Guanfacine, used as a medication for attention-deficit/hyperactivity disorder (ADHD), leads to a high incidence of somnolence, in contrast to methylphenidate, which leads to a high incidence of ...insomnia. The impact of somnolence on continuing guanfacine treatment is unclear. Therefore, we investigated the reasons for discontinuing guanfacine and analyzed the factors associated with discontinuation caused by somnolence. We surveyed 96 patients under guanfacine from July 2017 to December 2021 at the Saga University Hospital. Patients who discontinued guanfacine by the end date of our study were divided into a median early and late group. We compared the reasons for discontinuation in both groups. Of all patients, 47 continued and 49 discontinued guanfacine. A higher percentage of patients discontinued guanfacine caused by somnolence for ≤70 d than for >70 d of treatment (44.0 vs. 8.3%; p = 0.008). When stratified by the concomitant use of other ADHD drugs, somnolence resulted in a higher discontinuation rate for ≤70 d than for >70 d of treatment without concomitant use (55.0 vs. 7.1%; p = 0.009). Nonetheless, concomitant use resulted in no difference. In conclusion, somnolence affects the early discontinuation of guanfacine as an ADHD drug. The combination of methylphenidate or atomoxetine may decrease withdrawal caused by somnolence.
In this study, an HPLC analysis method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) was developed for the determination of o-phosphoethanolamine (PEA), ...which is a potential biomarker for the diagnosis of major depressive disorder, in human plasma sample. After PEA was derivatized with AQC under mild conditions, the obtained derivative was subjected to purification with a titanium dioxide-modified monolithic silica spin column (MonoSpin® TiO). The eluate from the MonoSpin® TiO was directly injected into an amide-type hydrophilic interaction liquid chromatography (HILIC) column-equipped HPLC system, and the resulting derivative could be separated on the column under alkaline mobile phase conditions and subsequently detected fluorometrically at excitation and emission wavelengths of 250 and 395 nm, respectively. The limit of detection and limit of quantification for a 10 µL injection volume of PEA were 0.052 and 0.17 µM, respectively. The method was validated at 0.2, 1.0, and 5.0 nmol/mL levels in plasma sample, and the precision values were 2.0–6.6% as relative standard deviation and the correlation coefficient (r) of the calibration curve was 0.9995. Furthermore, applicability of this method was demonstrated by analyzing PEA levels in plasma samples from mental illness patients.
Background: Selection of test-negative controls takes less time and costs less than traditional control selection for evaluating vaccine effectiveness (VE). Here, rotavirus VE was evaluated using ...hospital controls and compared with test-negative controls to determine whether using the latter can substitute for the former. Methods: We recorded gastroenteritis in children from 2 months to 2 years of age at six medical facilities in Saga City between January 4th and May 31st, 2014. Stools from all identified acute gastroenteritis patients were tested for rotavirus using immunochromatography. Rotavirus gastroenteritis (RVGE) cases had test-positive stool, whereas test-negative controls had gastroenteritis but no rotavirus infection; hospital controls were outpatients visiting the same facility for indications other than gastroenteritis. Vaccination status was verified by inspecting maternal and child health records, and demographic data were obtained from a questionnaire completed by the patients’ guardians or from the medical records. Unconditional logistic regression analysis was used to adjust for possible confounding factors. Results: Sixty-four RVGE cases, 260 test-negative controls, and 589 hospital controls were enrolled. The characteristics of the two control groups, including RV vaccination history, were similar. The RVGE cases were more likely to have used daycare services than children from either of the two control groups. The VE against RVGE estimated using hospital controls was 86.6% (95% confidence interval CI, 55.9–96.0%), very similar to the VE using test-negative controls (84.9% 95% CI, 49.6–95.5%). Conclusions: The estimated VE using test-negative controls and hospital controls is similar. Therefore, test-negative controls are considered appropriate for establishing VE.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
ObjectivesThe purpose of this study was to compile the currently available evidence on the clinical characteristics of the locomotive syndrome (LS) categorised by the 25-question Geriatric Locomotive ...Function Scale (GLFS-25) and clarify its clinical usefulness for assessing mobility function.DesignSystematic review.Data sourcesThe PubMed and Google Scholar were searched for the relevant studies on 20 March 2022.Eligibility criteriaWe included relevant peer-reviewed articles, available in English language, on clinical LS characteristics categorised with the GLFS-25.Data extraction and synthesisPooled ORs or mean differences (MDs) of the LS groups were calculated and compared with the non-LS groups for each clinical characteristic.ResultsIn total, 27 studies that involve 13 281 participants (LS, n=3385; non-LS, n=9896) were examined in this analysis. Older age (MD 4.71; 95% (CI) 3.97 to 5.44; p<0.00001), female gender (OR 1.54; 95% CI 1.38 to 1.71; p<0.00001), higher body mass index (MD 0.78; 95% CI 0.57 to 0.99; p<0.00001), osteoporosis (OR 1.68; 95% CI 1.32 to 2.13; p<0.0001), depression (OR 3.14; 95% CI 1.81 to 5.44; p<0.0001), lower lumbar lordosis angle (MD −7.91; 95% CI −10.08 to −5.74; p<0.00001), higher spinal inclination angle (MD 2.70; 95% CI 1.76 to 3.65; p<0.00001), lower grip strength (MD −4.04; 95% CI −5.25 to −2.83; p<0.00001), lower back muscle strength (MD −15.32; 95% CI −23.83 to −6.81; p=0.0004), lower maximum stride (MD −19.36; 95% CI −23.25 to −15.47; p<0.00001), higher timed up-and-go (MD 1.36; 95% CI 0.92 to 1.79; p<0.00001), lower one-leg standing time (MD −19.13; 95% CI −23.29 to −14.97; p<0.0001) and slower normal gait speed (MD −0.20; 95% CI −0.22 to −0.18; p<0.0001) were found to be associated with LS. No significant differences were noted in other clinical characteristics between the two groups.ConclusionsGLFS-25 is clinically useful for assessing mobility function according to the evidence available on the clinical characteristics of LS categorised by the GLFS-25 questionnaire items until.
Immune-related adverse events (irAEs) affect all organs and are associated with various symptoms. The identification of biomarkers that can predict irAEs may be particularly clinically useful. This ...study aimed to investigate whether the prognostic nutritional index (PNI) before the initiation of immune checkpoint inhibitor (ICI) treatment can predict the occurrence of irAEs. We conducted a survey of 111 patients with cancer who were receiving ICI fixed-dose monotherapy at Saga University Hospital from the time each ICI became available until January 2020. We compared the PNI between the patients with and without irAE expression, established a cutoff value for PNI associated with the development of irAEs, and investigated the incidence of irAEs and progression-free survival (PFS) in groups divided by the cutoff value. Patients with irAEs had significantly higher PNI than did those without, and there was a significant association between PNI and irAEs after adjusting for potential factors (odds ratio, 1.12; 95% confidence interval, 1.03–1.21). In addition, PNI ≥44.2 was associated with a significantly higher incidence of irAEs (75.0% vs. 35.2%, p = 0.0001) and significantly longer PFS than PNI <44.2 (p = 0.025). In conclusion, pretreatment PNI may be associated with the risk of developing irAEs in patients with advanced recurrent solid tumors. When the PNI is ≥44.2, patient management is important for avoiding serious AEs because while the treatment may be effective, the occurrence of irAEs is a concern.
Background: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness ...and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study.Methods: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35–69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted.Results: The mean follow-up period was 11 years, and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR 0.73; 95% CI, 0.55–0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction.Conclusion: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.
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•The method is applicable and well-prepared for large-scale study.•12 urine samples (100μL each) are extracted within 30min.•The LLOQ for cortisol and cortisone was 2.5ng/mL (injection volume: ...10μL).•Minimal degradation of urine samples at room temperature during first 24h.•The extracted urine samples are quantifiable for up to 5days after extraction.
Levels of urinary glucocorticoids and their concentration ratios have been analyzed as potential markers for various pathological statuses. Large-scale studies may possibly accelerate the investigations; however, a suitable method needs to be established. Analytical conditions for measurement of urinary glucocorticoids with LCMS were examined. Electrospray ionization in the positive ion mode was applied for detection of cortisol (precursor>product ion: 363.3>121.0), cortisol-d4 (internal standard, IS, 367.4>121.1), and cortisone (361.2>163.2). To maximize ionization, acetic acid-ammonium acetate buffer (18mM) at pH 5.3 was employed as eluent A. A C18 column (100mm×2.1mm, 2.7μm) at 50°C was used for the 9.5min binary gradient separation starting with 60% eluent A with methanol being eluent B. Linear correlations were observed between the concentrations and the peak areas in the concentration range of 1–300ng/mL with correlation coefficients (r) of 0.998 and 0.997 for cortisol and cortisone, respectively, without IS adjustment, and 0.999 with IS adjustment for both cortisol and cortisone. Solid-phase extraction (SPE) using a 2mL centrifuge column was performed for the urine samples, with the original and final volumes being 100μL. The SPE of 12 urine specimens could be performed within 30min. The effect of the sample matrix on the quantification of endogenous compounds present in the urine extract was limited (coefficient of variation (CV) of IS-adjusted matrix factor: 4.4–8.1%; urine extracts of 8 individuals); however, substantial peak reduction of cortisol was observed at low concentrations. Exogenous contaminants originating from the SPE centrifuge column seemed to be a main cause for this phenomenon because the pure-water extract showed similar peak reduction. A recovery of ∼50% was obtained for both cortisol and cortisone. Adjustment with the IS improved the apparent recovery, with ∼100% being obtained for both cortisol and cortisone. The recovery rate decreased when the urine samples were concentrated in the SPE step; the reduction was greater for cortisol than for cortisone. The lower limit of quantification (LLOQ) was set at 2.5ng/mL when the injection volume was 10μL, based on the reproducibility of the standards which were measured (CV of 12 repetitions: 10.1% for 0.5ng/mL cortisol and 19.6% for 1ng/mL cortisone), the matrix effect (−55% at 2ng/mL concentrations of cortisol), and the recovery rate (∼50%). Furthermore an alternative approach for preparation of the cortisol standards was required for low concentration range (2.5–20ng/mL) because of the effect of the matrix. Degradation of original urine specimens at room temperature was minimal during the first 24h. The extracted urine samples degraded over time; however, their concentrations were corrected with the IS, allowing for analysis up to 5days after extraction. In conclusion, an analytical method for urinary glucocorticoids was established, which is fast, sensitive, and well suited for practical application to large-scale study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Aims: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between ...dietary patterns and serum LDL cholesterol in a large general population.Methods: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35–69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score.Results: We identified dietary patterns; “vegetable rich pattern” , “meat and fried food rich pattern” and “high bread and low rice pattern” in women and men; “fish and shellfish rich pattern” and “high confectioneries and low alcohol pattern” in men; “healthy Japanese diet pattern” and “high alcohol and low rice pattern” in women. Serum LDL cholesterol in men was associated with “high bread and low rice pattern” score (Q5 was 4.2 mg/dL higher than Q1, p for trend ＜0.001) and “high confectioneries and low alcohol pattern” scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ＜0.001). In women, serum LDL cholesterol was associated with “high bread and low rice pattern” score (Q5 was 7.1 mg/dL higher than Q1, p for trend ＜0.001).Conclusion: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.
Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and ...stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (P
= 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (P
= 0.003). Unexpectedly, problem solving in men (P
< 0.001) and positive reappraisal in women (P
= 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the ...dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose.
Cross-sectional study.
The study included 7949 community-dwelling middle-aged and older adults (aged 45–74 years) from Japan.
Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men: <28 kg, women: <18 kg) and low SMM (lowest quartile in each sex-specific category) were defined as having sarcopenia. Daily step counts were measured for 10 days using a waist-mounted accelerometer. To examine the association between daily step count and sarcopenia, a multivariate logistic regression analysis was performed, adjusting for potential confounding factors such as age, sex, body mass index, smoking status, alcohol consumption, protein intake, and medical history. The odds ratios (ORs) and confidence intervals (CIs) were calculated based on the daily step counts categorized into quartiles (Q1-Q4). Finally, a restricted cubic spline curve was fitted to further investigate the dose-response relationship between daily step count and sarcopenia.
The prevalence of sarcopenia in the overall participants was 3.3 % (259/7949 participants), with a mean daily step count of 7292 ± 2966 steps. Expressed in quartiles, the mean daily step counts were 3873 ± 935 steps in Q1, 6025 ± 503 steps in Q2, 7942 ± 624 steps in Q3, and 11,328 ± 1912 steps in Q4. The prevalence of sarcopenia in each quartile of daily step count was 4.7 % (93/1987 participants) in Q1, 3.4 % (68/1987 participants) in Q2, 2.7 % (53/1988 participants) in Q3, and 2.3 % (45/1987 participants) in Q4. The ORs and 95 % CIs adjusted for covariates demonstrated a statistically significant inverse association between daily step count and sarcopenia prevalence (P for trend <0.01), as follows: Q1, reference; Q2, 0.79 (95 % CI: 0.55–1.11); Q3, 0.71 (95 % CI: 0.49–1.03); Q4, 0.61 (95 % CI: 0.41–0.90). The restricted cubic spline curve indicated that the ORs leveled off at approximately 8000 steps per day, and no statistically significant decrease in ORs was observed for daily step counts above this threshold.
The study found a significant inverse association between daily step count and the prevalence of sarcopenia, with the association plateauing when the daily step count exceeded approximately 8000 steps. These findings suggest that 8000 steps per day may be the optimal dose to prevent sarcopenia. Further intervention and longitudinal studies are needed to validate the results.
•Study aims to find dose-response relationship between daily steps and sarcopenia prevalence.•Inverse association found between step count and sarcopenia prevalence.•Dose-response relationship plateaus at approximately 8,000 steps.•Results suggest 8,000 daily steps as optimal dose to prevent sarcopenia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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