Perceived Health Status and Capability after Hip Fracture: Secondary Outcomes from an Randomized Controlled Trial.

INTRODUCTION: Hip fractures can have a significant impact on the lives of older people and their families. We conducted a pragmatic randomized controlled trial of post-discharge comprehensive geriatric care (CGC) for community-dwelling older adults after a surgically repaired hip fracture. The objective of this study was to conduct a secondary analysis to compare changes in health status and perceived capability from baseline to 12 months after randomization with: the EuroQol 5-Dimension (EQ-5D-5L) (1) utility score and (2) visual analog scale (VAS); and (3) well-being as measured by participants' perceptions of their ability (or capability) toward completing life activities using the ICEpop Capability Measure for Older People (ICECAP-O). METHODS: We tested the effect of usual care (control) versus usual care and an outpatient CGC clinic (intervention) on mobility after hip fracture in community-dwelling older adults (65 years+). In this secondary analysis, we report the following outcomes: EQ-5D-5L utility score and VAS collected monthly via telephone and ICECAP-O collected in person three times at baseline, 6 months, and 12 months. Data were analyzed using area under the curve and regression adjusted for baseline values for utility scores and capability, and constrained longitudinal data analysis for VAS. RESULTS: We enrolled 53 older adults, including 34 women and 19 men, with mean (SD) age of 80 (8) years. There were no statistical or clinically meaningful differences between groups (control group - intervention group values) for all variables: utility score = -0.028 (95% CI: -0.071, 0.014; p = 0.18); VAS: -0.03 (95% CI: -0.39 to 0.33; p = 0.86); and capability = -0.021 (95% CI: -0.090, 0.046; p = 0.54). CONCLUSIONS: There were no differences in outcomes between groups over 12 months, but values remained constant, contrary to a potential decline for this age group, especially after a major life event like a hip fracture.

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome.

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.

Co-Designing a Mobile-Based Game to Improve Misinformation Resistance and Vaccine Knowledge in Uganda, Kenya, and Rwanda.

Misinformation can decrease public confidence in vaccines, and reduce vaccination intent and uptake. One strategy for countering these negative impacts comes from inoculation theory. Similar to biological vaccination, inoculation theory posits that exposure to a weakened form of misinformation can develop cognitive immunity, reducing the likelihood of being misled. Online games offer an interactive, technology-driven, and scalable solution using an active form of inoculation that engages and incentivizes players to build resilience against misinformation. We document the development of the critical thinking game Cranky Uncle Vaccine. The game applies research findings from inoculation theory, critical thinking, humor in science communication, and serious games. The game content was iterated through a series of co-design workshops in Kampala (Uganda), Kitale (Kenya), and Kigali (Rwanda). Workshop participants offered feedback on cartoon character design, gameplay experience, and the game's content, helping to make the game more culturally relevant and avoid unintended consequences in East African countries. Our co-design methodology offers an approach for further adaptation of the Cranky Uncle Vaccine game to other regions, as well as a template for developing locally relevant interventions to counter future infodemics.

Exploring the Shared Experiences of Yazidis Who Survived Genocide.

In August 2014, the Islamic State of Iraq (ISIS) and the Levant (ISIL) brutally attacked the Yazidi people and occupied Sinjar and other villages in Northern Iraq. The massacre of Yazidis that began in August 2014 was declared by the United Nations as genocide. To gain a better understanding and raise awareness of these atrocities, we conducted a qualitative, phenomenological study with 35 Yazidis, who survived the genocide. The aim of the study was to elucidate the Yazidis' processing of the genocide and how it affects their psychological functioning. Coding and theming were the methods used to categorize, bring meaning and identity to Yazidis'genocidal experiences. The interviews took place between April and June 2019. Data analysis of the interview transcripts revealed that Yazidis, who survived the genocide of 2014, commonly experienced 11 themes related to hopelessness, fear, loss, grief, distrust, change, advocacy, optimism, shock, intrusive memories, and guilt. Results from this study reveal the vulnerabilities of ethnic minorities at risk of being abducted, killed, raped, and displaced. Moreover, the inherent risk of future genocides is illustrated through the experiences shared by the Yazidis.

Comprehensive Geriatric Care to Improve Mobility after Hip Fracture: An RCT.

BACKGROUND: Comprehensive geriatric care (CGC) for older adults during hospitalization for hip fracture can improve mobility, but it is unclear whether CGC delivered after a return to community living improves mobility compared with usual post-discharge care. OBJECTIVE: To determine if an outpatient clinic-based CGC regime in the first year after hip fracture improved mobility performance at 12 months. METHODS: A two-arm, 1:1 parallel group, pragmatic, single-blind, single-center, randomized controlled trial at 3 hospitals in Vancouver, BC, Canada. Participants were community-dwelling adults, aged ≥65 years, with a hip fracture in the previous 3-12 months, who had no dementia and walked ≥10 m before the fracture occurred. Target enrollment was 130 participants. Clinic-based CGC was delivered by a geriatrician, physiotherapist, and occupational therapist. Primary outcome was the Short Physical Performance Battery (SPPB; 0-12) at 12 months. RESULTS: We randomized 53/313 eligible participants with a mean (SD) age of 79.7 (7.9) years to intervention (n = 26) and usual care (UC, n = 27), and 49/53 (92%) completed the study. Mean 12-month (SD) SPPB scores in the intervention and UC groups were 9.08 (3.03) and 8.24 (2.44). The between-group difference was 0.9 (95% CI -0.3 to 2.0, p = 0.13). Adverse events were similar in the 2 groups. CONCLUSION: The small sample size of less than half our recruitment target precludes definitive conclusions about the effect of our intervention. However, our results are consistent with similar studies on this population and intervention.

Effect of a Home-Based Exercise Program on Subsequent Falls Among Community-Dwelling High-Risk Older Adults After a Fall: A Randomized Clinical Trial.

Importance: Whether exercise reduces subsequent falls in high-risk older adults who have already experienced a fall is unknown. Objective: To assess the effect of a home-based exercise program as a fall prevention strategy in older adults who were referred to a fall prevention clinic after an index fall. Design, Setting, and Participants: A 12-month, single-blind, randomized clinical trial conducted from April 22, 2009, to June 5, 2018, among adults aged at least 70 years who had a fall within the past 12 months and were recruited from a fall prevention clinic. Interventions: Participants were randomized to receive usual care plus a home-based strength and balance retraining exercise program delivered by a physical therapist (intervention group; n = 173) or usual care, consisting of fall prevention care provided by a geriatrician (usual care group; n = 172). Both were provided for 12 months. Main Outcomes and Measures: The primary outcome was self-reported number of falls over 12 months. Adverse event data were collected in the exercise group only and consisted of falls, injuries, or muscle soreness related to the exercise intervention. Results: Among 345 randomized patients (mean age, 81.6 [SD, 6.1] years; 67% women), 296 (86%) completed the trial. During a mean follow-up of 338 (SD, 81) days, a total of 236 falls occurred among 172 participants in the exercise group vs 366 falls among 172 participants in the usual care group. Estimated incidence rates of falls per person-year were 1.4 (95% CI, 0.1-2.0) vs 2.1 (95% CI, 0.1-3.2), respectively. The absolute difference in fall incidence was 0.74 (95% CI, 0.04-1.78; P = .006) falls per person-year and the incident rate ratio was 0.64 (95% CI, 0.46-0.90; P = .009). No adverse events related to the intervention were reported. Conclusions and Relevance: Among older adults receiving care at a fall prevention clinic after a fall, a home-based strength and balance retraining exercise program significantly reduced the rate of subsequent falls compared with usual care provided by a geriatrician. These findings support the use of this home-based exercise program for secondary fall prevention but require replication in other clinical settings. Trial Registration: ClinicalTrials.gov Identifiers: NCT01029171; NCT00323596.

Quantity and Quality of Economic Evaluations in U.S. Nursing Research, 1997-2015: A Systematic Review.

BACKGROUND: The United States has a complex healthcare system that is undergoing substantial reformations. There is a need for high-quality, economic evaluations of nursing practice. An updated review of completed economic evaluations relevant to the field of nursing within the U.S. healthcare system is timely and needed. OBJECTIVES: The purpose of this study was to evaluate and describe the quantity and quality of economic evaluations in nursing-relevant research performed in the United States between 1997 and 2015. METHODS: Four databases were searched. Titles, abstracts, and full-text content were reviewed to identify studies that analyzed both costs and outcomes, relevant to nursing, performed in the United States, and used the quality-adjusted life year to measure effectiveness. For included studies, data were extracted from full-text articles using criteria from U.S. Public Health Service's Panel on Cost-Effectiveness in Health and Medicine. RESULTS: Twenty-eight studies met the inclusion criteria. Most (n = 25, 89%) were published in the last decade of the analysis, from 2006 to 2015. Assessment of quality, based on selected items from the panel guidelines, found that the evaluations did not consistently use the recommended societal perspective, use multiple resource utilization categories, use constant dollars, discount future costs and outcomes, use a lifetime horizon, or include an indication of uncertainty in results. The only resource utilization category consistently included across studies was healthcare resources. DISCUSSION: Only 28 nursing-related studies meeting the inclusion criteria were identified as meeting robust health economic evaluation methodological criteria, and most did not include all important guideline items. Despite increases in absolute numbers of published studies over the past decade, economic evaluation has been underutilized in U.S. nursing-relevant research in the past two decades.

US Military Service Members' Reasons for Deciding to Participate in Health Research.

Researchers have reported challenges in recruiting US military service members as research participants. We explored their reasons for participating. Eighteen US military service members who had participated in at least one health-related research study within the previous 3 years completed semi-structured individual interviews in person or by telephone, focused on the service members' past decisions regarding research participation. Service members described participation decisions for 34 individual research experiences in 27 separate studies. Service members' reasons for participation in research clustered in three themes: others-, self-, and fit-focused. Each decision included reasons characterized by at least two themes. Reasons from all three themes were apparent in two-thirds of individual participation decisions. Reasons described by at least half of the service members included a desire to make things better for others, to improve an organization, to help researchers, and to improve one's health; understanding how they fit in studies; and convenience of participation. Findings may help researchers, study sponsors, ethicists, military leaders, and military decision-makers better understand service members' reasons for participating in research and improve future recruitment of service members in health research. © 2017 Wiley Periodicals, Inc.

Collaborating With Parents of Children With Chronic Conditions and Professionals to Design, Develop and Pre-pilot PLAnT (the Parent Learning Needs and Preferences Assessment Tool).

PURPOSE: This study aimed to design, develop and pre-pilot an assessment tool (PLAnT) to identify parents' learning needs and preferences when carrying out home-based clinical care for their child with a chronic condition. DESIGN AND METHODS: A mixed methods, two-phased design was used. Phase 1: a total of 10 parents/carers and 13 professionals from six UK's children's kidney units participated in qualitative interviews. Interview data were used to develop the PLAnT. Eight of these participants subsequently took part in an online survey to refine the PLAnT. Phase 2: thirteen parents were paired with one of nine professionals to undertake a pre-pilot evaluation of PLAnT. Data were analyzed using the Framework approach. RESULTS: A key emergent theme identifying parents' learning needs and preferences was identified. The importance of professionals being aware of parents' learning needs and preferences was recognised. Participants discussed how parents' learning needs and preferences should be identified, including: the purpose for doing this, the process for doing this, and what would the outcome be of identifying parents' needs. CONCLUSIONS: The evidence suggests that asking parents directly about their learning needs and preferences may be the most reliable way for professionals to ascertain how to support individual parents' learning when sharing management of their child's chronic condition. PRACTICE IMPLICATIONS: With the increasing emphasis on parent-professional shared management of childhood chronic conditions, professionals can be guided by PLAnT in their assessment of parents' learning needs and preferences, based on identified barriers and facilitators to parental learning.

IAPs limit activation of RIP kinases by TNF receptor 1 during development.

Inhibitor of apoptosis (IAP) proteins cIAP1, cIAP2, and XIAP (X-linked IAP) regulate apoptosis and cytokine receptor signalling, but their overlapping functions make it difficult to distinguish their individual roles. To do so, we deleted the genes for IAPs separately and in combination. While lack of any one of the IAPs produced no overt phenotype in mice, deletion of cIap1 with cIap2 or Xiap resulted in mid-embryonic lethality. In contrast, Xiap(-/-)cIap2(-/-) mice were viable. The death of cIap2(-/-)cIap1(-/-) double mutants was rescued to birth by deletion of tumour necrosis factor (TNF) receptor 1, but not TNFR2 genes. Remarkably, hemizygosity for receptor-interacting protein kinase 1 (Ripk1) allowed Xiap(-/-)cIap1(-/-) double mutants to survive past birth, and prolonged cIap2(-/-)cIap1(-/-) embryonic survival. Similarly, deletion of Ripk3 was able to rescue the mid-gestation defect of cIap2(-/-)cIap1(-/-) embryos, as these embryos survived to E15.5. cIAPs are therefore required during development to limit activity of RIP kinases in the TNF receptor 1 signalling pathway.

Sedentary Behavior and Physical Activity Patterns in Older Adults After Hip Fracture: A Call to Action.

OBJECTIVES: To characterize patterns of sedentary behavior and physical activity in older adults recovering from hip fracture and to determine characteristics associated with activity. METHODS: Community-dwelling, Canadian adults (65 years+) who sustained hip fracture wore an accelerometer at the waist for seven days and provided information on quality of life, falls self-efficacy, cognitive functioning, and mobility. RESULTS: There were 53 older adults (mean age [SD] 79.5 [7.8] years) enrolled in the study; 49 had valid data and demonstrated high levels of sedentary time (median [p10, p90] 591.3 [482.2, 707.2] minutes/day), low levels of light activity (186.6 [72.6, 293.7]), and MVPA (2 [0.1, 27.6]), as well as few daily steps (2467.7 [617.1, 6820.4]). Regression analyses showed that age, gender, gait speed, and time since fracture were associated with outcomes. CONCLUSIONS: Older adults have long periods of sedentary time with minimal activity. Results are a call to action to encourage people to sit less and move more.

Cost effectiveness analysis for nursing research.

BACKGROUND: With ever-increasing pressure to reduce costs and increase quality, nurses are faced with the challenge of producing evidence that their interventions and care provide value. Cost effectiveness analysis (CEA) is a tool that can be used to provide this evidence by comparative evaluation of the costs and consequences of two or more alternatives. OBJECTIVES: The aim of this article is to introduce the essential components of CEA to nurses and nurse researchers with the protocol of a recently funded cluster randomized controlled trial as an example. METHODS: This article provides (a) a description of the main concepts and key steps in CEA and (b) a summary of the background and objectives of a CEA designed to evaluate a nursing-led pain and symptom management intervention in rural communities compared with the current usual care. DISCUSSION: As the example highlights, incorporating CEA into nursing research studies is feasible. The burden of the additional data collection required is offset by quantitative evidence of the given intervention's cost and impact using humanistic and economic outcomes. At a time when U.S. healthcare is moving toward accountable care, the information provided by CEA will be an important additional component of the evidence produced by nursing research.

In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-kappaB and activation of caspase-8.

RIPK1 is involved in signaling from TNF and TLR family receptors. After receptor ligation, RIPK1 not only modulates activation of both canonical and NIK-dependent NF-κB, but also regulates caspase-8 activation and cell death. Although overexpression of RIPK1 can cause caspase-8-dependent cell death, when RIPK1(-/-) cells are exposed to TNF and low doses of cycloheximide, they die more readily than wild-type cells, indicating RIPK1 has pro-survival as well as pro-apoptotic activities. To determine how RIPK1 promotes cell survival, we compared wild-type and RIPK1(-/-) cells treated with TNF. Although TRAF2 levels remained constant in TNF-treated wild-type cells, TNF stimulation of RIPK1(-/-) cells caused TRAF2 and cIAP1 to be rapidly degraded by the proteasome, which led to an increase in NIK levels. This resulted in processing of p100 NF-κB2 to p52, a decrease in levels of cFLIP(L), and activation of caspase-8, culminating in cell death. Therefore, the pro-survival effect of RIPK1 is mediated by stabilization of TRAF2 and cIAP1.

Adaptation and Testing of a Military Version of the Measure of Moral Distress for Healthcare Professionals.

BACKGROUND: Moral distress is well-documented among civilian critical care nurses and adversely affects patient outcomes, care delivery, and retention of health care providers. Despite its recognized significance, few studies have addressed moral distress in military critical care nurses. OBJECTIVES: To refine and validate an instrument to assess moral distress in military critical care nurses. METHODS: This study examined moral distress in military critical care nurses (N = 245) using a new instrument, the Measure of Moral Distress for Healthcare Professionals-Military (MMD-HP-M). The psychometric properties of the refined scale were assessed by use of descriptive statistics, tests of reliability and validity, exploratory factor analysis, correlations, and qualitative analysis of open-ended responses. RESULTS: Initial testing showed promising evidence of instrument performance. The Cronbach α (0.94) suggested good internal consistency of the instrument for the overall sample. Scores for the MMD-HP items and the MMD-HP-M items showed a strong, significant correlation (α= 0.78, P < .001). Unique attributes of military nursing that contribute to moral distress included resource access, futile care, and austere conditions. Exploratory factor analysis established a new military-centric factor for question items associated with inadequate training for patient care, providing care in resource-limited settings, and personal exhaustion. CONCLUSIONS: These results will help guide specific, targeted interventions to reduce the negative effects of moral distress on our military health care providers, especially in terms of readiness for the next global pandemic and retention of these invaluable personnel.

Economic Evaluation of Using Daily Prednisolone versus Placebo at the Time of an Upper Respiratory Tract Infection for the Management of Children with Steroid-Sensitive Nephrotic Syndrome: A Model-Based Analysis.

BACKGROUND: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. OBJECTIVE: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. METHODS: A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. RESULTS: The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. CONCLUSION: A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.

Daily low-dose prednisolone to prevent relapse of steroid-sensitive nephrotic syndrome in children with an upper respiratory tract infection: PREDNOS2 RCT.

BACKGROUND: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5-7 days during an upper respiratory tract infection reduces the risk of relapse. OBJECTIVES: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. DESIGN: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. SETTING: A total of 122 UK paediatric departments, of which 91 recruited patients. PARTICIPANTS: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. RESULTS: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference -0.024, 95% confidence interval -0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. LIMITATIONS: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. CONCLUSIONS: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. FUTURE WORK: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information.

Steroid-sensitive nephrotic syndrome is a kidney condition in which protein leaks into the urine, causing generalised swelling. In most children, the condition recurs or relapses. Relapses often occur following an upper respiratory tract infection (i.e. a cough, cold or sore throat). Research in tropical countries suggests that if children have a small dose of daily steroids for a week at the time of an upper respiratory tract infection then they are less likely to relapse. The selection of children for these studies and the different patterns of infection mean that we are not certain if this treatment would work in the UK. A total of 365 children with relapsing nephrotic syndrome took part. Half of the children took a steroid and the other half took dummy tablets (placebo) for 6 days at the start of an upper respiratory tract infection. We followed up the children for 12 months and collected information on relapses and other treatments and information from questionnaires about behaviour and quality of life. We also investigated whether or not there were cost savings with this treatment. There were 271 children who had an upper respiratory tract infection in the 12 months of the study and so only these children were included in the analyses. Giving 6 days of a low-dose steroid at the time of an upper respiratory tract infection did not reduce the risk of a relapse. There was also no effect on the overall number of relapses, the number of children needing to start extra preventative treatments or side effects of steroids. Although there was no clinical effect, the economic evaluation found that giving prednisolone led to lower treatment costs overall and higher quality of life and might, therefore, offer better value for money, but this has to be interpreted against the clinical evidence of no significant effect. Our conclusion is that there is no clinical benefit to giving children low-dose prednisolone at the time of an upper respiratory tract infection.

Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome: The PREDNOS 2 Randomized Clinical Trial.

IMPORTANCE: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. OBJECTIVE: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. RESULTS: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). CONCLUSIONS AND RELEVANCE: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.

Post-discharge management following hip fracture--get you back to B4: a parallel group, randomized controlled trial study protocol.

BACKGROUND: Fall-related hip fractures result in significant personal and societal consequences; importantly, up to half of older adults with hip fracture never regain their previous level of mobility. Strategies of follow-up care for older adults after fracture have improved investigation for osteoporosis; but managing bone health alone is not enough. Prevention of fractures requires management of both bone health and falls risk factors (including the contributing role of cognition, balance and continence) to improve outcomes. METHODS/DESIGN: This is a parallel group, pragmatic randomized controlled trial to test the effectiveness of a post-fracture clinic compared with usual care on mobility for older adults following their hospitalization for hip fracture. Participants randomized to the intervention will attend a fracture follow-up clinic where a geriatrician and physiotherapist will assess and manage their mobility and other health issues. Depending on needs identified at the clinical assessment, participants may receive individualized and group-based outpatient physiotherapy, and a home exercise program. Our primary objective is to assess the effectiveness of a novel post-discharge fracture management strategy on the mobility of older adults after hip fracture. We will enrol 130 older adults (65 years+) who have sustained a hip fracture in the previous three months, and were admitted to hospital from home and are expected to be discharged home. We will exclude older adults who prior to the fracture were: unable to walk 10 meters; diagnosed with dementia and/or significant comorbidities that would preclude their participation in the clinical service. Eligible participants will be randomly assigned to the Intervention or Usual Care groups by remote allocation. Treatment allocation will be concealed; investigators, measurement team and primary data analysts will be blinded to group allocation. Our primary outcome is mobility, operationalized as the Short Physical Performance Battery at 12 months. Secondary outcomes include frailty, rehospitalizations, falls risk factors, quality of life, as well as physical activity and sedentary behaviour. We will conduct an economic evaluation to determine health related costs in the first year, and a process evaluation to ascertain the acceptance of the program by older adults, as well as clinicians and staff within the clinic. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01254942.