Adverse Cardiovascular Outcomes in Young Cannabis Users: A Nationwide Analysis
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
Comments and suggestions for authors
General comment (originality, scientific accuracy, strengths and/or weaknesses):
The authors of the manuscript entitled “Adverse Cardiovascular Outcomes in Young Cannabis Users: A Nationwide Analysis” aimed to provide data on cannabis use disorder and ACS and VF occurrence. The idea is interesting, however, in my opinion, major revision on the methodology and results should be done to increase the quality of the manuscript and to be accepted.
1. Abstract
The abstract is insufficient, lacking numbers in the abstracts results. The abstract needs to be rewritten after major corrections in the manuscript is done.
2. Introduction
The aim of the study is not clearly stated.
3. Methods
The methodology is not clearly written. The exact inclusion and exclusion criteria need to be pointed out. Which patients were included, just F12 (Cannabis) or F14 (Cocaine) users as well? Groups need to be clearly selected in order to derive results and conclusions. From this method section I can not conclude what exactly type of the study is, which patients were included and what was the outcome of the study.
The last paragraph needs to be statistic section with clearly stated statistics that was done.
After propensity matching you selected all-cause mortality, requirement of IABP, mean length of stay and mean of total charges. Why did you choose these endpoints, especially IABP? It would be more appropriate to use cardiogenic shock instead of IABP or just to exclude IABP.
4. Results
Please check in authors guidelines if bold letters are allowed in text.
In Table 1 you described that 543445 patients were admitted with documented Cannabis use disorder (CUD). Where were they admitted and for what admission diagnosis? This also need to be clarified in the methods. Or you can just concentrate on ACS/VF diagnosis and CUD diagnosis.
Table 2 columns need to be labeled properly. The numbers should be added in the first row (number of admissions due to ACS, number and % of ACS plus CUD, number of VF admission and number and % of VF plus CUD). We need also p value in the table between groups. Furthermore, is in Table 1 you should add prevalence of hypertension, diabetes, HLP, cocaine use (thus table 1 may be unnecessary). Also, if you are reporting Median (IQR), this need to be labeled as well.
In tables 3 and 4 are you examined is CUD associated with outcomes of ACS and VF. Did you take a whole group of patients admitted with ACS and VF diagnosis or did you analyze the Cannabis only patients. This needs to be clarified in methods also.
Table 4 : Correct capital letters in the title
Propensity table is not labeled, not unit not measures, there is no p calculated. Also in other tables not p value is calculated.
5. Discussion needs to be corrected based on methods and results corrections.
6. There is no Conclusion section in the manuscript.
7. The literature is not cited properly.
The last remark-abbreviation should be explained first time they are mentioned (NIH, CMR etc.) and should be constant (ventricular fibrillation either VF, Vfib or V.fib).
Author Response
- Abstract
The abstract is insufficient, lacking numbers in the abstracts results. The abstract needs to be rewritten after major corrections in the manuscript is done.
Reply: Changes have been made and numbers have been included
- Introduction
The aim of the study is not clearly stated.
Reply: the aim of the study has been specifically added to the end of the discussion section
- Methods
The methodology is not clearly written. The exact inclusion and exclusion criteria need to be pointed out. Which patients were included, just F12 (Cannabis) or F14 (Cocaine) users as well? Groups need to be clearly selected in order to derive results and conclusions. From this method section I can not conclude what exactly type of the study is, which patients were included and what was the outcome of the study.
The last paragraph needs to be statistic section with clearly stated statistics that was done.
After propensity matching you selected all-cause mortality, requirement of IABP, mean length of stay and mean of total charges. Why did you choose these endpoints, especially IABP? It would be more appropriate to use cardiogenic shock instead of IABP or just to exclude IABP.
Reply: The study design and inclusion criteria have been revised. IABP has been removed. F14 codes were not used (codes have been updated). Details of the statistics used have been specified.
In Table 1 you described that 543445 patients were admitted with documented Cannabis use disorder (CUD). Where were they admitted and for what admission diagnosis? This also need to be clarified in the methods. Or you can just concentrate on ACS/VF diagnosis and CUD diagnosis.
Reply: the ICD codes for cannabis use were used to select admissions (all admissions) in the age group of 18-45: this was used to a rough estimate of young adults with cannabis use. Their characteristics were further analyzed.
Table 2 columns need to be labeled properly. The numbers should be added in the first row (number of admissions due to ACS, number and % of ACS plus CUD, number of VF admission and number and % of VF plus CUD). We need also p value in the table between groups. Furthermore, is in Table 1 you should add prevalence of hypertension, diabetes, HLP, cocaine use (thus table 1 may be unnecessary). Also, if you are reporting Median (IQR), this need to be labeled as well.
Reply: since this table did not add much to the study overall, has been removed
In tables 3 and 4 are you examined is CUD associated with outcomes of ACS and VF. Did you take a whole group of patients admitted with ACS and VF diagnosis or did you analyze the Cannabis only patients. This needs to be clarified in methods also.
Reply: changed to tables 2 and 4. The patients with admission diagnosis of Vfib/ACS were used as the study population (inclusion criteria). Cannabis use documented group became the cases and others were controls. This has been specified in the methods too
Table 4 : Correct capital letters in the title
Propensity table is not labeled, not unit not measures, there is no p calculated. Also in other tables not p value is calculated.
Reply: P value has been added to the table, IABP removed and units ( dollars for mean of total charges) and days ( for length of stay). Mortality was mentioned in %
5. Discussion needs to be corrected based on methods and results corrections.
6. There is no Conclusion section in the manuscript.
7. The literature is not cited properly.
The last remark-abbreviation should be explained first time they are mentioned (NIH, CMR etc.) and should be constant (ventricular fibrillation either VF, Vfib or V.fib).
reply: discussion and citations have been changed. Vfib was unified
Reviewer 2 Report
Comments and Suggestions for Authors
Adverse Cardiovascular Outcomes in Young Cannabis Users: A Nationwide Analysis
This manuscript performs a retrospective analysis to analyze the association between cannabis use disorder in 18 to 45-year-old adults (young adults) and acute coronary syndrome and ventricular fibrillation, using 2019-2020 national inpatient sample database. This study is interesting and well put together. I have made some minor comments that will improve the manuscript.
1. Abstract
a. This is not clear that the age range is what you are referring to “…young adults (18 – 45).” Page 1. Line 8. Can say “…young adults aged 18 to 45.
b. Some words are capitalized while other times are not, same for hyphenations. For example, Cannabis; Cannabis use disorder, National In-patient, etc. Please correct this throughout the entire manuscript.
c. It would be appropriate to mention the confounders used in the analyses rather than just use the term confounders. Page 1. Line 14. Can keep line 20 confounders as is.
2. Introduction
a. “…higher percent-age…”, please add the exact percentage from the cited paper. Page 1. Line 27-28.
b. “…less than <34…”, use either less than or < but not both. Page 1. Line 28.
c. “…recent NIH monitor the future survey…”, either a word is missing, or unnecessary word(s) added. Page 2. Line 28-29.
d. “…disease cannabidiol…”, needs a comma in between words. Page 1. Line 35.
3. Materials and Methods
i. No changes, would suggest rephrasing some sentences when the term “was done” is used.
4. Table 1.
i. Title, either capitalize only the first word or all the non-conjunctions. Apply throughout the manuscript.
ii. Clarify states that fall in the hospital regions (northwest, Midwest, south, west)
iii. Mention what the values in the brackets are. for example, are categorial variables expressed as numbers and percentages? Are continuous variables expressed as means ± SD? Then add these sentences above or below the table.
5. Tables 2-4
a. Overall nicely displayed. Please apply the comments for Table 1 to these tables as well.
b. There is a lot of data, perhaps data can also be presented as a flowchart. See the example flowchart figure below.
c. IMPORTANT - Tables 3-5 -> For p <0.000, please add more decimal places, or give asterisks, and in the table description provide p values that the asterisks correspond to.
6. Results
a. Explained well!
b. IABP. Page 5. Lines 121 and 128, spelled out form should be at line 121.
c. The last table needs a heading.
7. Discussion
a. Fine as is. No comments to improve
b. Vfib is now mentioned as V.fib.
c. Manuscript could be improved with more references.
This review is well put together and requires a moderate amount of revisions.
Comments for author File: 
Comments.pdf
Author Response
- Abstract
- This is not clear that the age range is what you are referring to “…young adults (18 – 45).” Page 1. Line 8. Can say “…young adults aged 18 to 45.
- Some words are capitalized while other times are not, same for hyphenations. For example, Cannabis; Cannabis use disorder, National In-patient, etc. Please correct this throughout the entire manuscript.
- It would be appropriate to mention the confounders used in the analyses rather than just use the term confounders. Page 1. Line 14. Can keep line 20 confounders as is.
reply: changes have been made; confounders have been specified. Age group was corrected
- “…higher percent-age…”, please add the exact percentage from the cited paper. Page 1. Line 27-28.
- “…less than <34…”, use either less than or < but not both. Page 1. Line 28.
- “…recent NIH monitor the future survey…”, either a word is missing, or unnecessary word(s) added. Page 2. Line 28-29.
- “…disease cannabidiol…”, needs a comma in between words. Page 1. Line 35.
reply:
- Is directly from the citation
- Other changes have been made
Reviewer 3 Report
Comments and Suggestions for Authors
The review is relevant and has clinical importance. Though not a very noxious habir, cannabis use carries a certain degree of cardiovascular risk in addition to long-term cognitivie effect.
Minor comments:
Though base on a large subject population I feel that quoting data with 4 digits after the point seems inappropriate, after all, we are dealing withis quantom physics. For example, in one of the tables: "Admissions with Black as the documented race 1.73848 (1.4428 - 2.09711)...."
I personally prefer to show an actual level of probabilty. E.g., p<0.0001 and not p 0.000
Comments for author File: Comments.pdf
Comments on the Quality of English Language
Minimal editing
Author Response
Though base on a large subject population I feel that quoting data with 4 digits after the point seems inappropriate, after all, we are dealing withis quantom physics. For example, in one of the tables: "Admissions with Black as the documented race 1.73848 (1.4428 - 2.09711)...
reply: tables formatted include 2 decimal places and has been unified
Methods have been updated
Round 2
Reviewer 1 Report
Comments and Suggestions for Authors
The manuscript has been modified according to reviewer's suggestions. However, I have few additional comments:
1. In the abstract section please unify age of included patients (18-44) or (18-45).
2. In the result section, it would be more convenient for readers to understand if you start with the total admission "543,445 admissions were identified..." (second paragraph), than to continue with admissions of ACS patients age < 45 years ("32,990 admissions under the age of 45 for the diagnosis of ACS were identified of which 2295 admissions had documented cannabis 107 use disorder..."etc.) and VF admission (the first paragraph of the result section). It is also advisable to put % (2295 (6.9%) as an example.
3. In the result section (line 158) the authors stated:" No difference in all-cause mortality was seen between the two cohorts". However, in the Table 5, p value is 0.032 and the % in two cohorts are the same. Please check.
4. In the discussion section (line 184), the IABP is mentioned. Yet, it was deleted from the endpoints, so shouldn't be mentioned in the discussion as well.
Author Response
- In the abstract section please unify age of included patients (18-44) or (18-45). Reply: changed
- In the result section, it would be more convenient for readers to understand if you start with the total admission "543,445 admissions were identified..." (second paragraph), than to continue with admissions of ACS patients age < 45 years ("32,990 admissions under the age of 45 for the diagnosis of ACS were identified of which 2295 admissions had documented cannabis 107 use disorder..."etc.) and VF admission (the first paragraph of the result section). It is also advisable to put % (2295 (6.9%) as an example. Reply: changed
- In the result section (line 158) the authors stated:" No difference in all-cause mortality was seen between the two cohorts". However, in the Table 5, p value is 0.032 and the % in two cohorts are the same. Please check Reply: Table 5 was the propensity matched cohorts, and the p value mentioned was for the overall matching. To avoid confusion, it has been changed and the percentages alone is used
- In the discussion section (line 184), the IABP is mentioned. Yet, it was deleted from the endpoints, so shouldn't be mentioned in the discussion as well. Reply: changed
