Title: Loneliness and analgesic overuse among low-dose estrogen-progestin users in Japan
Version: 2 Date: 04 Feb 2025
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This study provides valuable insights into the relationship between
loneliness, analgesic use, and menstrual health among LEP users, highlighting important factors
associated with analgesic overuse. The discussion effectively connects key findings to existing
literature but lacks deeper exploration of potential mechanisms linking loneliness to increased
medication use. While the study acknowledges health literacy as a modifiable factor, it does
not clearly explain how improving it could reduce loneliness. The analysis of prophylactic
analgesic use raises concerns but does not differentiate between physician-guided and self-
medicated use, which limits the applicability of recommendations. The inclusion of frailty and
cold hypersensitivity introduces relevant health considerations, though their connection to the
main findings is not well integrated. Some recommendations, such as enhancing medication
follow-up, are practical but would benefit from more concrete implementation strategies. The
limitations section is thorough but introduces additional health factors without clearly linking
them to the study’s objectives. The conclusion effectively summarizes findings but could
better emphasize their clinical and public health significance. The study's strengths include
its novel focus and robust methodology, but self-reporting bias and selection bias should be
acknowledged more explicitly. Overall, this research is well-structured and informative, but a
more nuanced discussion of causality, clinical applications, and intervention strategies would
enhance its impact.
REQUESTED REVISIONS:
I recommend to take into account the following suggestions:
- Introduction: The introduction mentions the Three-Item Loneliness Scale (TIL) but does not
explain how it measures loneliness or why it is particularly relevant to this study. Providing
a brief explanation of its validity and application in previous research would strengthen the
argument for its use.
- Introduction: The transition between loneliness and analgesic use is abrupt, making it difficult
to understand the connection between these two topics. A clearer linkage between loneliness
and medication use, particularly analgesics, should be established to improve the logical flow.
- Introduction: The discussion of MOH includes statistics from Japan but lacks comparative
data from other countries, making it unclear how Japan's prevalence compares globally.
Adding global context would provide a better understanding of the significance of the reported
prevalence.
- Introduction: The reference to loneliness being associated with menstrual disorders is made
without a clear explanation of the underlying mechanism or supporting evidence. Including a
brief discussion of potential physiological or psychological pathways would help substantiate
this claim.
- Introduction: The paragraph on dysmenorrhea includes data on the prevalence of menstrual
pain but does not specify the severity levels or whether analgesic use differs by severity.
Providing more detail on this would add nuance to the discussion.
- Introduction: The introduction states that LEP can alleviate dysmenorrhea but then suggests
that patients on LEP may still require analgesics. This statement appears contradictory and
should be clarified by explaining whether LEP alone is insufficient for some women or if
adherence issues contribute to continued analgesic use.
- Introduction: The introduction suggests that frequent analgesic use may lead to more headaches
and lower quality of life, but no mechanism or supporting studies are cited. Providing references
or elaborating on how this occurs would strengthen the argument.
- Introduction: The statement that loneliness is more prevalent among certain demographic
groups lacks a clear citation or supporting data. Including references for this claim would
improve credibility.
- Methods: The study does not provide details on how participants were recruited beyond
being selected from a web panel, which raises concerns about selection bias. Clarifying how
randomization was performed and whether any stratification was applied would improve
transparency.
- Methods: The exclusion criteria mention healthcare professionals but do not specify why they
were excluded, even though their inclusion could provide valuable insights. Providing a rationale
for their exclusion would strengthen the justification.
- Methods: The survey instruments (HLS-14 and PSQI) are introduced with general descriptions
but lack justification for their inclusion in this specific study. Briefly explaining their relevance
to loneliness and analgesic use would enhance clarity.
- Methods: The LEP classification question lists multiple options but does not explain whether
participants could select multiple choices or if there were restrictions. Clarifying how LEP use
was categorized would help ensure accurate data interpretation.
- Methods: The statistical analysis section does not specify how missing data, if any, were
handled, which is crucial in survey-based research. Adding a statement on missing data
management would improve methodological rigor.
- Methods: The logistic regression model includes multiple explanatory variables, but there is
no mention of how multicollinearity was assessed. Addressing whether multicollinearity checks
were performed would strengthen the statistical approach.
- Methods: The study defines TIL #6 as an indicator of loneliness but does not justify why the
median of 5 was chosen as the cutoff. Providing a rationale for this decision or referencing prior
studies using similar cutoffs would improve validity.
- Methods: The description of statistical methods does not mention how model goodness-of-fit
was evaluated, such as through Hosmer-Lemeshow tests or AUC values. Including these details
would provide more confidence in the model’s robustness.
- Methods: The study states that logistic regression was performed for analgesic use #10 days per
month but does not specify whether potential confounders were adjusted for. Clarifying whether
adjustments were made would improve the reliability of the conclusions.
- Results: The introduction to the results section does not summarize key findings before
presenting tables and figures, making it harder to follow. Adding a brief introductory paragraph
outlining major findings would improve clarity.
- Results: The description of Table 2 does not indicate whether any comparisons were made
between different subgroups (e.g., age groups or symptom severity). Including statistical
comparisons would provide deeper insights into the data.
- Results: The definition of a "high TIL score" is not explicitly stated in the results section,
making it unclear what threshold was used. Clarifying the cutoff value would improve
interpretability.
- Results: The term "risk of sleep disorder" in the analysis of TIL scores is vague, as PSQI
measures sleep quality rather than explicitly diagnosing sleep disorders. Clarifying this phrasing
would make the interpretation more precise.
- Results: The text does not mention how missing data (if any) were handled in the statistical
analysis, which could impact the validity of findings. Including a statement on missing data
treatment would enhance methodological transparency.
- Discussion: The first paragraph introduces key findings but does not clearly establish their
significance in the broader context of healthcare. Adding a sentence explaining the clinical
implications of analgesic overuse and loneliness would enhance the introduction.
- Discussion: The discussion states that loneliness is associated with analgesic use but does
not explain potential mechanisms for this relationship. Including a brief discussion on why
loneliness might lead to increased analgesic use (e.g., psychological distress, lack of support)
would strengthen the interpretation.
- Discussion: The paragraph on health literacy suggests that improving health literacy could
reduce loneliness but does not explain the rationale behind this claim. Providing evidence or a
theoretical framework linking health literacy and loneliness would improve credibility.
- Discussion: The section on prophylactic analgesic use does not clarify whether overuse is
primarily due to lack of medical guidance or self-medication. Differentiating between physician-
guided and self-directed analgesic use would help inform recommendations for intervention.
- Discussion: The mention of frailty in the context of low back pain is abrupt and lacks sufficient
explanation. Adding a sentence explaining the relevance of frailty in this study population would
clarify the connection.
- Discussion: The limitations section introduces several additional factors (cold hypersensitivity,
dyspareunia, nutritional intake) without linking them directly to the study’s findings. Clarifying
how these factors might influence analgesic use or loneliness would improve cohesion.
- Discussion: The discussion suggests that menstrual symptoms and analgesic overuse are often
self-recorded together but does not explain why. Providing a hypothesis for this association (e.g.,
heightened symptom awareness) would add depth to the analysis.
- Discussion: The recommendation for counseling on prophylactic analgesic use lacks detail on
specific strategies. Including examples of how healthcare providers could improve medication
follow-up would make the recommendation more actionable.
- Discussion: The conclusion largely repeats the results without summarizing broader
implications. Adding a sentence on how these findings could inform clinical practice or future
research would improve the impact of the conclusion.
- Discussion: The study’s strengths are well stated, but the limitations section could be expanded
to address potential biases, such as self-reporting errors or selection bias. Acknowledging these
issues would enhance transparency.