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The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

Purpose: A portable accelerometer-based navigation system can be useful for achieving the target alignment. Tibial registration is based on the medial and lateral malleoli; however, the identification of landmarks may be difficult in obese (body mass index [BMI] >30 kg/m2) patients whose bones are not easily palpable from the body surface. This study compared tibial component alignment achieved using a portable accelerometer-based navigation system (Knee Align 2) in obese and control groups and aimed to validate the accuracy of bone cutting in obese patients. Methods: A total of 210 knees that underwent primary total knee arthoplasty (TKA) using the Knee Align 2 system were included. After 1:3 propensity score matching, there were 32 and 96 knees in the BMI >30 group (group O) and BMI ≤30 group (group C), respectively. The absolute deviations of the tibial implant from the intended alignment were evaluated in the coronal plane (hip-knee-ankle angle [HKA] and medial proximal tibial angle [MPTA]) and sagittal plane (posterior tibial slope [PTS]). The inlier rate of each cohort, which was defined as tibial component alignment within 2° of the intended alignment, was investigated. Results: In the coronal plane, the absolute deviations of the HKA and MPTA from the intended alignment were 2.2° ± 1.8° and 1.8° ± 1.5° in group C and 1.7° ± 1.5° and 1.7° ± 1.0° in group O (P=1.26, and P=0.532). In the sagittal plane, the absolute deviations of the tibial implant were 1.6° ± 1.2° in group C and 1.5° ± 1.1° in group O (P=0.570). The inlier rate was not significantly different between group C and group O (HKA: 64.6% vs 71.9%, P=0.521; MPTA: 67.7% vs 78.1%, P=0.372; PTS: 82.2% vs 77.8%, P=0.667). Conclusion: The accuracy of tibial bone cutting for the obese group was comparable to that of the control group. An accelerometer-based portable navigation system can be useful when attempting to achieve the target tibial alignment in obese patients.

Purpose Restricted kinematic alignment (rKA) is a modified technique of kinematic alignment (KA) total knee arthroplasty (TKA) for patients with an outlier or atypical knee anatomy, striving to preserve the native knee joint line parallel to the ground in a bipedal stance. This study aimed to evaluate the accuracy of rKA TKA with a computed tomography (CT)-based patient-specific instrument (PSI) to achieve the preoperative plan with the joint line parallel to the ground level. Methods Using a CT-based PSI, 74 closed-leg standing long-leg radiographs were obtained before and after rKA TKA. The hip-knee-ankle angle (HKA), joint line orientation angle (JLOA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. Bone resection accuracy was evaluated by postoperative HKA deviations from the planned alignment and joint line by postoperative JLOA deviations from the ground level. Results The mean postoperative JLOA and HKA were 2.1° valgus (range, standard deviation: 6.0° valgus to 3.0° varus, 2.0) and 2.6° varus (3.5° valgus to 12.5° varus, 3.2), respectively. Postoperative JLOA and HKA were within ± 3° of the planned alignment for 69% and 86% of cases, respectively. Conclusions Despite a static verification, we clarified how the joint line after rKA TKA was reproduced in the closed-leg long leg radiographs to mimic the limb position during gait. However, this imaging method is not well-established, and lack of long-term survivorship and the relationship between joint line inclination and clinical outcomes represented limitations of this study. Level of evidence Level IV.

Background: The number of elderly sports participants is increasing, and the possibility of return to sport (RTS) has become an important part of surgical decision making in this population. Purpose: To investigate RTS after elective spinal surgery in elderly patients. Study Design: Case series; Level of evidence, 4. Methods: We enrolled patients aged ≥65 years with a history of preoperative or preinjury sports participation who underwent elective spinal surgery at a single institution between 2019 and 2021. At minimum 12-month follow-up, a questionnaire was administered to each participant to assess postoperative RTS, timing of return, frequency and type of pre- and postoperative activities, and satisfaction (scored 1-10). Descriptive statistical analyses were performed, and regression models were developed to examine the influence of age and sex, as well as surgical site, on RTS. Results: A total of 53 patients (mean ± SD age, 73.8 ± 5.2 years; 24 women) were included, and 23 (43.4%) returned to sports at a median 6 months (interquartile range, IQR, 2-6 months). The RTS rate by surgical site was 17 of 34 (50%) for the lumbar spine and 6 of 17 (35.3%) for the cervical spine. There were no statistically significant differences in RTS rate by surgical site, age, or sex. Overall, 6 of 17 patients returned to golf, 4 of 6 to dance, 2 of 5 to swimming, and 1 of 5 to tennis. Of patients who returned, 34.8% participated in sports 5 times per week and 26.1% participated 3 times per week. The median satisfaction score after RTS was 8 (IQR, 6-9). Conclusion: RTS after spinal surgery was achieved in 43% patients at 1-year minimum follow-up, with high satisfaction scores. More than half of the returning patients participated in sports activities ≥3 times per week.

Blinatumomab (Blincyto® injection solution) is classified as a bispecific T-cell engaging (BiTE) antibody and is intended for the treatment of relapsed/refractory acute lymphoblastic leukemia. It requires continuous infusion to maintain therapeutic levels. Therefore, it is often administered at home. Monoclonal antibodies, which are administered intravenously, have the potential to leak depending on the nature of the administration devices. Therefore, we investigated device-associated causes of blinatumomab leakage. We observed no apparent changes to the filter and its materials after exposure to the injection solution and surfactant. From scanning electron microscopic images, precipitate on the surface of the filters was observed after physical stimulation of the injection solution. Therefore, physical stimulations should be avoided during the prolonged administration of blinatumomab. In conclusion, the findings of this study assist in the safe administration of antibodies using portable infusion pumps, taking into consideration the composition of drug excipients and the choice of filter type and structure.

Although excellent results of cephalomedullary nailing for femoral trochanteric fractures have been reported, excessive sliding has recently been noted as a cause of lag screw cut-out. Excessive sliding is reported as sliding of ≥8mm, which occurs in approximately 40%of cases. This study aimed to evaluate the risk factors for excessive sliding.Overall, 551 patients who underwent cephalomedullary nail surgery between 2016 and 2021 were recruited. Patients aged ≥65 years who underwent preoperative computed tomography (CT), experienced low-energy trauma, and received follow-up for4 months were included. Cases were retrospectively reviewed for their postoperative sliding distance and the percentage of excessive sliding (8 mm). 3D-CT classification, reduction pattern (subtypes A, N, and P) in the lateral view, medullary mismatch, and implant type (short/long Gamma3 nail and INTERTAN) were investigated fortheirimpact on sliding distance andtheincidence of excessive sliding. Complication rates (lag screw cut-out and non-union) were also assessed.Overall, 263 patients (mean age, 84.0±7.4; 186 women) were recruited. The median (range) sliding distance was 3.5 (0-20) mm, and 42 cases (16.0%) had excessive sliding. Sliding distance was significantly smaller in the 2-fragment group than in the 3-fragment group (GP+GA and GP+L) (p=0.02); however, there were no significant differences between the 2-fragment and other fracture-type groups, including the 3-fragment group (GP, GA, GP ± GA, GP ± L), 4-fragmentgroup(GP/L, GP ± L/GA, GP±GA/L), and 5-fragmentgroup. There was no significant difference in sliding distance according to postoperative reduction type between the groups (p=0.83) and no correlation between medullary mismatch and sliding distance. The amount of sliding and rate of excessive sliding were significantly lower in the INTERTAN group than in the Gamma3 nail groups (p0.01). Logistic regression analysis with excessive sliding as the variable revealed reduction type P as the only risk factor (p=0.024, odds ratio 2.99). There were three lag screw cut-out (1.1%) cases and one non-union (0.4%) case.Postoperative subtype P is a risk factor for excessive sliding; there was significantly less sliding in the INTERTAN nail group. It is necessary to avoid reduction to subtype P to prevent postoperative excessive sliding.IV.

To clarify the genetic mechanisms of fertility restoration in sorghum F1 hybrids produced in Japan ('Ryokuryu', 'Hazuki', 'Haretaka', 'Natsuibuki', 'Hanaaoba', 'Akidachi' and 'Kazetachi'), we analyzed QTLs for fertility restoration using seven F2 populations derived from those hybrids. By QTL mapping with a series of SSR markers, we detected three major QTLs for fertility restoration. These data and the results of haplotype analysis of known fertility restorer (Rf) genes showed that qRf5, corresponding to the Rf5 locus, was the most widely used Rf gene for fertility restoration of sorghum F1 hybrids among the lines tested. Other major Rf genes detected were qRf8, corresponding to Rf1, and qRf2, corresponding to Rf2. QTLs for grain weight also corresponded to these Rf loci. A minor QTL, qRf3, may also affect restoration of fertility. Our data show that three major Rfs-Rf1, Rf2, and Rf5-were used in F1 hybrid sorghum production in Japan. This knowledge can be used to improve the efficiency of the F1 sorghum breeding program.

The choice of graft for anterior cruciate ligament (ACL) reconstruction remains controversial. The quadriceps tendon (QT) autograft is a good alternative for ACL reconstruction. However, concerns regarding its use in short-statured patients, related to donor site morbidity, anterior knee pain, or loss of muscle strength remain. This study aimed to compare muscle strength and morbidity between patients with short and normal statures following ACL reconstruction with a QT autograft.A total of 73 female patients (mean age, 33.8 ± 11.5 years) who underwent primary ACL reconstruction between 2016 and 2019 were included. Patients were categorized into two groups: group S, with a height ≤ 163 cm, and group L, with a height 163 cm. Muscle strength, harvesting site morbidity, and ACL-return to sport after injury scale (ACL-RSI) were evaluated, with a mean timing of the follow-up of 9.0 ± 2.3 months.The mean quadriceps strength for the isokinetic measurements at 60° and 240° was 65.0% and 74.0% in group S, respectively, and 70.0% and 75.7% in group L, respectively. There was no significant difference in the postoperative muscle strength or mean ACL-RSI (group S, 70.0; group L, 65.9) between the groups. No donor site morbidity was observed in either group.Muscle strength recovery, morbidity, and readiness to return to sports were similar in both groups, which supports the possibility of QT autografts for patients with a small stature. The results of this study may provide useful information for surgeons who are hesitant to perform QT autografts because of patient physique.IV.

Occupational exposure to anticancer drugs may increase the risk of cancer and the risk of miscarriage and stillbirth, and cause other adverse events such as hypersensitivity reactions, skin/mucous reactions, and digestive symptoms. Several studies have investigated the use of closed-system drug-transfer devices (CSTDs) to reduce the environmental pollution by hazardous drugs. However, few reports have verified whether CSTDs contain the hazardous drugs within the vials. The BD PhaSealTM System is a CSTD that is frequently used in Japan. However, the fit of each anti-cancer drug vial has not been investigated. We investigated the fit of 71 major anti-cancer drug vials and protectors released and frequently used in Japan by means of a pressure compatibility test that we developed. The pressure compatibility test involved attaching a three-way stopcock to a Luer lock syringe and attaching an injector in line with the syringe. The pressure tubing was connected to the other side of the three-way stopcock and connected to the pressure inlet of the pressure gauge. The pressure in the anti-cancer drug vial was raised to 100 kPa and connected/disconnected repeatedly. If the pressure fluctuation during the 10th connection was within 6%, it was defined as "no change", and the compatibility of the protector and the vial was evaluated. The median pressure reduction rates at the 10th connection ranged from -1.98% to -4.95%. All drugs surveyed had an error rate within 6%. The BD PhaSealTM Protector was shown to be compatible with the 71 anti-cancer drugs we surveyed.

Background Many reports support the use of closed system drug transfer devices (CSTDs) to protect against exposure to hazardous drugs during their preparation. However, leakage may occur if the CSTD fails to maintain hermeticity when fitted into the vial. Our aims were to devise a measure to prevent HD exposure and to develop a test method to verify CSTD function when a BD PhaSeal™ protector is used in HD preparation. Methods We selected the BD PhaSeal™ System, which is the most commonly used CSTD device in Japan. The sealability of the BD PhaSeal™ protector and vial is considered to be due to the hermeticity of the protector and the rubber stopper of the vial. We constructed a protector with a damaged sealing rim and monitored the pressure fluctuation 10 times when the BD PhaSeal™ injector was connected to the pressurized vial. Results The reduction in pressure of the protector in the group without a damaged sealing rim was 5%, while that in the group with the damaged sealing rim was 84.9%. Conclusion It was suggested that leakage occurred through the gap between the protector and the rubber stopper when using a vial that was not in close contact with the sealing rim. In this study, we developed a test that can be easily used to verify the compatibility of the BD PhaSeal™ protector and a vial in the clinical setting. Thus, when new hazardous drugs are being prepared, these measures can be taken to ensure that the risk of exposure is reduced or eliminated.

Background/Purpose Hamstring tendon autografts are commonly used for double-bundle anterior cruciate ligament reconstruction (DB-ACLR). If the volume of the semitendinosus (ST) tendon is insufficient, the gracilis (G) tendon is also harvested. Additional harvesting of the G autograft can affect patients’ short-term postoperative outcome, such as muscle recovery; thus, preoperative information about whether an additional G autograft is needed would be useful. The purpose of this study was to investigate whether preoperative measurement of the ST tendon using ultrasonography could inform the intraoperative decision to harvest the G tendon. Methods We enrolled 20 patients (13 men and seven women) who underwent DB-ACLR between October 2017 and March 2019. The mean patient age was 28.5 years. The ipsilateral ST tendon was measured using ultrasonography before surgery. Measurements included the diameter and breadth of the short-axis image. The cross-sectional area (CSA) was calculated from these measurements. During surgery, when two grafts with diameters of ≥ 5.0 mm could not be made, the G tendon was also harvested. Patients were categorized into two groups: the ST group where only the ST tendon was harvested, and the semitendinosus gracilis tendon (STG) group where the ST and G tendons were both harvested. The CSA value was compared between the two groups, and the cutoff value was calculated. Results In the ST group (n = 8), the mean diameter and breadth of the semitendinosus tendon were 4.21 and 2.34 mm, respectively. In the STG group (n = 12), the mean diameter and breadth of the ST tendon were 3.39 and 1.78 mm, respectively. The CSAs calculated for the ST group and the STG group were 7.74 mm2 and 4.79 mm2, respectively. A cutoff value of 7.0 mm2 was found to correspond to a specificity and sensitivity to harvest the G tendon of 87.5% and 75.0%, respectively. Conclusions The preoperative CSA of the ST tendon determined using ultrasonography can, therefore, be informative for deciding whether to harvest the G tendon for DB-ACLR. The results of this study provide valuable information for graft selection in anterior cruciate ligament reconstruction. Level of Evidence IV (Retrospective case series design).

Purple corn is a maize variety (Zea mays L.) with high anthocyanin content. When purple corn is used as forage, its anthocyanins may mitigate oxidative stresses causing lower milk production in dairy cows. In this study, we analyzed quantitative trait loci (QTLs) for anthocyanin pigmentation of maize organs in an F2 population derived from a cross between the Peruvian cultivar 'JC072A' (purple) and the inbred line 'Ki68' (yellowish) belonged to Japanese flint. We detected 17 significant QTLs on chromosomes 1-3, 6, and 10. Because the cob accounts for most of the fresh weight of the plant ear, we focused on a significant QTL for purple cob on chromosome 6. This QTL also conferred pigmentation of anther, spikelet, leaf sheath, culm, and bract leaf, and was confirmed by using two F3 populations. The gene Pl1 (purple plant 1) is the most likely candidate gene in this QTL region because the amino acid sequence encoded by Pl1-JC072A is similar to that of an Andean allele, Pl-bol3, which is responsible for anthocyanin production. The markers designed for the Pl1 alleles will be useful for the breeding of F1 lines with anthocyanin pigmentation in cobs.

Anterior cruciate ligament (ACL) tears continue to be one of the most common sports injuries. ACL reconstruction (ACLR) are also common, and the number of ACL reconstruction (ACLR) has increased over the last years [1, 2]. Despite improved methods and techniques for primary ACLR, graft re-rupture rates have been reported between 0 and 5.6% [3]. Subsequently, the number of ACL revision surgeries has increased [4]. Outcomes after revision ACLR are generally inferior to those after primary ACLR. Only 43% of patients have been reported to return to their previous activity level, a significantly lower figure than that reported for primary ACLR [5]. In addition, the rates of re-revision ACLR after revision ACLR are higher than after primary ACLR (6.5% at 5 years and 9.0% at 8 years) [6]. The exact reasons why revision ACLR results in inferior outcomes are not completely known. However, it is a common perception for surgeons that revision ACLR is a challenging operation.

To clarify the genetic mechanisms of fertility restoration in sorghum F1 hybrids produced in Japan (‘Ryokuryu’, ‘Hazuki’, ‘Haretaka’, ‘Natsuibuki’, ‘Hanaaoba’, ‘Akidachi’ and ‘Kazetachi’), we analyzed QTLs for fertility restoration using seven F2 populations derived from those hybrids. By QTL mapping with a series of SSR markers, we detected three major QTLs for fertility restoration. These data and the results of haplotype analysis of known fertility restorer (Rf) genes showed that qRf5, corresponding to the Rf5 locus, was the most widely used Rf gene for fertility restoration of sorghum F1 hybrids among the lines tested. Other major Rf genes detected were qRf8, corresponding to Rf1, and qRf2, corresponding to Rf2. QTLs for grain weight also corresponded to these Rf loci. A minor QTL, qRf3, may also affect restoration of fertility. Our data show that three major Rfs—Rf1, Rf2, and Rf5—were used in F1 hybrid sorghum production in Japan. This knowledge can be used to improve the efficiency of the F1 sorghum breeding program.

A central patellar (CP) portal can be used to view the native femoral insertion site of the anterior cruciate ligament (ACL). It aids in the drilling of an anatomical tunnel; however, its impact on the patellar tendon and the infrapatellar fat pad remains a concern. The aim of this study was to investigate complications associated with the CP portal use in arthroscopic ACL reconstruction (ACLR). A total of 105 patients (107 knees, 60 females) who underwent ACLR with a CP portal from 2012 to 2017 were included in this study. The mean age was 28.3 ± 12.4 years. All surgeries were single-bundle reconstructions using the trans-tibial technique via the CP and anteromedial portals. Post-operative events, magnetic resonance imaging (MRI), and arthroscopic findings associated with CP portal creation were evaluated. Five patients (4.7%) had symptomatic postoperative complications, which included two patients with patellar tendonitis and three patients with fibrosis in the anterior knee compartment. Abnormal signal intensity of the patellar tendon on MRI and increased thickness at the CP portal area were found in 18 of 25 knees (72%). Three of 56 knees (5.4%) that underwent second-look arthroscopy showed fibrosis of the infrapatellar fat pad. Seven patients (12.5%) showed hypertrophy of the ligamentum mucosum. The rate of symptomatic complications associated with CP portal placement was 4.7%; however, abnormal MRI or follow-up arthroscopy findings were much higher than clinically symptomatic patients. This study suggests that CP portal placement could provoke anterior knee compartment fibrosis or hypertrophy. IV.

The aim of this study was to evaluate the usefulness of low-level laser therapy (LLLT) for the control of painful stomatitis in patients with hand-foot-and-mouth disease (HFMD).LLLT has been successfully applied to various painful oral mucosal diseases, although there have been few reports on LLLT for HFMD patients.Through a randomized double-blind placebo controlled trial, the painful period of HFMD stomatitis was compared between the LLLT group (n=11) and the placebo LLLT one (n=9), which had similar clinical backgrounds. The LLLT parameters supplied were as follows: wavelength of 830 nm, power of 30 mW, frequency of 30 Hz, and energy output of 1.1 J/cm2. Acceptability and safety of the treatment were also evaluated.The painful period was shorter in the LLLT group (4.0 +/- 1.3 days) than in the placebo LLLT one (6.7 +/- 1.6 days) with a statistically significant difference (p0.005). The treatment was judged acceptable for 90.0% (18 of 20) of patients. No adverse events were observed in any cases.LLLT is a useful method to control HFMD stomatitis by shortening the painful period, with its high acceptability and lack of adverse events.

Sho-ju-sen (SK), a Japanese herbal medicine with a nourishing tonic action, is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) (SS), and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. et Zucc) (PN) and Ginseng roots (Panax ginseng C. A. Meyer) (PX) in the ratio 8:1:1. In this study, an elevated plus-maze test in mice was carried out to assess whether SK had an anxiolytic effect. No significant change was observed in either the plus-maze or activity test following a single administration of SK (10 and 20 mL/kg p.o.). However, mice allowed a free intake of SK (10% solution) for 5 days and longer showed a significant prolongation of the time spent in the open arms (an anxiolytic effect), as long as that caused by the benzodiazepine anxiolytic diazepam (1 mg/kg p.o.). SK (1%, 3% and 30% solutions for 7 days) tended to develop the anxiolytic effect. Of the constituents of SK, SS (8% solution), but not PN (1% solution) or PX (1% solution), resulted in the anxiolytic effect. Except for a slight acceleration in the motor activity by PN (1% solution), no significant change in the motor activity was produced by any treatment with SK, SS or PX. The combined treatment of SK (10% solution) or SS (8% solution) with 1 mg/kg diazepam enhanced the anxiolytic effect. Flumazenil (0.1 mg/kg s.c.), a benzodiazepine receptor antagonist, alone did not change the time spent in the open arms. However, it completely reversed the anxiolytic effect of SK, SS and diazepam. The present results suggest that: (1) long-term treatment with SK develops an anxiolytic effect, (2) SS is the main constituent for the anxiolytic effect of SK, and (3) benzodiazepine receptors are involved in the anxiolytic effect of SK and SS. Copyright © 2001 John Wiley & Sons, Ltd.

N. suralis, taken from a patient in the chronic state of “Subacute Myelo-Optico-Neuropathy (SMON)” was examined by electron microscopy. The nerve showed a depletion of myelinated nerve fibres. Vacuoles or degenerated mitochondria were observed in the axis cylinders of myelinated and unmyelinated nerve fibres. Schwann cells were increased in number and many of them were atrophic. Onion-bulb formations were seen diffusely; regeneration of myelinated nerve fibres was sparse.

Eye movements and facial expressions were assessed in 177 normal neonates and infants under 150 days of age after the examiner gazed into their eyes for 20 seconds. Blinking to a threatening stimulus and turning of the eyes towards a red object near the examiner's face were tested. The eye movements abruptly changed from fine nystagmoid movements to distinct rolling movements suggesting observation of the examiner's face after 70–80 days of age. Rapid turning of the eyes towards the red object also appeared from the same age, while blinking developed gradually after 40 days of age. Most infants under 80–90 days of age knitted their brows and showed esophoria in response to the examiner's face or facial movements, but such responses gradually disappeared after 90 days of age when social smiles developed. Eye movements and facial expressions during early infancy are very informative in developmental evaluations.