was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.DENTISTRY. REC.1399.136).

The minimum sample size was calculated to be 350 for each time period considering 0.29 ratio (prevalence of SMA) in a previous study [18] before the emergence of COVID-19 and 0.42 ratio according to a pilot study, alpha = 0.05, and d = 0.13. The sample size was calculated according to the main objective of the study. From the 2 years ago, a question about SMA has been added to the records of this clinic, and among the routine dental examination, the history of SMA is also recorded in the hospital records of the patients

Data collection

A general dentist evaluated patient records and retrieved the required information including the patients’ gender, age, place of residence (capital city of the province, other urban areas, rural areas), smoking status, chief complaint, and SMA. All available complete records in the specified periods were evaluated, and the required data were entered to the data collection form.

Statistical analysis

Normal distribution of data was evaluated using the Shapiro-Wilk test, Kolmogorov-Smirnov test, or the kurtosis and skewness measurement. Chi-square test was used to find significant associations between the categorical independent (time before and after the COVID-19 pandemic) and dependent variables. The logistic regression model was fitted to the data to control for the effect of possible confounders. SPSS version 24 (IBM Corp, Armonk, NY, USA) served for statistical analysis at 0.05 level of significance.

Results

Of 756 patients included in this study, 412 (54.5%) were recruited from the pre-pandemic and 344 (45.5%) were recruited from the post-pandemic period. Of those recruited before the pandemic emergence, 195 (47.3%) were males. The mean age of patients recruited before the pandemic was 39.02 ± 13.84 years. Of those recruited after the pandemic emergence, 160 (46.5%) were males, and the mean age of these patients was 40.38 ± 15.91 years. The patients were homogeneous in terms of gender (p = 0.822) and age (p = 0.217) before and after the COVID-19 pandemic emergence (Table 1).

Table 1

Comparisons of the studied variables before and after the COVID-19 pandemic emergence among a group of dental patients (n = 756) in Iran.

	Time		P-value (χ2)
	Before the pandemic n (%)	After the pandemic n (%)
Gender
Male	195 (47.3)	160 (46.5)	0.822 (0.05)
Female	217 (52.7)	184 (53.5)
Place of residence
Capital city	229 (55.6)	214 (62.2)	0.142 (3.90)
Urban areas	113 (27.4)	75 (21.8)
Rural areas	70 (17)	55 (16)
Smoking status
Non-smoker	319 (77.4)	289 (84)	0.023 (5.16)
Smoker	93 (22.6)	55 (16)
Chief complaint
Checkup	70 (17)	7 (2)	<0.001 (115.43)
Pain	123 (29.9)	166 (48.3)
Pus and abscess	93 (22.6)	124 (36)
Fracture	36 (8.7)	30 (8.7)
Hypersensitivity	39 (9.5)	16 (4.7)
Esthetic problems	51 (12.4)	1 (0.3)
Self-medication with antibiotics
No	303 (73.5)	151 (43.9)	<0.001 (68.69)
Yes	109 (26.5)	193 (56.1)
Medication
None	303 (73.5)	151 (43.9)	<0.001 (80.57)
Amoxicillin	44 (10.7)	78 (22.7)
Co-amoxiclav	11 (2.7)	13 (3.8)
Metronidazole	8 (1.9)	8 (2.3)
Azithromycin	3 (0.7)	16 (4.7)
cefixime	3 (0.7)	3 (0.9)
Penicillin	7 (1.7)	6 (1.7)
Doxycycline	4 (1)	3 (0.9)
Clindamycin	1 (0.2)	2 (0.6)
Incomplete information	19 (4.6)	51 (14.8)
Amoxicillin & Metronidazole	9 (2.2)	12 (3.5)
Azithromycin & Penicillin	0 (0)	1 (0.3)

Table 1 shows that smoking, chief complaint, SMA, and the type of antibiotics taken varied significantly before and after the pandemic emergence. The prevalence of smoking and the frequency of such chief complaints as dental checkups, tooth hypersensitivity, and esthetic dental problems decreased after the pandemic emergence compared to before that. However, the frequency of dental pain, pus discharge, and abscess as the chief complaints of patients increased after the pandemic emergence (Fig 1). SMA also significantly increased during the pandemic, with Amoxicillin and Azithromycin being the most commonly used antibiotics.

Fig 1

Changes in the chief complaints of patients after the COVID-19 pandemic emergence compared with before among a group of dental patients (n = 756) in Iran.

To evaluate the strength of the associations, simple and multiple logistic regression models were fitted to the data (Table 2). According to the adjusted model, patients presented to the clinic after the pandemic were more likely to report SMA compared to those before the pandemic (OR = 3.38, 95% CI = 2.42–2.71, P<0.001). Moreover, having pain (OR = 1.96, 95% CI = 1.02–3.78, P = 0.04), and pus an abscess (OR = 2.14, 95% CI = 1.09–4.18, P = 0.03) as the chief complaint of the patients was significantly associated with higher SMA report.

Table 2

Association of smoking, COVID-19 pandemic, and chief complaint with self-medication with antibiotics among a group of dental patients (n = 756) in Iran using simple (unadjusted) and multiple (adjusted) logistic regression models.

	P value	Unadjusted OR	95% C.I. for OR		P value	Adjusted OR	95% C.I. for OR
			Lower	Upper			Lower	Upper
COVID-19 pandemic	<0.001	3.55	2.62	4.82	<0.001	3.38	2.42	4.71
Smoking	0.089	1.39	0.95	2.02	0.29	1.24	0.83	1.84
Chief complaint *
Pain	<0.001	3.53	1.89	6.58	0.04	1.96	1.02	3.78
Pus and abscess	<0.001	3.78	1.10	7.14	0.03	2.14	1.09	4.18
Fractures	0.04	2.25	1.04	4.87	0.40	1.41	0.63	3.17
Tooth hypersensitivity	0.007	3.00	1.36	6.62	0.04	2.40	1.06	5.43
Tooth coloration and esthetic	0.036	2.38	1.06	5.37	0.02	2.68	1.18	6.12
				Constant	<0.001	0.16

* Reference: Checkup as the chief complaint

Discussion

The present study investigated SMA and its associated factors among the dental patients before and after the COVID-19 pandemic. According to the results, the rate of SMA increased by 30% after the pandemic emergence, compared to that before. SMA was also associated with the chief complaints of the patients.

Considering the complications and adverse consequences of SMA, and the fact that SMA is a major public health concern, the increase in SMA after pandemic is an alarming finding that calls for attention of dental clinicians and health care professionals, and highlights the need for public awareness on this topic. The increased rate of SMA appears to be due to the postponement of dental visits by patients as the result of fear of contracting COVID-19, leading to self-medication. On the other hand, late seeking of dental care would further complicate the problem and increase the rate of emergency cases [4, 19], which was also highlighted in the present study since the results showed a shift in the chief complaints of patients from non-emergency dental problems before the pandemic to emergency problems after the pandemic emergence.

Of self-medicated antibiotics (including Amoxicillin, Co-amoxiclav, Metronidazole, Azithromycin, Cefixime, Penicillin, Doxycycline and Clindamycin), Azithromycin and Amoxicillin had been more commonly used compared to others. Amoxicillin is commonly prescribed by dental practitioners [20]. Self-medication with Azithromycin is probably related to the primary assumptions of patients regarding the effectiveness of this antibiotic against the coronavirus [21].

No significant correlation was noted between SMA and place of residence (urban versus rural areas) or age of patients in the present study. Gender had no significant correlation with SMA before or after the pandemic emergence. Also, the referral rate of male and female patients was almost the same in the present study while Radeva et al. reported higher referral rate of females both before and after the pandemic emergence [22]. Another study on utilization of dental services also reported higher utilization of dental services by females [23].

The chief complaints of patients in our study mainly included dental checkup, esthetic dental problems, tooth discoloration, and tooth hypersensitivity before the pandemic emergence; while, after the emergence of the pandemic, the chief complaints included dental pain, abscess, and tooth fracture. The increase in SMA after the pandemic can be partly explained by the association of SMA with chief complaint of the patients. That the patients with acute problems such as pain, and pus and abscess were more likely to report SMA is not surprising, and similar findings have been reported in Malik et al. [24] and Zhang et al. [25] studies. Moreover, our findings indicate patients sought dental care for more serious and more acute conditions after the pandemic emergence due to the fear of contracting COVID-19 and the set restrictions, which is in line with previous studies [26]. This, in turn, seems to leading more SMA among patients. Anyway, the public should be aware that even for such acute and discomforting problems, and even in pandemic era antibiotics should be prescribed by an authorized health professional [27]. On the other hand, emergency dental care should be accessible for the public during disasters and pandemics [28]. Another reason for increased SMA after pandemic might be the lack of patient information regarding provision of dental care services during the pandemic period, resulting in higher percentage of emergency cases. This calls for sufficient and timely provision of health service information for public during the pandemics and disasters.

In addition to home quarantine, depression, fear, and anxiety related to COVID-19 pandemic have resulted in an increase in the prevalence of hysterical dental pain. Also, home quarantine and greater consumption of sugary substances have aggravated the pattern of dental caries [29].

Our findings highlight the significance of patient education, prevention, and oral health promotion during the pandemics, and dental practitioners should more actively participate in preventive programs and oral health instruction during the COVID-19 pandemic and possible future pandemics.

The present study was carried out in a large professional dental clinic, which is a referral center for all types of oral and dental conditions in a large city in Iran. Also, all the information was extracted and recorded by one dentist, which was another strength of this study.

Limitations of the study

The cross-sectional design was the main limitation of the present study, as this study type is unable to assess causation. Cross-sectional studies are used to look for the presence or absence of an outcome as well as the presence or absence of an exposure at a certain period. Because both the outcome and the exposure are investigated at the same time, the temporal link between the outcome and the exposure cannot be ascertained in cross-sectional research [30]. Because a chronological sequence cannot be established, the cross-sectional study cannot be utilized to infer causality. This type of study is still used to obtain descriptive data about a population’s disease/outcome burden or to assess background exposure rates [31].

Another limitation was the self-report nature of the study, which induces the risk of recall bias. Moreover, it increases the possibility of giving favorable responses by the respondents, which is called “social desirability” [32]. Thus, the results may be an optimistic estimation of the real situation. In questionnaire research, there’s a chance of misunderstandings and errors [33]. That our questionnaire was a part of routine medical and dental records of the patients reduces the likelihood of this bias, however. Anyway, the results should be interpreted cautiously

Conclusion

There is indication that during the COVID-19 pandemic, SMA and prevalence of acute dental problems in patients have increased. With regard to the consequences of SMA, there is a need to raise public awareness on the subject. Moreover, the public should be informed about the significance of early referral to dentists in order to prevent acute dental problems. The role of dental practitioners is pivotal in this regard.

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16 Jul 2021

PONE-D-21-19078

COVID-19-related changes in the pattern of dental visits and self-medication with antibiotics

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Reviewer #1: The current study assessed the impact of the COVID-19 pandemic on the pattern of dental visits and self-medication with antibiotics.

I have some comments which are given below:

Title

The title covers two domains i.e., changes in dental visits, and practice of self-medication with antibiotics. But the results, discussion, and conclusion only cover and discuss the SMA. I will suggest rewriting the title according to the results presented and discussed.

Abstract

The abstract is well written and well presented. Regarding keywords, kindly refer to Mesh terms.

Introduction

The introduction is written well. Kindly limit the introduction to the aims and objectives of the study. Moreover, kindly provide a detail of the rationale of the study, why this study was conducted?.

In the second paragraph, lines between references 5 and 6, the authors were not citing any reference. Kindly cite here a relevant reference.

Method

In the method section, there is great confusion regarding study design. The authors stated that data was retrieved from the hospitals' records in the mentioned specified durations. But the authors have presented this study as cross-sectional rather than a retrospective study. Kindly explain.

If the study was retrieved from the hospital records, then how the authors took informed consent?

Why the authors used sample size calculation based on SMA prevalence?.

In the 2nd line of the statistical analysis, the author stated, “Independent t-test, test and confidence interval”, name the “test”, or remove it.

Results

The results are well presented. But in table 1, numbers with p-values are not clearly mentioned. Have the authors tabulated here chi-square values?

Kindly marked the type of applied test on the study variables and mention it in the table’s legend (Table 1)

Kindly clarify, if the data was retrieved from the hospital records, then how the responses of the study variable i.e., self-practice with antibiotics were recorded?

Discussion and conclusion

The discussion is well written and well compared. Again, the discussion and conclusion only discuss SMA, it doesn’t assess how the pattern of the dental visits was changed.

Reviewer #2: Abstract

• In results, line no. 4 there would be 6.6 rather than 6,6.

• Conclusion should be based on the results of the study. Was the association between antibiotic resistance and SMA assessed in your study?

• P=<0.001? this is not the correct way to write significance.

Introduction

• Introduction seems to lengthy. It is better to make it to-the-point and crisp.

• World health organization should be World Health Organization. There are several other typos which should be corrected throughout the manuscript.

• In the first paragraph, “and” is written repeatedly line 5 & 7.

• In paragraph 3, second last line, it should be complicates rather than complications.

Methodology

• Based on the fact that it is a pre and post COVID-19 study, please explain the study design.

• I will suggest that the study setting should be part of methods section rather than the introduction section.

• How the authors approached the participants to take their written consent specifically for post COVID-19 patients?

• Please explain if the sample size calculation formula is correct for cross sectional studies.

• What was the sampling strategy?

• In data collection section, what about the sampling criteria?

• Please follow the standard format of writing SPSS.

Results

• In the Table 1, what P() column refers to?

• Table 2 is not in the standard format to present result of logistic regression analysis. It is equally not clear from the Table that what is the dependent variable. Further, Table 2 does not justify the use of logistic regression analysis to show the variation in SMA before and after COVID-19 era.

• Overall, the results section needs a major re-write.

Discussion and conclusion

• I would suggest healthcare professionals rather than personnel.

• Paragraph 2, second last line “the” instead of “he.”

• Can you please give the list of self-medicated antibiotics other than amoxicillin and azithromycin?

• Overall, the Discussion part should be improved and elaborated.

• Conclusion section needs improvement and should be coherent with the results. The recommendations made in the conclusion section should be aligned with the results and main objectives of the study.

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Reviewer #2: No

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13 Oct 2021

Reviewer #1:

Dear reviewer, we appreciate your time and accurate comments. Your comments help us to improve our manuscript.

1- Title

The title covers two domains i.e., changes in dental visits, and practice of self-medication with antibiotics. But the results, discussion, and conclusion only cover and discuss the SMA. I will suggest rewriting the title according to the results presented and discussed.

Response: The title has now been revised. “COVID-19-related Changes in Self-medication with Antibiotics”. The aim of the study in both abstract and introduction has now been revised to put SMA first (Abstract: last sentence of Background, and page 4, first paragraph)

2- Abstract

The abstract is well written and well presented. Regarding keywords, kindly refer to Mesh terms.

Response: We greatly appreciate your comment, the keywords are written according to MeSH. “Self-Medication, Anti-Bacterial Agents, Dentistry, COVID-19”

Introduction

3-The introduction is written well. Kindly limit the introduction to the aims and objectives of the study. Moreover, kindly provide a detail of the rationale of the study, why this study was conducted?.

Response: Thank you for your comment. We revised the introduction to address your comment. The detail of the rationale for the study has now been added (Page 4, first paragraph)

4. In the second paragraph, lines between references 5 and 6, the authors were not citing any reference. Kindly cite here a relevant reference.

Response: There is no sentence without reference between references 5 and 6.

Method

5-In the method section, there is great confusion regarding study design. The authors stated that data was retrieved from the hospitals' records in the mentioned specified durations. But the authors have presented this study as cross-sectional rather than a retrospective study. Kindly explain.

Response: Thank you for your constructive comment. The type of study was revised to cross sectional (Page4, line10).

6- If the study was retrieved from the hospital records, then how the authors took informed consent?

There is a routine statement in the hospital records, requiring the patients to show if they give consent to use their data anonymously for research purposes. The patients have the option to deny. In our study, all the patients’ had shown agreement to use their data for research purposes. This was considered as written informed consent. This has now been added to the manuscript (page:4, line:15-19).

7- Why the authors used sample size calculation based on SMA prevalence?.

Response: The SMA was the point of focus in our study, which is now more highlighted after the revisions. That’s why we used this variable to calculate sample size.

8- In the 2nd line of the statistical analysis, the author stated, “Independent t-test, test and confidence interval”, name the “test”, or remove it.

Response: The test was removed (Page5, line12).

Results

9- The results are well presented. But in table 1, numbers with p-values are not clearly mentioned. Have the authors tabulated here chi-square values?

Response: Thank you. Yes, the Chi square values are tabulated. The p value is reported and the Chi square value is reported in the parenthesis. ¬P-value ( )

10- Kindly marked the type of applied test on the study variables. (Table 1)

Response: The applied test for table 1 was Chi-square test. This has now been added to the Table 1 (Page5, line 11).

11- Kindly clarify, if the data was retrieved from the hospital records, then how the responses of the study variable i.e., self-practice with antibiotics were recorded?

Response: From the 2 years ago, a question about SMA has been added to the records of this clinic, and among the routine dental examination, the history of SMA is also recorded in the hospital records of the patients. This explanation has now been added to the manuscript (Page 5, line1,2,3).

Discussion and conclusion

12. The discussion is well written and well compared. Again, the discussion and conclusion only discuss SMA, it doesn't assess how the pattern of the dental visits was changed.

Response: According to your valuable previous comments, we changed the title, and now the focus of the manuscript is on SMA. The change in dental visit, as a possible justification of change in SMA has been discussed in the discussion. (Page 10,11,12)

Reviewer #2:

Abstract

With great regards, we kindly appreciate your time and accurate comments. Your comments help us to improve our manuscript. We revised the manuscript according to the comments, as explained below.

1- In results, line no. 4 there would be 6.6 rather than 6,6.

Response: 6,6 was revised to 6.6 (Page 1, line 20)

2- Conclusion should be based on the results of the study. Was the association between antibiotic resistance and SMA assessed in your study?

Response: The association between antibiotics resistance and SMA was not assessed in this study, and the conclusion was revised (Page 2, line 4,5,6).

3- P=<0.001? this is not the correct way to write significance.

Response: The P value was corrected (Page 1, line 19).

Introduction

4- Introduction seems to lengthy. It is better to make it to-the-point and crisp.

Response: We revised and shortened the introduction (Pages 2,3,4).

5- World health organization should be World Health Organization.

Response: The correction was done (Page 2 line10).

6- In the first paragraph, “and” is written repeatedly line 5 & 7.

Response: The corresponded sentences were revised (Page 2, lines 5 and 7).

7- In paragraph 3, second last line, it should be complicates rather than complications.

Response: Complications was revised to complicates (Page 3, line 5).

Methodology

8- Based on the fact that it is a pre and post COVID-19 study, please explain the study design.

Response: Thank you for your valuable comment. The study design was revised to cross sectional study (Page 4, line 10).

9- I will suggest that the study setting should be part of methods section rather than the introduction section.

Response: Thank you for your suggestion. We added the study setting to methods, and removed it from introduction

10- How the authors approached the participants to take their written consent specifically for post COVID-19 patients?

Response: There is a routine statement in the hospital records, requiring the patients to show if they give consent to use their data anonymously for research purposes. The patients have the option to deny. In our study, all the patients’ had shown agreement to use their data for research purposes. This was considered as written informed consent. (Page 4, line 15-19).

11- Please explain if the sample size calculation formula is correct for cross sectional studies.

Since our main outcome was the proportion of the patients with SMA, we used the following formula, which uses proportions to calculate sample size in cross sectional studies. We used an estimated proportion of SMA from previous studies.

The formula is available in the attached word file (Response-Reviewer 2), as it was not possible to copy it here.

12- What was the sampling strategy?

Any patient referring to the Faculty Clinic of Rasht School of Dentistry during the morning shifts and was older than 18 years old was included in the study.” (Page 4, line 10,11)

13- In data collection section, what about the sampling criteria?

Response: Inclusion criteria is added to the method. “Any patient referring to the Faculty Clinic of Rasht School of Dentistry during the morning shifts and was older than 18 years old was included in the study.” (Page 4, line10,11, and page 5, lines 8 and 9)

14- Please follow the standard format of writing SPSS.

Response: Revised to “SPSS version 24 (IBM Corp, Armonk, NY, USA)”

Results

15- In the Table 1, what P() column refers to?

Response: The P refers to p value and X2 refers to the Chi-square value.

16- Table 2 is not in the standard format to present result of logistic regression analysis. It is equally not clear from the Table that what is the dependent variable. Further, Table 2 does not justify the use of logistic regression analysis to show the variation in SMA before and after COVID-19 era.

Response: Thank you for your valuable comment. The table 2 was revised substantially. Now the dependent variable is SMA, and the data presentation format has been revised (Pages 9,10).

17-Overall, the results section needs a major re-write.

The results part has now been revised (Pages 9,10).

Discussion and conclusion

18- I would suggest healthcare professionals rather than personnel.

Response: The healthcare professional was changed to personnel (Page10, line9).

19- Paragraph 2, second last line “the” instead of “he.”

Response: Revised. We kindly appreciate your accuracy.

20- Can you please give the list of self-medicated antibiotics other than amoxicillin and azithromycin?

Response: Revised to “Of self-medicated antibiotics (including Amoxicillin, Co-amoxiclav, Metronidazole, Azithromycin, Cefixime, Penicillin, Doxycycline and Clindamycin), Azithromycin and Amoxicillin had been more commonly used compared to others” (Page11, line3,4).

21- Overall, the Discussion part should be improved and elaborated

Response: The Discussion part has now been revised and elaborated substantially, with the main focus on SMA (Pages:10,11,12)

22- Conclusion section needs improvement and should be coherent with the results. The recommendations made in the conclusion section should be aligned with the results and main objectives of the study.

Response: We revised Conclusion part to address this comment (Page13, line1-5).

Submitted filename: Response-Reviewer 2.docx

Click here for additional data file.

23 Dec 2021

Submitted filename: PONE-D-21-19078_reviewer.pdf

Click here for additional data file.

5 Mar 2022

We would like to cordially thank the reviewer for the constructive comments. Here is our point by point responses to the comments

1. the add "A cross-sectional study on............." to the title to give a reader the full picture.

Response: The title was revised according to the comment.

2. rewording of some parts of the write-up to provide clarity (pl refer to the reviewed article)

Response: All requested rewordings were done.

3. Details of Data Collection Form to be included in the write-up.

Response: A sentence on data collection form was added to the paragraph on data collection (page 5). The data collection form included the variables explained in the same paragraph.

4. There is a mis-match of the number of respondents - 350 required and only 344 studied?

Response: We collected the data from all available complete records in the specified time periods. The number of these records in the post-pandemic period was 344. The biostatistician author confirmed that this will not affect the analyses and results.

5. Table 1 and Figure 1 descriptions to be separated.

Response: The results part was revised to address this comment (page 8, first paragraph).

Comments inserted in the text:

Suggest reword - There is indication that during the Covid-19 pandemic, SMA and prevalence of acute dental problems.

Response: The conclusion in the abstract and in the main text was revised according to the comment.

“patients who smoke” in the results of abstract.

Response: The results of abstract was revised.

Maintain consistency and use Antibiotics (in the keywords).

Response: Revised

“complicates” (in the introduction)

Response: Revised.

Need this be in capitals?? (the Ethics Code)

Response: Yes. The Ethics Approval Codes issued by Tehran University of Medical Sciences are all in this format. It might be better to keep it in capital.

Restate to reflect true meaning (the statistical analysis section)

Response: We revised the paragraph on statistical analysis to reflect true meaning (page 5, last paragraph). We hope it is quite clear now.

antibiotics taken

Response: Revised (page 8, first paragraph).

after the emergence of the pandemic (in discussion).

Response: Revised (page 12, first paragraph).

Check spacing of paragraphs (in discussion part).

Response: Checked and revised.

Submitted filename: Point by point response to the reviewer.docx

Click here for additional data file.

21 Mar 2022