Unintentional drug-related deaths in people with mental illness in NSW Australia, 2012-2016: a retrospective cohort study.

PURPOSE: People with mental illness are a vulnerable and stigmatised group with poor health outcomes including greater premature mortality. This study aimed to investigate trends and rates of change in unintentional drug-related deaths for people with mental illness, describe types of medicines involved, and identify populations at risk in a cohort from New South Wales, Australia. METHODS: Features of unintentional drug-related deaths for people with mental illness between 2012 and 2016 were identified in a retrospective review of data from the National Coronial Information System. RESULTS: A total of 495 unintentional drug-related deaths were identified (1.6 deaths/100,000 population), showing an upward trend (p < 0.01). The most common substance involved was diazepam in both genders (males 135/319, 42%, female 76/176, 43%) and more than one contributory drug was included in 80% of cases. Between 2012 and 2016, amphetamine-related deaths showed the highest increase (3.2-fold), followed by codeine (2.5-fold) and quetiapine (2.5-fold). Males (RR 1.8, 95% CI 1.5-2.2) and people aged 35-44 (RR 1.7, CI 1.3-2.2) were more likely to die from unintentional drug-related deaths compared with the reference (females and people aged 25-34). CONCLUSION: This study found that the drugs commonly involved in deaths are also the drugs commonly used by and prescribed to people with mental illness. There were also significant differences between gender, age group, and marital status in the trend and rate of unintentional drug-related deaths for people with mental illness. A multifaceted approach encompassing both pharmaceutical prescribing and targeted public health messaging is required to inform intervention and prevention strategies.

Anteromedial plating without filling the gap in open wedge high tibial osteotomy may increase the risk of screw breakage, which can be reduced by medial plating and bone-substitute insertion.

BACKGROUND: Open wedge high tibial osteotomy (OWHTO) brings new complications such as screw breakages with or without correction loss and time-dependent increased posterior tibial slopes (PTS) due to the opening gap. For preventive purposes, we changed our OWHTO procedure from anteromedial plating without filling the gap (non-grafted group, n = 40, 2009-2012) to medial plating with bone-substitute insertion (grafted group, n = 45, 2012-2015). The objectives of this study were to evaluate the complication patterns and the effects of the modifications. METHODS: Patients undergoing OWHTO with TomoFix plates were included in this retrospective study. Demographics, clinical outcomes (flexion range and Japanese Orthopaedic Association score) and radiological outcomes (femorotibial angle) were assessed in both groups pre-operatively and 2-years postoperatively. The plate installation angle [PIA] and screw insertion depth [SID] were measured on computed tomographic slices at 6 months. PIA/SID was defined as the angle between the tibial anteroposterior axis and plate-width axis/the distance between the proximal screw tip and the proximal tibiofibular joint. The non-grafted group was further divided into complication and non-complication subgroups. Screw breakages were assessed during plate removal (1.5-2.5 years postoperatively). RESULTS: There were no differences in baseline characteristics or radiological/clinical outcomes between the non-grafted and grafted groups. There were 0 and 11 complications in the grafted and non-grafted groups, respectively. Complications included 7 screw breakages, 4 correction losses, and 5 time-dependent increased PTS with some overlaps. PIA and SID were significantly lower (p < 0.001) and higher (p < 0.001), respectively, in the grafted group and significantly lower (p = 0.018) and higher (p = 0.040), respectively, in the non-complication subgroup within the non-grafted group. The cutoff value of PIA for complications was calculated at 48.0°. CONCLUSIONS: Medial plating OWHTO (PIA<48°) using bone-substitute with deeper screw insertion reinforces the opening gap for better angular stability compared with anteromedial plating without bone-substitute.

Influence of lateral hinge fractures on biplanar medial closing-wedge distal femoral osteotomy for valgus knee: a new classification of lateral hinge fracture.

BACKGROUND: The purpose of this study was to examine the influence of lateral hinge fractures in medial closing-wedge distal femoral osteotomy (MCWDFO) on bone union. METHODS: Twenty-one patients were followed-up for more than 1 year after MCWDFO. The incidence and type of hinge fracture, as well as the course of bone healing, were investigated. Slow healing was defined as bone union was not obtained until 3 months after surgery. RESULTS: Hinge fractures were observed in 12 cases (57%). There were three types of hinge fractures. Type 1: the lateral cortex was completely cut through (4 cases), type 2: the osteotomy line was too proximal (6 cases), and type 3: the hinge point was significantly medial (2 cases). There was a significant difference in the mean correction angles between hinge fracture and no-fracture cases, with the mean angles being 13.8 ± 4.0° and 9.6 ± 3.1°, respectively. Sixty-seven percent (8/12) of cases with hinge fractures developed slow healing. Among the hinge fracture cases, when there was no displacement of the hinge fracture and good contact with the anterior flange, 40% (2/5) of cases developed slow healing. If there was displacement of the hinge or no contact of the anterior flange, 86% (6/7) of cases developed slow healing. In contrast, only 11% (1/9) of subjects who did not have a hinge fracture, developed slow healing. In 67% (6/9) of cases with slow healing, a correction loss of 2° or greater (average: 4.3 degrees valgus) was observed. There were no cases of non-union. Clinical outcomes at 1 year showed no significant difference between the groups with and without hinge fractures. CONCLUSIONS: There is a very high risk of hinge fracture in patients undergoing MCWDFO. Hinge fractures often lead to slow healing and a loss of correction. We recommend the endpoint of the distal lateral cortex of the femur as the ideal hinge point for the prevention of hinge fractures. Bone union is obtained slowly in even all hinge fracture cases without revision surgery. Consequently, surgical results are not affected by the occurrence of hinge fracture at 1 year.

Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).

Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children.

PURPOSE: Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1. METHODS: This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an estimated glomerular filtration rate >45 mL/min/1.73 m2, if aged ≥12 months, or normal serum creatinine, if aged <12 months. The primary end point was percent change in spot urinary oxalate to creatinine ratio (UOx:Cr) from baseline to month 6. Secondary end points included proportion of patients with urinary oxalate ≤1.5× upper limit of normal and change in plasma oxalate. RESULTS: All patients (N = 18) completed the 6-month primary analysis period. Median age at consent was 50.1 months. Least-squares mean percent reduction in spot UOx:Cr was 72.0%. At month 6, 50% of patients (9/18) achieved spot UOx:Cr ≤1.5× upper limit of normal. Least-squares mean percent reduction in plasma oxalate was 31.7%. The most common treatment-related adverse events were transient, mild, injection-site reactions. CONCLUSION: Lumasiran showed rapid, sustained reduction in spot UOx:Cr and plasma oxalate and acceptable safety in patients aged <6 years with PH1, establishing RNA interference therapies as safe, effective treatment options for infants and young children.

Developing and testing a set of quality indicators for pharmacist home visit services: A mixed methods study in Japan.

OBJECTIVE: Quality indicators (QIs) are an important mechanism by which health services can be evaluated. We aimed to develop a set of QIs for pharmacist home visit services and assess their measurement properties. METHODS: A three-step procedure was applied: (1) Selection of existing content-validated QIs from the international literature and the development of QIs based on national guidelines and home healthcare professionals' opinions; (2) Expert panel consensus of a preliminary set of QIs using the RAND/UCLA Appropriateness Method; (3) Field testing to evaluate their measurement properties (feasibility, applicability, improvement potential, discriminatory capacity, sensitivity to change, acceptability and implementation issues) followed by exploratory semistructured interviews in Japan. RESULTS: Fifty-two preliminary QIs were prepared and 45 were judged as "appropriate"by the expert panel. Sixty-one community pharmacies were recruited to this study with 41 contributing QI data monthly over the 6-month period. Field testing showed that 20 QIs met six measurement properties (ie, feasibility, applicability, improvement potential, discriminatory capacity, acceptability and implementation issues). Nine of these QIs also had high sensitivity to change. Additionally, interviews identified that the main positive impact on practice of using QIs was the early detection of causes of drug-related problems but a negative impact was decrease of pharmacists' motivation. Auto extraction of QIs was seen as a major facilitator, given the time taken to manually extract QI data. CONCLUSIONS: A set of QIs for pharmacist home visit services was rigorously developed and tested. This QI set may be useful in evaluating the quality of such services.

Independent predictors affecting the reduction of pediatric supracondylar humerus fractures: a retrospective cohort study.

BACKGROUND: Although it is important to understand the risk factors affecting the reduction of pediatric supracondylar humerus fractures (PSHFs), no inclusive study has been conducted so far. We performed a retrospective cohort study to identify the risk factors affecting the quality and difficulty of reduction for PSHFs. METHODS: We reviewed 160 cases with a PSHF that had been surgically treated in our hospital between January 2007 and December 2019. We investigated age, sex, injured side, body mass index (BMI), modified Gartland classification, neurological deficit or an absent radial artery pulse at an initial examination, start time of the operation, waiting time from injury to surgery, operative time, reduction technique, and perioperative radiographic parameters. We calculated independent predictors of unsuccessful closed reduction, prolonged operative time, and malreduction using multivariate analyses. RESULTS: In a logistic regression analysis, modified Gartland type III was a significant predictor of unsuccessful closed reduction (OR 14.50 [95% CI 4.03-51.90]; P < 0.01) and BMI was a significant predictor of malrotation (OR 1.59 [95% CI 1.06-2.39]; P = 0.025). In a multiple linear regression analysis, BMI and open reduction were significant predictors of prolonged operative time (BMI, P = 0.011; open reduction, P < 0.01). CONCLUSIONS: If closed reduction fails, we should not hesitate to immediately switch to other methods. Obesity was an independent predictor of both prolonged operative time and malrotation, a finding that has not been previously reported. Rotational alignment should be carefully checked, especially for obese children, and accurately be reduced. Open reduction also extended operative time.

Plate removal without loss of correction after open-wedge high tibial osteotomy is possible when posterior cortex bone union reaches osteotomy gap center even in incompletely filled gaps.

PURPOSE: The study aimed to evaluate the optimal timing for plate removal after open-wedge high tibial osteotomy (OWHTO) without loss of correction and to investigate risk factors for loss of correction after plate removal. The study presents the hypothesis that plate removal without loss of correction was possible when gap filling reached zone 2 (25-50%) on anteroposterior radiographs. METHODS: Ninety-one patients (101 knees) who underwent OWHTO using the TomoFix® plate were enrolled. Plate removal was performed at an average 16.4 ± 5.4 months after OWHTO. Clinical evaluation included plate-related symptoms, the Japanese Orthopedic Association Knee Score (JOA score), and Oxford Knee Score (OKS). Radiological outcomes, including the hip-knee-ankle angle (HKA), weight-bearing line ratio (WBLR), medial proximal tibial angle (MPTA), and posterior tibial slope (PTS), were evaluated preoperatively, at plate removal and at 1 year after plate removal. Computed tomography (CT) was performed at plate removal to evaluate the flange bone union, progression rates of gap filling, and posterior cortex bone union. In addition, the risk factors for loss of correction after plate removal were evaluated. RESULTS: At plate removal, 63 (62.4%) knees had plate-related symptoms (mild, 56 knees; moderate, 7 knees; severe, 0). After plate removal, the JOA score did not change, whereas OKS further improved; six knees developed loss of correction. On CT evaluation at plate removal, the flange bone union was achieved in all cases; the progression rates of gap filling and posterior cortex bone union were 47.0% ± 16.6% and 62.8% ± 16.5%, respectively. A posterior cortex union rate of < 43.3% was the only predictor for loss of correction after plate removal (odds ratio: 1.38, P < 0.01). CONCLUSIONS: Plate removal without loss of correction after OWHTO was possible when bone union of the posterior cortex reached the center of the osteotomy gap even in incompletely filled gaps. LEVEL OF EVIDENCE: Therapeutic case series, Level IV.

Optimizing leg length correction in total hip arthroplasty.

PURPOSE: Residual feeling of leg length discrepancy (LLD) is a common cause of patient dissatisfaction following total hip arthroplasty (THA). The purpose of this study is to propose a method for determining an optimal leg length correction goal in THA. METHODS: We conducted a retrospective study of 132 patients to examine the radiographic LLD (R-LLD), perceived LLD (P-LLD), and whether or not the patient has an uncomfortable feeling about the leg length after THA. RESULTS: The residual discomfort rate in all patients was 9.1% (12/132 patients), and ten of these 12 patients felt uncomfortable due to a longer leg length. When R-LLD was within 7 mm, the rate was 6.8% (8/118 patients), which is nearly equal to the rate of 7.8% (5/64 patients) in cases in which R-LLD was within 2 mm. On the other hand, when R-LLD was 8 mm or more, the rate was 57.1% (4/7 patients). CONCLUSIONS: The results of our study show that 7 mm may be a reasonable threshold for reducing the residual discomfort. However, even with little or no R-LLD, some patients will continue to experience discomfort. We think that this is because of pre-operative differences between R-LLD and P-LLD in such cases. If the patient has a pelvic declination on the affected hip side and a lumbar scoliosis angle that is convex toward the affected hip side before surgery, the ideal length may be a little shorter than the radiographic isometry, since such patients are likely to feel a longer leg length than that shown radiographically.

[A Case of Symptomatic Nonhemorrhagic and Nonthrombotic Cervicothoracic Epidural Varices].

We describe an extremely rare case of symptomatic nonhemorrhagic and nonthrombotic cervicothoracic epidural varices. A 45-year-old man presented with back pain and left leg weakness. MRI revealed an epidural mass at the Th1 level, on the dorsal aspect of the spinal canal on the right side. Although MRI scans obtained 10 days after the initial scans(obtained at the first visit to our hospital)revealed disappearance of the epidural mass at the Th1 level on non-contrast images and on images obtained 90 s after intravenous gadolinium injection, the images obtained 5 min after intravenous gadolinium injection revealed the epidural mass at the Th1 level. The patient's symptoms had resolved;therefore, we administered conservative therapy. Although the patient initially continued to show symptomatic improvement, he developed clinical relapse without any evidence of relapse on MRI. Left leg weakness and back pain worsened a year later, and repeat MRI revealed reappearance of the epidural mass at the Th1 level. Cervicothoracic laminectomy revealed nonhemorrhagic epidural varices, and we performed total en bloc resection. Histopathological examination of the resected specimen showed nonthrombotic varices. The patient's neurological symptoms improved postoperatively without relapse. Intermittent expansion of varicose veins in accordance with changes in venous pressure may cause compressive myelopathy. Clinicians should consider the possibility of spinal epidural varices in patients who present with spinal epidural lesions that tend to show intermittent improvement with subsequent worsening.

Natural History of Perinatal and Infantile Hypophosphatasia: A Retrospective Study.

OBJECTIVE: To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia. STUDY DESIGN: Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age <6 months were eligible: vitamin B6-dependent seizures, respiratory compromise, or rachitic chest deformity (NCT01419028). Patient demographics and characteristics, respiratory support requirements, invasive ventilator-free survival, and further complications of hypophosphatasia were followed for up to the first 5 years of life. RESULTS: Forty-eight patients represented 12 study sites in 7 countries; 13 patients were alive, and 35 were dead (including 1 stillborn). Chest deformity, respiratory distress, respiratory failure (as conditioned by the eligibility criteria), failure to thrive, and elevated calcium levels were present in >70% of patients between birth and age 5 years. Vitamin B6-dependent seizures and respiratory distress and failure were associated significantly (P < .05) with the risk of early death. Serum alkaline phosphatase activity in all 41 patients tested (mean [SD]: 18.1 [15.4] U/L) was below the mean lower limit of normal of the reference ranges of the various laboratories (88.2 U/L). Among the 45 patients with relevant data, 29 had received respiratory support, of whom 26 had died at the time of data collection. The likelihood of invasive ventilator-free survival for this cohort decreased to 63% at 3 months, 54% at 6 months, 31% at 12 months, and 25% at 5 years. CONCLUSIONS: Patients with perinatal or infantile hypophosphatasia and vitamin B6-dependent seizures, with or without significant respiratory distress or chest deformities, have high morbidity and mortality in the first 5 years of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419028.

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis.

INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.

Comparison of Clinical and Radiologic Outcomes Between Normal and Overcorrected Medial Proximal Tibial Angle Groups After Open-Wedge High Tibial Osteotomy.

PURPOSE: To evaluate whether the overcorrected medial proximal tibial angle (MPTA) affects the clinical outcomes after open-wedge high tibial osteotomy (OWHTO) and to assess the correlation between knee joint line obliquity (KJLO) changes and the compensatory changes in the hip and ankle joints. METHODS: Consecutive patients who underwent OWHTO from July 2006 to August 2015 were included. Exclusion criteria were bilateral OWHTO and follow-up of <2 years. The patients were retrospectively divided into 2 groups according to postoperative MPTA; a normal group (MPTA <95°) and an overcorrected MPTA group (MPTA ≥95°). The groups were compared with respect to the clinical and radiologic outcomes after OWHTO. Clinical parameters, including Japanese Orthopedic Association (JOA) score, Oxford Knee Score (OKS), and Knee Injury and Osteoarthritis Outcome Score (KOOS), were evaluated. Radiologic outcomes, including the hip-knee-ankle angle (HKA), joint line convergence angle (JLCA), MPTA, KJLO, ankle joint line obliquity (AJLO), and hip abduction angle (HAA), were evaluated preoperatively and at the final follow-up. RESULTS: Ninety-four patients (normal group; n = 52, overcorrected group; n = 42) were included in this study. After OWTHO, the mean increases in HKA and MPTA were 11.0° ± 3.2° and 10.4° ± 2.7°, respectively, whereas the change in KJLO was only 3.7° ± 2.9°. The mean AJLO (4.3 ± 3.9 to -1.3 ± 3.3, P < .001) and HAA (3.7 ± 2.5 to -1.1 ± 2.3, P < .001) significantly decreased after OWHTO. The mean postoperative MPTA in the overcorrected group was 96.9° ± 1.5°, whereas the mean postoperative KJLO was only 3.1° ± 2.0°. No significant differences were noted in all clinical scores between the groups at the final follow-up. CONCLUSIONS: A certain degree of overcorrected MPTA (≥95°) did not affect the clinical outcomes after OWHTO because of compensatory changes in the hip and ankle joints. LEVEL OF EVIDENCE: Level Ⅲ, retrospective comparative study.

Development of clinical pharmacy services in Australia, Austria, Belgium, Bosnia-Herzegovina, Canada, Germany, Japan, Kosovo, Switzerland, the Netherlands, Thailand, USA and correlation with educational standards, level of research, and implemen.

OBJECTIVE: This study aimed to compare determinants of professional development between different countries to identify barriers and facilitators of development towards clinical pharmacy services and stimulate discussion of under-used potential and opportunities. MATERIALS: The study was conceived as a survey. The questionnaire was administered to a group of experts. METHODS: The survey was conducted as a cross-sectional study with descriptive and correlation analysis. A questionnaire was developed and adjusted to the study focus, covering aspects on general regulations for community pharmacies, professional education, implementation of clinical pharmacy services, and research in patient care. Results were compared for analyses. RESULTS: A total of twelve countries were included in this survey. Pharmacy studies took between 4 and 6 years plus residency in most countries. Curricula remained drug-oriented only in Austria, Bosnia-Herzegovina, and Germany; these three countries had the least pharmacotherapy content in their curricula. Canada, the USA, and Australia have established clinical pharmacy services in almost all fields of practice. Most other countries have implemented at least some clinical services, with the exception of Bosnia-Herzegovina, Germany, and Kosovo. The correlation coefficient between education, research, and implementation was 0.91. CONCLUSION: The results of the survey show that clinical pharmacy services are established to very different extents among the participating countries. The strong correlation suggests that achieving a successful transition in professional practice needs to address several aspects of education and research to reach progress. The collected data might help to identify potential areas of improvement to foster implementation of clinical pharmacy services.
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Quantitative analysis of the Trendelenburg test and invention of a modified method.

BACKGROUND: While the Trendelenburg test has been used for 120 years to detect hip abductor muscle weakness, the methodology has not been standardised. PURPOSES: This study undertook to quantitatively analyze the relation between abductor muscle activity and pelvic tilt angle in the Trendelenburg one-leg stance, examine the pitfalls associated with performing the T-test, and develop a modified method that will produce reliable results. METHODS: A convenience sample of 15 healthy males was asked to assume a one-leg stance in ten different postures, five with mild flexion on the unsupported side, and five with severe flexion. Trunk sway angle, pelvic tilt angle, and the pelvic on femur (POF) angle were measured for each posture. Statistical analysis was used to assess differences in hip abductor activity and public tilt angle between the control posture and the test postures. RESULTS: With minimum trunk sway, hip abductor muscle activity increases when the pelvis is elevated and decreases when it is dropped. With trunk sway toward the test side, abductor muscle activity decreased when the pelvis was elevated; with trunk sway toward the non-test side, muscle activity stayed approximately constant when the pelvis was dropped. CONCLUSIONS: Based on the results we developed a modified T-test methodology that would improve reliability. This test should be performed with minimum trunk sway and severe flexion on the non-test side. The assessment of muscle weakness is based on whether the patient can keep the single-leg standing posture when forced to elevate the pelvis, not simply on the pelvic drop. In future research, we will perform the modified T-test on patients with a suspected hip abductor deficiency, and assess the usefulness of the modified test.

Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension.

Japanese patients with uncontrolled essential hypertension received single-blind losartan 50 mg/hydrochlorothiazide 12.5 mg (L50/H12.5) for 8 weeks. Patients whose blood pressure (BP) remained uncontrolled were randomized double-blind to fixed-dose losartan 50 mg/hydrochlorothiazide 12.5 mg/amlodipine 5 mg (L50/H12.5/A5) or L50/H12.5 for 8 weeks followed by open-label L50/H12.5/A5 for 44 weeks. Adverse events were assessed. After 8 weeks, diastolic and systolic BP were reduced significantly more with L50/H12.5/A5 versus L50/H12.5 (both p < 0.001). Mean changes in diastolic and systolic BP were sustained for 44 weeks. L50/H12.5/A5 was well-tolerated and improved BP significantly versus L50/H12.5 in Japanese patients with uncontrolled essential hypertension.

The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression.

BACKGROUND: This study aimed to determine whether intra-articularly injected adipose-derived stem cells (ADSCs) inhibited articular cartilage degeneration during osteoarthritis (OA) development in a rabbit anterior cruciate ligament transection (ACLT) model. The paracrine effects of ADSCs on chondrocytes were investigated using a co-culture system. METHODS: ACLT was performed on both knee joints of 12 rabbits. ADSCs were isolated from the subcutaneous adipose tissue. ADSCs with hyaluronic acid were intra-articularly injected into the left knee, and hyaluronic acid was injected into the right knee. The knees were compared macroscopically, histologically, and immunohistochemically at 8 and 12 weeks. In addition, cell viability was determined using co-culture system of ADSCs and chondrocytes. RESULTS: Macroscopically, osteoarthritis progression was milder in the ADSC-treated knees than in the control knees 8 weeks after ACLT. Histologically, control knees showed obvious erosions in both the medial and lateral condyles at 8 weeks, while cartilage was predominantly retained in the ADSC-treated knees. At 12 weeks, the ADSC-treated knees showed a slight suppression of cartilage degeneration, unlike the control knees. Immunohistochemically, MMP-13 expression was less in the ADSC-treated cartilage than in the control knees. The cell viability of chondrocytes co-cultured with ADSCs was higher than that of chondrocytes cultured alone. TNF-alpha-induced apoptotic stimulation was similar between the two groups. CONCLUSIONS: Intra-articularly injected ADSCs inhibited cartilage degeneration progression by homing to the synovium and secreting a liquid factor having chondro-protective effects such as chondrocyte proliferation and cartilage matrix protection.

Value of computed tomography-based three-dimensional surgical preoperative planning software in total hip arthroplasty with developmental dysplasia of the hip.

INTRODUCTION: Preoperative planning with computed tomography (CT)-based three-dimensional templating has been expanded to achieve more precise placement of hip components. However, few reports have addressed the utility of three-dimensional surgical planning software for secondary osteoarthritis cases. This study therefore investigated the value of CT-based three-dimensional templating software for preoperative planning in primary total hip arthroplasty (THA), with an emphasis on developmental dysplasia of the hip. MATERIALS AND METHODS: We performed a retrospective review of 65 hips in 57 patients who underwent cementless primary THA. The preoperative diagnosis was secondary osteoarthritis in all cases due to developmental dysplasia of the hip. All preoperative planning and postoperative evaluations were completed using CT-based three-dimensional templating software. We analyzed the accuracy of stem size prediction and cup size prediction, the reproducibility of preoperative and postoperative stem anteversion, and the absolute error in preoperative and postoperative stem anteversion using CT-based three-dimensional templating software. RESULTS: The sizes of 65 % of the femoral stems (42/65) were estimated exactly, and 98 % (63/65) were accurately estimated to within one stem size. The final acetabular cup sizes corresponded exactly to the preoperatively planned size in 92 % of all cases (62/65). 100 % of the cup size estimates were accurate to within one cup size. There was strong reproducibility of preoperative and postoperative stem anteversion (r = 0.88, P < 0.05). The absolute error in stem anteversion was 4.0° ± 3.6°. CONCLUSIONS: Using CT-based three-dimensional templating software made it possible to achieve reproducible stem anteversion and choose accurate stem and cup sizes in patients with developmental dysplasia of the hip.

Usefullness of three-dimensional templating software to quantify the contact state between implant and femur in total hip arthroplasty.

BACKGROUND: It would be ideal if surgeons could precisely confirm whether the planned femoral component achieves the best fit and fill of implant and femur. However, the cortico-cancellous interfaces can be difficult to standardize using plain radiography, and therefore, determining the contact state is a subjective decision by the examiner. Few reports have described the use of CT-based three-dimensional templating software to quantify the contact state of stem and femur in detail. The purpose of this study was to use three-dimensional templating software to quantify the implant-femur contact state and develop a technique to analyze the initial fixation pattern of a cementless femoral stem. METHODS: We conducted a retrospective review of 55 hips in 53 patients using a short proximal fit-and-fill anatomical stem (APS Natural-Hip™ System). All femurs were examined by density mapping which can visualize and digitize the contact state. We evaluated the contact state of implant and femur by using density mapping. RESULTS: The varus group (cases that had changed varus 2° by 3 months after surgery) consisted of 11 hips. The varus group showed no significant difference with regard to cortical contact in the proximal medial portion (Gruen 7), but the contact area in the distal portion (Gruen 3 and Gruen 5) was significantly lower than that of non-varus group. Density mapping showed that the stem only has to be press-fit to the medial calcar, but also must fill the distal portion of the implant in order to achieve the ideal contact state. CONCLUSIONS: Our results indicated that quantifying the contact state of implant and femur by using density mapping is a useful technique to accurately analyze the fixation pattern of a cementless femoral stem.

Genetic dissection of black grain rice by the development of a near isogenic line.

Rice (Oryza sativa L.) can produce black grains as well as white. In black rice, the pericarp of the grain accumulates anthocyanin, which has antioxidant activity and is beneficial to human health. We developed a black rice introgression line in the genetic background of Oryza sativa L. 'Koshihikari', which is a leading variety in Japan. We used Oryza sativa L. 'Hong Xie Nuo' as the donor parent and backcrossed with 'Koshihikari' four times, resulting in a near isogenic line (NIL) for black grains. A whole genome survey of the introgression line using DNA markers suggested that three regions, on chromosomes 1, 3 and 4 are associated with black pigmentation. The locus on chromosome 3 has not been identified previously. A mapping analysis with 546 F2 plants derived from a cross between the black rice NIL and 'Koshihikari' was evaluated. The results indicated that all three loci are essential for black pigmentation. We named these loci Kala1, Kala3 and Kala4. The black rice NIL was evaluated for eating quality and general agronomic traits. The eating quality was greatly superior to that of 'Okunomurasaki', an existing black rice variety. The isogenicity of the black rice NIL to 'Koshihikari' was very high.