Objective: To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. Methods: An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. Results: The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). Conclusion Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS.

Objective: To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. Methods: An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. Results: The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). Conclusion Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS.

Objective: To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. Methods: An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. Results: The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). Conclusion Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS.

Objectives: The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats. Methods: Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points. Results: In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone. Conclusions These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.

BACKGROUND: The Rugby World Cup (RWC) is one of the biggest international mega sports events in the world. This study was conducted to identify and evaluate the volume, nature, and severity of spectator medical care in the stadiums of 12 venues across Japan during RWC 2019. METHOD: This was a retrospective review of medical records from spectator medical rooms of 45 official matches of RWC 2019 between September 20 and November 2, 2019. All patients in the stadium who visited the spectator medical room and were transferred to a hospital were included. The wet bulb globe temperature (WBGT) value at the kick-off time of each match, the number of visits to the spectator medical room, and the number of transfers to a hospital were reviewed and analyzed. The patient presentation rate (PPR) was calculated per 10,000 attendees. Severity categories were defined as mild or severe. Mild cases were considered non-life threatening requiring minimal medical intervention, and severe cases required transport to a hospital. RESULT: The total number of visits to the spectator medical room was 449 with a PPR of 2.63. Most cases (91.5%) were mild in severity. The PPR was significantly higher for the matches held with a WBGT over 25 °C than for the matches under 21 °C (PPR 4.27 vs 2.04, p = 0.04). Thirty-eight cases were transferred to a hospital by ambulance; the PPR was 0.22. The most common reasons for transfer to the hospital were heat illness and fracture/dislocation, at a rate of 15.8% each. The incidence rate of cardiopulmonary arrest per 10,000 attendees was 0.0059 during RWC 2019. CONCLUSION Preparation and provision of appropriate medical service for spectators is a key factor for mass-gathering events. During RWC 2019, the majority (91.5%) of patients who sought medical attention did so for minor complaints, which were easily assessed and managed. On the other hand, a higher WBGT situation contributes significantly to an increased PPR (< 21 versus > 25, 2.04 versus 4.27, p = 0.04). Careful medical preparation, management, and development of public education programs for higher WBGT situations will be required in the future for similar international mega sports events.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Ambulatory Care/statistics & numerical data* ; Anniversaries and Special Events ; Child ; Child, Preschool ; Emergency Service, Hospital/statistics & numerical data* ; Female ; Football ; Hospitalization/statistics & numerical data* ; Humans ; Infant ; Infant, Newborn ; Japan ; Male ; Mass Behavior ; Middle Aged ; Retrospective Studies ; Young Adult

Objective: The use of generic drugs is promoted to reduce medical costs and copayments. However, tumor agents are expensive and generic drugs are not widelyused. Thus, it is necessaryto evaluate the safetyof generic drugs in more detail. We compared the incidence of adverse events between the original drug (Gemzar®: GEM) and generic drug (Gemcitabine [Sandoz]: GE-GEM) using propensityscore (PS) matching.Methods: We investigated adverse events in patients who received one course of GEM or GE-GEM. The patient background (age,sex, BSA, cancer type, stage, metastasis, surgical history, and radiotherapy) and administration status (administration route and RDI) were used to calculate the PS.Results: Among all patients (GEM: 51, GE-GEM: 54), a significantlygreater number in the GE-GEM group had cancer metastasis. On comparison of adverse events, there were significantlymore cases of vascular pain (p＜0.05) in the GEM group, and manycases of nausea (p＝0.08) and rash (p＝0.08). Fortypatients in each group were extracted byPS matching. There were no significant differences in the patient background between the groups, and on comparison of adverse events, the two groups did not significantly differ.Conclusion: Our studysuggested that there is no difference in side effects between Gemzar® and gemcitabine [Sandoz]. To compare the incidence of adverse events, it is useful to use PS matching in clinical practice.

Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS). Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI ≥70％(RDI 70 group,N=70)or RDI＜70％(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were ＜0.10 in univariate analysis. Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3％ vs. 28.3％,P＜0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7％ vs. 11.3％,P＜0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P＜0.01).Multivariate analysis showed that RDI ≥70％(hazard ratio(HR)=0.55,P=0.025),hypertension grade ≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P＜0.01)were independently associated with improved OS.RDI ≥70％ was not statistically significant in multivariate analysis. Conclusions:Our study revealed the importance of achieving RDI ≥70％ in the first 30 days of treatment to maximize the effects of LEN.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.

This study aimed to clarify the resources required to relieve distress during palliative care delivery to cancer patients. Between April 2015 and March 2017, 1479 outpatients receiving chemotherapy for cancer were screened using the Japanese version of the Support Team Assessment Schedule (STAS-J). When the STAS-J result was 2 points and higher, the patient was considered positive for distress. A certified nurse or pharmacist performed STAS-J screening and, in cases where the patient exhibited distress, took steps to alleviate the problem themselves or consulted another resource. Distress was identified in 181 (12.2%) of the 1479 patients. These 181 patients needed 288 resources. The resources used to alleviate distress were categorized as follows: direct support by certified nurse or pharmacist (153), consultation with the attending physician (98) and other (37). The required resource included the following twelve professionals: attending physician, ophthalmologist, dermatologist, dentist, orthopedic surgeon, palliative care physician, certified nurse, certified pharmacist, medical social worker, clinical psychologist, volunteers for cancer patients, and palliative care team. The frequency of the intervention by the certified nurse or pharmacist (61, 39.9%) in directly alleviating psychiatric distress was significantly higher than by consultation with the attending physician (10, 10.2%) (p<0.0001). However, the frequency of consultation with the attending physician in alleviating physical distress (88, 89.8%) was significantly higher than that of the certified nurse or pharmacist (92, 60.1%) (p<0.0001). We conclude that the certified nurse or pharmacist is important for the delivery of palliative cancer care, because they can directly provide relief from psychiatric distress.

OBJECTIVES: The purpose of this study is to evaluate the effects of teriparatide (TPTD) on bone mineral density (BMD), bone strength, and bone quality in Akita mouse models of diabetes mellitus. METHODS: Twelve-week-old female Akita mice and control mice (C57/BL/6NCrSlc) were divided into 4 groups: control mice treated with vehicle (n = 7) or TPTD (n = 6); and Akita mice treated with vehicle (n = 6) or TPTD (n = 7). TPTD or vehicle was administered subcutaneously 3 times a week for 8 weeks. Blood glucose, serum sclerostin, total tibial BMD, femoral shaft bone strength, and bone quality using Fourier-transform infrared spectroscopy imaging were evaluated. RESULTS: No significant differences in serum sclerostin levels were evident among these groups after 8 weeks of treatment. TPTD significantly increased BMD in control mice (+12.7%, P = 0.02) and Akita mice (+29.2%, P = 0.001) compared with vehicle. Maximum load and stiffness were significantly higher in Akita mice treated with TPTD than in Akita mice treated with vehicle (+56.6%, P = 0.03 and + 90.5%, P = 0.02, respectively). On Fourier-transform infrared spectroscopy imaging, the mineral/matrix ratio was significantly lower in Akita mice treated with vehicle than in control mice (−12.2%, P = 0.02), and TPTD treatment significantly increased the mineral/matrix ratio (P = 0.003). CONCLUSIONS TPTD thus improved BMD and bone strength in both control mice and Akita mice, with improvements in the mineral/matrix ratio among Akita mice.