( = 315 patients)
The remaining five high-alert medications were not administered during the study period: cyclosporine, phenytoin, amiodarone, vecuronium, and rocuronium
Analyzing each patient’s electronic documentation, we identified 20,150 pDDIs involving at least one HAM on the basis of our database search in UpToDate and drugs.com. We calculated a rate of 78.7 pDDIs per patient that involved at least one HAM (20,150 pDDI involving at least one HAM/256 patients receiving HAM). The 20,150 pDDIs resulted from 469 different drug pairs. Of these potentially interacting drug pairs, 14.3% (67/469) were administered on at least 2% of patient days. The frequency of the potentially interacting drug pairs and their classifications according to the databases is presented in Online Resource 3.
We observed at least one symptom after 14.0% (2830/20,150) of pDDIs, resulting in a total of 3203 observed symptoms affecting 56.3% (144/256) of patients receiving HAM (Table 4 ). While we observed one symptom after the administration of 87.7% (2482/2830) of those pDDIs, more than one symptom was observed after 12.3% (348/2830) of pDDIs.
Frequency of symptoms observed after potential drug–drug interactions involving high-alert medications
Symptom | Frequency of symptoms, | Frequency related to total of symptoms, % ( = 3203) | Frequency of patients affected by the respective symptom after a pDDI involving HAM, (%) ( = 256 patients receiving HAM) |
---|---|---|---|
Increased heart rate | 781 | 24.4 | 62 (24.2) |
Hyponatremia | 390 | 12.2 | 52 (20.3) |
Vomiting | 262 | 8.2 | 41 (16.0) |
Hypokalemia | 243 | 7.6 | 18 (7.0) |
Decreased blood pressure | 237 | 7.4 | 28 (10.9) |
Respiratory depression | 164 | 5.1 | 24 (9.4) |
Urinary retention | 137 | 4.3 | 29 (11.3) |
Hyperkalemia | 131 | 4.1 | 43 (16.8) |
Edema | 128 | 4.0 | 13 (5.1) |
Nausea | 119 | 3.7 | 24 (9.4) |
Agitation | 118 | 3.7 | 21 (8.2) |
Decreased diuresis | 112 | 3.5 | 23 (9.0) |
Decreased heart rate | 96 | 3.0 | 10 (3.9) |
Hypomagnesemia | 57 | 1.8 | 14 (5.5) |
Sweating | 46 | 1.4 | 9 (3.5) |
Hypocalcemia | 43 | 1.3 | 12 (4.7) |
Increased blood pressure | 43 | 1.3 | 12 (4.7) |
Fever | 19 | 0.6 | 12 (4.7) |
Dyspnea | 14 | 0.4 | 7 (2.7) |
Seizures | 14 | 0.4 | 5 (2.0) |
Constipation | 10 | 0.3 | 4 (1.6) |
Diarrhea | 9 | 0.3 | 2 (0.8) |
Dizziness | 8 | 0.2 | 3 (1.2) |
Abdominal pain | 5 | 0.2 | 3 (1.2) |
Sedation | 4 | 0.1 | 1 (0.4) |
Excessive diuresis | 3 | 0.1 | 2 (0.8) |
Hypercalcemia | 3 | 0.1 | 2 (0.8) |
Increased PTH | 3 | 0.1 | 1 (0.4) |
Exanthema | 2 | 0.1 | 2 (0.8) |
Tachypnea | 2 | 0.1 | 2 (0.8) |
HAM high-alert medication, pDDI potential drug–drug interaction, PTH parathyroid hormone
The most pDDIs after which we observed at least one symptom involved potassium salts (2.4%; 493/20,150), followed closely by digoxin (2.4%; 480/20,150) and fentanyl (2.4%; 476/20,150; Fig. Fig.2 2 ).
For each high-alert medication, the number of potential drug–drug interactions (total interactions: N = 20,150) is plotted against how often at least one symptom was observed after a potential drug–drug interaction involving the respective high-alert medication (total interactions followed by symptoms: N = 2830)
For 33.1% (1061/3203) of observed symptoms, the preconditions for the calculation of the OR were fulfilled (Table (Table5). 5 ). We found an increased OR for hyponatremia, hypokalemia, decreased blood pressure, increased heart rate, urinary retention, edema, sweating, and restlessness (each p ≤ 0.05; Table Table5). 5 ). Those eight specific symptoms accounted for 28.0% (897/3203) of all observed symptoms potentially related to DDI. These DDIs involved eight different drugs in eight different combinations. Of the eight drugs, 75% (6/8) were defined as HAM for pediatric patients: digoxin, fentanyl, midazolam, phenobarbital, potassium salts, and vancomycin. The remaining 25% (2/8) were diuretics not defined as HAM: furosemide and hydrochlorothiazide. The highest OR was found for decreased blood pressure observed after administration of the drug pair fentanyl and furosemide (OR 5.06; 95% CI 3.5–7.4; p < 0.001), followed by hypokalemia observed after administration of the drug pairs digoxin and furosemide (OR 4.16; 95% CI 3.1–5.6; p < 0.001) and digoxin and hydrochlorothiazide (OR 3.86; 95% CI 2.9–5.1; p < 0.001).
Drug–drug interactions involving high-alert medications and subsequent symptoms observed within 24 h after the administration of the respective drug–drug interaction
pDDI | Classification | Associated symptom | Patient days with/without pDDI and symptom, | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Drug 1 | Drug 2 | UpToDate | drugs.com | pDDI | Yes | Yes | No | No | Odds ratio [95% CI] | value | |
Symptom | Yes | No | Yes | No | |||||||
Potassium salts | Furosemide | B | n/a | Hyponatremia | 163 | 667 | 341 | 2617 | 1.88 [1.5; 2.3] | < 0.001* | |
Fentanyl | Furosemide | C | Moderate | Decreased blood pressure | 43 | 275 | 104 | 3366 | 5.06 [3.5; 7.4] | < 0.001* | |
Urinary retention | 86 | 232 | 541 | 2929 | 2.01 [1.5; 2.6] | < 0.001* | |||||
Increased heart rate | 76 | 242 | 521 | 2949 | 1.78 [1.3; 2.3] | < 0.001* | |||||
Vancomycin | Furosemide | n/a | Moderate | Edema | 83 | 150 | 490 | 3065 | 3.46 [2.6; 4.6] | < 0.001* | |
Decreased diuresis | 42 | 191 | 575 | 2980 | 1.14 [0.8; 1.6] | 0.459 | |||||
Vomiting | 36 | 197 | 502 | 3053 | 1.11 [0.8; 1.6] | 0.573 | |||||
Digoxin | Furosemide | n/a | Moderate | Hypokalemia | 89 | 134 | 523 | 3042 | 3.86 [2.9; 5.1] | < 0.001* | |
Nausea | 10 | 213 | 177 | 3388 | 0.90 [0.5; 1.7] | 0.748 | |||||
Increased heart rate | 35 | 188 | 562 | 3003 | 0.99 [0.7; 1.4] | 0.978 | |||||
Hypomagnesemia | 12 | 211 | 238 | 3327 | 0.80 [0.4; 1.4] | 0.451 | |||||
Digoxin | HCT | n/a | Moderate | Hypokalemia | 86 | 120 | 526 | 3056 | 4.16 [3.1; 5.6] | < 0.001* | |
Increased heart rate | 29 | 177 | 568 | 3014 | 0.87 [0.6; 1.3] | 0.496 | |||||
Fentanyl | Phenobarbital | D | Major | Restlessness | 80 | 59 | 961 | 2688 | 3.79 [2.7; 5.4] | < 0.001* | |
Sweating | 30 | 109 | 480 | 3169 | 1.82 [1.2; 2.8] | 0.005* | |||||
Potassium salts | HCT | B | n/a | Hyponatremia | 85 | 229 | 419 | 3055 | 2.71 [2.1; 3.5] | < 0.001* | |
Midazolam | HCT | n/a | Moderate | Decreased blood pressure | 20 | 168 | 127 | 3473 | 3.26 [2.0; 5.3] | < 0.001* | |
Increased heart rate | 56 | 132 | 541 | 3059 | 2.40 [1.7; 3.3] | < 0.001* |
For each drug combination and observed symptom, the frequencies of patient days on which the respective potential drug–drug interaction was or was not administered and whether the symptom was observed is shown. From those numbers, the odds ratios, 95% confidence intervals, and p -values were calculated using a univariate logistic regression
HCT hydrochlorothiazide, n/a not applicable (not listed in the respective database), pDDI potential drug–drug interaction
*Significant
a Categorized as high-alert medication for hospitalized pediatric patients according to Schilling et al. [ 6 ]
b Classification used in UpToDate: “D—Consider therapy modification; C—Monitor therapy; B—No action needed. Agents may interact with each other”
c Classification used in Drugs.com: “Major—Avoid combinations; Moderate—Usually avoid combination. Use it only under special circumstances; Minor—Take steps to circumvent the interaction risk and/or establish a monitoring plan”
According to the ISMP, HAMs carry a higher risk of patient harm compared with ordinary drugs [ 7 ]. Even when used as prescribed, they significantly increase the risk of drug-related problems [ 11 ]. In our study, 81% of critically ill children received at least one drug defined as HAM for pediatric patients by Schilling et al. [ 6 ]. Potassium salts, midazolam, and vancomycin were the HAMs most frequently administered. This is in line with a previous study in a pediatric emergency setting reporting that 91% of patients were prescribed at least one HAM, with potassium salts being the most frequently administered [ 12 ].
It is widely known that pDDIs are highly prevalent in PICUs. They are associated with various factors, such as a high number of administered drugs, a complex chronic condition, or an increased length of hospitalization [ 4 , 13 , 14 ]. Although previous studies determined pDDI as a cause of drug-related problems with HAM for pediatric patients, there is only limited knowledge about the frequency of pDDIs in pediatric intensive care [ 6 , 8 , 10 ]. In our study, we found more than 20,000 pDDIs involving HAM in 256 pediatric patients over the 1-year study period. A previous Brazilian study of adult intensive care patients reported 846 HAM-related pDDIs in 60 patients [ 15 ]. Compared with our research, the Brazilian study reported a considerably lower rate of HAM-related pDDIs per patient (79 versus 14). Part of this difference may be explained by the fact that pediatric patients requiring intensive care are more susceptible to drug–drug interactions [ 16 ]. However, it may also be related to the fact that the Brazilian study was performed on the basis of the database Micromedex 2.0 only [ 15 ]. Several studies recommended using at least two databases to determine pDDIs in daily routine [ 17 – 19 ] . Thus, we used the two databases, UpToDate and drugs.com, to avoid underestimating any potential risks. However, since the concordance between different databases is limited, comparing various studies can be challenging [ 20 , 21 ].
For 2830 pDDIs, we observed 3203 symptoms occurring after the administration of the potentially interacting drug pairs. More than one in four detected symptoms were eventually associated with a DDI. Those interaction-associated symptoms comprised eight specific symptoms, mainly hemodynamic alterations or electrolyte and fluid balance disturbances. These symptoms were frequently reported in previous pediatric intensive care studies [ 3 , 22 – 24 ]. The study presented here shows that DDI involving HAM should be considered a likely trigger for symptoms in addition to other factors, such as the underlying disease or non-drug treatments, such as surgeries. It can also be assumed that various factors contribute to the occurrence of a symptom. When identifying DDIs and following interaction-associated symptoms, we did not distinguish between different severity grades of DDI or symptoms, as the main aim of our study was to identify drug pairs that are frequently associated with symptoms that are considered clinically relevant by the responsible physicians and nurses. Physicians usually receive a considerable number of alerts when using a database-related interaction checker. This may quickly lead to over-alerting. Therefore, we aimed to provide physicians with a concise overview of clinically relevant DDIs that occur frequently in a PICU. Our findings could be implemented in commonly used database-related interaction checkers to draw physicians’ attention to drug pairs involving HAM that are potentially associated with an increased risk of adverse events.
We identified eight specific drug pairs composed of eight different drugs that may lead to an increased risk of interaction-associated symptoms. By calculating the OR for a DDI and a respective symptom, we took into account how often a symptom was observed on patient days when the interacting drug pair was administered compared with days when the respective drug pair was not administered. In particular, this should minimize the risk that certain combinations of DDI and symptoms are over- or underestimated. For the interaction of fentanyl and furosemide, we found the highest OR for the symptom of decreased blood pressure. Both drugs have been shown to belong to the top ten of the most frequently administered drugs and to be among the drugs most commonly involved in pDDIs in the pediatric intensive care setting [ 4 ]. In our study, DDI was associated with a potential fivefold increased risk of decreased blood pressure. The second highest OR, indicating a potential fourfold increased risk, was found for the interaction of digoxin with hydrochlorothiazide and the observed symptom of hypokalemia. Consequently, when the administration of drug pairs associated with a potentially increased risk of interaction-associated symptoms is unavoidable, patients should be closely monitored for potential symptoms.
Until now, few studies have dealt with interaction-associated symptoms in the pediatric intensive care setting [ 14 , 25 , 26 ]. One of those studies only focused on cytochrome P450-mediated drug–drug interactions [ 25 ]. Two other studies concentrated on symptoms on the basis of clinical monitoring and laboratory results, as we did in our research. Both studies also identified hemodynamic alterations and electrolyte and fluid balance disturbances as symptoms following DDIs. However, neither of those studies noted specific interactions that increased the risk of the detected symptoms [ 14 , 26 ]. Our study went one step further by revealing eight interacting drug pairs that may increase the risk of the identified interaction-associated symptoms in clinical practice. We found symptoms that are widely known to follow the respective DDI, such as the association of hyponatremia with the DDI of potassium salts and furosemide, or the increased risk for hypokalemia associated with the DDI of digoxin and furosemide. However, we also observed symptoms after a DDI that we did not expect. For example, we unexpectedly found that the DDI of fentanyl and furosemide was associated with a potential risk increase for urinary retention, or that the DDI of vancomycin and furosemide was associated with edema. Especially for symptoms that unexpectedly are observed after a specific DDI, other factors, such as the state of illness or a surgery that could also lead to the symptom, should be critically evaluated.
Some limitations have to be considered when interpreting our study results. First of all, the relevance of some drugs administered in our study can vary in different PICUs around the world. However, the 15 drugs defined as HAM that were in the focus of our study are used in many PICUs worldwide [ 4 , 27 – 31 ].
As recommended by previous studies [ 17 – 19 ], we used two databases to prevent failure to detect interactions that could lead to interaction-associated symptoms. However, we could not identify a database specializing in DDI for pediatrics. Previous studies did not find an age-related trend in the magnitude of DDIs, although it should be noted that there are insufficient data for children under 2 years of age [ 32 , 33 ]. In addition, extrapolating data from adults to children may over- or underestimate the severity of DDIs [ 34 ]. Additionally, as most databases are limited to the information on the interactions of two drugs, potential synergistic or antagonistic effects of combinations consisting of three or more drugs might be overlooked.
Furthermore, the allowed maximum time interval of 24 h between the administration of two drugs may be too long for an interaction for some drug pairs. According to a previous review by Bakker et al., the optimal time interval would consider the half-lives of interacting drugs [ 21 ]. However, due to the developmental variability of pharmacokinetics and pharmacodynamics in children, it is very challenging to determine standardized drug half-lives in the pediatric population [ 35 ]. In addition, the individual patients’ conditions, such as renal function, can also have significant influence on drugs’ half-lives [ 36 ]. In addition, a constant plasma concentration is aimed for with many drugs, which is why a longer-lasting interaction potential can be assumed, although the half-lives of the individual drugs are varying. To ensure a standardized approach for evaluating DDI, we established a 24-h time interval as described in the review by Bakker et al. if consideration of drug half-lives is not feasible [ 21 ]. This methodological approach might potentially increase the risk of overestimation.
The retrospective design is another limitation of this study, as using nurses’ and physicians’ daily documentation entails the risk of missing data. That could lead to information bias, as the documentation was not primarily compiled to answer research questions. Consequently, using the patient documentation as data basis may have an impact on the identification of symptoms themselves, and on the observed associations between interacting drugs pairs and subsequent symptoms. Furthermore, due to the retrospective design, we could not assess whether the physicians accepted certain expectable symptoms as an inevitable consequence of the chosen drug therapy because the patient’s state of health required the administration.
In addition, it should be kept in mind that the administration of a HAM alone and the underlying disease may also increase the risk of adverse events. However, we focused on acknowledged DDIs and interaction-associated symptoms reported in established databases. We endeavored to identify symptoms prone to being associated with a DDI by calculating ORs, as those interactions potentially contribute to evoking symptoms, or to prolonging or exacerbating existing symptoms. These drug combinations should therefore be given special consideration in the routine care of critically ill pediatric patients who are already at risk.
Our study sheds light on a topic about which knowledge is limited: symptoms associated with DDIs involving HAM. We showed that pDDIs involving HAM are very common in pediatric intensive care. More than one in four observed symptoms were associated with a DDI. These symptoms were mainly disturbances of electrolyte and fluid balance and hemodynamic alterations. Focusing on drug pairs with a potentially increased risk of triggering these symptoms, we identified eight specific drug pairs composed of eight different drugs. However, administration of these drug pairs may be unavoidable. In that case, patients should be carefully monitored for electrolyte and fluid balance disturbances and hemodynamic alterations, which were observed as the most frequent interaction-associated symptoms.
Below is the link to the electronic supplementary material.
We thank all the physicians and nurses in the participating PICU for their helpful collaboration.
Open Access funding enabled and organized by Projekt DEAL.
A. Bertsche reports grants from UCB Pharma GmbH and honoraria for speaking engagements from Biogen GmbH, Desitin Arzneimittel GmbH, Eisai GmbH, GW Pharma GmbH, Neuraxpharm GmbH, Shire/Takeda GmbH, UCB Pharma GmbH, and ViroPharma GmbH. The other authors declare they have no conflicts of interests.
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to ethical and privacy considerations to protect the confidentiality of patients.
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Medical Faculty, Leipzig University, Germany (127/19-ek). The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.
As this was a retrospective study and data were collected from patient records without any influence on patients’ treatment, the ethics committee waived informed consent.
Not applicable.
Conceptualization: Lisa Marie Kiesel and Martina Patrizia Neininger; methodology: Lisa Marie Kiesel, Martina Patrizia Neininger, Astrid Bertsche, Thilo Bertsche, Manuela Siekmeyer, and Wieland Kiess; formal analysis: Lisa Marie Kiesel; investigation: Lisa Marie Kiesel and Martina Patrizia Neininger; writing—original draft preparation: Lisa Marie Kiesel and Martina Patrizia Neininger; writing—review and editing: Astrid Bertsche, Thilo Bertsche, Manuela Siekmeyer, and Wieland Kiess; supervision: Martina Patrizia Neininger; project administration: Lisa Marie Kiesel and Martina Patrizia Neininger. All authors read and approved the final version.
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Writing a Research Paper Conclusion | Step-by-Step Guide
How to Write the Conclusion in Research Papers ...
A research paper conclusion is the final section of a research paper that summarizes the key findings, significance, and implications of the research. It is the writer's opportunity to synthesize the information presented in the paper, draw conclusions, and make recommendations for future research or actions. ...
6 Conciseness. Above all, every research paper conclusion should be written with conciseness. In general, conclusions should be short, so keep an eye on your word count as you write and aim to be as succinct as possible. You can expound on your topic in the body of your paper, but the conclusion is more for summarizing and recapping.
The conclusion is intended to help the reader understand why your research should matter to them after they have finished reading the paper. A conclusion is not merely a summary of the main topics covered or a re-statement of your research problem, but a synthesis of key points derived from the findings of your study and, if applicable based on your analysis, explain new areas for future research.
Begin your conclusion by restating your thesis statement in a way that is slightly different from the wording used in the introduction. Avoid presenting new information or evidence in your conclusion. Just summarize the main points and arguments of your essay and keep this part as concise as possible. Remember that you've already covered the ...
Highlight the "so what". At the beginning of your paper, you explain to your readers what's at stake—why they should care about the argument you're making. In your conclusion, you can bring readers back to those stakes by reminding them why your argument is important in the first place. You can also draft a few sentences that put ...
Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and ...
Step 1: Restate the problem. Always begin by restating the research problem in the conclusion of a research paper. This serves to remind the reader of your hypothesis and refresh them on the main point of the paper. When restating the problem, take care to avoid using exactly the same words you employed earlier in the paper.
Step 2: Summarize and reflect on your research. Step 3: Make future recommendations. Step 4: Emphasize your contributions to your field. Step 5: Wrap up your thesis or dissertation. Full conclusion example. Conclusion checklist. Other interesting articles. Frequently asked questions about conclusion sections.
The conclusion of a research paper is essential in tying together the different parts of the paper and offering a final perspective on the topic. It reinforces the main idea or argument presented and summarizes the key points and findings of the research, highlighting its significance. Additionally, the conclusion creates a full circle of the ...
In summary, (summarize your findings). Looking ahead, it is obvious that (propose the next action or an alternative idea). My conclusion is (restate your thesis with greater emphasis). One last word must be said. (Follow with your opinion and propose a next action.) One concludes that (give your opinion).
A well-written conclusion can leave the reader satisfied and inspired, while a poorly executed one may undermine the credibility of the entire paper. Therefore, it is essential to give careful thought and attention to crafting an effective conclusion. When writing a research paper, the conclusion acts as the final destination for the reader.
Summarize the findings/argument. Your research paper conclusion should also revisit the evidence, findings, and limitations of your research, but as an overview, not in detail. State only the most important points, what they mean, and how they illustrate the main idea you want the reader to take away. 3. Look toward the future.
The point of a conclusion to a research paper is to summarize your argument for the reader and, perhaps, to call the reader to action if needed. 5. Make a call to action when appropriate. If and when needed, you can state to your readers that there is a need for further research on your paper's topic.
The conclusion is where you describe the consequences of your arguments by justifying to your readers why your arguments matter (Hamilton College, 2014). Derntl (2014) also describes conclusion as the counterpart of the introduction. Using the Hourglass Model (Swales, 1993) as a visual reference, Derntl describes conclusion as the part of the ...
Offer a solution or suggestion for future research. To successfully conclude a research paper, it is important to apply certain tricks and advice from experts. Future research should focus on understanding the ways in which a good conclusion can be written so as to add value to the overall paper. Discussions could focus on elements that are ...
Crafting an effective conclusion in research paper requires thoughtful consideration and deliberate effort. After presenting your findings and analysis, the conclusion allows you to close your work with a flourish. Begin by briefly summarizing the main points of your paper, provide a quick recap of your thesis, methodology, and key findings ...
The conclusion of a research paper has several key objectives. It should: Restate your research problem addressed in the introduction section. Summarize your main arguments, important findings, and broader implications. Synthesize key takeaways from your study. The specific content in the conclusion depends on whether your paper presents the ...
Step 7: End with a Strong Closing Statement: Conclude your research paper with a memorable closing statement. This could be a thought-provoking reflection, a call to action, or a suggestion for future research. A strong closing leaves a lasting impression on your readers and emphasizes the importance of your work.
Tips for writing a conclusion. 1. Don't include new data or evidence. Your conclusion should provide closure to your paper, so introducing new information is not appropriate and will likely confuse your reader. 2. Don't simply restate your thesis. You should never simply copy and paste your thesis statement into your conclusion.
A conclusion is the final paragraph of a research paper and serves to help the reader understand why your research should matter to them. The conclusion of a conclusion should: Restate your topic and why it is important. Restate your thesis/claim. Address opposing viewpoints and explain why readers should align with your position.
Follow the steps below for how to write a research paper conclusion. Open With The Research Topic. To begin a conclusion paragraph, use the first sentence to reiterate the comprehensive subject matter that your paper covered. Since this is just a sentence-long retelling of your research topic and why it's important, it doesn't have to be ...
Review paper format usually includes the citation list - it is your nod to the scholarly community, acknowledging the contributions of others. Each citation is a thread in the larger tapestry of academic discourse, enabling readers to delve deeper into the research that has shaped your review.
This study aimed to analyze articles published in the Web of Science database from 2012 to 2021 to examine the educational goals and instructional designs for STEM education. We selected articles based on the following criteria: (a) empirical research; (b) incorporating instructional design and strategies into STEM teaching; (c) including intervention; (d) focusing on K-12 education and on ...
Conclusions. In a cohort of PICU patients, this study identified eight specific drug pairs involving high-alert medications that may increase the risk of interaction-associated symptoms, mainly hemodynamic alterations and electrolyte/fluid balance disturbances. ... Compared with our research, the Brazilian study reported a considerably lower ...
We use cross-sectional data from the Global Early Adolescent Study in São Paulo, Brazil, among 10- to 14-year-old girls who have experienced menarche (n = 325) and completed a home-based self-administered questionnaire in 2021."Attitudes toward menstruation" was created based on five indicators on a Likert scale, with a higher score indicating more positive attitudes.