Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial

IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.

Risks and neurological benefits of meningioma surgery in elderly patients compared to young patients

Introduction While surgery is the primary treatment choice for intracranial meningiomas in young patients, surgery in elderly patients, especially those with pre-existing comorbidities, has been the subject of repeated discussion. This study investigated the postoperative risks and neurological benefits of meningioma surgery in elderly patients compared to young patients. Methods In total, 768 patients were included and divided into two main groups: group I (age: ≤ 64 years; 484 young patients) and group II (age: ≥ 65 years; 284 elderly patients). Group II was subdivided into: IIa (age: 65–69 years), IIb (age: 70–79 years); and IIc (age: ≥ 80 years). Results The total tumor resection rate was higher in the elderly cohort than in the young cohort (84.5 and 76.2%, respectively). 154 young patients (31.8%) and 132 elderly patients (46.5%) developed postoperative morbidities, with the three most common being bleeding (12.9%), cranial nerve disorder (10%) and CSF fistula (8.1%). Postoperative bleeding, palsy, speech disorder, pneumonia and renal insufficiency were dependent on age (r = 0.123, p = 0.001; r = 0.089, p = 0.014; r = 0.100, p = 0.006; r = 0.098, p = 0.007 and r = 0.084, p = 0.020) and presented more often in elderly patients. 6 young and 15 elderly patients died during the 17.4-year observation period. Most patients showed a significant improvement in postoperative KPS (p < 0.001), except those over 80 years old (p = 0.753). The KPS at the last follow-up was significantly improved in all patients (p < 0.001). Conclusion Meningioma surgery is associated with a higher rate of postoperative complications in elderly patients than in young patients. Most elderly patients, similar to young patients, show a significant improvement in neurological status postoperatively.

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins

Background: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. Methods: This is an observational, multicenter, case–control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. Results: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. Conclusion: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts.