Neurofilament Light Chain as a Biomarker of Global Cognition in Individuals With Possible Vascular Mild Cognitive Impairment.

BACKGROUND: Neurofilament Light Chain (NfL) is a biomarker of axonal injury elevated in mild cognitive impairment (MCI) and Alzheimer's disease dementia. Blood NfL also inversely correlates with cognitive performance in those conditions. However, few studies have assessed NfL as a biomarker of global cognition in individuals demonstrating mild cognitive deficits who are at risk for vascular-related cognitive decline. OBJECTIVE: To assess the relationship between blood NfL and global cognition in individuals with possible vascular MCI (vMCI) throughout cardiac rehabilitation (CR). Additionally, NfL levels were compared to age/sex-matched cognitively unimpaired (CU) controls. METHOD: Participants with coronary artery disease (vMCI or CU) were recruited at entry to a 24-week CR program. Global cognition was measured using the Montreal Cognitive Assessment (MoCA) and plasma NfL level (pg/ml) was quantified using a highly sensitive enzyme-linked immunosorbent assay. RESULTS: Higher plasma NfL was correlated with worse MoCA scores at baseline (ß = -.352, P = .029) in 43 individuals with vMCI after adjusting for age, sex, and education. An increase in NfL was associated with worse global cognition (b[SE] = -4.81[2.06], P = .023) over time, however baseline NfL did not predict a decline in global cognition. NfL levels did not differ between the vMCI (n = 39) and CU (n = 39) groups (F(1, 76) = 1.37, P = .245). CONCLUSION: Plasma NfL correlates with global cognition at baseline in individuals with vMCI, and is associated with decline in global cognition during CR. Our findings increase understanding of NfL and neurobiological mechanisms associated with cognitive decline in vMCI.

Ultrasound-guided suprainguinal fascia iliaca compartment block and early postoperative analgesia after total hip arthroplasty: a randomised controlled trial.

BACKGROUND: Hip replacement surgery can be painful; postoperative analgesia is crucial for comfort and to facilitate recovery. Regional anaesthesia can reduce pain and postoperative opioid requirements. The role of ultrasound-guided suprainguinal fascia iliaca block for analgesia after elective total hip arthroplasty is not well defined. This randomised trial evaluated its analgesic efficacy. METHODS: Consenting participants (134) scheduled for elective primary total hip arthroplasty under spinal anaesthesia were randomly allocated to receive ultrasound-guided fascia iliaca block with ropivacaine 0.5% or sham block with saline. The primary outcome was opioid consumption in the first 24 h after surgery. Additional outcomes included pain scores at 4, 8, 12, and 16 h, opioid-related side-effects (nausea, vomiting, pruritis), ability to perform physiotherapy on the first postoperative day, and physiotherapist-assessed quadriceps weakness. RESULTS: There were no significant differences in 24-h opioid consumption (block vs sham block, mean difference -3.2 mg oral morphine equivalent, 95% confidence interval -15.3 to 8.1 mg oral morphine equivalent, P=0.55) or any other prespecified outcomes. CONCLUSIONS: In patients undergoing primary total hip arthroplasty, ultrasound-guided suprainguinal fascia iliaca block with ropivacaine did not confer a significant opioid-sparing effect compared with sham block. There were no differences in other secondary outcomes including pain scores, opioid-related side-effects, or ability to perform physiotherapy on the first postoperative day. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT03069183).

Modifiable Risk Factors Associated With Cognitive Decline in Late Life Depression: Findings From the Canadian Longitudinal Study on Aging: Facteurs de risque modifiables associés au déclin cognitif dans la dépression en fin de vie : constatations de l'Étude longitudinale canadienne sur le vieillissement.

OBJECTIVE: Depression in later life is associated with a two-fold increased risk of dementia. It is not clear to what extent potentially modifiable risk factors account for this association. METHOD: Older adults (age 50 + ) with objective health measures (n = 14,014) from the Canadian Longitudinal Study on Aging were followed for a mean duration of 35 months. Linear regression analyses were used to determine if clinically significant depression (Centre for Epidemiologic Studies Depression scale score (CESD) ≥ 10) was associated with global cognitive decline, assessed with a neuropsychological battery during follow-up, and if modifiable risk factors mediated this association. RESULTS: Depression was associated with an excess of risk factors for cognitive decline including: vascular disease, hypertension, diabetes, apnoea during sleep, higher body mass index, smoking, physical inactivity and lack of social participation. In regression analyses depression remained independently associated with cognitive decline over time (beta -0.060, P = 0.038) as did cerebrovascular disease (beta -0.197, P < 0.001), HbA1C (beta -0.059, P < 0.001), visual impairment (beta -0.070, P = 0.007), hearing impairment (beta -0.098, P < 0.001) and physical inactivity (beta -0.075, P = 0.014). In mediation analyses, we found that cerebrovascular disease (z = -3.525, P < 0.001), HbA1C (z = -4.976, P < 0.001) and physical inactivity (z = -3.998, P < 0.001) partially mediated the association between depression and cognitive decline. CONCLUSIONS: In this large sample of Canadian older adults incorporating several objective health measures, older adults with depression were at increased risk of cognitive decline and had an excess of potentially modifiable risk factors. Clinicians should pay particular attention to control of diabetes, physical inactivity and risk factors for cerebrovascular disease in older adults presenting with depression as they can contribute to accelerated cognitive decline and may be addressed during routine clinical care.

Drivers of Emergency Department Use Among Oncology Patients in the Era of Novel Cancer Therapeutics: A Systematic Review.

BACKGROUND: Patients diagnosed with cancer are frequent users of the emergency department (ED). While many visits are unavoidable, a significant portion may be potentially preventable ED visits (PPEDs). Cancer treatments have greatly advanced, whereby patients may present with unique toxicities from targeted therapies and are often living longer with advanced disease. Prior work focused on patients undergoing cytotoxic chemotherapy, and often excluded those on supportive care alone. Other contributors to ED visits in oncology, such as patient-level variables, are less well-established. Finally, prior studies focused on ED diagnoses to describe trends and did not evaluate PPEDs. An updated systematic review was completed to focus on PPEDs, novel cancer therapies, and patient-level variables, including those on supportive care alone. METHODS: Three online databases were used. Included publications were in English, from 2012-2022, with sample sizes of ≥50, and reported predictors of ED presentation or ED diagnoses in oncology. RESULTS: 45 studies were included. Six studies highlighted PPEDs with variable definitions. Common reasons for ED visits included pain (66%) or chemotherapy toxicities (69.1%). PPEDs were most frequent amongst breast cancer patients (13.4%) or patients receiving cytotoxic chemotherapy (20%). Three manuscripts included immunotherapy agents, and only one focused on end-of-life patients. CONCLUSION: This updated systematic review highlights variability in oncology ED visits during the last decade. There is limited work on the concept of PPEDs, patient-level variables and patients on supportive care alone. Overall, pain and chemotherapy toxicities remain key drivers of ED visits in cancer patients. Further work is needed in this realm.

Lipopolysaccharide, Immune Biomarkers and Cerebral Amyloid-Beta Deposition in Older Adults With Mild Cognitive Impairment & Major Depressive Disorder.

OBJECTIVE: Inflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD). DESIGN: Cross-sectional analysis. SETTING: Five academic health centers in Toronto. PARTICIPANTS: Older adults with MCI with/without rMDD. MEASUREMENTS: We investigated the associations among serum LPS, LBP, biomarkers of inflammatory activation - Interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and cerebral Abeta deposition quantified by positron emission tomography. RESULTS: Among 133 study participants (82 with MCI and 51 with MCI+rMDD) there was no association between LPS (beta - 0.17, p = 0.8) or LBP (beta - 0.11, p = 0.12) and global deposition of Abeta following adjustment for age, gender, and APOE genotype in multivariable regression analyses. LBP was positively correlated with CRP (r = 0.5, p <0.001) and IL-6 (r = 0.2, p = 0.02) but no inflammatory biomarker was associated with Abeta deposition; rMDD was not associated with deposition of Abeta (beta -0.09, p = 0.22). CONCLUSION: In this cross-sectional analysis, we did not find an association among LPS/LBP, immune biomarkers or rMDD and global deposition of Abeta. Future analyses should assess the longitudinal relationships between peripheral and central biomarkers of immune activation, depression and cerebral Abeta deposition.

Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

BACKGROUND: This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive. METHODS: A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors. RESULTS: Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001). DISCUSSION: Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer's disease while considering the burden on the healthcare system.

Assessing the Nasal Midline in Rhinoplasty: How Good Are We?

BACKGROUND: The challenge of assessing nasal alignment and asymmetry can contribute to high revision rates in rhinoplasty. Comparing to a validated computer algorithm for nasal alignment, the accuracy with which plastic surgeons can assess deviation of the nasal midline from the facial midline was measured. METHODS: Using 20 faces from the Binghamton University 3-dimensional face database, deviation was evaluated from facial midline of the middorsal line for the upper, middle, and lower thirds of the nose. Surgeons were asked to assess extent of deviation from facial midline for each third of the nose using a linear analog scale. Spearman correlations were performed comparing the surgeons' results to the algorithm measurements. Eleven residents and 9 consultant surgeons were tested. RESULTS: Surgeons' assessment of deviation correlated poorly with the algorithm in the upper third ( r =0.32, P <0.0001) and moderately in the middle third ( r =0.49, P <0.0001) and lower third ( r =0.41, P <0.0001) of the nose. No difference in accuracy was found between trainee and consultant surgeons ( P =0.51), and greater experience (>10 y performing nasal surgery) did not significantly affect performance ( P =0.15). The effect of fatigue on the accuracy of assessment was found to be significant ( P =0.0009). CONCLUSIONS: Surgeons have difficulty in visually assessing the 3-dimensional nasal midline irrespective of experience, and surgeon fatigue was found to be adversely affect the accuracy of assessments.

Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET.

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aß) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aß deposition (18 F-AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or 18 F fluorodeoxyglucose PET) in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aß and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aß status. In summary, our study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive function via localized neurodegeneration. HIGHLIGHTS: Alzheimer's disease often co-exists with vascular pathology. We studied a unique cohort enriched for high white matter hyperintensities (WMH). High WMH related to cognitive impairment of semantic fluency and executive function. This relationship was mediated via temporo-parietal atrophy rather than metabolism. This relationship was, to lesser extent, serially mediated via amyloid beta and atrophy.

Gender-Based Differences in Outcomes Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival. METHODS: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants. RESULTS: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P<0.001 for all). A significantly higher proportion of women received DNR orders (35.7% versus 32.1%, P=0.009) and had WLST (32.8% versus 29.8%, P=0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P<0.001; adjusted odds ratio, 0.78 [95% CI, 0.66-0.93]; P=0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P=0.005; adjusted odds ratio, 0.74 [95% CI, 0.60-0.91]) or did not have WLST (32.3% versus 50.7%, P=0.002; adjusted odds ratio, 0.73 [95% CI, 0.60-0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P=0.90) or had WLST (2.8% versus 2.4%, P=0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort. CONCLUSIONS: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis.

Association between depression, gender and Alzheimer's neuropathology in older adults without dementia.

OBJECTIVES: Previous studies regarding the relationship between depression and Alzheimer's neuropathology in older adults without dementia have reported conflicting findings. This study examined whether depression is associated with Alzheimer's neuropathology and whether sex moderates these relationships. METHODS: This is a cross-sectional study of older adults without dementia (normal cognition or mild cognitive impairment, age 50+; CDR ≤ 0.5) who had autopsy within 1 year of their last clinic visit in the National Alzheimer's Coordinating Center database (2005-2020). Logistic regression models were fitted to determine if a recent or remote history of depression was associated with amyloid spread beyond the neocortex measured by modified Thal phase score, density of amyloid plaques measured by CERAD score or tau neuropathology measured by modified Braak score. A moderator analysis was performed to determine if any of these associations were moderated by sex. RESULTS: This study included 407 participants (96 Thal, 405 Braak, and 406 CERAD). Those who had recently active depression (within previous 2 years) but not remote depression only were more likely to have higher Thal phase score compared to those without a history of depression (OR = 3.74; 95% CI, 1.15-12.17; p = 0.028). Sex did not moderate this association. No significant associations between recent depression and Braak or CERAD scores were observed. CONCLUSION: Our findings indicate that the association between late life depression and Alzheimer's neuropathology is associated with spread of amyloid pathology beyond the neocortex to include allocortical and subcortical regions critical for regulation of mood and motivated behavior.

Prevalence, management and outcomes of unrecognized delirium in a National Sample of 1,493 older emergency department patients: how many were sent home and what happened to them?

BACKGROUND: Retrospective studies estimate Emergency Department (ED) delirium recognition at <20%; few prospective studies have assessed delirium recognition and outcomes for patients with unrecognized delirium. OBJECTIVES: To prospectively measure delirium recognition by ED nurses and physicians, document their confidence in diagnosis and disposition, actual dispositions, and patient outcomes. METHODS: Prospective observational study of people ≥65 years. We assessed delirium using the Confusion Assessment Method, then asked ED staff if the patient had delirium, confidence in their assessment, if the patient could be discharged, and contacted patients 1 week postdischarge. We report proportions and 95% confidence intervals (Cls). RESULTS: We enrolled 1,493 participants; mean age was 77.9 years; 49.2% were female, 79 (5.3%, 95% CI 4.2-6.5%) had delirium. ED nurses missed delirium in 43/78 cases (55.1%, 95% CI 43.4-66.4%). Nurses considered 12/43 (27.9%) patients with unrecognized delirium safe to discharge. Median confidence in their delirium diagnosis for patients with unrecognized delirium was 7.0/10. Physicians missed delirium in 10/20 (50.0%, 95% CI 27.2-72.8) cases and considered 2/10 (20.0%) safe to discharge. Median confidence in their delirium diagnosis for patients with unrecognized delirium was 8.0/10. Fifteen patients with unrecognized delirium were sent home: 6.7% died at 1 week follow-up vs. none in those with recognized delirium and 1.1% in the rest of the cohort. CONCLUSION: Delirium recognition by nurses and physicians was sub-optimal at ~50% and may be associated with increased mortality. Research should explore root causes of unrecognized delirium, and novel strategies to systematically improve delirium recognition and patient outcomes.

Outcomes of prolonged mechanical ventilation and tracheostomy in critically ill elderly patients: a historical cohort study.

PURPOSE: With an aging global population, the increased proportion of elderly patients in the intensive care unit (ICU) raises important questions regarding optimal management. Currently, data on tracheostomy and its outcomes in the elderly are limited. We aimed to determine the in-hospital survival of elderly ICU patients following tracheostomy, and describe impacts on discharge disposition and functional outcomes. METHODS: We conducted a historical cohort study at two academic hospitals in Toronto. All patients aged ≥ 70 yr who received a tracheostomy during their ICU stay between January 2010 and June 2016 were included in a retrospective chart review. Data on patient demographics, frailty, tracheostomy indication, and outcomes were collected. RESULTS: The study included 270 patients with a mean (standard deviation) age of 81 (6) yr. The majority were admitted to ICU for respiratory failure (147/270, 54%) and received a tracheostomy for prolonged mechanical ventilation (202/270, 75%). Intensive care unit and hospital mortality were 26% (68/270) and 46% (125/270), respectively. Twenty-five percent (67/270) of patients were decannulated during hospital admission, a median [interquartile range (IQR)] of 41 [25-68] days after tracheostomy. Intensive care unit and hospital length of stay were 31 [17-53] and 81 [46-121] days, respectively. At hospital discharge, 6% (17/270) of patients were discharged home, all were frail (median Clinical Frailty Score of 7) and most were tube-fed (101/270, 70%), unable to speak (81/270, 56%), and nonambulatory (98/270, 68%). CONCLUSIONS: In patients aged ≥ 70 yr, tracheostomy during ICU stay marked a transition toward prolonged chronic critical illness. Nearly half of the patients died during the admission, and although a quarter were successfully decannulated, the majority of survivors were left with severe frailty and functional impairment.

RéSUMé: OBJECTIF: Avec le vieillissement de la population mondiale, la proportion accrue de patients âgés aux soins intensifs (USI) soulève d'importantes questions concernant leur prise en charge optimale. À l'heure actuelle, les données sur la trachéotomie et ses issues chez les personnes âgées sont limitées. Nous avions pour objectif de déterminer la survie hospitalière des patients âgés en soins intensifs après une trachéotomie et d'examiner les impacts sur la disposition au congé et les devenirs fonctionnels. MéTHODE: Nous avons mené une étude de cohorte historique dans deux hôpitaux universitaires de Toronto. Tous les patients âgés de ≥ 70 ans ayant reçu une trachéotomie pendant leur séjour à l'USI entre janvier 2010 et juin 2016 ont été inclus dans un examen rétrospectif des dossiers. Les données sur la démographie des patients, leur fragilité, l'indication pour la trachéotomie et les devenirs ont été recueillies. RéSULTATS: L'étude a inclus 270 patients avec un âge moyen (écart type) de 81 (6) ans. La majorité d'entre eux ont été admis à l'USI pour insuffisance respiratoire (147/270, 54 %) et ont subi une trachéotomie pour une ventilation mécanique prolongée (202/270, 75 %). La mortalité à l'USI et à l'hôpital était de 26 % (68/270) et 46 % (125/270), respectivement. Vingt-cinq pour cent (67/270) des patients ont été décanulés pendant leur admission à l'hôpital, [écart interquartile (ÉIQ)] 41 [25-68] jours après la trachéotomie en moyenne. La durée du séjour à l'USI et à l'hôpital était de 31 [17-53] et 81 [46-121] jours, respectivement. Lors du congé de l'hôpital, 6 % (17/270) des patients sont rentrés chez eux, tous étaient fragiles (score médian de fragilité clinique de 7) et la plupart étaient nourris par sonde (101/270, 70 %), incapables de parler (81/270, 56 %) et non ambulatoires (98/270, 68 %). CONCLUSIONS: Chez les patients âgés de ≥ 70 ans, la trachéotomie pendant le séjour aux soins intensifs a marqué une transition vers une maladie chronique grave prolongée. Près de la moitié des patients sont décédés pendant leur séjour, et bien qu'un quart aient été décanulés avec succès, la majorité des survivants se sont retrouvés avec une fragilité sévère et une déficience fonctionnelle.

Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. METHOD: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. RESULT: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Association Between Hospital Outbreaks and Hand Hygiene: Insights from Electronic Monitoring.

BACKGROUND: Hand hygiene (HH) is an important patient safety measure linked to the prevention of health care-associated infection, yet how outbreaks affect HH performance has not been formally evaluated. METHODS: A controlled, interrupted time series was performed across 5 acute-care academic hospitals using group electronic monitoring. This system captures 100% of all hand sanitizer and soap dispenser activations via a wireless signal to a wireless hub; the number of activations is divided by a previously validated estimate of the number of daily HH opportunities per patient bed, multiplied by the hourly census of patients on the unit. Daily HH adherence 60 days prior and 90 days following outbreaks on inpatient units was compared to control units not in outbreaks over the same period, using a Poisson regression model adjusting for correlations within hospitals and units. Predictors of HH improvement were assessed in this multivariate model. RESULTS: In the 60 days prior to outbreaks, units destined for outbreaks had significantly lower HH adherence compared to control units (incidence rate ratio [IRR], 0.91; 95% confidence interval [CI], .90-.93; P < .0001). Following an outbreak, the HH adherence among the outbreak units increased above that of the controls (IRR, 1.04; 95% CI, 1.02-1.06; P < .0001). Greater improvements were noted for outbreaks on surgical units, for outbreaks involving antibiotic-resistant organisms and enteric pathogens, and in those outbreaks where health-care workers became ill. CONCLUSIONS: Hospital outbreaks tend to occur in units with lower HH adherence and are associated with rapid improvements in HH performance. Group electronic monitoring of HH could be used to develop novel, prospective feedback interventions designed to avert hospital outbreaks.

Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study.

BACKGROUND: Breast cancer is the most common cancer among women worldwide and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS). MATERIALS AND METHODS: We conducted a retrospective analysis of women (≥18 years of age) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT), or SRS to the brain at the Sunnybrook Odette Cancer Centre, Toronto, Canada, between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed with subgroup analyses by breast cancer subtype. RESULTS: Among 683 eligible patients, 153 (22.4%) had triple-negative breast cancer, 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2-, and 61 (13.3%) had breast cancer of an unknown subtype. The majority of patients received first-line WBRT (n = 459, 67.2%) or SRS (n = 126, 18.4%). The median brain-specific progression-free survival and median overall survival (OS) were 4.1 months (interquartile range [IQR] 1.0-9.6 months) and 5.1 months (IQR 2.0-11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first-line WBRT, and HER2- subtype were independently prognostic for shorter OS. CONCLUSION: Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system-active systemic therapies warrant further investigation. IMPLICATIONS FOR PRACTICE: Although triple-negative breast cancer and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor-positive/HER2- breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS-specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, this study suggests that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery.

Maternal Diet and Infant Feeding Practices Are Associated with Variation in the Human Milk Microbiota at 3 Months Postpartum in a Cohort of Women with High Rates of Gestational Glucose Intolerance.

BACKGROUND: Human milk contains a diverse community of bacteria believed to play a role in breast health and inoculation of the infant's gastrointestinal tract. The role of maternal nutrition and infant feeding practices on the human milk microbiota remains poorly understood. OBJECTIVE: Our aim was to explore the associations between maternal diet (delivery to 3 mo postpartum), infant feeding practices, and the microbial composition and predicted function in milk from women with varied metabolic status. METHODS: This was an exploratory analysis of a previously completed prospective cohort study of women with varying degrees of gestational glucose intolerance (NCT01405547). Milk samples (n = 93 mothers) were collected at 3 mo postpartum. Maternal dietary information (validated food-frequency questionnaire) and infant feeding practices (human milk exclusivity, frequency of direct breastfeeding per day) were collected. V4-16S ribosomal RNA gene sequencing (Illumina MiSeq) was conducted to determine microbiota composition. RESULTS: Intake of polyunsaturated fat [ß estimate (SE): 0.036 (0.018), P = 0.047] and fiber from grains [0.027 (0.013), P = 0.048] were positively associated with ɑ-diversity (Shannon index) of human milk. Overall microbial composition of human milk clustered based on human milk exclusivity (weighted UniFrac R2 = 0.034, P = 0.015; Bray-Curtis R2 = 0.041, P = 0.007), frequency of direct breastfeeding per day (Bray-Curtis R2 = 0.057, P = 0.026), and maternal fiber intake from grains (Bray-Curtis R2 = 0.055, P = 0.040). Total fiber, fiber from grains, dietary fat, and infant feeding practices were also associated with a number of differentially abundant taxa. The overall composition of predicted microbial functions was associated with total fiber consumption (Bray-Curtis R2 = 0.067, P = 0.036) and human milk exclusivity (Bray-Curtis R2 = 0.041, P = 0.013). CONCLUSIONS: Maternal consumption of fiber and fat, as well as mother's infant feeding practices, are important determinants of the human milk microbiota. Understanding whether these microbial changes impact an infant's overall health and development requires future study.

Oligosaccharides and Microbiota in Human Milk Are Interrelated at 3 Months Postpartum in a Cohort of Women with a High Prevalence of Gestational Impaired Glucose Tolerance.

BACKGROUND: Human milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment. OBJECTIVES: The objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance. METHODS: This was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function). RESULTS: Prepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): -9.3 × 102 (3.4 × 102); P = 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [-1.7 (0.78); P = 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2 = 0.040, P = 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2 = 0.039, P = 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate < 0.1). CONCLUSIONS: HMOs are associated with the microbial composition and predicted microbial functions in human milk at 3 mo postpartum. Further research is needed to investigate the role these relations play in maternal and infant health.

Depression and Increased Risk of Alzheimer's Dementia: Longitudinal Analyses of Modifiable Risk and Sex-Related Factors.

OBJECTIVE: Our understanding of why older adults with depression are at increased risk of Alzheimer's disease (AD) remains incomplete. Most adults living with AD are women, and women have a near twofold lifetime risk of depression. We examined the risk of depression upon incident AD, and how sex influences this risk. METHODS: Using the National Alzheimer's Coordinating Center database, older adults (age 50+) with normal cognition, who visited memory clinics across the United States between September 2005 and December 2019, were followed until first diagnosis of AD or loss to follow up. Multivariable survival analyses were performed to determine if recent and/or remote depression were independent risk factors for AD, if this depression-related risk exists for each sex or was moderated by sex. RESULTS: Six hundred and fifty-two of 10,739 enrolled participants developed AD over a median follow-up of 55.3 months. Recent depression (active within the last 2 years) was independently associated with increased risk of AD (hazard ratio [HR] = 2.0; 95%CI, 1.5-2.6) while a remote history of depression was not (HR = 1.0; 95%CI, 0.7-1.5). After stratification by sex, recent depression was an independent predictor in females (HR = 2.3; 95%CI, 1.7-3.1) but not in males (HR = 1.4; 95%CI, 0.8-2.6). No interaction between recent depression and sex was observed. CONCLUSION: Only a recent history of depression was associated with higher risk of AD. This association was significant among women only, but was not moderated by sex. Future analyses should determine if these findings extend to other populations and may be explained by variable distribution of neurobiological or other modifiable risk factors between the sexes.

Comparison of the Analgesic Duration of 0.5% Bupivacaine With 1:200,000 Epinephrine Versus 0.5% Ropivacaine Versus 1% Ropivacaine for Low-Volume Ultrasound-Guided Interscalene Brachial Plexus Block: A Randomized Controlled Trial.

BACKGROUND: Bupivacaine and ropivacaine are the preferred long-acting local anesthetics for peripheral nerve blocks as they provide prolonged analgesia in the postoperative period. No studies have directly compared the analgesic duration of these commonly used local anesthetics in the setting of low-volume ultrasound-guided interscalene block (US-ISB). This study was designed to determine which local anesthetic and concentration provides superior analgesia (duration and quality) for low-volume US-ISB. METHODS: Sixty eligible patients scheduled for arthroscopic shoulder surgery were randomized (1:1:1) to receive US-ISB (5 mL) with 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine. All individuals were blinded including study participants, anesthesiologists, surgeons, research personnel, and statistician. All participants received a standardized general anesthetic and multimodal analgesia. The primary outcome was duration of analgesia defined as the time from the end of injection to the time that the patients reported a significant increase in pain (>3 numeric rating scale [NRS]) at the surgical site. RESULTS: The mean duration of analgesia for 0.5% bupivacaine with 1:200,000 epinephrine, 0.5% ropivacaine, or 1% ropivacaine was 14.1 ± 7.4, 13.8 ± 4.5, and 15.8 ± 6.3 hours, respectively (analysis of variance [ANOVA], P = .51). There were no observed differences in analgesic duration or other secondary outcomes between the 3 groups with the exception of a difference in cumulative opioid consumption up to 20h00 on the day of surgery in favor of ropivacaine 0.5% over bupivacaine of minimal clinical significance. CONCLUSIONS: In the context of single-injection low-volume US-ISB, we have demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 1% did not prolong the duration of US-ISB.

Exercise priming with transcranial direct current stimulation: a study protocol for a randomized, parallel-design, sham-controlled trial in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive type of brain stimulation that uses electrical currents to modulate neuronal activity. A small number of studies have investigated the effects of tDCS on cognition in patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), and have demonstrated variable effects. Emerging evidence suggests that tDCS is most effective when applied to active brain circuits. Aerobic exercise is known to increase cortical excitability and improve brain network connectivity. Exercise may therefore be an effective, yet previously unexplored primer for tDCS to improve cognition in MCI and mild AD. METHODS: Participants with MCI or AD will be randomized to receive 10 sessions over 2 weeks of either exercise primed tDCS, exercise primed sham tDCS, or tDCS alone in a blinded, parallel-design trial. Those randomized to an exercise intervention will receive individualized 30-min aerobic exercise prescriptions to achieve a moderate-intensity dosage, equivalent to the ventilatory anaerobic threshold determined by cardiopulmonary assessment, to sufficiently increase cortical excitability. The tDCS protocol consists of 20 min sessions at 2 mA, 5 times per week for 2 weeks applied through 35 cm2 bitemporal electrodes. Our primary aim is to assess the efficacy of exercise primed tDCS for improving global cognition using the Montreal Cognitive Assessment (MoCA). Our secondary aims are to evaluate the efficacy of exercise primed tDCS for improving specific cognitive domains using various cognitive tests (n-back, Word Recall and Word Recognition Tasks from the Alzheimer's Disease Assessment Scale-Cognitive subscale) and neuropsychiatric symptoms (Neuropsychiatric Inventory). We will also explore whether exercise primed tDCS is associated with an increase in markers of neurogenesis, oxidative stress and angiogenesis, and if changes in these markers are correlated with cognitive improvement. DISCUSSION: We describe a novel clinical trial to investigate the effects of exercise priming before tDCS in patients with MCI or mild AD. This proof-of-concept study may identify a previously unexplored, non-invasive, non-pharmacological combination intervention that improves cognitive symptoms in patients. Findings from this study may also identify potential mechanistic actions of tDCS in MCI and mild AD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03670615 . Registered on September 13, 2018.