Person:

Lin, Sheng-Hsuan

Background: On-call duty among medical interns is characterized by sleep deprivation and stressful working conditions, both of which alter cardiac autonomic modulation. We hypothesized that sleep stability decreased in medical interns during on-call duty. We used cardiopulmonary-coupling (CPC) analysis to test our hypothesis. Methods: We used electrocardiogram (ECG)-based CPC analysis to quantify physiological parameters of sleep stability in 13 medical interns during on-call and on-call duty-free periods. There were ten 33.5-h on-call duty shifts per month for interns, each followed by 2 on-call duty-free days, over 3 months. Measurements during sleep were collected before, during, and after an on-call shift. Measurements were repeated 3 months later during an on-call duty-free period. Results: The medical interns had significantly reduced stable sleep, and displayed increased latency to the first epoch of stable sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Interns also had significantly increased rapid-eye-movement (REM) sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Conclusion: Medical interns suffer disrupted sleep stability and continuity during on-call night shifts. The ECG-based CPC analysis provides a straightforward means to quantify sleep quality and stability in medical staff performing shift work under stressful conditions.

Background: Phantom vibration syndrome is a type of hallucination reported among mobile phone users in the general population. Another similar perception, phantom ringing syndrome, has not been previously described in the medical literature. Methods: A prospective longitudinal study of 74 medical interns (46 males, 28 females; mean age, 24.8±1.2 years) was conducted using repeated investigations of the prevalence and associated factors of phantom vibration and ringing. The accompanying symptoms of anxiety and depression were evaluated with the Beck Anxiety and Depression Inventories before the internship began, and again at the third, sixth, and twelfth internship months, and two weeks after the internship ended. Results: The baseline prevalence of phantom vibration was 78.1%, which increased to 95.9% and 93.2% in the third and sixth internship months. The prevalence returned to 80.8% at the twelfth month and decreased to 50.0% 2 weeks after the internship ended. The baseline prevalence of phantom ringing was 27.4%, which increased to 84.9%, 87.7%, and 86.3% in the third, sixth, and twelfth internship months, respectively. This returned to 54.2% two weeks after the internship ended. The anxiety and depression scores also increased during the internship, and returned to baseline two weeks after the internship. There was no significant correlation between phantom vibration/ringing and symptoms of anxiety or depression. The incidence of both phantom vibration and ringing syndromes significantly increased during the internship, and subsequent recovery. Conclusion: This study suggests that phantom vibration and ringing might be entities that are independent of anxiety or depression during evaluation of stress-associated experiences during medical internships.

Abstract To determine whether physicians with harm avoidance (HA) personality traits were more prone to developing increased anxiety and depression during the medical internship. A prospective longitudinal study of 74 medical interns was carried out using repeated measures of symptoms of anxiety and depression with the Beck Anxiety and Depression Inventories (BAI and BDI) before, at the 3rd, 6th, and 12th months during the internship, and 2 weeks after the internship was completed. Baseline personality was assessed by the Tridimensional Personality Questionnaire with 3 dimensions: novelty-seeking, HA, and reward dependence (RD). Levels of both depression and anxiety increased (6.4 and 3.4 on scores for BDI and BAI, respectively) during the internship and returned to baseline 2 weeks after it ended. HA scores were significantly correlated with depression and anxiety (0.3 scores on both the BDI and the BAI) and the scores for RD were significantly correlated with anxiety but not with depression. The interaction of HA and point in internship showed no significant differences. Internship plays a major role in the increase in depression and anxiety. A HA personality was also associated with the development of both depression and anxiety.

The assessment of direct and indirect effects with time-varying and multiple mediators is a common but challenging problem, and standard mediation analysis approaches are generally not applicable in this context. This dissertation focused on extending mediation analysis into a setting with time-varying and multiple mediators. An interventional approach has been used to define and identify the direct and indirect effects as well as path specific effects based in a causal inference framework, propose a parametric approach to estimate these effects, and provide an algorithm as well as corresponding software for practical application. In the first paper, we develop a parametric estimation approach to the mediational g-formula, including a feasible algorithm implemented in a freely available SAS macro. In the Framingham Heart Study data, we apply this method to estimate the interventional analogues of natural direct and indirect effects of smoking behaviors sustained over a 10-year period on blood pressure when considering weight change as a time-varying mediator. Compared with non-smoking, smoking 20 cigarettes per day for 10 years was estimated to increase blood pressure by 1.18 (95 % CI: -0.68, 2.69) mm-Hg. The direct effect was estimated to increase blood pressure by 1.52 (95 % CI: -0.25, 2.90) mm-Hg, and the indirect effect was -0.34 (95 % CI: -0.52, -0.13) mm-Hg, which is negative because smoking leads to lower weight which leads to lower blood pressure. These results provide evidence that weight change in fact partially conceals the detrimental effects of cigarette smoking on blood pressure. Our work represents the first application of the parametric mediational g-formula in an epidemiologic cohort study. The second paper proposes an approach to conduct mediation analysis for survival data with time-varying exposures, mediators, and confounders. We identify the direct and indirect effects through a survival mediational g-formula and provide the required assumptions. We also provide a feasible parametric approach along with an algorithm and software to estimate these effects. We apply this method to analyze the Framingham Heart Study data to investigate the causal mechanism of smoking on mortality. The risk ratio of smoking 30 cigarettes per day for ten years compared with no smoking on mortality is 2.34 (95 % CI = (1.44, 3.70)). Of the effect, 7.91 % is mediated by coronary artery disease. The survival mediational g-formula constitutes a powerful tool for conducting mediation analysis with longitudinal data. Finally, the third paper further proposes a method, defining a randomly interventional analogue of path-specific effect, which can always be non-parametrically identified under assumptions of no unmeasured confounding. This method also allows settings with mediators dependent on each other, interaction, and mediator-outcome confounders which are affected by exposure. In addition, under linearity and no-interaction, our method has the same form of traditional path analysis for path-specific effect. Furthermore, under a single mediator without a mediator-outcome confounder affected by exposure, it also has the same form of the results of causal mediation analysis. We also provide SAS code for settings of linear regression with exposure-mediator interaction and perform analysis in Framingham Heart Study dataset, investigating the mechanism of smoking on systolic blood pressure mediated by both cholesterol and body weight. Allowing decomposition of total effect into several analogues of path-specific effects, our method contributes to the investigation of complicated causal mechanisms in settings with multiple mediators.