Patient-generated health data collection using a wearable activity tracker in cancer patients-a feasibility study.

PURPOSE: Incorporation of patient-generated health data (PGHD) into clinical research requires an investigation of the validity of outcomes and feasibility of implementation. This single-arm pilot trial investigated the feasibility of using a commercially available activity tracking wearable device in cancer patients to assess adherence to the device and real-time PGHD collection in a clinical research setting. METHODS: From July to November 2017, enrolled adult patients were asked to wear a wristband-style device. Brief Fatigue Inventory (BFI) and MD Anderson Symptom Inventory (MDASI) were assessed at baseline and on day 29. Furthermore, 29-day Pittsburgh Sleep Quality Index, global impression of the devices, and NCI CTCAE v4 were evaluated. RESULTS: Of 30 patients (mean age, 58.6 years; male, 21 [70%]), 15 (50%) and 11 (36.7%) had gastrointestinal and lung cancer, respectively, and 27 (90%, 95% CI: 0.74-0.98) were well adhered (> 70%) to the device for 28 days. The mean adherence was 84.9% (range: 41.7-95.2%). More frequent PGHD synchronization tended to show better device adherence, with moderate correlation (r = 0.62, 95% CI: 0.33-0.80, p < 000.1). CONCLUSIONS: The feasibility of using a wearable activity tracker was confirmed in cancer patients receiving chemotherapy for a month. For future implementation in clinical trials, there is a need for further comprehensive assessment of the validity and reliability of wearable activity trackers. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN: UMIN000027575.

Prognostic factors for long-term improvement from stroke-related aphasia with adequate linguistic rehabilitation.

In the past decade, several studies have reported potential prognostic factors for aphasia after stroke. However, these reports covered no more than 1 year after stroke onset, even though patients often continue to improve over longer periods. The present study included 121 patients with aphasia who received cognitive-based linguistic rehabilitation for at least 2 years post-onset. All were right-handed and had a lesion only in the left hemisphere. Aphasia outcome was predicted using multiple linear regression analysis. Age at onset, lesion in the left superior temporal gyrus including Wernicke's area, and baseline linguistic abilities including aphasia severity and both phonological and semantic functions were significant predictors of long-term aphasia outcome. These findings suggest that the long-term outcome of aphasia following adequate linguistic rehabilitation can be predicted by age at onset, lesion area, and baseline linguistic abilities and that linguistic rehabilitation is particularly recommended for younger individuals with aphasia.

Ground Reaction Forces During Sprinting in Unilateral Transfemoral Amputees.

Understanding the characteristics of ground reaction forces (GRFs) on both limbs during sprinting in unilateral amputees wearing running-specific prostheses would provide important information that could be utilized in the evaluation of athletic performance and development of training methods in this population. The purpose of this study was to compare GRFs between intact and prosthetic limbs during sprinting in unilateral transfemoral amputees wearing running-specific prostheses. Nine sprinters with unilateral transfemoral amputation wearing the same type of prosthesis performed maximal sprinting on a 40-m runway. GRFs were recorded from 7 force plates placed in the center of the runway. Peak forces and impulses of the GRFs in each direction were compared between limbs. Peak forces in vertical, braking, propulsive, and medial directions were significantly greater in intact limbs than those in prosthetic limbs, whereas there were no significant differences in peak lateral force between limbs. Further, significantly less braking impulses were observed in prosthetic limbs than in intact limbs; however, the other measured impulses were not different between limbs. Therefore, the results of the present study suggest that limb-specific rehabilitation and training strategies should be developed for transfemoral amputees wearing running-specific prostheses.

Leg stiffness during sprinting in transfemoral amputees with running-specific prosthesis.

Carbon fiber running-specific prostheses are designed to reproduce the spring-like stepping behavior of individuals similar to springs loaded by the entire body mass (i.e. spring-mass model). The aim of this study was to test whether leg stiffness would be modulated differently between intact and prosthetic legs in transfemoral amputees wearing RSP during sprinting. Eight unilateral transfemoral amputees performed maximum sprinting along an indoor overground runway. Leg stiffness was calculated from kinetic and kinematic data in intact and prosthetic legs. The results showed that leg stiffness was for the prosthetic limb approximately 12% decreased compared to the intact limb. Although there was no difference in leg compression between the legs, maximal vertical ground reaction force was significantly greater in the intact leg than in the prosthetic one. These results indicate that asymmetric modulation of leg stiffness in transfemoral amputees with running-specific prostheses is mainly associated with asymmetric ground reaction force.

The Japanese version of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE): psychometric validation and discordance between clinician and patient assessments of adverse events.

BACKGROUND: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed by the National Cancer Institute as an adverse event assessment system to evaluate patients' symptoms, which tend to be underestimated in cancer clinical trials. The aim of this study was to assess the psychometric properties of the Japanese version of the PRO-CTCAE and the degree of adverse event assessment discordance between clinicians and patients. METHODS: A total of 187 cancer patients receiving systemic therapy were enrolled. Reproducibility, criterion validity, and responsiveness of the Japanese version of PROCTCAE were assessed. The EORTC QLQ-C30 was used as an external anchor. Discordance of assessment of adverse events between clinician and patients were also assessed using the CTCAE and PRO-CTCAE. RESULTS: A total of 187 participants (187 for criterion validity, 80 for reproducibility, and 100 for responsiveness), were analyzed (Mage = 62.4 years). All patients responded to at least one symptom item (M = 16). The mean (SD) intra-class correlation coefficients of overall reproducibility for the Japanese PRO-CTCAE was 0.63 (0.02). The correlation coefficient for the corresponding items in the EORTC QLQ-C30 and the Japanese PRO-CTCAE was high (Pearson r = 0.56-0.76). The analysis of responsiveness revealed significant dose-response trends (Jonckheere-Terpstra test, ps < 0.001). Depending on the adverse events, a discrepancy was observed in evaluation between the clinician and patient. CONCLUSIONS: These results revealed that there is underestimation in the assessment of adverse events in Japan, and that the Japanese version of the PRO-CTCAE had acceptable reliability and validity for common and clinically important symptoms.

Does amputation side influence sprint performances in athletes using running-specific prostheses?

BACKGROUND: For athletes using running-specific prostheses (RSPs), current Paralympic guidelines for track events are generally based on level of amputation, not side of amputation. Although 200- and 400-m sprint races are performed in a counterclockwise direction, little is known about the effects of amputation side on race performance in athletes with unilateral lower limb amputation. The study aim was to test whether athletes using RSPs on their left side have slower race times than those using RSPs on their right side. FINDINGS: Athletes with unilateral lower limb amputation (N = 59 in total) participating in elite-level 200-m races were analyzed from publicly available Internet broadcasts. These races included the 2008 Beijing and 2012 London Paralympics, and the International Paralympic Committee Athletics World Championships in 2011 and 2013. For each athlete the official race time and amputation side were determined. There was no significant difference in number of participants and race time between left and right side amputees in T42 men, T44 men, and T44 women. CONCLUSION: The results of the present study suggest that sprint performance of athletes using RSPs is not affected by amputation side on a standard 400-m track.

Correlations between stress hormone levels in umbilical cord blood and duration of delivery.

Correlations between umbilical cord blood concentration of stress response hormone cortisol and prolactin, and delivery duration were examined. Thirty-three cases were selected in which both mothers and neonates were healthy, and the neonates were delivered at full term. The umbilical cord blood was collected at the time of delivery and concentrations of cortisol and prolactin were measured. The cortisol level was significantly higher after vacuum-assisted delivery than after spontaneous delivery (p=0.044). Significant positive correlations (p=0.0289) were observed between cortisol level and delivery duration. In particular, the duration of the second stage of delivery showed stronger positive correlation (p=0.0304) with the cortisol level. The prolactin level showed weak correlation with the duration of full delivery and the second stage of delivery. The findings suggest that foetuses may respond to stress by uterine contraction during delivery.

Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan.

OBJECTIVE: An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan. METHODS: Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness. RESULTS: A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score-erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously. CONCLUSION: These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.

Prenatal diagnosis of Holt-Oram syndrome: role of 3-D ultrasonography.

Holt-Oram syndrome (HOS) is an autosomal dominant disorder consisting of a congenital heart defect in combination with upper limb abnormalities. This report presents the ultrasonographic follow-up of a fetus at risk for this syndrome. An abnormal four-chamber view of the heart and slight shortening of the forearm were found by prenatal ultrasound performed at 16 weeks of gestation. At 25 weeks of gestation, detailed sonographic examination clearly revealed abnormalities in the upper limbs and heart of the fetus. At 39 weeks of gestation, spontaneous labor and delivery produced a female infant weighting 2940 g. Postnatal examination of the infant confirmed the prenatal sonographic findings. 3-D ultrasound has an important role in prenatal diagnosis of HOS, which is essential for proper genetic counseling.

Two cases of infants who needed cardiopulmonary resuscitation during early skin-to-skin contact with mother.

Early skin-to-skin contact (SSC) results in significantly better overall performance on all measures of breastfeeding status and duration. SSC is widely believed to be free of adverse effects. We recently encountered two cases having life-threatening episodes during SSC. An experienced nurse should be placed in the delivery room for periodic observation and recording of vital signs of newborns who are in SSC (color, respirations, tone and heart rate) and to alert the physician to any cardiorespiratory changes. The point should also be emphasized to mothers that infants must be observed carefully and medical staff called immediately if the infant displays any vital changes during SSC.

Autonomic modulation of sinus and atrioventricular nodes in premature low-birth-weight infants.

Respiratory vagal activity is expressed by heart rate variability (HRV) at approximately 1 month of age in premature low-birth-weight infants (PLBWI). However, the autonomic inputs into the sinus node (SAN) and atrioventricular node (AVN) in PLBWI are unclear. We evaluated the variability in PP and PR intervals at day zero (day 0) and 1 month (1 month) after birth in 16 PLBWI (gestation 32.3 +/- 1.3 weeks, birth weight 1.578 +/- 257 g). The polygraph was recorded during sleep on day 0 and at 1 month. PP and PR intervals and the number of respiratory cycles were measured, and frequency analysis was performed by auto-correlation fast Fourier transforms. Power spectral density (PSD: ms(2)) was calculated for the low frequency domain (LF: 0.036 approximately 0.146 Hz), high frequency domain (HF: 0.146 approximately 0.390 Hz), total frequency (TF: 0.036 approximately 2.000 Hz), and respiratory sinus arrhythmia (RSA: frequency bandwidth of 0.3 Hz with peak respiratory frequency as median), and the PSD ratio in the PP and PR intervals (LF/HF, RSA/TF) were compared. Compared with day 0, a decrease in the LF/HF ratio and an increase in the RSA/TF ratio in PP intervals were observed at 1 month, consistent with expression of respiratory vagal activity. For PR intervals, on the other hand, the LF/HF ratio increased, indicative of accentuated sympathetic activity. However, the respiratory vagal input was weak, and the RSA/TF ratio remained unchanged. These observations suggest that, in PLBWI at 1 month, AVN conduction was not predominatly influenced by respiratory-related vagal activity, but was controlled by autonomic regulation, independent of the SAN.

Fish protein stimulated the fibrinolysis in rats.

OBJECTIVE: We hypothesized that fish protein affects blood coagulation and/or fibrinolysis, and compared the activity and amounts of factors involved in blood coagulation and fibrinolysis in rats fed the fish protein, which was treated to remove water-soluble and ethanol-soluble elements, from sardine (sardine protein). METHODS: In the first experiment, rats were fed for 21 days an AIN-93G-based control diet, and diets in which the casein of the control diet was exchanged for sardine protein at 5, 10 and 20% levels. In the second experiment, rats were fed an AIN-93G control diet and diets containing 5% fish oil, 10% sardine protein or both (5% fish oil + 10% sardine protein) for 21 days. At the end of the experiments, blood coagulation time, hemostatic parameters and fibrinolysis parameters were measured. RESULTS: The activated partial thromboplastin time (APTT), which is an assay for blood coagulation time in the intrinsic blood coagulation pathway, of rats fed the 20% sardine protein diet was significantly prolonged compared to that of rats fed the control diet. The prolonged APTT by dietary sardine protein was due to a significant decrease of the activities of plasma blood coagulation factors VIII, IX, XI and XII. On the other hand, dietary sardine protein significantly increased the activity of tissue-type plasminogen activator, and the amount of plasma plasmin-alpha(2)-plasmin inhibitor complex, which are markers of activated plasmin. Moreover, we observed that the 20% sardine protein diet increased the amount of plasma D-dimer, which is a degraded product of the fibrin polymer by plasmin. In the second experiment, the APTT and PT of rats fed the F diet were prolonged compared to those of rats fed the control diet, however the concentration and amount of fibrinolytic parameters in the plasma were almost the same as those of rats fed the control diet. In contrast, the F+S diet not only prolonged APTT and PT, but also increased the concentration and amount of fibrinolytic parameters in plasma. CONCLUSIONS: We consider that the beneficial effects to health and amelioration of cardiovascular and cerebrovascular diseases by fish consumption are caused by a combination of the suppressing effect on blood coagulation of n-3 polyunsaturated fatty acids and the promoting effect on fibrinolysis of fish protein.

Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid.

OBJECTIVE: We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA). METHODS: DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200 u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 microg/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h. RESULTS: In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone. CONCLUSIONS: Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH.

Role of fibrinolysis in tissue-factor-induced disseminated intravascular coagulation in rats - an effect of tranexamic acid.

We clarified the role of fibrinolysis in tissue-factor (TF)-induced rat disseminated intravascular coagulation (DIC) using tranexamic acid (TA). TA suppressed the elevation in D-dimer levels normally observed following TF-induced DIC, and an increase in organ dysfunction was seen. Enhanced fibrinolysis plays an important role in preventing the development of organ failure in TF-induced DIC.

Significance of decreased plasma D-dimer levels following lipopolysaccharide-induced disseminated intravascular coagulation in rats.

Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.

Correlation of PP and PR intervals in premature low birth weight infants.

We examined the developmental change by which autonomic neural activity associated respiration modulates spontaneous firing rate of sinus (SA) node and atrioventricular (AV) conduction in premature infants born with low birth weight (LBWI). The purpose of this study was to clarify whether variation of PR is correlated with that of PP or those are independent in LBWI with immature autonomic nervous system. We investigated, therefore, whether there are spontaneous functional differences in the innervation of SA and AV nodes. Further, we evaluated the maturation of autonomic nervous system progressing in the period, on the day of birth (Day 0) to approximately one month after the birth (Month 1). This study was performed in thirteen LBWI during deep sleep. EEG, EOG, ECG, respiratory waves were digitized on line, spontaneous firing cycle of SA node (PP), and AV nodal conduction time (PR) that were recorded on Day 0 and Month 1. Then, the data were analyzed as follows: 1) correlations among the means and standard deviations (SD) of PP, PR and RR, 2) variance evaluation of PP and PR intervals by Lorenz plot analysis method, 3) correlation analysis among PP, PR and RR intervals by linear regression method and 4) frequency analysis for PP and PR intervals by high-speed Fourier transform method (FFT) and determination of frequency density. The PP interval decreased as growing in the period. Contrary PR interval increased. In LBWI, the automatic nervous activities including parasympathetic nerve activity for spontaneous firing cycle of SA node and ventricular excitation cycle on Month 1 were higher than Day 0. It was assumed that the vagal nerve activity for the AV conduction was enhanced. However, there was no significant change in linear regression slope for the spontaneous firing cycle of SA node and the AV conduction time. Postnatal LF/HF changes for PP and PR obtained by frequency analysis, were opposite. Therefore, it was suggested that the maturity of autonomic nervous system progresses in the period, Day 0 to approximately Month 1, but the variations in PP and PR are independent each other.

Blood coagulation and fibrinolysis of rats fed fish oil: reduced coagulation factors especially involved in intrinsic pathway and increased activity of plasminogen activator inhibitor.

Differences in the coagulation and fibrinolytic system of rats fed a fish oil based diet (fish oil diet) and fed a soybean oil based diet (control diet) were determined. Concentrations of plasma lipids were depressed in rats fed the fish oil diet. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of rats fed the fish oil diet were longer than for the rats fed the control diet. Fish oil intake lowered the activities of most of the blood coagulation factors, and strongly depressed the factors involved in the intrinsic pathway. Fish oil also affected the fibrinolysis of rats. Plasminogen activator inhibitor (PAI) activity was elevated in rats fed the fish oil diet. In this study, both blood coagulation and fibrinolysis were down-regulated by feeding the fish oil diet.

Dietary fish oil and Undaria pinnatifida (wakame) synergistically decrease rat serum and liver triacylglycerol.

Japanese eating habits are characterized by the consumption of various food materials such as cereals, vegetables, fish, shellfish, marine algae and meat. Therefore, properties of functional substances in food materials may be enhanced or lessened by the combination of various food materials. In the present study, we examined how the combination of wakame and fish containing polyunsaturated fatty acids, which are typical Japanese food materials, affected rat lipid metabolism. Rats were fed one of four diets [control diet (C), AIN-76 diet with 5 g/100 g rapeseed oil; wakame diet (W) containing 19.1 g/100 g Undaria pinnatifida (wakame) dried powder in the C diet; fish oil diet (FO), AIN-76 diet with 4.1 g/100 g fish oil; wakame-fish oil diet (W + FO), the FO diet containing 19.1 g/100 g dried wakame powder] for 4 wk. We measured the concentration of lipids in serum and liver and hepatic activities of enzymes involved in fatty acid metabolism. The W diet, FO diet and W + FO diet significantly reduced the concentration of triacylglycerols in the serum and liver compared with the C diet. This decrease in the concentration of hepatic triacylglycerol was greatest in rats fed the W + FO diet. The activity of glucose-6-phosphate dehydrogenase, which is involved in fatty acid synthesis in the liver, of rats fed the W, FO and W + FO diets was lower than that in rats fed the C diet. However, the activities of malic enzyme and fatty acid synthetase did not differ among the four groups. In contrast, the W diet and W + FO diet increased the serum concentration of beta-hydroxybutyrate. Further, the activity of 3-hydroxyacyl-CoA dehydrogenase, which is involved in fatty acid beta-oxidation in the liver, was greater in rats fed the W diet (42%), the FO diet (154%) and the W + FO diet (381%) than in those fed the C diet. Because the decrease in the concentration of triacylglycerol in the liver was greatest when rats were fed wakame and fish oil at the same time (W + FO diet), we conclude that there was a synergistic process affecting fatty acid beta-oxidation in the liver. These results suggest that the simultaneous consumption of fish (fish oil) and wakame decreases the concentration of triacylglycerol in the serum and liver.

Evaluation of respiratory modulation on the pulse wave amplitude in low-birth-weight neonate.

A slow oscillation of sympathetic vasoconstriction (Mayer waves) which is affected by the respiratory movements seems to appear as the fluctuation of pulse wave amplitude (PPG.P-P) in the frequency domain (0.1 Hz). Whether the vasomotor in low frequency has appeared in the pulse wave of the neonate and whether Mayer waves appear as the pulse wave oscillation of the immature low-birth-weight neonate are not fully understood from the point of autonomic nerve regulation mechanism. We therefore analyzed the frequency characteristics of PPG.P-P, respiration wave and its amplitude (RW.P-P) together with the heart rate variability (HRV) to examine the relationships between the frequency spectra.