Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Brain function effects of exercise interventions for cognitive decline: a systematic review and meta-analysis

IntroductionExercise is recognized as a modifiable lifestyle factor that can mitigate cognitive decline and dementia risk. While the benefits of exercise on cognitive aging have been reported on extensively, neuronal effects in adults experiencing cognitive decline have not been systematically synthesized. The aim of this systematic review was to assess the effects of exercise on cognition and brain function in people with cognitive decline associated with dementia risk.MethodA systematic search was conducted for randomized controlled trials of ≥ 4 weeks exercise (aerobic, resistance, or mind-body) that assessed cognition and brain function using neuroimaging and neurophysiological measures in people with subjective or objective cognitive decline. Study characteristics and brain function effects were narratively synthesized, while domain-specific cognitive performance was subjected to meta-analysis. Study quality was also assessed.Results5,204 records were identified and 12 unique trials met the eligibility criteria, representing 646 adults classified with cognitive frailty, mild or vascular cognitive impairment. Most interventions involved 40-minute sessions conducted 3 times/week. Exercise improved global cognition (g = −0.417, 95% CI, −0.694 to −0.140, p = 0.003, I2 = 43.56%), executive function (g = −0.391, 95% CI, −0.651 to −0.131, p = 0.003, I2 = 13.28%), but not processing speed or general short-term memory (both p >0.05). Across fMRI and ERP studies, significant neuronal adaptations were found with exercise cf. control throughout the brain and were linked with improved global cognition, memory, and executive function. Cerebral blood flow was also found to improve with 24 weeks of exercise, but was not linked with cognitive changes.DiscussionThe cognitive improvements associated with exercise are likely driven by increased metabolic activity, cerebrovascular mechanisms, and neuroplasticity throughout the brain. Our paper shows the promise in, and need for, high-quality trials integrating cognitive and brain function measures to elucidate the functional relationship between exercise and brain health in populations with a high risk of dementia.Systematic review registrationPROSPERO, identifier: CRD42022291843

Study protocol for a phase III randomised controlled trial of Sailuotong (SLT) for vascular dementia and Alzheimer's disease with cerebrovascular disease.

Vascular dementia (VaD) accounts for 15-20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng C.A Mey, Ginkgo biloba L and Crocus sativus L extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention. A rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimer's disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinician's Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies. Primary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD

Study protocol for a phase III randomised controlled trial of Sailuotong (SLT) for vascular dementia and Alzheimer’s disease with cerebrovascular disease

Vascular dementia (VaD) accounts for 15–20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng C.A Mey, Ginkgo biloba L and Crocus sativus L extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention. A rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimer’s disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinician’s Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies. Primary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD

The effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation

Development and manufacture of nanomaterials is growing at an exponential rate, despite an incomplete understanding of how their physicochemical characteristics affect their potential toxicity. Redox activity has been suggested to be an important physicochemical property of nanomaterials to predict their biological activity. This study assessed the influence of redox activity by modification of cerium dioxide nanoparticles (CeO2 NPs) via zirconium (Zr) doping on the biodistribution, pulmonary and cardiovascular effects in mice following inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE−/−, western-diet fed) and a mouse model of neurological disease (5 × FAD) were exposed via nose-only inhalation to CeO2 NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m3 for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO2 NP exposure had no major toxicological effects apart from some modest inflammatory histopathology in the lung, which was not related to the amount of Zr-doping. In ApoE−/− mice CeO2 did not change the size of atherosclerotic plaques, but there was a trend towards increased inflammatory cell content in relation to the Zr content of the CeO2 NPs. These findings show that subacute inhalation of CeO2 NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO2 NPs has limited effect on these responses. Further studies with nanomaterials with a higher inherent toxicity or a broader range of redox activities are needed to fully assess the influence of redox activity on the toxicity of nanomaterials