Spinal or general anaesthesia for surgical repair of hip fracture and subsequent risk of mortality and morbidity: a database analysis using propensity score‐matching

Around 76,000 people fracture their hip annually in the UK at a considerable personal, social and financial cost. Despite longstanding debate, the optimal mode of anaesthesia (general or spinal) remains unclear. Our aim was to assess whether there is a significant difference in mortality and morbidity between patients undergoing spinal anaesthesia compared with general anaesthesia during hip fracture surgery. A secondary analysis examined whether a difference exists in mortality for patients with pre‐existing cardiovascular disease or chronic obstructive pulmonary disease. This was a clinical database analysis of patients treated for hip fracture in Nottingham, UK between 2004 and 2015. Propensity score‐matching was used to generate matched pairs of patients, one of whom underwent each mode of anaesthesia. Data were analysed using conditional logistic regression, with 7164 patients successfully matched. There was no difference in 30‐ or 90‐day mortality in patients who had spinal rather than general anaesthesia (OR [95%CI] 0.97 [0.8–1.15]; p = 0.764 and 0.93 [0.82–1.05]; p = 0.247 respectively). Patients who had a spinal anaesthetic had a lower‐risk of blood transfusion (OR [95%CI] 0.84 [0.75–0.94]; p = 0.003) and urinary tract infection (OR [95%CI] 0.72 [0.61–0.84]; p [less than] 0.001), but were more likely to develop a chest infection (OR [95%CI] 1.23 [1.07–1.42]; p = 0.004), deep vein thrombosis (OR [95%CI] 2.18 [1.07–4.45]; p = 0.032) or pulmonary embolism (OR [95%CI] 2.23 [1.16–4.29]; p = 0.016). The mode of anaesthesia for hip fracture surgery resulted in no significant difference in mortality, but there was a significant difference in several measures of postoperative morbidity

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients

OBJECTIVES: While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium. METHODS: Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study "A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aβ) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)181. RESULTS: For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02-1.25). Both CSF Aꞵ42/t-tau (β = -1.52, 95%CI = -2.1 to -0.05) and Aꞵ42/p-tau181 (β = -0.29, 95%CI = -0.48 to -0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers. CONCLUSIONS: In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome

Sigma-1 receptor agonist fluvoxamine for postoperative delirium in older adults: report of three cases

<p>Abstract</p> <p>Background</p> <p>Postoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat this syndrome, these drugs are associated with a variety of adverse events, including sedation, extrapyramidal side effects, and cardiac arrhythmias. Drug treatment for postoperative delirium requires careful consideration of the balance between the effective management of symptoms and potential adverse effects.</p> <p>Methods</p> <p>We report on a Japanese woman (an 86-year-old (open reduction and internal fixation of the right femoral neck fracture), and two Japanese men (an 86-year-old (abdominal aortic aneurysm stent grafting), and a 77-year-old (right upper lobectomy due to lung tumour)) in which the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the postoperative delirium of these patients.</p> <p>Results</p> <p>Delirium Rating Scale scores in these patients dramatically decreased after treatment with fluvoxamine.</p> <p>Conclusions</p> <p>Doctors should consider fluvoxamine as an alternative approach to treating postoperative delirium in older patients in order to avoid the risk of side effects and increased mortality by antipsychotic drugs.</p

Abnormal Csf Amyloid-beta 42 and Tau Levels in Hip Fracture Patients Without Dementia

BACKGROUND: There is strong association of Alzheimer’s disease (AD) pathology with gait disorder and falls in older adults without dementia. The goal of the study was to examine the prevalence and severity of AD pathology in older adults without dementia who fall and sustain hip fracture. METHODS: Cerebrospinal fluid (CSF) was obtained from 168 hip fracture patients. CSF Aβ42/40 ratio, p-tau, and t-tau measures were dichotomized into normal vs. abnormal, and categorized according to the A/T/N classification. RESULTS: Among the hip fracture patients, 88.6% of the cognitively normal (Clinical Dementia Rating-CDR 0; n = 70) and 98.8% with mild cognitive impairment (CDR 0.5; n = 81) fell in the abnormal biomarker categories by the A/T/N classification. CONCLUSIONS: A large proportion of older hip fracture patients have CSF evidence of AD pathology. Preoperative determination of AD biomarkers may play a crucial role in identifying persons without dementia who have underlying AD pathology in perioperative settings

Does using a femoral nerve block for total knee replacement decrease postoperative delirium?

<p>Abstract</p> <p>Background</p> <p>The effect of peripheral nerve blocks on postoperative delirium in older patients has not been studied. Peripheral nerve blocks may reduce the incidence of postoperative opioid use and its side effects such as delirium via opioid-sparing effect.</p> <p>Methods</p> <p>A prospective cohort study was conducted in patients who underwent total knee replacement. Baseline cognitive function was assessed using the Telephone Interview for Cognitive Status. Postoperative delirium was measured using the Confusion Assessment Method postoperatively. Incidence of postoperative delirium was compared in two postoperative management groups: femoral nerve block ± patient-controlled analgesia and patient-controlled analgesia only. In addition, pain levels (using numeric rating scales) and opioid use were compared in two groups.</p> <p>Results</p> <p>85 patients were studied. The overall incidence of postoperative delirium either on postoperative day one or day two was 48.1%. Incidence of postoperative delirium in the femoral nerve block group was lower than patient controlled analgesia only group (25% vs. 61%, <it>P </it>= 0.002). However, there was no significant difference between the groups with respect to postoperative pain level or the amount of intravenous opioid use.</p> <p>Conclusions</p> <p>Femoral nerve block reduces the incidence of postoperative delirium. These results suggest that a larger randomized control trial is necessary to confirm these preliminary findings.</p

Evidence for Antisense Transcription Associated with MicroRNA Target mRNAs in Arabidopsis

Antisense transcription is a pervasive phenomenon, but its source and functional significance is largely unknown. We took an expression-based approach to explore microRNA (miRNA)-related antisense transcription by computational analyses of published whole-genome tiling microarray transcriptome and deep sequencing small RNA (smRNA) data. Statistical support for greater abundance of antisense transcription signatures and smRNAs was observed for miRNA targets than for paralogous genes with no miRNA cleavage site. Antisense smRNAs were also found associated with MIRNA genes. This suggests that miRNA-associated “transitivity” (production of small interfering RNAs through antisense transcription) is more common than previously reported. High-resolution (3 nt) custom tiling microarray transcriptome analysis was performed with probes 400 bp 5′ upstream and 3′ downstream of the miRNA cleavage sites (direction relative to the mRNA) for 22 select miRNA target genes. We hybridized RNAs labeled from the smRNA pathway mutants, including hen1-1, dcl1-7, hyl1-2, rdr6-15, and sgs3-14. Results showed that antisense transcripts associated with miRNA targets were mainly elevated in hen1-1 and sgs3-14 to a lesser extent, and somewhat reduced in dcl11-7, hyl11-2, or rdr6-15 mutants. This was corroborated by semi-quantitative reverse transcription PCR; however, a direct correlation of antisense transcript abundance in MIR164 gene knockouts was not observed. Our overall analysis reveals a more widespread role for miRNA-associated transitivity with implications for functions of antisense transcription in gene regulation. HEN1 and SGS3 may be links for miRNA target entry into different RNA processing pathways