Comparing the Efficacy of Fosnetupitant, an NK1 Receptor Antagonist in CDDP-Based Regimens, with That of Fosaprepitant and Aprepitant: A Retrospective Observational Study.

Existing antiemetic therapy against emetic-risk agents across malignancies 24 h post-dose in the acute period in cisplatin (CDDP)-based regimens yields a satisfactory complete response (CR) rate of ≥90%. However, the control rate after 24 h in the delayed period is unsatisfactory. This study compared the efficacy of fosnetupitant (F-NTP), a neurokinin 1 receptor antagonist, with that of fosaprepitant (F-APR) and aprepitant (APR) in the treatment of patients with cancer at high emetic risk due to chemotherapy. In this retrospective case-control study involving patients receiving cisplatin-containing regimens and neurokinin 1 receptor antagonists, patients were divided into three groups based on prophylactic antiemetic therapy: F-NTP, F-APR, and APR. The CR rate was evaluated for each period up to 168 h and further subdivided into acute (0-24 h), delayed (24-120 h), overall (0-120 h), and beyond-delayed (120-168 h) periods. Eighty-eight patients were included in the F-NTP group, 66 in the F-APR group, and 268 in the APR group. The CR rates at 0-168 and 120-168 h after cisplatin administration were significantly higher in the F-NTP group than in the F-APR and APR groups. After adjusting for confounding factors, F-NTP use was an independent factor in the multivariate analysis. Prophylactic antiemetic therapy, including F-NTP, was effective and well-tolerated during the delayed period. The efficacy of F-NTP in managing chemotherapy-induced nausea and vomiting was superior to those of F-APR and APR during the study period.

Physical activity according to sit-to-stand, standing, and stand-to-sit abilities in subacute stroke with walking difficulty: a cross-sectional study.

OBJECTIVE: This study investigated the characteristics of physical activity according to sit-to-stand, standing, and stand-to-sit abilities in subacute stroke with walking difficulty. METHODS: In this study, 29 participants with subacute stroke and walking difficulty were enrolled and classified into two groups: participants who successfully completed three items (i.e., sit-to-stand, standing, and stand-to-sit) of the Functional Balance Scale (independent group, n = 13) and those who showed incomplete scores on any of the three items (dependent group, n = 16). Light-intensity physical activity (LIPA) and moderate-to-vigorous physical activity (MVPA) were measured using an accelerometer at three periods (i.e. daytime, therapy time, and non-therapy time) for a week. RESULTS: Two-way analysis of variance (groups × physical activity intensity) demonstrated a significant interaction in each period. Post-hoc tests showed significantly more LIPAs and MVPAs in the independent group in all periods, except for MVPA in the non-therapy time. Particularly, LIPA showed significant between-group differences in each period. CONCLUSIONS: Among individuals with subacute stroke and walking difficulty, those who could completely perform sit-to-stand, standing, and stand-to-sit could perform more LIPAs. Increasing sit-to-stand, standing, and stand-to-sit abilities could be an important factor in increasing the opportunity to perform LIPAs.

Reliability of measurement using Image J for reach distance and movement angles in the functional reach test.

[Purpose] The purpose of this study was to examine the test-retest reliability and minimal detectable change (MDC) of reach distance and movement angle analyses using Image J. [Participants and Methods] Thirty-eight healthy young males performed the functional reach test (FRT) twice, and their reach movements were recorded using a digital video camera. Image J was used to combine the digital photographs taken at the start position and maximum reach and to measure each movement. The measurements recorded were the movement distance of the third metacarpal bone (reach distance), anterior-superior iliac spine, and trochanter major, and the angles recorded were the acromion-malleolus lateralis, acromion-trochanter major, and trochanter major-malleolus lateralis. The reliability of all the measurements was analyzed using intraclass correlation coefficients (ICCs), Bland-Altman plots, and MDCs. [Results] The ICCs (1, 1) were >0.80 for all the outcomes. The Bland-Altman analysis revealed no systematic bias in any outcome. The MDC of reach distance was 18.3 mm. [Conclusion] Measurement using Image J for reach distance and movement angles in the FRT showed acceptable high test-retest reliability. Measurement of the FRT and the MDC calculated in this study could be used as a reference for further research.

Retroperitoneal Metastasis, with Marked Fibrosis, of Lung Adenocarcinoma after Afatinib Treatment: An Autopsy Case Report.

A 73-year-old woman was admitted to our hospital for treatment of vomiting. Four months previously, she had been diagnosed with lung adenocarcinoma (cT3N3M1a stage IVA) and started receiving afatinib as first-line treatment. On admission, the primary tumor had shrunk, but abdominal computed tomography revealed a new retroperitoneal lesion causing duodenal obstruction and hydronephrosis. She underwent gastrojejunostomy, and a biopsy of the peritoneum revealed adenocarcinoma. She was treated with second-line chemotherapy but developed cerebral infarction and died 104 days after admission. An autopsy revealed marked fibrosis with scattered tumor cells in the retroperitoneum. The underlying mechanism of the metastasis is discussed.

Long-Term Safety and Efficacy of Sitagliptin for Type 2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

INTRODUCTION: A post-marketing surveillance (PMS) study was conducted to confirm the long-term risk-benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions. METHODS: This prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010-June 2012; observation period, 3 years). Safety was assessed via collection of data on adverse drug reactions (ADRs), estimated glomerular filtration rate (eGFR) and cardiovascular events whereas efficacy was assessed via changes in glycated hemoglobin (HbA1c). RESULTS: In 3265 patients evaluated for safety, 270 ADRs occurred in 207 (6.3%) patients overall. Metabolism and nutrition disorders were the most common class of ADRs, occurring in 58 patients overall (53 non-serious, 5 serious) with hypoglycaemia (17 patients, 0.52%) the most common ADR. In patients with eGFR > 90 mL/min/1.73 m2 at baseline (mean ± SD, 106.42 ± 18.11 mL/min/1.73 m2, n = 584), eGFR declined by 11.83 ± 17.53 mL/min/1.73 m2 (P < 0.0001; n = 360) over the observation period whereas eGFR appeared to be relatively maintained in patients with lower baseline eGFR levels. Cardiovascular events were infrequent [occurring in 4 of 84 (4.76%) patients at high cardiovascular risk] with no distinct features in this Japanese population and the cumulative incidence [8.42% (3.12-21.70) at 36 months; n = 32] was similar to that noted in previous studies involving sitagliptin. In patients evaluated for efficacy, the overall change in HbA1c from baseline to final evaluation was mean ± SD - 0.68 ± 1.34% (P < 0.0001, n = 2070). Reductions in HbA1c tended to be greater in younger patients and patients with higher body mass index (BMI) and HbA1c values at the start of administration. CONCLUSION: Long-term sitagliptin administration in the routine clinical practice setting is associated with good efficacy, including as monotherapy, with no additional safety concerns.

Daytime physical activity at admission is associated with improvement of gait independence 1 month later in people with subacute stroke: a longitudinal study.

Background: Little is known about the benefits of daytime physical activity on gait ability in subacute stroke.Objectives: We investigated association between daytime physical activity at hospital admission and improvement of gait independence 1 month later in subacute stroke.Methods: Thirty-four participants with subacute stroke who could not walk independently were assessed. An accelerometer (HJA 350-IT, OMRON) was used to record the mean duration of light-intensity physical activity (LIPA) and moderate-to-vigorous-intensity physical activity (MVPA). LIPA and MVPA were recorded for 12 h per day for 7 consecutive days, and at three different time periods (daytime, therapy time, non-therapy time) at rehabilitation hospital admission (baseline). Gait independence was assessed by the functional ambulation category (FAC) at baseline and 1 month later. Participants were categorized into two groups based on the change of gait independence, as follows: the improved group, in which the FAC increased by ≥1; the non-improved group, in which the FAC did not increase.Results: Compared with the non-improved group, the improved group demonstrated significantly higher values of all physical activity variables, except for non-therapy time MVPA (p < .05). Logistic regression analysis showed that higher daytime LIPA was significantly associated with FAC improvement (OR = 1.068, 95% CI 1.009 to 1.140). In particular, higher non-therapy time LIPA was closely associated with FAC improvement (OR = 1.253, 95% CI 1.002 to 1.568).Conclusions: To promote recovery of gait independence in first month from admission, increasing daytime physical activity, especially LIPA during daytime or non-therapy time, is an important treatment target in subacute stroke.

Characteristics of intensity-based physical activity according to gait ability in people hospitalized with subacute stroke: a cross-sectional study.

OBJECTIVE: Gait ability may be related to the level of intensity-based physical activity in people who have experienced a stroke; however, this relationship has not been explored in previous studies. This study aimed to investigate the characteristics of intensity-based physical activity according to gait ability and to explore the factors related to different intensity physical activity. METHOD: Eighty hospitalized participants with subacute stroke were assigned to three groups based on their gait ability: group 1 (n = 28) could walk independently with a maximal gait speed (MGS) of more than 0.9 m/s; group 2 (n = 11) could walk independently with a MGS of less than 0.9 m/s; group 3 (n = 41) could not walk independently. Light-intensity physical activity (LIPA) and moderate-to-vigorous physical activity (MVPA) were measured for 12 hours using an accelerometer (OMRON, HJA350-IT) for 7 consecutive days and were calculated throughout three time periods (daytime, non-therapy time, or therapy time). RESULTS: In each time period, a two-way ANOVA showed an interaction between the groups and intensity-based physical activity (p < 0.05). Bonferroni post hoc test showed a significantly higher LIPA in groups 1 and 2 compared with group 3 in daytime or non-therapy time. In contrast, group 1 showed a significantly higher MVPA compared with group 2 and 3 for each time period. CONCLUSION: During daytime and non-therapy time, the results suggested that gait independence is related to LIPA rather than gait speed, and gait speed and gait independence is related to MVPA.

Early effects of a knee-ankle-foot orthosis on static standing balance in people with subacute stroke.

[Purpose] The purpose of this study was to evaluate the early effects of a knee-ankle-foot orthosis on static standing balance in people with subacute stroke. [Participants and Methods] Timed static standing balance in four standing conditions (feet apart with eyes open, feet apart with eyes closed, feet together with eyes open, and tandem stance with eyes open) was assessed in 29 inpatients (mean age: 67.3 ± 13.3 years) with subacute stroke with and without a knee-ankle-foot orthosis on the paretic lower limb. [Results] In the group of participants who were unable to stand without a knee-ankle-foot orthosis, the proportion of participants who were able to stand with a knee-ankle-foot orthosis was significantly increased in the following conditions: feet apart with eyes open and feet apart with eyes closed. In the group of participants who were able to stand without a knee-ankle-foot orthosis, the mean duration of time for which the participants with a knee-ankle-foot orthosis were able to stand was significantly longer than that for those without a knee-ankle-foot orthosis for all standing conditions. [Conclusion] A knee-ankle-foot orthosis may be a useful assistive device to support static standing balance for people with subacute stroke.

Differences in activities of daily living between people with subacute stroke who received knee-ankle-foot and ankle-foot orthoses at admission.

[Purpose] This study aimed to identify the preferential factor of activities of daily living disabilities for selecting between knee-ankle-foot orthosis and ankle-foot orthosis prescription in the early stage after admission. [Participants and Methods] This study included 442 inpatients who had a subacute stroke and received either knee-ankle-foot orthosis or ankle-foot orthosis after admission (mean age, 69 years). The functional independence measure was investigated within 1 week after admission. [Results] Inpatients who had a stroke and received knee-ankle-foot orthosis had significantly lower scores for all individual functional independence measure items than those who received ankle-foot orthosis. Logistic regression analysis revealed that functional independence measure transfer (bed, chair, and wheelchair) was closely associated with the difference in the prescribed lower limb orthosis after multivariate adjustment. [Conclusion] Compared with ankle-foot orthosis, knee-ankle-foot orthosis was prescribed to inpatients with more-severe disabilities, and the difference in the disability related to performing transfer activities was more noticeable than that in disability related to mobility between inpatients for whom knee-ankle-foot orthosis was prescribed and those for whom ankle-foot orthosis was prescribed. To provide effective rehabilitation for people who had a subacute stroke, for whom use of knee-ankle-foot orthosis or ankle-foot orthosis is recommended. The evaluation and intervention focused on standing performance related to performing transfer such as sit-to-stand, standing, moving while standing, and stepping might be a priority in the early stage after admission.

Difference in independent mobility improvement from admission to discharge between subacute stroke patients using knee-ankle-foot and those using ankle-foot orthoses.

[Purpose] To verify differences in independent mobility improvements between people with subacute stroke with knee-ankle-foot orthoses (KAFOs) and those with ankle-foot orthoses (AFOs) from admission to discharge, and to identify the relationship between mobility improvements and their characteristics. [Participants and Methods] This study included 381 hospitalized patients with subacute stroke who required complete mobility assistance at admission and for whom KAFOs (KAFO group) or AFOs (AFO group) were prescribed after admission. The functional independence measure (FIM) score at admission and discharge, FIM gain, age, Brunnstrom stage (BS) of the paretic lower limb at admission, and the period from admission to prescription for lower limb orthoses were investigated. [Results] Repeated-measures two-way analysis of variance revealed a significant group × time interaction in the walk/wheelchair and stair-climbing items of the FIM. Improvements in the scores in the KAFO group were significantly lower than those in the AFO group. Age, BS, FIM at admission, and period from admission to lower limb orthosis prescription significantly correlated with FIM gain in the walk/wheelchair and stair-climbing items. [Conclusion] A more effective intervention using lower limb orthoses with consideration of the influence of age, motor paralysis, and activities of daily living at admission is required to promote the improvements of people with subacute stroke prescribed KAFOs or AFOs.

The known-groups validity of intensity-based physical activity measurement using an accelerometer in people with subacute stroke.

[Purpose] This study aimed to assess the known-groups validity of the estimated metabolic equivalents during physical activities using accelerometer, Active Style Pro HJA 350-IT, in people with subacute stroke. [Subjects and Methods] Ten participants with subacute stroke and ten healthy people performed six activities (lying, sitting, standing, sitting with reaching task, standing with reaching task, and walking) and metabolic equivalents were estimated using the accelerometer during each activity. These estimated metabolic equivalents were compared with reported metabolic equivalents through compendiums or previous studies. Additionally, the estimated metabolic equivalents were compared between subacute stroke and healthy control participants. [Results] The estimated metabolic equivalents of both groups during maintaining posture showed significantly lower values in comparison with previous studies. There were no significant differences between the estimated metabolic equivalents during sitting with reaching tasks or standing with reaching tasks when compared with compendium metabolic equivalents across both groups. The estimated metabolic equivalents during walking were inevitable values significantly differed from previous study which conducted with stroke patients with lower gait abilities in both groups. [Conclusion] The estimated metabolic equivalents using accelerometer may be suitable to assess movement activity rather than motionless activity, and accelerometer demonstrated acceptable validity in people with subacute stroke.

Reliability of intensity-based physical activity measurement using an activity monitor in people with subacute stroke in the hospital setting: a cross-sectional study.

Background Activity monitors are known to provide quantitative evaluation of physical activity in people with stroke. However, little evidence is available on the test-retest reliability and suitable measuring conditions for evaluating physical activity with an activity monitor in people with subacute stroke at a hospital setting. Objectives To evaluate reliability of physical activity measurement using an activity monitor in different measuring conditions in hospitalized people with subacute stroke according to gait ability. Methods Sixty-nine participants with subacute stroke were categorized based on their gait ability: group 1 (n = 22), could walk independently at sufficient gait speed (≥0.9 m/s); group 2 (n = 11), could walk independently with insufficient gait speed (<0.9 m/s); group 3 (n = 36), required assistance in walking. Physical activity (sedentary behavior, light-intensity physical activity, moderate-to-vigorous physical activity) was measured using an activity monitor (OMRON, HJA350-IT) for seven consecutive days. All physical activity variables were calculated in five conditions defined according to measurement periods (3, 5, or 7 days with or without weekends). Results In groups 1 and 2, intraclass correlation coefficients were high across all measuring conditions in all physical activity variables (>0.7). In group 3, intraclass correlation coefficients were high in all measuring conditions (>0.7) except for three weekdays measuring condition (0.563-0.922). Conclusions In hospitalized people with subacute stroke, the central tendency of intensity-based physical activity could be assessed with good reliability using an activity monitor. For reliable measurement, more measurement days are needed in those with dependent walking compared to those with independent walking.

A case of herpes zoster ophthalmicus preceded one week by diplopia and ophthalmalgia.

A 66-year-old man presented with headache and ophthalmalgia. Diplopia developed, and he was hospitalized. The left eye had abducent paralysis and proptosis. We diagnosed him with Tolosa-Hunt syndrome and administered methylprednisolone at 1 g/day for 3 days. However, the patient did not respond to treatment. No abnormality was found on his MRI or cerebrospinal fluid examination. Tests showed his serum immunoglobulin G4 and antineutrophil cytoplasmic antibody titers were within normal limits. He also had untreated diabetes mellitus (HbA1c 9.2). One week after first presenting with symptoms, herpes zoster appeared on the patient's dorsum nasi, followed by keratitis and a corneal ulcer. Herpes zoster ophthalmicus with ophthalmoplegia was diagnosed. We began treatment with acyclovir (15 mg/kg) and prednisolone (1 mg/kg, decreased gradually). Ophthalmalgia and the eruption improved immediately. The eye movement disorder improved gradually over several months. It is rare that diplopia appears prior to cingulate eruption of herpes zoster ophthalmicus. We speculated that onset of the eruption was inhibited by strong steroid therapy and untreated diabetes mellitus.

A case of Cefepime encephalopathy, being difficult to distinguish from non-convulsive status epilepticus during the treatment of bacterial meningitis.

A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime-induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients.

Sex differences in the pharmacokinetics of levodopa in elderly patients with Parkinson disease.

OBJECTIVES: Levodopa (LD) is the most effective antiparkinsonian drug used in the treatment of Parkinson disease (PD). Sex differences in the bioavailability of LD have been shown previously. In addition, epidemiological sex differences in PD have been reported, suggesting an involvement of estrogen. In this study, we evaluated the pharmacokinetics of LD in elderly patients with PD to examine the influence of estrogen. METHODS: After the oral administration of a tablet of LD 100 mg/carbidopa 10 mg in 128 PD patients (including 91 elderly patients; age at examination, 75 years or older), plasma LD concentrations were measured at 6 points until 180 minutes, and pharmacological parameters were calculated. Then, differences in these parameters between sex were compared. RESULTS: The area under the curve (AUC) and the AUC adjusted for body weight were found to be significantly greater in the female subjects compared with the male subjects (P < 0.0001 and P < 0.0001, respectively). Furthermore, in the elderly patients, the AUC and the AUC adjusted for body weight were significantly greater among the female subjects (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: Even in the elderly cohort, the women had a significantly greater bioavailability of LD. In conclusion, to avoid the development of motor complications during LD treatment, it is important to consider the sex differences in the bioavailability of LD.

Calcium oxalate crystal deposition in a patient with Aspergilloma due to Aspergillus niger.

Discrimination between aspergilloma and chronic necrotizing pulmonary aspergillosis (CNPA) based on radiological findings can difficult. We describe a patient with aspergilloma and organizing pneumonia that was possibly caused by Aspergillus niger infection and radiologically mimicked CNPA. A postmortem histological analysis showed diffuse alveolar damage that had originated in peri-cavitary lung parenchyma. Calcium oxalate or Aspergillus niger was located inside, but not outside the cavity in the right upper lobe. Calcium oxalate or other unknown hyphal bioactive components might provoke severe lung inflammation not only adjacent to the cavity, but also on the contralateral side.

Retrospective analysis of efficacy and safety of amrubicin in refractory and relapsed small-cell lung cancer.

BACKGROUND: Amrubicin, a totally synthetic 9-aminoanthracycline, was evaluated retrospectively for the treatment of refractory and relapsed small-cell lung cancer (SCLC). METHODS: Retrospective analysis was performed in 32 patients. Amrubicin was infused over 5 min on days 1-3, with courses repeated at 3- or 4-week intervals. Amrubicin was given at a dose of 45 mg/m(2) per day, 40 mg/m(2) per day, 35 mg/m(2) per day, 30 mg/m(2) per day, or 25 mg/m(2) per day depending on medical conditions (patients' age and performance status [PS]), and the dose was modulated according to myelosuppression. RESULTS: The median number of treatment cycles was 3 (range, 1-6). Seventeen patients (53.1%) had a partial response. Median progression-free survival time for all patients was 96 days, and median survival time was 166 days. Grade 3 or 4 hematologic toxicities comprised neutropenia (78.1%), anemia (65.6%), and thrombocytopenia (50.0%). Febrile neutropenia was observed in 8 patients (25.0%). Nonhematologic toxicities were mild. Treatment-related death was observed in 1 patient. CONCLUSION: Treatment with amrubicin appeared effective in SCLC patients previously treated with chemotherapy, although it was not necessarily safe, because of myelosuppression. Further research is warranted to investigate amrubicin treatment for patients with SCLC.

Increased oxidative stress in patients with chronic obstructive pulmonary disease (COPD) as measured by redox status of plasma coenzyme Q10.

STUDY OBJECTIVES: The percentage of oxidized coenzyme Q10 in total coenzyme Q10 (%CoQ-10) has been shown to indicate the degree of systemic oxidative stress. Chronic obstructive pulmonary disease (COPD) is regarded as a systemic disease that is linked to oxidative stress in its pathogenesis. In this study, the plasma %CoQ-10 levels in COPD patients were determined and assessed. In addition, the effect of oxygen supplementation on plasma %CoQ-10 was also evaluated. MATERIAL AND METHODS: Thirteen COPD patients who had not received oxygen supplementation (COPD-Pt), five COPD patients who had received oxygen supplementation (COPD + O2) and 20 age-matched control subjects (CONTROL) were enrolled. We have also enrolled 83 young healthy non/slight smokers (smoking index <20 pack-year) and 24 young healthy smokers (smoking index > or = 20 pack-year) in order to assess the effect of smoking history on %CoQ-10 level. Their plasma was collected and plasma %CoQ-10 levels were determined and compared. RESULTS AND CONCLUSION: The plasma %CoQ-10 of COPD-Pt was 6.3 +/- 2.3, significantly higher than that of CONTROL, 4.7 +/- 1.6 (p < 0.05), indicating an increased oxidative stress in the patients. In contrast, no significant difference in %CoQ-10 was observed between young healthy non/slight smokers (%CoQ-10 = 3.2 +/- 0.9) and young healthy smokers (%CoQ-10 = 3.7 +/- 1.3). Our observation of five COPD patients who received an oxygen supplementation revealed that their %CoQ-10 values (4.0 +/- 1.5) were significantly lower than those in COPD-Pt subjects (p < 0.05), suggesting that oxygen supplementation ameliorates the oxidative stress. In contrast, our study showed that no significant difference was observed among the three groups in plasma levels of Vitamin C or E. In conclusion, plasma %CoQ-10 levels are increased in COPD patients and oxygen supplementation attenuates this increasing effect by COPD. This implies that %CoQ-10 might be used practically to assess the COPD patients systemically.