Rehospitalisation rates after long-term follow-up of patients with severe mental illness admitted for more than one year: a systematic review.

AIMS: This study aimed to conduct a systematic review of studies on the outcomes of long-term hospitalisation of individuals with severe mental illness, considering readmission rates as the primary outcome. METHODS: Studies considered were those in which participants were aged between 18 and 64 years with severe mental illness; exposure to psychiatric hospitals or wards was long-term (more than one year); primary outcomes were readmission rates; secondary outcomes were duration of readmission, employment, schooling, and social participation; and the study design was either observational or interventional with a randomised controlled trial (RCT) design. Relevant studies were searched using MEDLINE, PsycINFO, Web of Science, CINAHL, and the Japan Medical Abstract Society. The final search was conducted on 1 February 2022. The risk of bias in non-randomised studies of interventions was used to assess the methodological quality. A descriptive literature review is also conducted. RESULTS: Of the 11,999 studies initially searched, three cohort studies (2,293 participants) met the eligibility criteria. The risk of bias in these studies was rated as critical or serious. The 1-10 years readmission rate for patients with schizophrenia who had been hospitalised for more than one year ranged from 33 to 55%. The average of readmission durations described in the two studies was 70.5 ± 95.6 days per year (in the case of a 7.5-year follow-up) and 306 ± 399 days (in the case of a 3-8-year follow-up). None of the studies reported other outcomes defined in this study. CONCLUSIONS: The readmission rates in the included studies varied. Differences in the follow-up period or the intensity of community services may have contributed to this variability. In countries preparing to implement de-institutionalisation, highly individualised community support should be designed to avoid relocation to residential services under supervision. The length of stay for readmissions was shorter than that for index admissions. The results also imply that discharge to the community contributes to improved clinical outcomes such as improved social functioning. The validity of retaining patients admitted because of the risk of rehospitalisation was considered low. Future research directions have also been discussed.

Osteoscopic versus open surgery for the treatment of enchondroma in the foot.

INTRODUCTION: The conventional treatment of enchondromas is the open surgery with curettage of lesions. Osteoscopic surgery is a minimally invasive endoscopic approach for lesions inside bone. The aim of this study was to evaluate the feasibility of the osteoscopic surgery in comparison with the conventional open surgery for patients with foot enchondromas. MATERIALS AND METHODS: A retrospective cohort study comparing patients with foot enchondromas treated with osteoscopic or open surgery from 2000 to 2019. Functional evaluations were based on both the AOFAS score and the Musculoskeletal Tumor Society (MSTS) functional rate. Complication and local recurrence were evaluated. RESULTS: Seventeen patients underwent endoscopic surgery, and eight patients underwent open surgery. The AOFAS score was higher in the osteoscopic group than the open group at 1 and 2 weeks after surgery (mean, 89.18 vs 67.25 [p = 0.001], 93.88 vs 79.38 [p = 0.004]). The MSTS functional rate was also higher in the osteoscopic group than the open group at 1 and 2 weeks after surgery (mean, 81.96 vs 59.58% [p = 0.00], 90.98 vs 75.00% [p = 0.02]). No statistical differences were found after 1-month of surgery. The osteoscopic group had lower complication rate than the open group (12 vs 50%; p = 0.04). No local recurrence was found in any groups. CONCLUSION: The osteoscopic surgery is feasible to provide earlier functional recovery and fewer complications than the open surgery.

Multiple stakeholders' perspectives on patient and public involvement in community mental health services research: A qualitative analysis.

BACKGROUND: Patient and public involvement (PPI) has become essential in health research. However, little is known about multiple stakeholders' perspectives on the implementation of PPI in community mental health research settings. The present study aimed to qualitatively analyse multiple stakeholders' views on PPI, including potential concerns, barriers and approaches. METHODS: This study involved conducting focus group interviews and collecting qualitative data from 37 participants in multiple stakeholder groups (patients = 6, caregivers = 5, service providers = 7, government staff = 5 and researchers = 14) in the community mental health field. The data were qualitatively analysed using a data-driven approach that derived domains, themes and subthemes related to perspectives on PPI and to specific challenges and approaches for implementing PPI. RESULTS: The qualitative analysis identified four domains. The 'Positive views and expectations regarding PPI' domain consisted of themes related to supportive views of PPI in a mental health service research setting and improvements in the quality of research and service. The 'General concerns about PPI' domain included themes concerning the need for non-PPI research and tokenism, excessive expectations concerning social changes and use of evidence from PPI research, and heavy burdens resulting from PPI. The 'Specific issues regarding the implementation of PPI' domain consisted of four themes, including academic systems, selection methods (e.g., representativeness and conflict of interest issues), relationship building, and ambiguous PPI criteria. In particular, all stakeholder groups expressed concerns about relational equality during PPI implementation in Japan. The 'Approaches to PPI implementation' domain included themes such as facilitating mutual understanding, creating a tolerant atmosphere, establishing PPI support systems (e.g., training, ethics and human resource matching) and empowering patient organizations. CONCLUSION: The study replicated most of the barriers and approaches to PPI reported by qualitative research in Western counties. However, utilization of evidence produced by PPI research and partnership in the PPI process may be particularly serious issues in Japan. Future PPI studies should carefully address solutions that fit each culture. PATIENT OR PUBLIC CONTRIBUTION: A patient-researcher was involved in all stages of this project, from development of the research topic and the protocol to manuscript preparation.

New insights into the role of Jmjd3 and Utx in axial skeletal formation in mice.

Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3. Previous reports indicate that Jmjd3 is essential for differentiation of various cell types, such as macrophages and epidermal cells in mice, whereas Utx is involved in cancer and developmental diseases in humans and mice, as well as Hox regulation in zebrafish and nematodes. Here, we report that Jmjd3, but not Utx, is involved in axial skeletal formation in mice. A Jmjd3 mutant embryo (Jmjd3Δ18/Δ18), but not a catalytically inactive Utx truncation mutant (Utx-/y), showed anterior homeotic transformation. Quantitative RT-PCR and microarray analyses showed reduced Hox expression in both Jmjd3Δ18/Δ18 embryos and tailbuds, whereas levels of Hox activators, such as Wnt signaling factors and retinoic acid synthases, did not decrease, which suggests that Jmjd3 plays a regulatory role in Hox expression during axial patterning. Chromatin immunoprecipitation analyses of embryo tailbud tissue showed trimethylated lysine 27 on histone H3 to be at higher levels at the Hox loci in Jmjd3Δ18/Δ18 mutants compared with wild-type tailbuds. In contrast, trimethylated lysine 4 on histone H3 levels were found to be equivalent in wild-type and Jmjd3Δ18/Δ18 tailbuds. Demethylase-inactive Jmjd3 mutant embryos showed the same phenotype as Jmjd3Δ18/Δ18 mice. These results suggest that the demethylase activity of Jmjd3, but not that of Utx, affects mouse axial patterning in concert with alterations in Hox gene expression.-Naruse, C., Shibata, S., Tamura, M., Kawaguchi, T., Abe, K., Sugihara, K., Kato, T., Nishiuchi, T., Wakana, S., Ikawa, M., Asano, M. New insights into the role of Jmjd3 and Utx in axial skeletal formation in mice.

Factors decreasing caregiver burden to allow patients with cerebrovascular disease to continue in long-term home care.

BACKGROUND: This study attempted to assess continued long-term home care by examining patients' independent activities of daily living (ADLs) and caregivers' free time. METHODS: We surveyed the main caregivers of 52 patients with cerebrovascular disease with continuous home care from 1999 to 2010. Survey items were patients' ADLs, the frequency of use of care services, care requirements, and caregiver sense of burden. We compared the survey results between years. RESULTS: ADLs of excretory control, verbal expression, verbal comprehension, and range of activities showed significant deterioration from 1999 to 2010. Patient need for care increased significantly but use of care services did not. Main caregivers were typically spouses who aged together with the patients. Main caregivers rarely changed; occasionally, a son or daughter-in-law became the main caregiver. Patients typically required less than 3 hours of care daily, which did not change over time. Caregivers had significantly more difficulty maintaining their own health in 2010 than 1999. However, they did not identify increases in difficulties with housework or coping with work. They felt that caregiving was a burden but did not indicate that the family relationship had deteriorated. CONCLUSIONS: Regardless of degree of independence of patients' ADLs, caregiver burden was severe. To decrease caregiver burden, it is necessary to use care services, reduce care time, and allow caregivers free time. In addition, it is possible to continue long-term home care by maintaining their relationships.

The relationship between bilateral knee muscle strength and gait performance after stroke: the predictive value for gait performance.

[Purpose] The purpose of this study was to assess the relationships between bilateral knee extension strengths and gait performance in subjects with poststroke hemiparesis and to predict gait performance by the paretic and nonparetic knee extension strength. [Subjects and Methods] This was a correlational study in which 238 consecutive inpatients with poststroke hemiparesis were enrolled. Knee extensor muscle strengths in paretic and nonparetic lower limbs were measured with a handheld dynamometer, and the presence or absence of impaired gait was also determined. [Results] The mean strength in the paretic lower limb was 0.90 Nm/kg, and that in the nonparetic lower limb was 1.24 Nm/kg. Discriminant analysis classified the difference between the possibility and impossibility of gait by knee extensor muscle strength (standardized discriminant coefficient: paretic, 1.32; nonparetic, 0.55). Thus, paretic and nonparetic knee extension strengths were integrated in the strength index. A threshold level of 2.0 provided the best balance between positive and negative predictive values for the strength index. [Conclusion] The results indicated that both paretic and nonparetic knee extension strengths were related to gait performance. The strength index deduced from bilateral knee extension strengths may serve as a clinically meaningful index for rehabilitation assessment and training.

Rehabilitation Treatment of a Patient With Total Humeral Endoprosthetic Replacement.

Total humeral endoprosthetic replacement (THR) is a rare surgery for malignant humeral bone tumors. Studies focusing on its surgical methods and functional status are limited. Furthermore, rehabilitation treatment after THR has not been reported. Therefore, this case report aimed to investigate its postoperative rehabilitation treatment and reinstatement. A 69-year-old woman was diagnosed with chondrosarcoma of her left humerus. THR was performed the day following patient admission. The wide resection caused the loss of her left shoulder motor function. She had a left ulnar nerve disorder and carpal tunnel syndrome. Rehabilitation treatments such as joint range of motion training were initiated on postoperative day (POD) 1. We designed a shoulder abductor brace to maintain her left shoulder in an abducted and flexed position so she could use her left hand effectively. The manual muscle testing scores for elbow joint movements gradually improved. On POD47, she was transferred to a convalescent rehabilitation hospital to receive training in activities of daily living and barber work. The patient was discharged on POD107. The Disabilities of the Arm, Shoulder, and Hand score improved from 86.2 (POD7) to 17.2 (POD107). She continued outpatient rehabilitation and reinstated work on POD143. The use of a brace and seamless rehabilitation from the acute phase to convalescence and community-based rehabilitation enabled the patient with THR to return to work. This study suggests that precise assessment of the disorders and consecutive rehabilitation treatment with a brace should be considered after THR.

Treatment Strategy of Fractured Osteochondroma in the Young Athlete's Knee.

Purpose: The main purpose of this study was to compare the clinical outcome of surgery versus observation in young athletes with fractured osteochondromas in the knee. The secondary aim was to evaluate displacement versus non-displacement fractures with regards to functional recovery. Methods: A retrospective analysis was performed in young athletes with fractures of osteochondromas in the knee. In the surgery group, resection of the osteochondromas was performed due to pain persisting at 4 weeks after injury. In contrast, patients with pain diminishing within 4 weeks after injury were observed without surgery. Displacement was defined as a gap widening of ≥1 mm between fragments, or translation of >50% of the distal fragment in relation to the proximal fragment. The time to return to the original sport was compared between groups. Results: The study sample was composed of 21 patients with a mean age of 12 years (range 9-16 years). There were 14 patients in the surgery group and 7 patients in the observation group. There were 10 patients (71%) with displacement and 4 patients (29%) with non-displacement fractures in the surgery group. Surgery was required more frequently in displacement than in non-displacement fracture patients (p = 0.01). The mean time to return to the original sport was 2.1 ± 1.1 and 7.2 ± 4.1 weeks in the surgery and observation groups, respectively (p < 0.01). Conclusions: Surgical excision is preferable in a young athlete's knee presenting with displacement of fractured osteochondromas due to disabling symptoms and in order to allow them to return faster to original sports activities.

Estimation of a Structural Equation Modeling of Quality of Life Mediated by Difficulty in Daily Life in Survivors of Breast Cancer.

BACKGROUND: The purpose of this study was to clarify the structural relationship of quality of life (QOL) in survivors of breast cancer, including difficulty in daily life and negative experiences in daily activities, as health-related indicators. METHODS: Participants were survivors of breast cancer for more than 2 years after primary breast cancer surgery and belonged to self-help groups. The assessment used FACT-B (QOL), HADS (anxiety and depression), SOC (sense of coherence), WHODAS 2.0 (difficulties in daily life), and CAOD (negative experiences in daily activities). Bayesian structural equation modeling (BSEM) was performed to analyze the hypothesized model. If the causal model was significant, multiplication of the path coefficient from emotional distress (anxiety and depression) to QOL, and from SOC to emotional distress, was considered a direct effect on QOL, and from SOC to difficulty in daily life, from difficulty in daily life to negative experiences in daily activities, and from negative experiences in daily activities to anxiety and depression were considered indirect effects on QOL. RESULTS: The participants comprised 73 survivors of breast cancer. The goodness of fit of the model in the BSEM was satisfactory. The direct effect was 0.274, and the indirect effect was 0.164. CONCLUSIONS: An additional finding of this study is that coping with difficulty in daily life and negative experiences in daily activities related to QOL may improve QOL.

Relationship between Lower Extremity Peripheral Arterial Disease and Mild Cognitive Impairment in Hemodialysis Patients.

BACKGROUND: The link between arterial stiffness and mild cognitive impairment (MCI) in patients on hemodialysis (HD) has been receiving increased attention. The purpose of this study was to investigate the relationship between cognitive function and ankle brachial index (ABI) and toe brachial index (TBI) values in patients on hemodialysis. Of the 100 participants (mean age: 67.9 years; average history of hemodialysis: 7.3 years). Of these, 46.0% had MCI. The MoCA-J scores were significantly higher in the ABI ≥ 1.06 group. However, the MoCA-J scores divided into the two groups according to the TBI cutoff value were not significantly different. In a multiple regression model with the MoCA-J scores as the objective variable, the ABI was a significantly associated factor. This study indicates that a low ABI might be associated with MCI.

Clinical Utility of Bland Embolization Using Microspheres for Painful Malignant Musculoskeletal Tumors.

BACKGROUND/AIM: To evaluate retrospectively whether bland embolization using microspheres is safe and useful for relieving pain in patients with painful malignant musculoskeletal (MSK) tumors. PATIENTS AND METHODS: Bland embolization using microspheres was performed for 20 patients (11 women/9 men) with a median age of 69 years (range=40-89 years) who had 22 painful malignant MSK tumors. The maximum tumor diameters were 2.4-13.8 cm (median, 7.5 cm). Pain was evaluated using the visual analog scale. A decrease of this score by 2 or more after embolization was defined as clinically effective pain relief. Adverse events (AEs) were evaluated using CTCAE v5.0. Objective response, disease control rates, and overall survival were also evaluated. RESULTS: Effective pain relief was achieved in 18 patients (90.0%, 18/20). Grade-3 AEs developed in four patients (20.0%, 4/20): skin ulcer (n=2), skin ulcer and pain (n=1), and muscle weakness with dysesthesia (n=1). No grade-4 or grade-5 AEs developed. Objective response and disease control rates were 26.7% (4/15) and 86.7% (13/15), respectively. The 1-year survival rate was 43.8%, with median survival of 9.2 months (range=0.5-41.0 months). CONCLUSION: Although the survival benefit is equivocal, bland embolization is acceptably safe and useful for relieving pain by controlling tumor growth in patients with painful malignant MSK tumors.

Occupational Dysfunction as a Mediator between Recovery Process and Difficulties in Daily Life in Severe and Persistent Mental Illness: A Bayesian Structural Equation Modeling Approach.

Background: This study is aimed at verifying a hypothetical model of the structural relationship between the recovery process and difficulties in daily life mediated by occupational dysfunction in severe and persistent mental illness (SPMI). Methods: Community-dwelling participants with SPMI were enrolled in this multicenter cross-sectional study. The Recovery Assessment Scale (RAS), the World Health Organization Disability Assessment Schedule second edition (WHODAS 2.0), and the Classification and Assessment of Occupational Dysfunction (CAOD) were used for assessment. Confirmatory factor analysis, multiple regression analysis, and Bayesian structural equation modelling (BSEM) were determined to analyze the hypothesized model. If the mediation model was significant, the path coefficient from difficulty in daily life to recovery and the multiplication of the path coefficients mediated by occupational dysfunction were considered as each the direct effect and the indirect effect. The goodness of fit in the model was determined by the posterior predictive P value (PPP). Each path coefficient was validated with median and 95% confidence interval (CI). Results: The participants comprised 98 individuals with SPMI. The factor structures of RAS, WHODAS 2.0, and CAOD were confirmed by confirmatory factor analysis to be similar to those of their original studies. Multiple regression analysis showed that the independent variables of RAS were WHODAS 2.0 and CAOD, and that of CAOD was WHODAS 2.0. The goodness of fit of the model in the BSEM was satisfactory with a PPP = 0.27. The standardized path coefficients were, respectively, significant at -0.372 (95% CI: -0.586, -0.141) from "difficulty in daily life" to "recovery" as the direct effect and at -0.322 (95% CI: -0.477, -0.171) mediated by "occupational dysfunction" as the indirect effect. Conclusions: An approach for reducing not only difficulty in daily life but also occupational dysfunction may be an additional strategy of person-centered, recovery-oriented practice in SPMI.

What outcomes in community mental health research are important to caregivers of people with schizophrenia? An exploratory qualitative analysis of an online survey.

AIMS: This study investigated outcomes in community mental health research that were important to caregivers of people with schizophrenia. METHODS: Using an online survey conducted from August 1 to 31, 2020, data were collected from caregivers belonging to the LINE Schizophrenia Family Association. Caregivers identified outcomes important in community mental health research. Two researchers categorized caregivers' statements into research outcomes. RESULTS: A total of 132 caregivers completed the online selfreported questionnaire, and 296 caregiver statements were identified. Qualitative analysis identified 17 outcome categories. The caregivers tended to value having more free time, maintaining an appropriate relationship with people with schizophrenia, and being able to cope with their symptoms. CONCLUSIONS: This exploratory study newly demonstrates the outcomes that caregivers of people with schizophrenia consider important in community mental health research. The findings may be useful in selecting outcomes for future studies of caregivers.

Discovery of Apararenone (MT-3995) as a Highly Selective, Potent, and Novel Nonsteroidal Mineralocorticoid Receptor Antagonist.

Overactivation of the mineralocorticoid receptor (MR) is involved in many diseases, such as hypertension, kidney disease, and heart failure. Thus, MR antagonists (MRAs) are expected to be beneficial to patients with these diseases. In order to identify novel nonsteroidal MRAs that overcome the issues of already marketed steroidal MRAs, we searched for new compounds guided by our hypothesis that T-shaped compounds with a hydrophobic core structure, two polar functional groups at both extremities able to interact with MR, and a bulky substituent that can interfere with the folding of the C-terminal helix 12 may exhibit antagonist activity toward MR. We discovered that the novel 1,4-benzoxazin-3-one derivative 19 (apararenone: MT-3995) acted as a highly selective and potent nonsteroidal MRA. Apararenone exhibited a more potent antihypertensive and organ-protective activity than steroidal MRA eplerenone in a primary aldosteronism rat model obtained by infusing aldosterone in uninephrectomized rats.

Paramecium Polycomb repressive complex 2 physically interacts with the small RNA-binding PIWI protein to repress transposable elements.

Polycomb repressive complex 2 (PRC2) maintains transcriptionally silent genes in a repressed state via deposition of histone H3K27-trimethyl (me3) marks. PRC2 has also been implicated in silencing transposable elements (TEs), yet how PRC2 is targeted to TEs remains unclear. To address this question, we identified proteins that physically interact with the Paramecium enhancer-of-zeste Ezl1 enzyme, which catalyzes H3K9me3 and H3K27me3 deposition at TEs. We show that the Paramecium PRC2 core complex comprises four subunits, each required in vivo for catalytic activity. We also identify PRC2 cofactors, including the RNA interference (RNAi) effector Ptiwi09, which are necessary to target H3K9me3 and H3K27me3 to TEs. We find that the physical interaction between PRC2 and the RNAi pathway is mediated by a RING finger protein and that small RNA recruitment of PRC2 to TEs is analogous to the small RNA recruitment of H3K9 methylation SU(VAR)3-9 enzymes.

Discovery of Novel 2-Carbamoyl Morpholine Derivatives as Highly Potent and Orally Active Direct Renin Inhibitors.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin, the first and rate-limiting enzyme of the RAAS, is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. Therefore, various direct renin inhibitors (DRIs) have been researched over recent decades; however, most exhibited poor pharmacokinetics and oral bioavailability due to the peptidomimetic or nonpeptidomimetic structures with a molecular weight (MW) of >600, and only aliskiren is approved. This study introduces a novel class of DRIs comprised of a 2-carbamoyl morpholine scaffold. These compounds have a nonpeptidomimetic structure and a MW of <500. The representative compound 26 was highly potent despite not occupying S1'-S2' sites or the opened flap region used by other DRIs and exerted a significant antihypertensive efficacy via oral administration on double transgenic mice carrying both the human angiotensinogen and the human renin genes.

Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor.

Renin is the rate-limiting enzyme in the renin-angiotensin-aldosterone system (RAAS) which regulates blood pressure and renal function and hence is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. However, the development of direct renin inhibitors (DRIs) with favorable oral bioavailability has been a longstanding challenge for many years. This problem was thought to be because most of the reported DRIs were peptide-like structures or nonpeptide-like structures with a molecular weight (MW) of > 600. Therefore, we tried to find nonpeptidomimetic DRIs with a MW of < 500 and discovered the promising 2-carbamoyl morpholine derivative 4. In our efforts to improve the pharmacokinetic profile of 4 without a significant increase in the MW, we discovered compound 18 (SPH3127), which demonstrated higher bioavailability and a more potent antihypertensive effect in preclinical models than aliskiren and has completed a phase II clinical trial for essential hypertension.

FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets.

White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARgamma in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

High antimetastatic efficacy of MEN4901/T-0128, a novel camptothecin carboxymethyldextran conjugate.

The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need.

Outcomes frequently specified in Cochrane reviews of community-based psychosocial interventions for adults with severe mental illness: A systematic search and narrative synthesis.

BACKGROUND: Outcome selection in intervention studies is a critical issue for synthesizing evidence. This study is aimed to investigate outcomes used in Cochrane reviews assessing community-based psychosocial interventions for adults with severe mental illness. METHODS: Cochrane reviews that evaluated a community-based psychosocial intervention for adults with severe mental illness were searched electronically and manually. We extracted all outcomes specified in the Methods section in each Cochrane review. Outcomes that represent the same concept and context were synthesized into an outcome term. Outcome terms were categorized according to the existing taxonomy. RESULTS: We included 33 Cochrane reviews. Of the 216 outcome terms identified, 13 were used in more than half of the reviews: quality of life, mental state, admission to hospital, economic outcome, leaving the study early, social functioning, satisfaction, global state, relapse, adverse events/effects, carer satisfaction, employment, and duration of admission. Most outcome terms were categorized into the life impact core area (55%), followed by the resource use area (21%). CONCLUSIONS: Our study provides a candidate outcome list for developing a core outcome set for severe mental illness and offers a basis for comparison for future outcome investigation on mental health research.