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Background: Ageing populations globally have contributed to increasing numbers of people living with frailty, which has significant implications for use of health and care services and costs. The British Geriatrics Society defines frailty as "a distinctive health state related to the ageing process in which multiple body systems gradually lose their inbuilt reserves". This leads to an increased susceptibility to adverse outcomes, such as reduced physical function, poorer quality of life, hospital admissions, and mortality. Case management interventions delivered in community settings are led by a health or social care professional, supported by a multidisciplinary team, and focus on the planning, provision, and co-ordination of care to meet the needs of the individual. Case management is one model of integrated care that has gained traction with policymakers to improve outcomes for populations at high risk of decline in health and well-being. These populations include older people living with frailty, who commonly have complex healthcare and social care needs but can experience poorly co-ordinated care due to fragmented care systems., Objectives: To assess the effects of case management for integrated care of older people living with frailty compared with usual care., Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, Health Systems Evidence, and PDQ Evidence and databases from inception to 23 September 2022. We also searched clinical registries and relevant grey literature databases, checked references of included trials and relevant systematic reviews, conducted citation searching of included trials, and contacted topic experts., Selection Criteria: We included randomised controlled trials (RCTs) that compared case management with standard care in community-dwelling people aged 65 years and older living with frailty., Data Collection and Analysis: We followed standard methodological procedures recommended by Cochrane and the Effective Practice and Organisation of Care Group. We used the GRADE approach to assess the certainty of the evidence., Main Results: We included 20 trials (11,860 participants), all of which took place in high-income countries. Case management interventions in the included trials varied in terms of organisation, delivery, setting, and care providers involved. Most trials included a variety of healthcare and social care professionals, including nurse practitioners, allied healthcare professionals, social workers, geriatricians, physicians, psychologists, and clinical pharmacists. In nine trials, the case management intervention was delivered by nurses only. Follow-up ranged from three to 36 months. We judged most trials at unclear risk of selection and performance bias; this consideration, together with indirectness, justified downgrading the certainty of the evidence to low or moderate. Case management compared to standard care may result in little or no difference in the following outcomes. • Mortality at 12 months' follow-up (7.0% in the intervention group versus 7.5% in the control group; risk ratio (RR) 0.98, 95% confidence interval (CI) 0.84 to 1.15; I 2 = 11%; 14 trials, 9924 participants; low-certainty evidence) • Change in place of residence to a nursing home at 12 months' follow-up (9.9% in the intervention group versus 13.4% in the control group; RR 0.73, 95% CI 0.53 to 1.01; I 2 = 0%; 4 trials, 1108 participants; low-certainty evidence) • Quality of life at three to 24 months' follow-up (results not pooled; mean differences (MDs) ranged from -6.32 points (95% CI -11.04 to -1.59) to 6.1 points (95% CI -3.92 to 16.12) when reported; 11 trials, 9284 participants; low-certainty evidence) • Serious adverse effects at 12 to 24 months' follow-up (results not pooled; 2 trials, 592 participants; low-certainty evidence) • Change in physical function at three to 24 months' follow-up (results not pooled; MDs ranged from -0.12 points (95% CI -0.93 to 0.68) to 3.4 points (95% CI -2.35 to 9.15) when reported; 16 trials, 10,652 participants; low-certainty evidence) Case management compared to standard care probably results in little or no difference in the following outcomes. • Healthcare utilisation in terms of hospital admission at 12 months' follow-up (32.7% in the intervention group versus 36.0% in the control group; RR 0.91, 95% CI 0.79 to 1.05; I 2 = 43%; 6 trials, 2424 participants; moderate-certainty evidence) • Change in costs at six to 36 months' follow-up (results not pooled; 14 trials, 8486 participants; moderate-certainty evidence), which usually included healthcare service costs, intervention costs, and other costs such as informal care., Authors' Conclusions: We found uncertain evidence regarding whether case management for integrated care of older people with frailty in community settings, compared to standard care, improved patient and service outcomes or reduced costs. There is a need for further research to develop a clear taxonomy of intervention components, to determine the active ingredients that work in case management interventions, and identify how such interventions benefit some people and not others., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Objective: To characterize delivery practices and factors associated with respectful, evidence-based care at a referral hospital in Western Kenya., Methods: An exploratory observational study used a standardized birth-observation form to record information on patient characteristics and healthcare practitioner behaviors during uncomplicated vaginal deliveries between June 30, 2014 and July 17, 2014. All deliveries were monitored for whether healthcare staff performed six specific evidence-based practices (three maternal and three neonatal practices)., Results: In total, 75 vaginal deliveries were observed. In 48 (64%) deliveries, nursing students were the only practitioners present. The mean number of evidence-based practices performed at each delivery was 3.58. The number of evidence-based practices performed by junior practitioners was higher when a nurse educator was assessing their performance (4.47 vs 3.36, P<0.001). Lower mean respectful-care scores were recorded when delivery teams comprised three or more practitioners (1.38; 95% confidence interval 0.93-1.84 vs 2.74; 95% confidence interval 2.16-3.31, P=0.002)., Conclusion: The present study found low rates of evidence-based practice and respectful maternity care; this could serve as a deterrent for women seeking care at the study facility. These findings emphasize the need for a comprehensive approach in increasing the quality of patient care to improve maternal and newborn health outcomes., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Increasingly, research grant awarding bodies are regarding involvement at all stages of research, including prior to funding, as good practice. However, it is unclear how researchers should pay for this. Therefore, a pre-funding bursary scheme was designed. Up to £500 could be requested for involvement to develop a grant application for which user involvement is a key requisite for the funding body concerned. As the bursary scheme had run for 2 years, an evaluation was conducted to ascertain whether the scheme was effective for incorporating early involvement and in developing the grant proposal., Results: Twelve applications were made of which all were funded. The mean amount requested was £432.91; with the mean amount awarded £308.72. The involvement activities conducted all used qualitative methodology. Feedback regarding the bursaries was positive: enabling refinement of the research question and design; developing dialogue between the service users and the researchers; and helping with team building, with service users sometimes becoming co-applicants or members of the steering groups. The bursaries provided a learning opportunity – about involvement for the researchers and about research for the service users. The ultimate aim of the scheme was to enhance the research grant. Regarding this, the involvement paid for by the bursary meant that applicants could complete the involvement sections with in-depth information and clarity., Conclusion: For a relatively small financial outlay, appropriate involvement was made possible at an important part of the research process which is usually neglected due to lack of funding. Recommendations for implementation made., (© 2013 John Wiley & Sons Ltd.)

Background: Clinical trials in pediatric acute myeloid leukemia (AML) determine induction regimen standards. However, these studies lack the data necessary to evaluate mortality trends over time and differences in resource utilization between induction regimens. Moreover, these trials likely underreport the clinical toxicities experienced by patients., Methods: The Pediatric Health Information System database was used to identify children treated for presumed de novo AML between 1999 and 2010. Induction mortality, risk factors for induction mortality, and resource utilization by induction regimen were estimated using standard frequentist statistics, logistic regression, and Poisson regression, respectively., Results: A total of 1686 patients were identified with an overall induction case fatality rate of 5.4% that decreased from 9.8% in 2003 to 2.1% in 2009 (P = .0023). The case fatality rate was 9.0% in the intensively timed DCTER (dexamethasone, cytarabine, thioguanine, etoposide, and rubidomycin [daunomycin]/idarubicin) induction and 3.8% for ADE (cytarabine, daunomycin, and etoposide) induction (adjusted odds ratio = 2.2, 95% confidence interval = 1.1-4.5). Patients treated with intensively timed DCTER regimens had significantly greater antibiotic, red cell/platelet transfusion, analgesic, vasopressor, renal replacement therapy, and radiographic resource utilization than patients treated with ADE regimens. Resource utilization was substantially higher than reported in published pediatric AML clinical trials., Conclusions: Induction mortality for children with AML decreased significantly as ADE use increased. In addition to higher associated mortality, intensively timed DCTER regimens had a correspondingly higher use of health care resources. Using resource utilization data as a proxy for adverse events, adverse event rates reported on clinical trials substantially underestimated the clinical toxicities of all pediatric AML induction regimens., (Copyright © 2013 American Cancer Society.)

Objective: To evaluate the acceptability, feasibility, rating, and potential impact of PRONTO, a low-tech and high-fidelity simulation-based training for obstetric and neonatal emergencies and teamwork using the PartoPants low-cost birth simulator., Methods: A pilot project was conducted from September 21, 2009, to April 9, 2010, to train interprofessional teams from 5 community hospitals in the states of Mexico and Chiapas. Module I (teamwork, neonatal resuscitation, and obstetric hemorrhage) was followed 3 months later by module II (dystocia and pre-eclampsia/eclampsia) and an evaluation. Four elements were assessed: acceptability; feasibility and rating; institutional goal achievement; teamwork improvement; and knowledge and self-efficacy., Results: The program was rated highly both by trainees and by non-trainees who completed a survey and interview. Hospital goals identified by participants in the module I strategic-planning sessions were achieved for 65% of goals in 3 months. Teamwork, knowledge, and self-efficacy scores improved., Conclusion: PRONTO brings simulation training to low-resource settings and can empower interprofessional teams to respond more effectively within their institutional limitations to emergencies involving women and newborns. Further study is warranted to evaluate the potential impact of the program on obstetric and neonatal outcome., (Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Tight regulation of Notch pathway signaling is important in many aspects of embryonic development. Notch signaling can be modulated by expression of fringe genes, encoding glycosyltransferases that modify EGF repeats in the Notch receptor. Although Lunatic fringe (Lfng) has been shown to play important roles in vertebrate segmentation, comparatively little is known regarding the developmental functions of the other vertebrate fringe genes, Radical fringe (Rfng) and Manic fringe (Mfng). Here we report that Mfng expression is not required for embryonic development. Further, we find that despite significant overlap in expression patterns, we detect no obvious synergistic defects in mice in the absence of two, or all three, fringe genes during development of the axial skeleton, limbs, hindbrain, and cranial nerves., ((c) 2009 Wiley-Liss, Inc.)

Background: Early prognosis for incident (new) heart failure (HF) patients in the general population is poor. Clinical trials suggest approximately half of chronic HF patients die suddenly but mode of death for incident HF cases in the general population has not been evaluated., Aims: To describe mode of death in the first six months after a new diagnosis in the general population., Methods: Two-centre UK population-based study., Results: 396 incident HF patients were prospectively identified. Overall mortality rates were 6% [3-8%], 11% [8-14%] and 14% [11-18%] at 1, 3 and 6months respectively. There were 59 deaths over a median follow-up of 10months; 86% (n = 51) were cardiovascular (CV) deaths. Overall, the mode of death was progressive HF in 52% (n = 31), sudden death (SD) in 22% (n = 13), other CV death in 12% (n = 7), and non-CV death in 14% (n = 8). On multivariable analysis, progressive HF deaths were associated with older age, lower serum sodium, systolic hypotension, prolonged QRS duration at baseline and absence of ACE inhibitor therapy at the time of discharge or death., Conclusion: Early prognosis after a new diagnosis of HF in the general population is poor and progressive HF, rather than sudden death, accounts for the majority of deaths.

Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS., (Copyright 2000 John Wiley & Sons, Inc.)

Objective: To describe the variability of reproductive life, from menarche to menopause, in the Geneva female population., Design: Women's Health Survey, 1992-1993., Setting: Mobile epidemiology unit of a University Hospital., Subjects: One thousand and thirty-two women aged 30 to 74 years, resident in Geneva, Switzerland., Main Outcome Measure: Menstrual and reproductive history., Results: A 'typical' woman of Geneva has her menarche at 13 years, regular 28 day cycles with 5 days of menstrual flow. She is 26 years old when she first gives birth and has her last baby (which is typically the second) at age 31. She has 37 years of potential fecundity and a natural menopause at age 50. In addition, 11% of the women have tried to be pregnant during two years without success, 67% have ever used oral contraceptives, 20% had a first birth at age 30 or more and 23% were nulliparous. Younger women reported earlier ages at menarche. Women with lower education tended to be a younger age at the birth of her first child., Conclusions: In this first study of the reproductive characteristics of women in Geneva, nulliparity and a late first birth appeared unusually frequent, especially when compared with American or Chinese women. The observed distributions of reproductive history are compatible with the very high incidence rate of breast cancer in the Geneva population.