Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial)

BACKGROUND: Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. DESIGN: Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. RESULTS: In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. CONCLUSION: There was a small reduction in falls. The intervention may be cost-effective. TRIAL REGISTRATION: ISRCTN ISRCTN68240461

Long-Lasting Consequences of Neonatal Maternal Separation on Social Behaviors in Ovariectomized Female Mice

Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to situations involving social as well as non-social novelty

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial.

BACKGROUND: Randomised controlled trials are generally regarded as the 'gold standard' experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial. METHODS: A three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial. RESULTS: Six thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77-1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71-1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65-1.31, p = 0.65)). CONCLUSIONS: This embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number registry, ISRCTN68240461 . Registered on 01 July 2011

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

The reform study protocol: a cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people

Introduction: Falls and fall-related injuries are a serious cause of morbidity and cost to society. Foot problems and inappropriate footwear may increase the risk of falls; therefore podiatric interventions may play a role in reducing falls. Two Cochrane systematic reviews identified only one study of a podiatry intervention aimed to reduce falls, which was undertaken in Australia. The REFORM trial aims to evaluate the clinical and cost-effectiveness of a multifaceted podiatry intervention in reducing falls in people aged 65 years and over in a UK and Irish setting. Methods and analysis: This multicentre, cohort randomised controlled trial will recruit 2600 participants from routine podiatry clinics in the UK and Ireland to the REFORM cohort. In order to detect a 10% point reduction in falls from 50% to 40%, with 80% power 890 participants will be randomised to receive routine podiatry care and a falls prevention leaflet or routine podiatry care, a falls prevention leaflet and a multifaceted podiatry intervention. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by patient self-report falls diary. Secondary self-report outcome measures include: the proportion of single and multiple fallers and time to first fall over a 12-month period; Short Falls Efficacy Scale-International; fear of falling in the past 4 weeks; Frenchay Activities Index; fracture rate; Geriatric Depression Scale; EuroQoL-five dimensional scale 3-L; health service utilisation at 6 and 12 months. A qualitative study will examine the acceptability of the package of care to participants and podiatrists. Ethics and dissemination: The trial has received a favourable opinion from the East of England-Cambridge East Research Ethics Committee and Galway Research Ethics Committee. The trial results will be published in peer-reviewed journals and at conference presentations

Cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people (the reform trial)

Background Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. Design Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. Results In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of 30,000 pound per QALY gained. Conclusion There was a small reduction in falls. The intervention may be cost-effective