Potential and challenges for an integrated management of tuberculosis, diabetes mellitus, and hypertension: A scoping review protocol.

In many low- and middle-income countries (LMICs), the epidemiological transition is characterized by an increased burden of non-communicable diseases (NCDs) and the persistent challenge of infectious diseases. The transmission of tuberculosis, one of the leading infectious diseases, can be halted through active screening of risk groups and early case findings. Studies have reported comorbidities between tuberculosis (TB) and NCDs, which necessitates the development of an integrated disease management model. This scoping review discusses the possibilities and problems of integration in managing TB and NCDs, with a particular emphasis on diabetic mellitus (DM) and hypertension screening and control. We will conduct this review following Arksey and O'Malley's framework for scoping review. We will use key terms related to integrated management, i.e., screening, diagnosis, treatment, and care, of TB, DM, and hypertension in PubMed, Scopus Database, and ScienceDirect for research published from January 2005 to July 2021. This review will also consider grey literature, including unpublished literature and international disease management guidelines on TB, DM, and hypertension from WHO or other health professional organization. We will export the search results to citation manager software (EndNote). We will remove duplicates and apply the inclusion and exclusion criteria to identify the set of papers for the review. After screening the titles and abstract, two authors will independently review the full text of selected studies and extract the data. We will synthesize all selected studies qualitatively and the results will be discussed with the experts. The results will be used as the basis of the development of a guideline for integrated TB, DM, and hypertension management.

Introduction

There has been a shift toward a more considerable burden of non-communicable diseases NCDs, particularly in low and middle-income countries (LMICs). In 2016, 71% of global death was related to NCDs [1], and 85% of premature mortality in LMICs was due to NCDs [2]. The two major contributors to NCD burdens are DM and hypertension. The prevalence of DM was 351.7 million in the working-age group (20–79 years) and 135.6 million among older people (65–99 years) [3]. Hypertension is the most common risk factor for death and disability, followed by smoking and high plasma glucose [1]. As the burden of NCDs increases, TB remains as a major cause of ill health and a leading cause of death, with an estimated 10 million new cases in 2019 [4].

The burden of TB is higher among patients with DM [5-7]. A meta-analysis in 16 countries reported that people with DM have a two to four-fold increased risk of TB [8], and TB prevalences among diabetic patients in developing Asian countries were 1.8–9.5 times higher than in the general population [9]. In 2013, approximately 15% of TB cases in adults were attributed to DM [10]. People with TB-DM comorbidities showed more severe TB presentations [11], increased risk of treatment failure, TB relapse, and delayed sputum culture conversion [12-15].

Several study also showed an association between TB and hypertension. Chung et al. reported a higher prevalence of hypertension (38.7% in the TB group vs 37.5% in the non-TB group) [16]. A study by Mandieka et al., also showed that people with latent TB have a higher risk of developing hypertension [17]. In a meta-analysis by Seegert et al., the prevalence of hypertension in TB patients ranges from 0.7% to 38.3%; however, there is no significant difference in hypertension cases between TB and non-TB patients in most case-control studies [18].

DM and hypertension also frequently occur together and worsen clinical outcomes [19, 20]. DM and hypertension share common risk factors and pathophysiology, resulting in the escalation of comorbidities, especially among low-income populations worldwide [21, 22]. Compared to people who only had DM or hypertension, people with DM and hypertension comorbidities had a higher rate of mortality [21] and are at increased risk for cardiovascular events [22]. Meanwhile, among TB patients, those with DM are at increased risk for cardiovascular diseases compared to those with only TB (24.5% vs 5.5%). Furthermore, TB patients with DM comorbidities are also more likely to use antihypertensive medication compared to patients with only a TB diagnosis (16.9% vs 3.2%) [23].

The relationship between TB and NCDs creates opportunities for the development of integrated management of these diseases [24-26]. Additionally, the management and control of chronic infectious diseases such as TB and NCD share many similarities. Both require long-term management and change in lifestyle, and most cases are being managed at the primary healthcare level [27]. Integrated management for TB, DM, and hypertension will be beneficial to improve the outcomes of these three diseases. Therefore, this scoping review will be carried out to explore the concept of health service integration in the management of TB, DM, and hypertension. In addition, this scoping review will seek to identify potential barriers and facilitators for integrated management of TB, DM, and hypertension.

Materials and methods

The proposed scoping review will be conducted in accordance with the framework from Arksey and O’Malley: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarizing, reporting results, and conducting consultation [28]. To obtain a comprehensive view of integrated management of tuberculosis, hypertension, and diabetes, we will include original papers, grey literature including unpublished literature and international disease management guidelines on TB, DM, and hypertension from WHO or other health professional organizations. We will include studies published from January 2005 to July 2021. The scoping review will be conducted from August 2021 to June 2022, starting with literature search, database creation and extraction.

Stage 1: Identifying the research question

We formulated the research question as: “What is the potential for integrated management of TB, DM, or Hypertension?” and “What are the challenges for integrated management of TB, DM, or Hypertension?” Through this scoping review, we aim to present examples and potentials and challenges of integrating the management of TB, DM, and hypertension in any combinations i.e., TB and DM, TB and hypertension, and DM and hypertension. We will include activities related to screening, diagnosis, and treatment of the diseases.

Stage 2: Identifying relevant studies

This scoping review includes the relevant studies based on the Joanna Briggs Institute (JBI) protocol [29]. Inclusion and exclusion criteria are presented in Table 1. Search strategy using keywords and queries can be found in Table 2. The literature search will be conducted in three databases: PubMed, Scopus Database, and ScienceDirect from January 2005 to July 2021. Hence, providing a review of literature for the past 15 years. Next, the title and abstract will be analyzed.

Table 1

Inclusion and exclusion criteria.

Population	Concept	Context	Type of Sources
The target population included adult people with comorbidities of TB and or DM and or hypertension, i.e., people with TB and hypertension or DM, people with hypertension and DM, and people with the three diseases. Excluding papers which focus on specific patient subgroups, for example, children, pregnant women, and patients with immunodepressive symptoms.	Integrated TB, DM, hypertension management (screening, diagnosis, treatment or care). These include screening, diagnosis, and treatment of people with TB and hypertension or DM, hypertension and DM, and people with the three diseases. Excluding papers with a focus on single disease screening, diagnosis and treatment;	All health facilities (hospitals, health centers, and clinics), and intervention take place at communities. All types of indicators (input, process, output) of disease management, i.e. resources needed (human resources, funding, equipment, system), fidelity and effectiveness of existing integrated management implementation. We also include all indicators (patient, institution, health system).As this scoping review aims to explore potential and challenges for integrated management of these diseases, we plan to include all studies explaining the context of the disease management, with no specific exclusion criteria for context.	All types of original research; Papers with quantitative, qualitative or mixed-method study design; and papers written in English and published between the period of 2005–2021Excluding case report/ case series

Table 2

Keywords and queries for search startegy of integrated TB, DM, and hypertension management.

Database	Keywords and Queries
Pubmed	Keyword: ‘Tuberculosis’ (MeSH), “tuberculosis”, “TB” ‘Diabetes Mellitus’ (MeSH), “diabetes mellitus”, “DM”. ‘Hypertension’ (MeSH), “hypertension”, “high blood pressure“, “integrated”, “integration”, “integrate”, “management”, “bidirectional screening”, “screening”, “diagnosis”, “treatment”, “care” Query: (((tuberculosis[MeSH Terms] OR tuberculosis OR TBC) AND (diabetes mellitus[MeSH Terms] OR “diabetes mellitus” OR DM) AND (hypertension[MeSH Terms] OR hypertension OR “high blood pressure”)) OR ((tuberculosis[MeSH Terms] OR tuberculosis OR TBC) AND (diabetes mellitus[MeSH Terms] OR “diabetes mellitus” OR DM)) OR ((tuberculosis[MeSH Terms] OR tuberculosis OR TBC) AND (hypertension[MeSH Terms] OR hypertension OR “high blood pressure”)) OR ((diabetes mellitus[MeSH Terms] OR “diabetes mellitus” OR DM) AND (hypertension[MeSH Terms] OR hypertension OR “high blood pressure”))) AND ((integrated OR integration OR integrate) AND (management OR “bidirectional screening” OR screening OR diagnosis OR treatment OR care))
Scopus	Keyword: “tuberculosis”, “TB”, “diabetes mellitus”, “DM”. “hypertension”, “high blood pressure“, “integrated”, “integration”, “integrate”, “management”, “bidirectional screening”, “screening”, “diagnosis”, “treatment”, “care” Query: ALL ((tuberculosis OR TB) AND ("diabetes mellitus" OR DM) AND (hypertension OR "high blood pressure“) AND (integrated OR integration OR integrate) AND (management OR “bidirectional screening” OR screening OR diagnosis OR treatment OR care))
ScienceDirect	Keyword: “tuberculosis”, “diabetes mellitus”, “DM”. “hypertension”, “integration”, “management”, “bidirectional screening”, “screening”, “diagnosis”, “treatment” Query: (tuberculosis) AND ("diabetes mellitus") AND (hypertension) AND (integrated OR integration OR integrate) AND (management OR "bidirectional screening" OR screening OR diagnosis OR treatment)

Stage 3: Study selection

Two authors will screen the titles and abstracts of studies according to the selection criteria. In the scoping review, we will include all studies that evaluate the integration of disease management in screening, diagnosis, and treatment for TB and Hypertension, TB and DM, Hypertension and DM, and studies assessing the integration of the three diseases. We will exclude studies focusing on pregnant women with gestational diabetes and preeclampsia or studies in patients with immunodepressive symptoms who had a particular condition and usually require specific management. Two authors will independently review the full text of selected studies according to Fig 1. We resolved disagreements on study selection and data extraction by a discussion with one more reviewer if needed.

Fig 1

Flow chart for the study selection.

Stage 4: Charting the data

The two reviewers independently charted the data, discussed the results, and continuously updated the data-charting form in an iterative process. Data extraction will be carried out following the form that has been prepared in Table 3.

Table 3

Extraction data template.

Data	Data description
Article information	Author, year of publication, location of the study
Type of sources	A peer-reviewed journal, grey literature, and international guideline
Study Design	Quantitative, qualitative, mixed methods
Article Type	Original article, guidelines, unpublished reports
Aim	Overall aim or objective of the study
Population	The target population of the study
Research methods	Study design, sample size, methods of data collection, instruments used in the study
Concept of integration	Information on the stage of integration (screening, diagnosis, management) as well as activities conducted, level of integration (primary health center, community, hospital), disease focus (TB-DM, DM-hypertension, hypertension-TB, or TB, DM, and hypertension)
Results	Main findings of the study in the forms of quantitative results (%, mean/median/std deviation of some indicators, Odds Ratio, 95% CI). We will include information on code, themes, and meaningful quotes for further analyses. We will extract information on disease management guidelines for guidelines, particularly those relevant to the integrated disease management.
Additional information	Additional information of the study that relevant to the scoping review, for example study limitation and recommendation.

Stage 5: Collating, summarizing, and reporting results

The findings obtained from the literature search from extracted data (Table 3) will be summarized in a table. Studies will be categorized by different characteristics, particularly on: study location (countries where the research was conducted: high and low middle-income countries), as well as types of integration (i.e., stage of integration and level of integration) (Table 3). A narrative report will be developed to map all the studies included in the scoping review. The summary of the findings will be presented in the different categories to present potentials and challenges for integrated management of the three diseases, particularly by the different types of integration. A qualitative synthesis will be conducted to present a robust summary of the literature, including barriers, facilitators, and recommendations on integrated diseases management. We will focus mainly on existing programs that have been implemented in the different stages of integration (screening, diagnosis, management) and levels of integration (primary health center, community, hospital). When possible, additional comparisons on whether there are differences between high and low-middle income countries will also be summarized and reported. Therefore, comprehensive information can be presented to address the potentials and challenges of integrated management of these diseases.

Stage 6: Conducting consultation

The results will be consulted the experts and relevant stakeholders including regulators (health officers and national insurance officers), clinicians, and patients. This step is essential to validate the findings, receive feedback and obtain additional insights into the findings. Experts from India and Indonesia on TB, DM, and hypertension management will be invited for in-depth interviews. India and Indonesia contribute to more than one-third of the TB burden globally [4]. Additionally, the two countries are also among the countries with the highest number of DM and hypertension [30, 31]. The selection of the experts will consider their research background and or program implementation experiences in TB, DM and hypertension management. After presenting the finding, the discussion will be centered on whether the findings are applicable in the context of healthcare in India and Indonesia and whether there are additional information on potential and barrier to integrated management of the diseases.

Meanwhile, the stakeholders’ consultations will be conducted as focus group discussions, in which the findings will be presented and discussed. As for the stakeholder consultation, we plan to invite relevant stakeholders, mainly from Indonesia, to validate and provide feedback on our findings. For each group of stakeholders, a key person who can provide adequate information on the topic of integrated TB-DM and hypertension management will be identified. The stakeholder includes the Ministry of Health officials coordinating TB and NCD management, district health officials, and the officials from the national health insurance. A separate FGD with patients with TB and DM or hypertension comorbidities will be conducted. The patient FGD is conducted in several communities and hospitals in Indonesia’s Central Java Province. This setting was because of the province’s high prevalence of TB, DM, and hypertension. Central Java is also one of Indonesia’s prioritized provinces for TB and NCD interventions.

Ethical considerations

We have obtained ethical permits for this review from the Research Ethics Committee, Faculty of Medicine, Universitas Sebelas Maret, Indonesia, with the ethical review number: 09/UN27.06.6.1/KEP/EC/2021.

Discussion

This scoping review will provide information on potential and challenges for integrated management of TB, DM, and hypertension, with different stages and levels of integration. A systematic review on integrating TB and NCDs care in low-middle income countries (LMICs) highlighted the benefit of integrated disease management in improving health service delivery, mainly if comprehensive management from screening, referral, and treatment is conducted [32]. However, in this scoping review, we will focus on TB, DM and hypertension integration. Our scoping review will strengthen the arguments for implementing TB-DM integrated management. Increased case detection through bi-directional screening lead to more effective management of the diseases [33]. The integration reduced treatment loss to follow up for both TB-DM, increasing treatment success among TB patients [34]. However, synthesis of the integration among three diseases, i.e. TB, DM and hypertension, is still lacking.

The strengths of the scoping review include the inclusion of all types of health facilities (primary, secondary, and tertiary healthcare), consultation with experts, and the inclusion of clinical guidelines and grey literature. However, there are several potential limitations of the scoping review, including only literature published in English, and individual country clinical guidelines on TB, DM, and hypertension will not be included in this scoping review. Despite the limitation, to our knowledge, this is the first scoping review to map concepts relevant to the integrated management of TB, DM and hypertension. The results will be helpful for relevant stakeholders to improve the guideline for TB, DM and hypertension management in a high burden of the diseases. The findings will highlight research gaps in relevant to integrated disease management.

PRISMA-ScR checklist.

(PDF)

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5 Jan 2022

Potential and challenges for an integrated management of Tuberculosis, Diabetes Mellitus, and Hypertension: a scoping review protocol

PLOS ONE

Dear Dr. Probandari,

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.

We have received the reports from our advisors on your manuscript, "Potential and challenges for an integrated management of Tuberculosis, Diabetes Mellitus, and Hypertension: a scoping review protocol", submitted to "PLOS ONE".

Based on the advice received, I feel that your manuscript could be reconsidered for publication should you be prepared to incorporate changes as suggested by reviewers. When preparing your revised manuscript, you are asked to carefully consider the reviewer comments which can be found below, and submit a list of responses to the comments. The final decision will be taken after your response letter and revision.

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Kind regards,

Masoud Foroutan, Ph.D; Assistant Professor

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

Dear Dr. Probandari,

We have received the reports from our advisors on your manuscript, "Potential and challenges for an integrated management of Tuberculosis, Diabetes Mellitus, and Hypertension: a scoping review protocol", submitted to "PLOS ONE".

Based on the advice received, I feel that your manuscript could be reconsidered for publication should you be prepared to incorporate changes as suggested by reviewers. When preparing your revised manuscript, you are asked to carefully consider the reviewer comments which can be found below, and submit a list of responses to the comments. The final decision will be taken after your response letter and revision.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: No

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

Reviewer #2: Yes

**********

5. 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: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. In line 148 (Stage 5): The author should explain in more detail about collating, summarizing, and reporting results.

2. In line 178 the parentheses have not closed.

3. In general, the discussion section is very short and concise, and it is better for the author to rewrite it in more detail.

Reviewer #2: General comments:

The introduction is well written and relevant citations are used. Overall, I think English needs improvement, authors use verb terms inconsistently. I would also suggest naming the sections of the protocol as per PLOS ONE requirements (https://journals.plos.org/plosone/s/what-we-publish/#loc-study-protocols) including the background, rationale, objectives, methodology, statistical plan, and organization of a research project. Content of the introduction section can be written under background and rationale; section, the identifying the research question, can be renamed as objective, all the rest can go under methodology and organization of the research project. I understand that a statistical plan is not relevant to your protocol.

Abstract

Line 33: Please specify key search terms for TB, DM, and Hypertension.

Line 36: Please specify in which citation manager software the results will be exported.

Introduction:

Lines 65, 66. Please mention the name of the author, as you do in the sentence before, otherwise it seems like that this finding is also from the same article (citation 16) and not from another article (citation 17).

Lines 71-72: Please provide a citation

Lines 74-75: Please mention: "… and DM and Cardiovascular events …", I understand that mortality rates were higher in both groups: Hypertension and DM and Cardiovascular events and DM vs Hypertension alone and Cardiovascular events alone

Lines 76-78: Not clear to me what do you mean. It is clear from previous citations (19-21) that DM is significantly associated with hypertension but citation 22 is interpreted so that TB can be an effect modifier among patients with DM. I believe that is not true. Could you please revise?

Materials and Methods

Lines 98-99: Why do you include studies published between January 2005 and July 2021, and not, for instance, including December 2021?

Lines 99-100: Have you already conducted the scoping review in Aug-Dec 2021 as it is mentioned in the protocol? If so, please ignore my comments above. If not, please revise the timeline.

Stage 1. Identifying the research question

Lines 103, 104: I would suggest splitting the research question into two research questions:

What is the potential for integrated management of Tuberculosis, Diabetes Mellitus, or Hypertension ?”

What are the challenges for integrated management of Tuberculosis, Diabetes Mellitus, or Hypertension ?”

Stage 2: identifying relevant studies

Line 118, Table 1: Could you please clarify whether the study population included patients only with TB or only with DM, or only with Hypertension? If so, how would you learn about integrating the management of TB with Hypertension, TB with DM, or DM and Hypertension in these groups? Also, is it your interest to review integrated management of TB and NCDs or are you also interested in reviewing integrated care of NCDs only, i.e., DM and Hypertension in your protocol?

The column of Context suggest specifying indicators for the program implementation process (input, process output, and outcome) and indicators at different levels of implementation (patient, institution, health system, region, district)

Would be good to see an annex with an exact list of inclusion and exclusion criteria.

Stage 3: study selection

Line 139: Figure1. Flow chart for the study selection is missing

Stage 4: Charting the data

Line 146 Table 4. Extraction Data Templates

Quantitative, Qualitative, Mixed Methods, etc. are study design examples and I suggest renaming the raw: Article type into study design or study type. Also, I suggest including research article, study protocols, Review, etc. in the separate raw named article type.

Stage 5: collating, summarizing, and reporting results

Line 151: specify what do you mean by study location, e.g., high income vs Low middle-income countries?

Stage 6: conducting consultation

Not sure what do you mean under the results will be consulted to the experts and relevant stakeholders. Do you mean focus group interviews with experts and relevant stakeholders? I understand that you plan to discuss the results and identify additional constructs and validate your findings from the article review? Please clarify how will you select experts and relevant stockholders? Will the discussion be structured facilitated as per the specially designed template? What questions do you plan to ask? How would you report the outcomes of the consultation?

Discussion

I suggest removing the discussion section. You can report about the limitations in your publication.

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Reviewer #1: No

Reviewer #2: Yes: Veriko Mirtskhulava

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22 Feb 2022

Thank you for the detailed and comprehensive suggestions from the reviewers, that have improved the quality of our manuscript. We have carefully considered your comments.

Here, we explain how we revised the paper based on the comments and recommendations. We have made major changes as follow:

1. We elaborate the methods and discussion section to improve clarity of the scoping review we plan to conduct, particularly on the expert/stakeholder consultation.

2. We provide point by point respond to the reviewers’ comments.

Please find attached in this submission, our detail changes, and clarifications.

Submitted filename: Rev2_Letter to Reviewer_Protocol_Widyaningsih, et al.docx

Click here for additional data file.

19 Apr 2022

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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Masoud Foroutan, Ph.D; Assistant Professor

Academic Editor

PLOS ONE

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Partly

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #2: No

**********

5. 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 #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: General comments:

1. To use abbreviations, you’ll first want to spell out the name or phrase, followed by the abbreviation in parentheses. Then, in any subsequent use of that name or phrase, only use the abbreviation.

Examples. In each case, you write out the full name and then introduce the abbreviation in parentheses: the word "tuberculosis (TB)" becomes the “TB” and the phrase “non-communicable disease (NCD)" becomes “NCD”.

2. Please make sure that the grammar and style used are for academic writing, please ask for assistance if needed.

3. Some of the sentences are in the past tense and some of them are in the future tense. My understanding is that since this is the study protocol, all sentences must be in the future tense, but I see that study according to this protocol has already been conducted. If that is so, I do not know what to recommend. Dear Editor, please provide guidance on that.

4. Study Protocols must also include the status and timeline of the study, including whether participant recruitment or data collection has begun where and when the data will be made available. See our Data Availability policy for more.

5. I would encourage you to remove the discussion section and use parts of it in the introduction and in the Materials and Methods.

6. Line 117, Table 1. Inclusion and exclusion criteria. The table is not clear enough. I have several questions/comments:

1. Did you include people with TB and hypertension?

2. Do you have age limitation for your study population?

3. I am not sure how this group (DM and hypertension) of the population addresses your research question; I understand your research questions are about the management of TB and NCDs (i.e., hypertension and DM); thus your population must have TB and at least one of the NCDs.

4. Do you exclude studies about people with TB only?

5. Do you exclude studies about all pregnant women, or the only the ones with gestational diabetes and/or preeclampsia/eclampsia?

Additional comments:

Abstract

Line 34-36, "This review will also 35 consider grey literature, including international disease management guidelines on tuberculosis, DM, and hypertension." Could you please specify what kind of gray literature other than clinical practice guidelines are you considering and what you mean by "international"? Do you mean WHO guidelines?

Lines 40-41, delete "will be synthesized"

Line 41, I suggest wording, the results will be used instead of could be used

Introduction

Line 63, please clarify what "previous study" you mean, as it is mentioned at the beginning of a new paragraph it is unclear what study you mean

Lines 95 -96, Could you please specify what kind of gray literature other than clinical practice guidelines are you considering and what you mean by "international"? Do you mean WHO guidelines? Do you consider the guidelines part of gray literature? I read from the text that you plan to review gray literature and international guidelines.

Stage 1: identifying the research question

Line 105, "… the management of any of hypertension, diabetes, and tuberculosis in any..", delete of any.

Line 112. correct spelling of "seatch"

Lines 114-115, "Hence, providing a review of literature for the past 15 years. Next, the title and abstract will be analyzed. " - something is missing, unclear to me, please clarify

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7. 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 #2: Yes: Veriko Mirtskhulava

[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.]

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6 May 2022

Thank you for your thorough review of our manuscript. We have revised and respond accordingly. Please find attached the revised version and the detailed description of the revisions. However, we have noticed that our first response to reviewer (RoR) is still available in addition to the second response to reviewer letter. We have tried several times to delete, but to no avail. Please refer to the RoR letter in the last section of the pdf

Submitted filename: Response to Reviewer_rev2.docx

Click here for additional data file.

29 Jun 2022

Potential and challenges for an integrated management of Tuberculosis, Diabetes Mellitus, and Hypertension: a scoping review protocol

PONE-D-21-26078R2

Dear Dr. Probandari,

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,

Masoud Foroutan, Ph.D; Assistant Professor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #2: Yes

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5. 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 #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I do not have any additional comments. Sorry for the delay in my response. It is an interesting study protocol.

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7. 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 #2: Yes: Veriko Mirtskhulava

**********

4 Jul 2022

PONE-D-21-26078R2

Potential and challenges for an integrated management of Tuberculosis, Diabetes Mellitus, and Hypertension: a scoping review protocol

Dear Dr. Probandari:

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. Masoud Foroutan

Academic Editor

PLOS ONE