Association Between Hypnotics and Dementia: A Mini Narrative Review.

OBJECTIVE: This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association. METHODS: Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs). RESULTS: The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings. CONCLUSION: The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.

Association between weekend catch-up sleep and the risk of prediabetes and diabetes: A cross-sectional study using KNHANES.

BACKGROUND: The objectives of this cross-sectional study were to explore the relationship between weekend catch-up sleep (WCUS) and the risk of prediabetes/diabetes and to assess how this risk varies based on WCUS duration, using a large population sample in South Korea. METHODS: Data were sourced from the 2021 Korea National Health and Nutrition Examination Survey, involving 2472 subjects aged 30 years and above, employed, and not using blood glucose-lowering medications. Prediabetes/diabetes risk was examined based on the presence of WCUS. Participants were categorized into four groups by WCUS duration (< 1, ≥ 1 and < 2, ≥ 2 and < 3, and ≥ 3 h) to evaluate the prediabetes/diabetes risk across varying WCUS durations. RESULTS: No significant difference in prediabetes/diabetes risk was observed between the WCUS and non-WCUS groups. In subgroup analysis, a WCUS duration of 1 to 2 h was related to a lower odds ratio of prediabetes (aOR = 0.618, 95% CI = 0.382-0.999), while 3 h or more was associated with a higher odds ratio of diabetes (aOR = 3.098, 95% CI = 1.561-6.149). CONCLUSIONS: In individuals who experience insufficient sleep during weekdays and manage to achieve the optimal average sleep duration of 1 to 2 h of WCUS, WCUS was associated with improved blood glucose regulation. However, compensating for excessive weekday sleep deprivation with WCUS of 3 h or more was associated with impaired blood glucose regulation.

Prolactin Level Changes according to Atypical Antipsychotics Use: A Study Based on Clinical Data Warehouse.

Objective: : Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia. This study aimed to investigate the levels of serum prolactin depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse (CDW). Methods: : We conducted a cohort search in the CDW application and got 260 patients' medical records diagnosed with schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders who were taking one of risperidone, blonanserin, amisulpride, and olanzapine. After that, we reviewed the medical data and used the ANCOVA analysis and the post hoc test to compare serum prolactin levels among four antipsychotic drug groups. Results: : Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.6 ± 54.6 ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between sex in the subjects who took amisulpride. Conclusion: : This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.

The Change of Suicidal Ideation Over a 12-Week Naturalistic Treatment of Depression: Comparison Between Young People and Older Adults.

OBJECTIVE: We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants. METHODS: A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13-24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups. RESULTS: At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group. CONCLUSION: These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

Community-based multi-site randomized controlled trial of behavioral activation for patients with negative symptoms of schizophrenia.

BACKGROUND: Negative symptoms are closely related to the poor prognosis of schizophrenia, for which there is no effective treatment to date. Behavioral activation (BA), which is an effective treatment for depression, is a behavioral approach that targets low levels of response-contingent positive reinforcement. This study aimed to explore BA as an effective intervention for relieving the negative symptoms of schizophrenia. METHODS: This was a randomized single-blind controlled trial. Eighty-four patients with schizophrenia were enrolled in community mental health settings. Excluding 14 patients who opted out of the study, 70 were randomly assigned to receive BA in addition to treatment-as-usual (BA + TAU) or treatment-as-usual (TAU) only. Negative symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and Brief Negative Symptom Scale (BNSS) at baseline, post-treatment, and 6-months follow-up. RESULTS: Significant differences between the BA + TAU and TAU only groups were observed in the measures of negative symptoms post-treatment. The total score of CAINS was significantly decreased after BA treatment (η2 = 0.13). The tendency of the BA + TAU treatment effect was also observed for the BNSS total score and PANSS negative symptom subscale (η2 = 0.10 and η2 = 0.11, respectively). However, the difference between the two groups was not sustained at the six-month follow-up. CONCLUSIONS: Our findings suggest that BA could be a promising time-limited and structured psychosocial intervention for schizophrenia-associated negative symptoms with the merit of easy dissemination. Further studies are needed to examine the factors involved in sustaining improvement.

Does panic disorder increase the risk of cardiovascular diseases in diabetics?: A nationwide population-based study.

BACKGROUND: Several studies have suggested a link between panic disorder (PD) and cardiovascular disease (CVD). However, the extent to which PD confers risk for CVD is still unclear, particularly in diabetics, a group showing high risk for CVD. METHODS: A nationwide population-based cohort of 1,624,718 patients with type 2 diabetes were selected from the National Health Screening Program database covering the years 2009 to 2012. The subjects were divided into two groups: those without panic disorder (non-PD group, n = 1,618,263) and those with newly diagnosed PD (PD-group, n = 6455). Follow-up of subjects for up to 10 years was conducted for evaluation of the incidences of myocardial infarction (MI), stroke, and death. RESULTS: After adjusting for the baseline covariates and diabetes mellitus (DM)-related variables, no difference in the future risk of MI and stroke was observed between the non-PD group and the PD group. Compared with the non-PD group, the PD group showed an increase in the future risk of death. [adjusted hazard ratio (aHR) = 1.120, 95 % confidence interval (CI): 1.039-1.206]. In contrast to the population aged <40 and > 65 years, in the age group of 40-64 years a significantly higher risk of stroke was observed in the PD group compared with the non-PD group (aHR = 1.352, 95%CI: 1.136-1.610). LIMITATION: The diagnoses were based on the diagnostic codes of the claim data. CONCLUSION: The current findings suggested that PD might not contribute to the risk of future MI and stroke in diabetics who have already been at risk of various cardiovascular complications.

Association Between Diabetic Retinopathy and Insomnia Risk: A Nationwide Population-Based Study.

Background: Previous studies have suggested a close link between sleep disturbances and diabetic retinopathy (DR). However, to date, no confirmatory findings have been reported. We aimed to explore the risk of insomnia in DR by considering demographic factors and diabetes mellitus (DM)-related variables. Methods: A nationwide population-based cohort of 2,206,619 patients with type 2 diabetes from the Korean National Insurance Service Database was followed up for insomnia incidence. DR, non-proliferative DR (NPDR), and proliferative DR (PDR) were defined according to ICD-10 codes. The interactive effects of sex, age, and DM-related variables were analyzed to evaluate their impact on insomnia risk in DR. Results: Compared with the non-DR group, insomnia risk was increased in the DR [(adjusted hazard ratio (aHR): 1.125, 95% confidence interval (CI):1.108-1.142), NPDR (aHR:1.117, 95% CI:1.099-1.134), and PDR (aHR:1.205, 95% CI: 1.156-1.256), even after controlling for comorbidities, lifestyle factors, and DM-related variables. The men and youngest age groups (<40 years) were most vulnerable to insomnia risk. Sex, age, DM duration, and chronic kidney disease (CKD) status exerted interactive effects with DR status in increasing the insomnia risk. In the PDR group, sex, age, DM duration, insulin therapy status, and CKD status exerted interactive effects that increased the risk of insomnia. Conclusion: Insomnia risk is significantly higher in patients with DR, and clinical attention is warranted.

Mediation Effect of the Coping Strategies on the Relation Between Stress and Sleep Quality.

OBJECTIVE: Recently data has been accumulated regarding the role of coping strategies in the relationship between stress and sleep quality. Therefore, we set out to identify the mediating effects of coping strategies between stress and sleep quality. METHODS: A online-based cross-sectional study was performed using the Perceived Stress Scale-10, the Pittsburgh Sleep Quality Index, and a simplification of the 60-item Coping Orientation to Problems Experienced (Brief COPE) inventory in the nonclinical adult sample. The 24 items of Brief COPE were categorized into four factors (social support, problem solving, avoidance, positive thinking). Then, we used the PROCESS macro to conduct the multiple mediation analysis for the four coping styles as potential mediators in the relationship between stress and sleep quality, and an additional subgroup analysis was examined to identify a gender difference for the mediation effect. RESULTS: As a group, four coping styles mediated significantly the association between perceived stress and poor sleep quality. And avoidance has maintained its significance thought all regression analyses. Finally, this results remained as same in the females. CONCLUSION: The effect of perceived stress on poor sleep quality was mediated by coping strategies, especially by avoidance. Thus, further research should consider the coping styles of individuals to reduce the influence of stress on sleep quality.

Suicide Risk in Patients With Diabetes Varies by the Duration of Diabetes: The Korea National Health and Nutrition Examination Survey (2019).

OBJECTIVE: The objectives of this study were to investigate the suicide risk in diabetes patients and evaluate the variations in suicide risk by the duration of diabetes using a large population sample in South Korea. METHODS: Data from 6,296 adults in the 2019 Korea National Health and Nutrition Examination Survey were included. The suicidal ideation, suicide plans, and suicidal behavior of diabetes patients were compared to the general population. After classifying the patients into ≤1 year, 2 to 9 years, and ≥10 years of diabetes duration, we evaluated the relationship between the duration of diabetes and the suicide risk. RESULTS: Diabetes patients had higher prevalences of suicidal ideation (9.1%, p<0.001) and suicide plans (3.6%, p<0.001) than the general population. After adjusting for potential confounding factors, suicide plans (adjusted odds ratio [aOR]=2.926, 95% confidence interval [CI]=1.325-6.463) were significantly associated with diabetes. In the 2 to 9 years group of diabetes patients, we found an increase in the risk of suicidal ideation (aOR=2.035, 95% CI=1.129-3.670), suicide plans (aOR=3.507, 95% CI=1.538-7.996), and suicidal behavior (aOR=7.130, 95% CI=2.035-24.978) after adjusting for the covariates. However, no increases in suicide risk were observed ≤1 year and ≥10 years after diabetes diagnosis. CONCLUSION: In adults, diabetes is associated with an increase in suicide risk. Suicide risk in diabetes patients showed an inverted U-shaped depending upon the duration of diabetes.

Community-Based Multi-Site Randomized Controlled Trial of Behavioral Activation for Patients with Depressive Disorders.

Behavioral activation (BA) is a beneficial and relatively cost-effective treatment option for depression. This study utilized a pragmatic randomized controlled research design to investigate whether BA, as compared with treatment as usual (TAU), led to superior treatment effects, when delivered in community mental health settings by retrained community mental health professionals. Patients with depressive disorders (n = 64) were randomly assigned to a 10-session BA (n = 31) or TAU (n = 33) group. The depressive symptoms and behavioral engagement were assessed at the baseline, post-treatment, and a six-month follow-up. Results showed that, as compared to the TAU group, the BA group had: (1) a reduction in depression severity, as evidenced by large effect sizes and greater response rates, and (2) an increase in behavioral engagement. However, the post-treatment gains were not maintained at the six-month follow-up. The implications and limitations of the study are also discussed (KCT0004098, June 27, 2019, retrospectively registered).

Differential characteristics of repeated polysomnography and multiple sleep latency test parameters in narcolepsy type 1 and type 2 patients: a longitudinal retrospective study.

PURPOSE: Narcolepsy is a chronic disorder and its phenotype is dichotomized into narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). The clinical course and pathophysiological mechanisms of these two clinical entities and their differences are not adequately defined. This study aimed to explore the differential longitudinal patterns of polysomnography (PSG) and multiple sleep latency test (MSLT) in NT1 and NT2. METHODS: In this retrospective study demographic characteristics, PSG, and MSLT parameters at baseline and follow-up were compared between NT1 and NT2 patients. Patients with both follow-up MSLT and PSG were selected for sub-group analysis. Baseline and follow-up MSLT and PSG parameters were compared. RESULTS: Of 55 patients with narcolepsy, mean follow-up periods were 7.4 ± 3.5 years for NT1 and 5.5 ± 2.9 for NT2. Demographic data showed increased body mass index and prevalence of sleep paralysis in NT1. Baseline PSG characteristics between NT1 and NT2 showed decreased sleep latency (p = 0.016) and REM latency (p = 0.046) in NT1 group when compared with NT2. Nocturnal SOREMP on PSG was more prevalent in NT1 (p = 0.017), and half of NT2 patients with nocturnal SOREMP on PSG changed their diagnoses to NT1. On follow-up PSG, NT1 displayed reductions in sleep stage N2 (p = 0.006) and N3 (p = 0.048), while wake after sleep onset (WASO) (p = 0.023) and apnea-hypopnea index (AHI) (p = 0.007) were significantly increased. CONCLUSION: Differential MSLT and PSG characteristics of NT1 and NT2 in at baseline and follow-up indicate that NT1 and NT2 are distinct disease phenotypes, and that they present with a contrasting course of disease.

Predictors of 1-year rehospitalization in inpatients with bipolar I disorder treated with atypical antipsychotics.

Bipolar disorder (BPD) is debilitating disorder, and patients can experience multiple relapses and subsequent hospitalizations. Since pharmacotherapy is the mainstay of treatment for patients with BPD, investigations on the effects of atypical antipsychotics (AAP) on reducing rehospitalization risk are crucial. The objective of study is to explore predictors of 1-year rehospitalization in patients with bipolar I disorder treated with AAP. A retrospective chart review on inpatients with bipolar I disorder was conducted. All participants were followed up for 1 year, and they were subdivided into three AAP treatment groups (olanzapine, risperidone, and quetiapine group). Kaplan-Meier survival analysis was implemented to detect time to rehospitalization due to any mood episodes within 1 year after discharge. Cox proportional regression model was adopted to find predictors of 1-year hospitalization in patients who experienced rehospitalization. One hundred thirty-eight participants were included in the study, and a 1-year rehospitalization rate was 18.1%. Time to rehospitalization did not differ between three AAP treatment groups. Predictors of rehospitalization due to any episode within 1 year were family history of depression and number of previous admission. Our findings can be conducive to understanding prognosis, and predicting rehospitalization risk in patients with BPD on AAP.

Anxiety and Depression of the Patients with Hematological Malignancies during Hospitalization for Hematopoietic Stem Cell Transplantation.

OBJECTIVE: This study aimed to assess the anxiety and depression in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Eighty-seven adult patients with various hematologic diseases, who were scheduled to receive autologous or allogeneic HSCT, were enrolled. The M.D. Anderson Symptom Inventory and the Hospital Anxiety Depression Scale were applied prospectively at hospital admission (D-14), on the day of transplantation (D day), and at 7 (D7) and 14 days (D14) after transplantation. RESULTS: The severity of both anxiety and depressive symptoms increased over time, with a peak at D7, and then showed a downturn at D14. Physical distresses also started with mild intensity at base line, which were continuously aggravated until D7, and then a partial recovery afterwards. Approximately, 52% of the participants had significantly high anxiety or depression before the start of HSCT. The occurrence of aggravation of pain, nausea, shortness of breath, and lack of appetite was associated with the development of anxiety during isolation period. The patients with significant baseline anxiety had higher scores on fatigue and shortness of breath items at D7 compared to those without. CONCLUSION: Our finding suggests the importance of psychiatric approaches, including preventive measures, for the patients undergoing HSCT.

Dimensional and compositional change of 1D chalcogen nanostructures leading to tunable localized surface plasmon resonances.

As part of the oxygen family, chalcogen (Se, Te) nanostructures have been considered important elements for various practical fields and further exploited to constitute metal chalcogenides for each targeted application. Here, we report a controlled synthesis of well-defined one-dimensional chalcogen nanostructures such as nanowries, nanorods, and nanotubes by controlling reduction reaction rate to fine-tune the dimension and composition of the products. Tunable optical properties (localized surface plasmon resonances) of these chalcogen nanostructures are observed depending on their morphological, dimensional, and compositional variation.

Ultrathin silver telluride nanowire films and gold nanosheet electrodes for a flexible resistive switching device.

We demonstrated a flexible resistive switching device based on ultrathin Ag2Te nanowire (NW) films and Au nanosheet (NS) electrodes by exploiting a monolayer assembly on the water surface for macroscale two-dimensional structures. Firstly, ultrathin TeNWs (diameter ≈ 10 nm) are rapidly assembled on the water surface as a form of monolayer and transferred to fabricate TeNW films on various substrates with any available size. An assembled TeNW film was used as a template to produce a Ag2TeNW film through chemical transformation. A well-aligned Ag2TeNW film device showed reversible resistive switching properties when the Ag composition of the silver telluride NW becomes stoichiometric Ag2Te. Additionally, a non-stoichiometric Ag2+δTeNW film shows an increased On/Off ratio. For a flexible memory device, ultrathin AuNSs (thickness ≤20 nm) were adopted as working electrodes, since thermally deposited gold electrodes tend to crack under strain, which can fail to maintain the electrical properties. A paper-like flexibility of AuNS proved its capability as optimal electrodes of ultrathin Ag2TeNW film-based resistive memory devices.

Erratum to "Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease".

[This corrects the article on p. 698 in vol. 14.].

A Longitudinal Follow-Up Study on Multiple Sleep Latency Test and Body Mass Index of Patients With Narcolepsy Type 1 in Korea.

STUDY OBJECTIVES: Narcolepsy is a chronic disorder with numerous adverse long-term consequences including increased obesity, high mortality rates, and decreased quality of life. With emerging attention to the long-term course of the disorder and importance of accurate diagnosis, the diagnostic stability of the Multiple Sleep Latency Test (MSLT)-the mostly frequently used test to identify narcolepsy-is often challenged. METHODS: In this study, we compared the baseline and follow-up demographic characteristics and body mass index (BMI) of patients with narcolepsy type 1. Moreover, MSLT results from repeated tests conducted on 48 patients with narcolepsy type 1 were compared, with mean follow-up of approximately 10 years. RESULTS: BMI from the baseline to the follow-up visit was significantly increased in the participants. There were no significantly different parameter changes in MSLT results. CONCLUSIONS: MSLT has good test-retest validity in patients with narcolepsy type 1. Close surveillance for the detection and management of obesity is warranted in clinical settings.

Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease.

Previous studies reported some relationships between donepezil treatment and hippocampus in Alzheimer's disease (AD). However, due to methodological limitations, their close relationships remain unclear. The aim of this study is to predict treatment response to donepezil by utilizing the automated segmentation of hippocampal subfields volumes (ASHS) in AD. Sixty four AD patients were prescribed with donepezil and were followed up for 24 weeks. Cognitive function was measured to assess whether there was a response from the donepezil treatment. ASHS was implemented on non-responder (NR) and responder (TR) groups, and receiver operator characteristic (ROC) analysis was conducted to evaluate the sensitivity, specificity, and accuracy of hippocampal subfields in predicting response to donepezil. The left total hippocampus and the CA1 area of the NR were significantly smaller than those of the TR group. The ROC curve analysis showed the left CA1 volumes showed highest area under curve (AUC) of 0.85 with a sensitivity of 88.0%, a specificity of 74.0% in predicting treatment response to donepezil treatment. We expect that hippocampal subfields volume measurements that predict treatment responses to current AD drugs will enable more evidence-based, individualized prescription of medications that will lead to more favorable treatment outcomes.

Visual Hallucinations and Amyloid Deposition in Parkinson's Disease Dementia: A Case Report.

Parkinson's disease dementia (PDD) is notorious for its debilitating clinical course and high mortality rates. Consequently, various attempts to investigate predictors of cognitive decline in Parkinson's disease (PD) have been made. Here we report a case of a 75-year-old female patient with PD who visited the clinic with complaints of recurrent visual hallucinations and cognitive decline, whose symptoms were ameliorated by the titration of rivastigmine. Imaging results showed pronounced diffuse cortical amyloid deposition evidenced by 18F-florbetaben amyloid positron emission tomography (PET) imaging. This observation suggests that pronounced amyloid deposition and visual hallucinations in PD patients could be clinically significant predictors of cognitive decline in PD patients. Future research should concentrate on accumulating more evidence for possible predictors of cognitive decline and their association with PD pathology that can enable an early intervention and standardized treatment in PDD patients.

Adjunctive Low-frequency Repetitive Transcranial Magnetic Stimulation over the Right Dorsolateral Prefrontal Cortex in Patients with Treatment-resistant Obsessive-compulsive Disorder: A Randomized Controlled Trial.

OBJECTIVE: The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. OBJECTIVE: The present study aimed to evaluate the efficacy of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC) for the treatment of obsessive-compulsive disorder (OCD). METHODS: Twenty-seven patients with treatment resistant OCD were randomly assigned to 3 week either active (n=14) or sham (n=13) rTMS. The active rTMS parameters consisted of 1 Hz, 20-minute trains (1,200 pulses/day) at 100% of the resting motor threshold (MT). OCD symptoms, mood, and anxiety were assessed at baseline and every week throughout the treatment period. RESULTS: A repeated-measures analysis of variance (ANOVA) was used to evaluate changes on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Our results revealed a significant reduction in YBOCS scores in the active group compared with the sham group after 3 weeks. Similarly, a repeated-measures ANOVA revealed significant effect of time and time×group interaction on scores on the Hamilton Depression Rating Scale and the Clinical Global Impression-Severity scale. There were no reports of any serious adverse effects following the active and sham rTMS treatments. CONCLUSION: LF rTMS over the right DLPFC appeared to be superior to sham rTMS for relieving OCD symptoms and depression in patients with treatment-resistant OCD. Further trials with larger sample sizes should be conducted to confirm the present findings.