The Impact of Incident Postoperative Delirium on Survival of Elderly Patients After Surgery for Hip Fracture Repair.

BACKGROUND: The impact of delirium on survival of elderly patients remains undetermined with conflicting results from clinical studies and meta-analysis. In this study we assessed the relationship between long-term mortality and incident postoperative delirium in elderly patients undergoing hip fracture repair. METHODS: Patients ≥ 65 years old who were not delirious before undergoing hip fracture repair were included in a database maintained prospectively from March 1999 until July 2009. All participating patients underwent delirium assessment on the 2(nd) postoperative day using the confusion assessment method. Survival of the participants was determined as of October 2012. RESULTS: In 459 patients the mean (SD) period of evaluation from surgery until death or study closure was 4.1 (3.5) years with patients followed for as long as 13.6 years. Preoperative cognitive impairment was present in 120 patients (26.1%) and delirium on the 2(nd) postoperative day was observed in 151 (32.9%) of these. Although univariate analysis demonstrated a strong association between incident postoperative delirium and survival, this relationship did not persist in a multivariate model. Survival was a function of age at the time of surgery (p < 0.001), illness severity as determined by the ASA physical status score (p < 0.001), and duration of admission to the intensive care unit after surgery (p < 0.001). Incorporation of incident postoperative delirium did not meaningfully (p = 0.22) enhance the final survival model. In such a model, the hazard ratio [CI95] for incident postoperative delirium was 1.25 [0.92, 1.48]. CONCLUSIONS: Incident postoperative delirium was not significantly associated with decreased survival in elderly patients undergoing hip fracture repair

Data from: Abnormal CSF amyloid-β42 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

Role of Fracture and Repair Type on Pain and Opioid Use After Hip Fracture in the Elderly

Background and Purpose: Pain after hip fracture repair is related to worse functional outcomes and higher fracture care costs than that for patients with no or less pain. However, to our knowledge, few studies have examined the roles of hip fracture type or surgical procedure as factors influencing postoperative pain or opioid analgesic requirements. Our goal was to determine whether the type of hip fracture or hip fracture repair affects postoperative pain or opioid analgesic requirements in the elderly patient. Methods: We conducted a retrospective review of 231 patients ≥65 years old admitted to a hip fracture center for surgical repair. Fracture patterns were classified into femoral neck (FN) versus intertrochanteric (IT), stable versus unstable, and type of surgical repair. Demographic and intraoperative variables, postoperative pain scores, and opioid analgesic use data were collected and analyzed according to the type of hip fracture and type of surgical repair. Results: There were no differences in postoperative pain when comparing FN versus IT fractures, stable versus unstable fractures, or type of surgical repair. Patients with FN fractures had higher analgesic requirements on postoperative days 1, 2, and 3. There was no difference in postoperative analgesic requirements among patients with stable versus unstable fractures or type of surgical repair. Otherwise, there were no differences in postoperative pain or opioid analgesic use based on the surgical repair or fracture type. Overall, patients with hip fracture experienced low levels of pain

Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake

Up to 99% of systemically administered nanoparticles are cleared through the liver. Within the liver, most nanoparticles are thought to be sequestered by macrophages (Kupffer cells), although significant nanoparticle interactions with other hepatic cells have also been observed. To achieve effective cell-specific targeting of drugs through nanoparticle encapsulation, improved mechanistic understanding of nanoparticle-liver interactions is required. Here, we show the caudal vein of the embryonic zebrafish (Danio rerio) can be used as a model for assessing nanoparticle interactions with mammalian liver sinusoidal (or scavenger) endothelial cells (SECs) and macrophages. We observe that anionic nanoparticles are primarily taken up by SECs and identify an essential requirement for the scavenger receptor, stabilin-2 (stab2) in this process. Importantly, nanoparticle-SEC interactions can be blocked by dextran sulfate, a competitive inhibitor of stab2 and other scavenger receptors. Finally, we exploit nanoparticle-SEC interactions to demonstrate targeted intracellular drug delivery resulting in the selective deletion of a single blood vessel in the zebrafish embryo. Together, we propose stab2 inhibition or targeting as a general approach for modifying nanoparticle-liver interactions of a wide range of nanomedicines

Regional versus General Anesthesia for Promoting Independence after Hip Fracture (REGAIN): protocol for a pragmatic, international multicentre trial.

INTRODUCTION: Hip fractures occur 1.6 million times each year worldwide, with substantial associated mortality and losses of independence. At present, anaesthesia care for hip fracture surgery varies widely within and between countries, with general anaesthesia and spinal anaesthesia representing the 2 most common approaches. Limited randomised evidence exists regarding potential short-term or long-term differences in outcomes between patients receiving spinal or general anaesthesia for hip fracture surgery. METHODS: The REGAIN trial (Regional vs General Anesthesia for Promoting Independence after Hip Fracture) is an international, multicentre, pragmatic randomised controlled trial. 1600 previously ambulatory patients aged 50 and older will be randomly allocated to receive either general or spinal anaesthesia for hip fracture surgery. The primary outcome is a composite of death or new inability to walk 10 feet or across a room at 60 days after randomisation, which will be assessed via telephone interview by staff who are blinded to treatment assignment. Secondary outcomes will be assessed by in-person assessment and medical record review for in-hospital end points (delirium; major inpatient medical complications and mortality; acute postoperative pain; patient satisfaction; length of stay) and by telephone interview for 60-day, 180-day and 365-day end points (mortality; disability-free survival; chronic pain; return to the prefracture residence; need for new assistive devices for ambulation; cognitive impairment). ETHICS AND DISSEMINATION: The REGAIN trial has been approved by the ethics boards of all participating sites. Recruitment began in February 2016 and will continue until the end of 2019. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets. TRIAL REGISTRATION NUMBER: NCT02507505, Pre-results