Incidence and associated risk factors for falls in older adults after elective total knee replacement surgery

Objective The aim of the study was to determine the incidence and associated risk factors for falls in older adults in the 12 mos after elective, primary total knee replacement surgery. Design A prospective observational cohort of older adults undergoing total knee replacement were followed. Baseline measurements included risk factors of history of falls, using a gait aid and number of medications. Falls data were recorded after discharge for 12 mos alongside patient reported outcomes (Oxford Knee Score). Analyses used logistic and negative binomial regression modeling. Results There were 267 participants (mean age = 70 [6.7] yrs) enrolled. Participants who fell (n = 102 [40.6%]) reported 200 falls in the 12 mos after surgery. The incidence of falls was 2.4 falls per 1000 patient days in the 12 mos after surgery, with the highest incidence (2.6 falls per 1000 patient days) in month 1. Risk factors for falling were a history of falls (adjusted odds ratio = 2.41, 95% confidence interval = 1.35–4.31) and number of central nervous system acting medications taken before surgery (adjusted odds ratio = 1.66, 95% confidence interval = 1.25–2.21). Using a walking aid at baseline was associated with falls after discharge (adjusted incident rate ratio = 2.38, 95% confidence interval = 1.57–3.60). Conclusions Older adults experience a high incidence of falls after elective total knee replacement. Further research that investigates falls prevention after total knee replacement is required

Incidence and associated risk factors for falls in older adults after elective total knee replacement surgery: A prospective cohort study

Objective The aim of the study was to determine the incidence and associated risk factors for falls in older adults in the 12 mos after elective, primary total knee replacement surgery. Design A prospective observational cohort of older adults undergoing total knee replacement were followed. Baseline measurements included risk factors of history of falls, using a gait aid and number of medications. Falls data were recorded after discharge for 12 mos alongside patient reported outcomes (Oxford Knee Score). Analyses used logistic and negative binomial regression modeling. Results There were 267 participants (mean age = 70 [6.7] yrs) enrolled. Participants who fell (n = 102 [40.6%]) reported 200 falls in the 12 mos after surgery. The incidence of falls was 2.4 falls per 1000 patient days in the 12 mos after surgery, with the highest incidence (2.6 falls per 1000 patient days) in month 1. Risk factors for falling were a history of falls (adjusted odds ratio = 2.41, 95% confidence interval = 1.35-4.31) and number of central nervous system acting medications taken before surgery (adjusted odds ratio = 1.66, 95% confidence interval = 1.25-2.21). Using a walking aid at baseline was associated with falls after discharge (adjusted incident rate ratio = 2.38, 95% confidence interval = 1.57-3.60). Conclusions Older adults experience a high incidence of falls after elective total knee replacement. Further research that investigates falls prevention after total knee replacement is required

NF-κB Signaling-Mediated Activation of WNK-SPAK-NKCC1 Cascade in Worsened Stroke Outcomes of Ang II-Hypertensive Mice

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this recordData availability: The data that support the findings of this study are available within the article and its Data Supplement.BACKGROUND: Worsened stroke outcomes with hypertension comorbidity are insensitive to blood pressure-lowering therapies. In an experimental stroke model with comorbid hypertension, we investigated causal roles of ang II (angiotensin II)-mediated stimulation of the brain WNK (with no lysine [K] kinases)-SPAK (STE20/SPS1-related proline/alanine-rich kinase)-NKCC1 (Na-K-Cl cotransporter) complex in worsened outcomes. METHODS: Saline- or ang II-infused C57BL/6J male mice underwent stroke induced by permanent occlusion of the distal branches of the middle cerebral artery. Mice were randomly assigned to receive either vehicle dimethyl sulfoxide/PBS (2 mL/kg body weight/day, IP), a novel SPAK inhibitor, 5-chloro-N-(5-chloro-4-((4-chlorophenyl)(cyano)methyl)-2-methylphenyl)-2-hydroxybenzamide (ZT-1a' 5 mg/kg per day, IP) or a NF-κB (nuclear factor-κB) inhibitor TAT-NBD (transactivator of transcription-NEMO-binding domain' 20 mg/kg per day, IP). Activation of brain NF-κB and WNK-SPAK-NKCC1 cascade as well as ischemic stroke outcomes were examined. RESULTS: Stroke triggered a 2- to 5-fold increase of WNK (isoforms 1, 2, 4), SPAK/OSR1 (oxidative stress-responsive kinase 1), and NKCC1 protein in the ang II-infused hypertensive mouse brains at 24 hours after stroke, which was associated with increased nuclear translocation of phospho-NF-κB protein in the cortical neurons (a Pearson correlation r of 0.77, P<0.005). The upregulation of WNK-SPAK-NKCC1 cascade proteins resulted from increased NF-κB recruitment on Wnk1, Wnk2, Wnk4, Spak, and Nkcc1 gene promoters and was attenuated by NF-κB inhibitor TAT-NBD. Poststroke administration of SPAK inhibitor ZT-1a significantly reduced WNK-SPAK-NKCC1 complex activation, brain lesion size, and neurological function deficits in the ang II-hypertensive mice without affecting blood pressure and cerebral blood flow. CONCLUSIONS: The ang II-induced stimulation of NF-κB transcriptional activity upregulates brain WNK-SPAK-NKCC1 cascade and contributes to worsened ischemic stroke outcomes, illustrating the brain WNK-SPAK-NKCC1 complex as a therapeutic target for stroke with comorbid hypertension.Veteran AffairsNational Institutes of Health (NIH)AH