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• MND-2119 is a self-emulsifying eicosapentaenoic acid ethyl ester. • MND-2119 was tested in hypertriglyceridemia patients. • MND-2119 2 g/day was non-inferior to Epadel 1.8 g/day in lowering TG levels. • MND-2119 4 g/day was superior to MND-2119 2 g/day in lowering TG levels. • MND-2119 appeared safe and well tolerated. In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E, which can be administered once-daily. The objective of this study was to assess non-inferiority in the efficacy of MND-2119 in patients with hypertriglyceridemia compared with highly purified EPA-E. In this multicenter, 12-week, double-blind study, patients with high triglyceride (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=145), MND-2119 4 g/day (n=145), EPA-E 1.8 g/day (n=145) or EPA-E 2.7 g/day (n=145). The primary endpoint was percentage change in TG levels from baseline to end of treatment. MND-2119 2, 4 g/day and EPA-E 1.8, 2.7 g/day reduced TG levels from baseline by −10.09%, −15.51%, −9.30%, and −8.80%, respectively. The TG reduction rate of MND-2119 2 g/day was non-inferior to that of EPA-E 1.8 g/day (LS mean difference: -0.42, 95%CI: -5.76 to 4.91). Moreover, the TG reduction rate of MND-2119 4 g/day was superior to that of MND-2119 2 g/day (LS mean difference: -5.74, 95%CI: -10.59 to -0.89). There were no remarkable safety differences between MND-2119 2 g/day and EPA-E 1.8 g/day and between MND-2119 4 g/day and EPA-E 2.7 g/day. Non-inferiority of MND-2119 2 g/day to EPA-E 1.8 g/day for efficacy, and superiority of MND-2119 4 g/day over MND-2119 2 g/day for efficacy were verified. MND-2119 was safe and well tolerated. [ABSTRACT FROM AUTHOR]

Background: Few treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time.Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety.Results: In total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26-6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred.Conclusion: Modafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time.Clinical Trial Registration: JapicCTI; 142539. [ABSTRACT FROM AUTHOR]

Hangovers are associated with negative economic consequences due to decreased job performance or frequent visits to physicians. Thus, a new strategy for the alleviation of hangover-related symptoms is needed to avoid this detriment to society. The purpose of this nationwide randomized, double-blind, placebo-controlled physicians' trial was to evaluate the efficacy of loxoprofen sodium for the alleviation of fatigue, headache, and nausea after hangover. A total of 229 participants were randomized to receive loxoprofen sodium (60 mg once orally) or placebo. The study was closed when the first 150 participants (n = 74 in the loxoprofen vs. n = 76 in the placebo groups) experienced hangovers. The primary endpoint was set as the difference in severity of general fatigue before and 3 h after taking the test drugs and was evaluated using a visual analogue scale. Secondary endpoints included difference in severity of headache, nausea, and incidence of adverse events. The study participants were 34 (interquartile range; 30-39) years old, 92.0% were men, and both groups were comparable for baseline characteristics. The alleviation of general fatigue did not differ statistically between the loxoprofen and placebo groups (24 [14-49] vs. 19 [9-35], p = 0.07). However, the alleviation of headache was statistically greater in the loxoprofen group (25 [10-50] vs. 10 [2-30], adjusted difference 14, 95% confidence interval 8-21, p < 0.001), whereas, there was no difference in nausea (7 [0-27] vs. 10 [0-24], p = 0.68). The incidence of adverse symptoms such as epigastric discomfort was also comparable between groups (2.7% vs. 3.9%, p = 0.25). Loxoprofen sodium was effective for relieving headaches after hangovers but did not alleviate general fatigue or nausea. [ABSTRACT FROM AUTHOR]

Background: Vedolizumab is a gut-selective humanized antibody that binds the α4β7 integrin. We evaluated efficacy and safety of vedolizumab in Japanese patients with moderate-to-severe Crohn's disease (CD).Methods: In this Phase 3, double-blind study (NCT02038920), 157 patients were randomized to receive intravenous vedolizumab 300 mg (n = 79) or placebo (n = 78) at Weeks 0, 2, and 6 (induction phase). Patients with CD activity index (CDAI)-70 response at Week 10 were randomized to receive vedolizumab 300 mg (n = 12) or placebo (n = 12) at Week 14, then every 8 weeks until Week 54 (maintenance phase). Primary endpoints were ≥ 100-point reduction in CDAI (CDAI-100 response) at Week 10 for induction, and clinical remission (CR: CDAI ≤ 150) at Week 60 for maintenance.Results: At Week 10, 26.6% of patients who received vedolizumab and 16.7% who received placebo achieved CDAI-100 response (odds ratio [OR] [95% confidence interval (CI)] 1.80 [0.82-3.96]; p = 0.145). At Week 60, 41.7% of vedolizumab-treated patients and 16.7% of placebo-treated patients achieved CR (OR [95% CI] 3.57 [0.53-23.95]; p = 0.178). The incidence of adverse events was similar in both treatment groups in both induction and maintenance phases. In patients without prior anti-TNFα exposure or with inadequate response to anti-TNFα, vedolizumab showed improved outcomes over placebo in the induction phase. Age might be a possible predictive factor of CR for future research.Conclusion: Vedolizumab showed a numerically greater efficacy versus placebo as induction therapy, but the difference was not statistically significant. Vedolizumab also showed a numerically greater efficacy in maintenance therapy, and was well tolerated. [ABSTRACT FROM AUTHOR]

This study investigated the efficacy of 10-module metacognitive training (MCT) among Japanese patients with schizophrenia by conducting a multicenter randomized controlled trial to test the influence of the most recent and extended version of MCT on positive symptoms. A six-center, randomized, assessor-blind, controlled trial between "treatment as usual" (TAU) and TAU + MCT was conducted. Fifty inpatients and outpatients with schizophrenia, schizotypal, and delusional disorders (ICD 10) were enrolled, then randomly assigned to TAU (n = 26) or TAU + MCT (n = 24). Assessments were made at baseline, after six weeks, immediately posttreatment, and 1-month post-treatment. The primary outcome was positive symptom score, as measured by the Positive and Negative Syndrome Scale (PANSS). General assessment of functioning (GAF) and measures of cognitive biases were secondary outcomes. Completion at post-treatment (10 weeks later) and 1-month follow-up was high-TAU + MCT, n = 22 (91.67%) and TAU, n = 23 (88.46%). The severity of PANSS positive symptoms declined significantly in the TAU + MCT treatment group compared with the TAU group. GAF also showed significantly greater improvement in the TAU + MCT group compared with the TAU group. There was also a trend for greater efficacy of MCT on cognitive biases. In conclusion, this study provides support for the efficacy of 10 module MCT concerning positive symptomatology (especially, delusion) and general functioning. [ABSTRACT FROM AUTHOR]

Summary: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen of teriparatide, while also improving safety. Introduction: While a 56.5-μg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-μg teriparatide can provide comparable efficacy to the 56.5-μg once-weekly regimen while improving safety. Methods: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-μg twice-weekly group (n = 277) or the 56.5-μg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2–L4) bone mineral density (BMD) at final follow-up. Results: The percentage changes in lumbar spine (L2–L4) BMD at final follow-up in the 28.2-μg twice-weekly and 56.5-μg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400–2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (− 1.6%), non-inferiority of the 28.2-μg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-μg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-μg twice-weekly group. Conclusions: A 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen while improving safety. Clinical trial registration: JapicCTI-163477. [ABSTRACT FROM AUTHOR]

Objective: To verify the effect of adjusting the challenge–skill balance with respect to rehabilitation process. Design: A single-blind, two-arm, parallel-group, randomized controlled trial. Setting: Recovery rehabilitation unit of Harue Hospital, Japan. Subjects: The trial included 72 clients (mean (SD): age, 74.64 (9.51) years; Functional Independence Measure score, 98.26 (15.27)) with cerebral or spinal disease or musculoskeletal disease. Interventions: Clients were randomly divided into two groups: the experimental group, who received occupational therapy with adjustment of the challenge–skill balance, and the control group who received conventional occupational therapy. Time from admission to discharge was considered the implementation period; the final evaluation was conducted at three months after discharge. Main measures: The primary outcome was subjective quality of life (Ikigai-9). Secondary outcomes were the health-related quality of life (EuroQol–5 Dimensions, Five Levels (EQ-5D-5L)), the Flow State Scale for Occupational Tasks, and the Functional Independence Measure. A cost-effectiveness analysis was conducted using total cost and quality-adjusted life-year based on the EQ-5D-5L. Results: Significant differences were observed between the experimental and control groups with respect to the Ikigai-9 score (P = 0.008) and EQ-5D-5L (P = 0.038), and the effect sizes were 0.76 (95% confidence interval [CI]: 0.27–1.24) and 0.62 (95% CI: 0.14–1.10), respectively. No significant between-group differences in other outcomes were observed, for example, the Functional Independence Measure score improved in both experimental and control groups (119.80 (5.50) and 118.84 (6.97), respectively. The incremental cost-effectiveness ratio was US$5518.38. Conclusions: Adjusting the challenge–skill balance may be a useful approach to improve the participant's subjective quality of life in the rehabilitation process. [ABSTRACT FROM AUTHOR]

Context: Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.Objectives: We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.Methods: A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]-Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.Results: Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002).Conclusion: Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of an education program for mid‐level Japanese public health nurses (PHNs) to improve their competencies in program planning, which will fulfill community health needs. Design: Randomized control trial. Sample: During 2017, 103 PHNs with 5–20 years of PHN work experience in Japan were enrolled and randomly allocated to the intervention (n = 51) or control group (n = 52). Measurements: The primary outcome measured competency in program planning based on Competency Measurement of Creativity for PHNs (CMC), knowledge, and skills regarding program planning. Intervention: Six web‐based learning modules followed by two face‐to‐face group sessions. Results: The PHN participants averaged about 12 years of experience. In the intervention group, 25 PHNs completed all modules (49.0%). Post intervention, there were no statistically significant differences among any between‐group CMC scores. However, the intervention group's CMC 3 score was significantly higher than that of the control group of ≥12 years of experience. Total knowledge and skill scores also improved significantly in the intervention group compared with the control group. Conclusions: The results suggest that PHNs with ≥12 years of experience are a suitable target of this educational program, and should play a key role in program planning. [ABSTRACT FROM AUTHOR]

Background: Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients.Aims: To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC.Methods: This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC).Results: An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient).Conclusions: BFM had no effect on time to relapse in UC patients compared with placebo.Study Registration: UMIN000007593. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and effectiveness of the MDT-2113 (IN.PACT Admiral) drug-coated balloon (DCB) for the treatment of de novo and native artery restenotic lesions in the superficial femoral and proximal popliteal arteries vs percutaneous transluminal angioplasty (PTA) with an uncoated balloon in a Japanese cohort.Methods: MDT-2113 SFA Japan ( ClinicalTrials.gov identifier NCT01947478) is an independently adjudicated, prospective, randomized, single-blinded trial that randomized (2:1) 100 patients (mean age 73.6±7.0 years; 76 men) from 11 Japanese centers to treatment with DCB (n=68) or PTA (n=32). Baseline characteristics were similar between the groups, including mean lesion length (9.15±5.85 and 8.89±6.01 cm for the DCB and PTA groups, respectively). The primary effectiveness outcome was primary patency at 12 months, defined as freedom from clinically-driven target lesion revascularization (CD-TLR) and freedom from restenosis as determined by duplex ultrasonography. The safety endpoint was a composite of 30-day device- and procedure-related death and target limb major amputation and clinically-driven target vessel revascularization within 12 months.Results: Patients treated with DCBs exhibited superior 12-month primary patency (89%) compared to patients treated with PTA (48%, p<0.001). The 12-month CD-TLR rate was 3% for DCB vs 19% for PTA (p=0.012). There were no device- or procedure-related deaths, major amputations, or thromboses in either group. Quality-of-life measures showed sustained improvement from baseline to 12 months in both groups.Conclusion: Results from the MDT-2113 SFA Japan trial showed superior treatment effect for DCB vs PTA, with excellent patency and low CD-TLR rates. These results are consistent with other IN.PACT SFA DCB trials and demonstrate the safety and effectiveness of this DCB for the treatment of femoropopliteal lesions in this Japanese cohort. [ABSTRACT FROM AUTHOR]

Background Self-management is an important step toward preventing and impeding the progression of chronic kidney disease. However, patients with chronic kidney disease may have few or no subjective symptoms and therefore might consider self-management to be unnecessary. Effective support and encouragement of self-management in patients with chronic kidney disease is therefore required. Objectives This study tested the effectiveness of the Encourage Autonomous Self-Enrichment patient education program, which supports patient autonomy and intrinsic motivations with the aim of improving self-efficacy and sustaining self-management, on perceived self-efficacy, self-management behaviors, and physiological endpoints (blood pressure and renal function parameters) in patients with chronic kidney disease. Design This was a randomized, controlled, single-blind trial with one-to-one allocation into two groups. Settings The study was conducted at 13 Japanese clinics or general hospitals that specialize in internal medicine and urology. Participants Participants included patients who were diagnosed with chronic kidney disease and were not receiving dialysis. Patients were recruited from among those attending follow-up visits at participating institutions. Methods A total of 65 participants were randomly allocated into the intervention (n = 33) and control (n = 32) groups. The intervention group followed the Encourage Autonomous Self-Enrichment program action plan for 12 weeks. The control group received standard education provided by nurses who distributed leaflets in accordance with physicians’ instructions, provided auxiliary medical services, and answered patients' questions. Results Except for 1 participant who died after 4 weeks, all 33 members of the intervention group continued the Encourage Autonomous Self-Enrichment program for 12 weeks. This program intervention yielded significant improvements in perceived self-efficacy (U = 318.5, p = 0.035, effect size r = 0.27) and self-management behaviors (U = 310.0, p = 0.026, effect size r = 0.29). There were no differences in blood pressure or renal function between the groups; however, serum potassium levels decreased in the intervention group and increased in the control group (t (58) = 1.047, p = 0.299, effect size d = 1.49). No intervention-related adverse events, such as worsening of patients' test results, were observed. Conclusions These findings indicate that the Encourage Autonomous Self-Enrichment program yielded improvements in perceived self-efficacy and self-management behaviors in patients with chronic kidney disease not treated with dialysis. [ABSTRACT FROM AUTHOR]

Aim To describe the programme and research protocol of our updated preventive home visit programme for ambulatory frail older adults in the Japanese Long-Term Care Insurance system. Background Our previous trials have shown that the nature of recommendations during preventive home visits is a key issue. The present programme has updated our previous one by including a unique structured assessment with treatment recommendations tied to an ongoing programme for quality assurance. Design A randomized, controlled trial. Methods Eligible participants ( n = 360) will be randomly assigned to home visit ( n = 179) and control ( n = 181) groups in three suburban municipalities. Nurses provide recommendations based on structured assessments to participants in visit group every 3 months from September 2011-October 2013. The primary outcomes are parameters related to quality of life, including activities of daily living, instrumental activities of daily living, depression, cognitive capacity, daily-life satisfaction and self-efficacy for health promotion; these are collected by mail at baseline, 12 and 24 months. The secondary outcome is long-term care use over the study period. To evaluate the visit process, we are qualitatively analysing documentation data from the assessment sheet and chart. Conclusion This study is collecting and analysing evidence regarding the process and outcomes of preventive home visits based on structured care-need assessments. Trial registration: The study protocol was registered for the UMIN clinical registry approved by ICMJE (No. UMIN000006463, October 04, 2011). [ABSTRACT FROM AUTHOR]

Background The efficacy of disulfiram in preventing an alcoholic relapse has been controversial. The aim of our study was to assess the efficacy of supervised disulfiram for the treatment of alcohol dependence with a multi-institutional study in Japan. Methods In a single-blinded, randomized placebo-controlled study, we recruited 109 patients diagnosed with alcohol dependence under ICD-10 criteria. The patients were randomly allocated to 4 treatment groups, depending on whether they took disulfiram (200 mg daily) or a placebo or whether they received adjunctive therapy consisting of mailed letters which delineated and emphasized the harmful effect of alcohol and the management of alcohol craving. The proportion of abstinence among the 4 groups at 26 weeks after discharge was the primary outcome measure. The proportion of abstinence was compared with the severity of alcohol dependence and craving. Furthermore, we examined the proportion of abstinence in patients with inactive aldehyde dehydrogenase-2 ( ALDH2). Results There were no significant differences among the 4 groups in terms of abstinent patients or study dropouts. The ratio of abstinence was not related to the severity of alcohol dependence or the degree of alcohol craving. Patients with inactive ALDH2 significantly sustained abstinence with the use of disulfiram ( p = 0.044). Conclusions Supervised oral disulfiram use followed by intervention via letters seems to be ineffective for increasing abstinence. Further studies are necessary to prove the efficacy of disulfiram for the pharmacological treatment of alcohol dependence. We indicated the effectiveness of disulfiram for the maintenance of abstinence in patients with inactive ALDH2. [ABSTRACT FROM AUTHOR]

Background To elucidate whether maternal vitamin D supplementation during lactation improves infantile eczema and other subsequent allergic disorders, a randomized, double-blind, placebo-controlled trial was performed. Methods Mothers ( n = 164) of infants with facial eczema at 1 month check-up were randomly assigned to receive vitamin D3 supplements ( n = 82; 800 IU/day) or placebo ( n = 82) for 6 weeks from May 2009 to January 2011. The primary outcome was infantile eczema quantified on Scoring Atopic Dermatitis ( SCORAD) index at 3 month check-up, and the secondary outcomes were atopic dermatitis, food allergy, and wheeze diagnosed by doctors up to 2 years of age. Results There was no significant difference in SCORAD at 3 month check-up between the two groups. Doctor-diagnosed food allergy was significantly more common up to age 2 years in the vitamin D group (10/39, 25.7%) than in the placebo group (3/40, 7.5%; risk ratio (RR), 3.42; 95% confidence interval [CI]: 1.02-11.77; P = 0.030). Moreover, at least one secondary outcome was also significantly more common in the vitamin D group (17/39, 43.6%) than in the placebo group (7/40, 17.5%; RR, 2.49; 95% CI: 1.16-5.34; P = 0.012). Conclusions Vitamin D supplementation may not decrease the severity of infantile eczema at 3 months of age, but may rather increase the risk of later food allergy up to 2 years of age. Because a large number of subjects was lost to follow up, further study is needed to confirm the findings. [ABSTRACT FROM AUTHOR]

Background: The authors developed a novel technique to improve tendon-bone healing by hybridizing calcium phosphate (CaP) with a tendon graft using an alternating soaking process. Hypothesis: Anterior cruciate ligament (ACL) reconstruction using the CaP-hybridized tendon graft would have a better clinical outcome and reduce the percentage of bone tunnel enlargement compared with a conventional method because of the enhanced anchoring between the tendon graft and the bone. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients (N = 64) with unilateral ACL rupture underwent arthroscopically assisted single-bundle ACL reconstruction using a 4-strand semitendinosus tendon or 4-strand semitendinosus and gracilis tendons with EndoButton femoral fixation and screw washer tibial fixation. These patients were equally randomized to undergo the CaP (n = 32) or conventional (n = 32) method using a transtibial tunnel approach according to the closed envelope method. In the CaP group, the tendon graft was hybridized with the CaP at both ends of the graft. One surgeon performed all reconstructions without knowing which graft was prepared. Patients’ backgrounds regarding age at surgery, gender, period before surgery, and associated meniscal injuries were similar in the 2 groups. All patients followed the same postoperative protocol. At 1 and 2 years after surgery, they were evaluated with the manual knee laxity test, KT-1000 arthrometry, International Knee Documentation Committee (IKDC) examination form, Tegner scale, and Lysholm scale. Also, 1 year postoperatively, bone tunnel enlargement was analyzed using computed tomography, intensity of the tendon graft by magnetic resonance imaging (MRI), and tendon graft appearance by arthroscopic examination. All the examinations were performed blindly. Results: All patients underwent a minimum 2-year follow-up. KT-1000 arthrometry data indicated statistically significant decreased average anterior tibial translation in the CaP group compared with the conventional method group: 1.0 6 2.0 mm versus 1.9 6 1.6 mm (P\.05), respectively, at 1 year; 1.6 6 2.1 mm versus 2.6 6 2.4 mm (P\.05), respectively, at 2 years. The Lysholm score was higher in the CaP group than in the conventional method group at 2 years (96.9 6 4.3 vs 91.7 6 13.3, P\.05). The CaP-hybridized tendon graft reduced the percentage of bone tunnel enlargement of the anteroposterior diameter at the main joint aperture site 1 year postoperatively (femoral side: 15.5% 6 13.4% vs 22.1% 6 16.4%, P\.05; tibial side: 19.3% 6 17.1% vs 26.1% 6 13.7%, P\.05). The results of the pivot-shift test, IKDC grade, and Tegner score; the intensity of the tendon graft (MRI); and arthroscopic appearance were not significantly different at both follow-up periods in the 2 groups. Conclusion: The CaP-hybridized tendon graft improved anterior knee stability and Lysholm scores at the 2-year follow-up and improved anterior knee stability and reduced the percentage of bone tunnel enlargement in both tunnels at the 1-year follow-up compared with the conventional method for single-bundle ACL reconstruction. However, longer follow-up is needed to investigate the appearance of any increased instability. [ABSTRACT FROM AUTHOR]

Background: Developing health services is a key strategy for improving the community health provided by public health nurses. However, an effective educational program for improving their skills in planning such services has not been developed. To describe our program and its evaluation protocol for the education of middle-level public health nurses to improve their skills in developing new health services to fulfil community health needs in Japan. Methods: In this randomized control trial, eligible participants in Japan will be randomly allocated to an intervention group and a control wait-list group. We will provide 8 modules of web-based learning for public health nurses from July to October 2018. To ensure fairness of educational opportunity, the wait-list group will participate in the same program as the intervention group after collection of follow-up data of the intervention group. The primary outcomes will be evaluated using the scale of competency measurement of creativity for public health nurses at baseline, immediately after the intervention. Secondary outcomes will be knowledge and performance regarding program development of public health nurses. Discussion: This study will enable the analysis of the effects of the educational program on public health nurses for improving their competency to develop new health services for fulfilling community health needs and enriching health care systems. Trial registration: We registered our study protocol to the University hospital Medical Information Network- Clinical Trials Registry approved by International Committee of Medical Journal Editors (No. UMIN000032176, April, 2018). [ABSTRACT FROM AUTHOR]