Point-of-care ultrasound associated with shorter length of stay than computed tomography for renal colic.

BACKGROUND: Despite similar diagnostic effectiveness for renal colic, computed tomography (CT) is more resource intensive than point-of-care ultrasound (PoCUS). We sought to compare Emergency Department (ED) length of stay (LOS) among patients with renal colic according to imaging modality utilized. We secondarily compared rates of infection, return ED visits, missed significant pathology, and urologic intervention. METHODS: This was a 12-month (1/1/22-12/31/22) multi-site retrospective cohort study of all patients diagnosed with renal colic who presented to the ED on days when at least one patient had a billable renal PoCUS examination performed. Patients with a history of genitourinary malignancy, pregnancy, renal transplant, hemodialysis, single kidney, prior visit for renal colic in the previous 30 days, or an incomplete workup were excluded. Median ED LOS was compared using a Wilcoxon rank sum test, and the 95% confidence limits for the difference between medians was calculated. Secondary outcomes were compared using a Fisher's Exact test. RESULTS: Of 415 patients screened, 325 were included for analysis: 150 had CT alone, 80 had PoCUS alone, 54 had PoCUS plus CT, and 41 had neither. Median LOS for PoCUS alone was 75.0 (95% CI 39.3-110.7) minutes shorter than CT alone (231.5 vs. 307.0 min, p < 0.0001). Similar rates of infection, return visits, and missed pathology occurred across all groups (p > 0.10). Urologic interventions were higher in the PoCUS plus CT (25.9%) group compared to CT alone (7.3%), PoCUS alone (2.5%), and neither (7.3%), p < 0.0001. CONCLUSION: Among patients with renal colic, PoCUS was associated with shorter ED LOS compared to CT, without differences in infection rates, return visits, or missed pathology. Patients with PoCUS plus CT had a higher rate of urologic interventions, suggesting PoCUS may have a role in identifying patients who would most benefit from CT.

Combination of naproxen and a chemically-stable eicosapentaenoic acid analog provide additive tumor protection in Pirc rats.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Patients with the genetic disorder Familial Adenomatous Polyposis (FAP) develop hundreds to thousands of polyps that unless removed by prophylactic colectomy will progress to CRC at an early age. Nonsteroidal anti-inflammatory drugs (NSAIDs) and the ω-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA), have been evaluated for their chemopreventive potential in delaying CRC onset in high-risk patients. In our study, we determined whether the NSAID, naproxen, alone or in combination with a chemically-stable EPA analog (TP-252), affects tumor formation in the ApcPirc rat model. When compared to control diet, animals fed naproxen or HD TP-252 had 66% and 82% fewer tumors, respectively. However, animals fed a combination of naproxen and HD TP-252, exhibited a 95% reduction in tumor formation and a 98% reduction in tumor volume, respectively. To elucidate potential mechanisms of tumor protection, a comprehensive, targeted lipidomic analysis was performed on colonic mucosa to determine changes in eicosanoid metabolism. Animals receiving TP-252 alone or in combination with naproxen had significantly reduced mucosal levels of proinflammatory ω-6 eicosanoids (PGE2 , 5-HETE and 14,15-DiHETrE), along with a simultaneous increase in anti-inflammatory EPA-derived ω-3 eicosanoids. A comprehensive lipidomic analysis also uncovered several potential pharmacodynamic (PD) lipid biomarkers, including resolvin E2, 9-HEPE, 12-HEPE and 18-HEPE, that were significantly correlated with tumor protection. Further studies with this drug combination should be focused on dose optimization and the role of EPA-derived lipid mediators in CRC initiation and progression.

Effects of Longitudinal Changes in Neuroticism and Stress on Cognitive Decline.

OBJECTIVE: The relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: The authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline. MEASUREMENTS: The authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates. RESULTS: In multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = -0.080[95%CL: -0.145 to -0.015], T = -2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition. CONCLUSION: Our findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Association of Race, Ethnicity, Education, and Neighborhood Context With Dementia Prevalence and Cognitive Impairment Severity Among Older Adults Receiving Medicaid-Funded Home and Community-Based Services.

OBJECTIVE: While racial, ethnic, and socioeconomic group disparities in cognitive impairment and dementia prevalence are well-documented among community-dwelling older adults, little is known about these disparity trends among older adults receiving Medicaid-funded home- and community-based services (HCBS) in lieu of nursing home admission. The authors determined how dementia prevalence and cognitive impairment severity compare by race, ethnicity, educational attainment, and neighborhood context in a Medicaid HCBS population. DESIGN/SETTING: A cross-sectional study in Connecticut. PARTICIPANTS: Adults age ≥65 in the HCBS program, January-March 2019 (N = 3,520). MEASUREMENTS: The data source was Connecticut's HCBS program Universal Assessment tool. The authors employed two outcomes: Cognitive Performance Scale (CPS2), a 9-point measure ranging from cognitively intact-very severe impairment; and presence or not of either diagnosed dementia or CPS2 score ≥4 (major impairment). Neighborhood context was measured using the Social Vulnerability Index (SVI). RESULTS: Cohort characteristics: 75.7% female; mean(SD) age = 79.1(8.2); Non-Hispanic White = 47.8%; Hispanic = 33.6%; Non-Hispanic Black = 15.9%. Covariate-adjusted multivariate analyses revealed no dementia/major impairment prevalence differences among White, Black, and Hispanic individuals, but impairment severity was greater among Hispanic participants (b = 0.22; p = 0.02). People with more than HS education had less severe impairment (b = -0.12; p <0.001) and lower likelihood of dementia/major impairment (AOR = 0.61; p <0.001). Dementia/major impairment likelihood and impairment severity were greater in less socially vulnerable neighborhoods. CONCLUSION: Racial and ethnic group differences in cognitive impairment are less pronounced in Medicaid-funded HCBS cohorts than in other community-dwelling older adult cohorts. SVI results suggest that, among other possible explanations, older adults with dementia may move to lower social vulnerability neighborhoods where supportive family members reside.

A calibrated cell-based functional assay to aid classification of MLH1 DNA mismatch repair gene variants.

Functional assays provide important evidence for classifying the disease significance of germline variants in DNA mismatch repair genes. Numerous laboratories, including our own, have developed functional assays to study mismatch repair gene variants. However, previous assays are limited due to the model system employed, the manner of gene expression, or the environment in which function is assessed. Here, we developed a human cell-based approach for testing the function of variants of uncertain significance (VUS) in the MLH1 gene. Using clustered regularly interspaced short palindromic repeats gene editing, we knocked in MLH1 VUS into the endogenous MLH1 loci in human embryonic stem cells. We examined their impact on RNA and protein, including their ability to prevent microsatellite instability and instigate a DNA damage response. A statistical clustering analysis determined the range of functions associated with known pathogenic or benign variants, and linear regression was performed using existing odds in favor of pathogenicity scores for these control variants to calibrate our functional assay results. By converting the functional outputs into a single odds in favor of pathogenicity score, variant classification expert panels can use these results to readily reassess these VUS. Ultimately, this information will guide proper diagnosis and disease management for suspected Lynch syndrome patients.

Cognitive Frailty is Associated With Elevated Proinflammatory Markers and a Higher Risk of Mortality.

BACKGROUND: Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms. METHODS: A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay. RESULTS: Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18-3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24-2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23-1.54]). CONCLUSION: Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality).

Association of 1-year change in neuroticism and 3-year change in cognitive performance among older depressed adults.

OBJECTIVES: The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism. MEASUREMENTS: We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates. RESULTS: We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score. CONCLUSIONS: Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Prevalence of gastrointestinal, cardiovascular, autonomic and allergic manifestations in hospitalized patients with Ehlers-Danlos syndrome: a case-control study.

OBJECTIVE: Previous observations suggest an association between Ehlers-Danlos syndrome (EDS) and gastrointestinal (GI), cardiovascular, immune, and autonomic nervous system dysfunction. We sought to determine whether a hospital diagnosis of EDS is associated with a higher prevalence of these manifestations vs hospitalized patients without EDS. We also evaluated hospital outcomes. METHODS: A total of 6,021 cases and matched controls were acquired from the 2016 National Inpatient Sample. In total, 2,007 EDS patients were identified via ICD-10 code. After bivariate analyses, multivariate logistic regression models were used to adjust for potential confounders. RESULTS: GI conditions were found in 44% of EDS patients vs 18% of controls [odds ratio (OR) = 3.57, 95% CI: 3.17, 4.02, P < 0.0001], with irritable bowel syndrome, gastroparesis and coeliac disease strongly associated with EDS. Autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope and orthostatic hypotension was found in 20% of EDS patients vs 6% of controls (OR = 4.45, 95% CI: 3.71, 5.32, P < 0.0001). EDS patients were more likely to have food allergy (OR = 3.88, 95% CI: 2.65, 5.66, P < 0.0001) and cardiovascular complications such as mitral valve disorders, aortic aneurysm and dysrhythmias (OR = 6.16, 95% CI: 4.60, 8.23, P < 0.0001). These conditions remained highly associated with EDS after considering confounders. EDS patients were 76% more likely to have longer than average hospitalizations (OR = 1.76, 95% CI: 1.54, 2.02, P < 0.0001). CONCLUSION: GI, cardiovascular, autonomic and allergic manifestations are significantly more prevalent in EDS patients compared with hospitalized patients without EDS. Physicians should consider EDS in patients with unexplained GI, cardiovascular, autonomic and allergic conditions and exercise precautions when treating EDS patients in a hospital setting.

Multilevel and Multifactorial Interventions to Reduce Alcohol Consumption and Improve ART Adherence and Related Factors Among HIV Positive Men in Mumbai, India.

Alcohol use has a deleterious effect on the health status of persons living with HIV, negatively affecting antiretroviral adherence and increasing the risk of transmission. Alcohol use is not an isolated behavior but intimately linked to stigma and poor psychological status among other factors. This paper utilizes a crossover design to test the efficacy of three multilevel interventions, individual counselling (IC), group intervention (GI) and collective advocacy (CA) for change, among HIV positive males who consume alcohol, treated at five ART Centers in urban Maharashtra, India. While GI shows a significant effect on the largest number of outcome variables, IC through its psychosocial emphasis demonstrated a significant impact over time on stigma and depression, and CA with its emphasis on societal change showed positive impact on stigma and advocacy for self and others. Each of the interventions had variable effects on CD4 count and viral load.Clinical Registration Number: NCT03746457; Clinical Trial.Gov.

RESUMEN: El consumo de alcohol tiene un efecto nocivo en el estado de salud de las personas que viven con VIH, afectando negativamente la adherencia a los antirretrovirales y aumentando el riesgo de transmisión del virus. El consumo de alcohol no es un comportamiento aislado, sino que está íntimamente relacionado con el estigma y el mal estado psicológico, entre otros factores. Este documento utiliza un diseño cruzado para evaluar la eficacia de tres intervenciones: asesoramiento individual, intervención grupal y defensa colectiva para el cambio, entre hombres con VIH que consumen alcohol que reciben tratamiento en cinco centros de terapia antiretroviral en la zona urbana de Maharashtra, India. Si bien la intervención grupal muestra un efecto significativo en el mayor número de variables de interés, el asesoramiento individual a través de su énfasis psicosocial demostró un impacto significativo en el estigma y la depression a largo plazo, y la defensa colectiva con su énfasis en el cambio social mostró un impacto positivo en el estigma y la defensa de sí mismo y otros.

Oral health-related quality of life outcomes in a randomized clinical trial to assess a community-based oral hygiene intervention among adults living in low-income senior housing.

BACKGROUND: Quality of life outcomes have been used frequently in clinical trials of oral health interventions. This study assessed the effects of a randomized trial on oral health related quality of life comparing an individual-based oral hygiene intervention to a community-based intervention. METHODS: Participants were recruited from six low-income senior housing residences. Buildings were randomly assigned to receive the individual-based intervention followed by the community-based intervention or to receive the community-based intervention followed by the individual intervention. Participants' oral hygiene was assessed at baseline (T0), one month after the first intervention (T1) and one month after the second intervention (T2) and six months after the T2 assessment (T3). Oral hygiene was measured by the Gingival Index (GI) and Plaque scores (PS). Surveys collected data on beliefs, attitudes, behaviors and self-reported health status at T0, T1 and T2. Only oral hygiene and quality of life, measured by the General Oral Health Assessment Index (GOHAI), was assessed at all time points. general linear mixed models (GLMM) were used to assess changes in GOHAI over time, the interaction of condition by time and the contribution of psychosocial, behavioral, health status and background variables to changes in GOHAI. RESULTS: 331 people completed T0 assessments; 306 completed T1; 285 completed T2 and 268 completed T3. Scores on GOHAI at T0 ranged from 10 to 48 with a mean of 39.7 (sd = 7.8) and a median of 42. At T1, mean GOHAI was 40.7 (sd = 8.2), at T2 mean GOHAI was 41.1 (sd = 7.8) and at T3, GOHAI was 42.3 (sd = 8.2). GLMM showed that GOHAI improved significantly from T0 to T3 (p = 0.01) but the time by intervention interaction was not significant indicating that both interventions were effective in improving GOHAI but one intervention was not better than the other. Ethnicity, health status, worries, self-efficacy, number of missing teeth and symptoms of dry mouth were related to improvements in GOHAI. Neither GI nor PS were related to GOHAI. CONCLUSIONS: The participants reported relatively good oral health related quality of life which improved significantly over time. Improvement occurred among all participants regardless of condition, suggesting that either intervention would be effective in future studies. TRIAL REGISTRY: Clinicaltrials.gov, Clinical Trials ID #NCT02419144; Title: A Bi-level Intervention to Improve Older Adult Oral Health Status; Registered 04/07/2015 URL: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005H9X&selectaction=Edit&uid=U0000KBK&ts=2&cx=-rajj5q.

Evaluating mechanisms of change in an oral hygiene improvement trial with older adults.

BACKGROUND: This paper compares the relationship between theoretically-driven mechanisms of change and clinical outcomes across two different interventions to improve oral hygiene of older adults participating in a group randomized trial. METHODS: Six low-income senior residences were paired and randomized into two groups. The first received a face to face counseling intervention (AMI) and the second, a peer-facilitated health campaign (three oral health fairs). Both were based on Fishbein's Integrated Model. 331 participants were recruited at baseline and 306 completed the post-assessment one month after intervention. Clinical outcomes were Gingival Index (GI) and Plaque score (PS), collected by calibrated dental hygienists. Surveys obtained data on patient background characteristics and ten mechanisms of change including oral health beliefs, attitudes, norms and behaviors. GLMM was used to assess the effects of time, intervention arm, participant characteristics, intervention mechanisms and differences between the two interventions over time in relation to outcomes. RESULTS: At baseline, both groups had similar background characteristics. Both groups improved significantly in outcomes. Overall GI scores changed from baseline mean of 0.38 (SD = .032) to .26 (SD = .025) and PS scores changed from baseline mean of 71.4 (SD = 18%) to 59.1% (SD = 21%). T-tests showed that fears of oral disease, oral health intentionality, oral health norms, worries about self-management of oral health, flossing frequency and sugar control improved significantly in both interventions from baseline to post intervention. Oral health self-efficacy, perceived risk of oral health problems, oral health locus of control and brushing frequency improved significantly only in the counseling intervention. GLMM models showed that the significant predictors of GI improvement were intentionality to perform oral hygiene, locus of control, and improvement in frequency of brushing and flossing in association with the counseling intervention. Predictors of PS improvement were worries about oral hygiene self-management and fear of oral diseases, in association with the counseling intervention. In the reduced final models, only oral health locus of control (predicting GI) and fears of oral diseases (predicting PS) were significant in association with the counseling intervention. Locus of control, a key concept in oral hygiene interventions including the IM was the main contributing mechanism for GI improvement. Fear, an emotional response, drove improvement in PS, reinforcing the importance of cognitive/emotional mechanisms in oral hygiene interventions. CONCLUSIONS: Though both groups improved in outcomes, GI and PS outcomes improved more in response to the counseling intervention than the campaign. The counseling intervention had an impact on more mechanisms of change than the campaign. Improvements in intervention mechanisms across both interventions however, suggest a closer examination of the campaign intervention impact on outcomes over time. TRIAL REGISTRATION: Clinicaltrials.gov NCT02419144, first posted April 17, 2015.

Gingivitis and plaque scores among residents of low-income senior housing.

OBJECTIVES: The purpose of this paper is to present Gingival Index (GI) and Plaque Scores (PS) of older and disabled adults living in low-income senior housing and their association with sociodemographic, health status and oral health behaviours. METHODS: Participants were recruited from six low-income senior housing residences in Connecticut. Primary outcome measures were Gingival Index (GI) and Plaque Scores (PS). Surveys assessed sociodemographic characteristic, beliefs and behaviours. Logistic regression analysis was used to model the binary outcomes of probability of unfavourable GI status (>=0.34) and unfavourable PS (>=74%) against variables including demographic characteristics, oral hygiene behaviours and health status. RESULTS: 331 participants volunteered for the study. Mean baseline GI was 0.38 (SD: 0.3), and mean PS was 71.7% (SD: 18%). Logistic regression showed that males were more likely to have higher GI and plaque scores than females. Those with less formal education were more likely to have worse GI scores and high PS compared to those with college educations. Those with lower incomes and those who rated their oral health poor/fair were more likely to have higher PS. CONCLUSION: Participants had remarkably good gingival health regardless of relatively high PS. Males and less educated individuals should receive special attention when implementing oral hygiene interventions because of their relatively poor oral hygiene status.

Functional interrogation of Lynch syndrome-associated MSH2 missense variants via CRISPR-Cas9 gene editing in human embryonic stem cells.

Lynch syndrome (LS) predisposes patients to cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes. Identifying the deleterious mutation, such as a frameshift or nonsense mutation, is important for confirming an LS diagnosis. However, discovery of a missense variant is often inconclusive. The effects of these variants of uncertain significance (VUS) on disease pathogenesis are unclear, though understanding their impact on protein function can help determine their significance. Laboratory functional studies performed to date have been limited by their artificial nature. We report here an in-cellulo functional assay in which we engineered site-specific MSH2 VUS using clustered regularly interspaced short palindromic repeats-Cas9 gene editing in human embryonic stem cells. This approach introduces the variant into the endogenous MSH2 loci, while simultaneously eliminating the wild-type gene. We characterized the impact of the variants on cellular MMR functions including DNA damage response signaling and the repair of DNA microsatellites. We classified the MMR functional capability of eight of 10 VUS providing valuable information for determining their likelihood of being bona fide pathogenic LS variants. This human cell-based assay system for functional testing of MMR gene VUS will facilitate the identification of high-risk LS patients.

Fecal Microbiota Transplantation for Clostridium difficile Infection: A One-Center Experience.

BACKGROUND: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis. OBJECTIVE: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut. METHODS: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review. RESULTS: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female. CONCLUSIONS: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.

Renal Function, Weaning, and Survival in Patients With Ventilator-Dependent Respiratory Failure.

BACKGROUND: Acute kidney injury in acute critical illness has been associated with poor weaning and survival outcomes. The relation between renal dysfunction as defined by creatinine clearance (CrCl) and weaning from prolonged mechanical ventilation (PMV) is not known. The objective of this study was to determine the relation of measured CrCl to weaning and survival in patients on PMV. METHODS: We retrospectively studied 167 patients on PMV admitted to a long-term acute care facility for weaning over a 3-year period. Data obtained included age, gender, admission blood urea nitrogen (BUN), serum creatinine, CrCl, random urine creatinine (RUCr), and 24-hour urinary creatinine (24UCr). Renal dysfunction was defined as normal (CrCl > 90 mL/min), mild (CrCl 60-90 mL/min), moderate (CrCl 30-59 mL/min), and severe (CrCl < 30 mL/min). Primary outcome measured was liberation from PMV, defined as being off ventilator for >7 days. Survival, defined as being alive at discharge, time to wean, and time to discharge alive were secondary outcomes. The association between the studied parameters and outcomes was determined by unpaired t test. The predictive value of studied parameters for weaning and survival was determined by multivariate logistic regression analysis. P < .05 was statistically significant. RESULTS: Mean age was 68.5 (14) years; 49% were males; 64% were liberated and 65.8% survived. Blood urea nitrogen, RUCr, 24Ucr, and CrCl had a significant association with successful weaning. These parameters (except BUN) also had a significant association with survival. A better outcome occurred with CrCl > 90 mL/min. CONCLUSION: Measured CrCl has a significant relation to successful weaning and survival in patients on PMV and may be useful in prognosticating their outcome.

A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal tumor development in ApcΔ14/+ mice.

Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.

Associations of dietary fat with risk of early neoplasia in the proximal colon in a population-based case-control study.

PURPOSE: Excess dietary fat consumption is strongly associated with the risk of colorectal cancer, but less is known about its role in the earliest stages of carcinogenesis, particularly within the proximal colon. In the following case-control study, we evaluated the relationship between the intake of dietary fats and the frequency of early proximal neoplasia [aberrant crypt foci (ACF) or polyps], detectable by high-definition colonoscopy with contrast dye-spray. METHODS: Average-risk screening individuals underwent a high-definition colonoscopy procedure as part of larger ongoing clinical study of precancerous lesions in the proximal colon. Dietary fat intake was assessed using the Block Brief Food Frequency Questionnaire, which estimates average dietary intake based on 70 food items. The diets of individuals with no endoscopically identifiable lesions (n = 36) were compared to those with either ACF or polyps detected in the proximal colon. RESULTS: In multivariate analysis, high dietary intake of total polyunsaturated fatty acids (PUFAs) and intake of omega-6 and omega-3 fatty acids were positively associated with neoplastic lesions in the proximal colon. When comparing ACF and polyp groups separately, a positive association was observed for both proximal polyps (OR 2.28; CI 1.16-7.09) and ACF (OR 2.86; CI 1.16-7.09) for total PUFA intake. Furthermore, the prevalence of proximal ACF was increased with higher intake of omega-6 (OR 3.54; CI 1.32-9.47) and omega-3 fatty acids (OR 2.29; CI 1.02-5.13), although there was no discernible difference in the omega-6/omega-3 ratio. CONCLUSIONS: These results suggest that dietary PUFAs may be positively associated with risk of early neoplasia in the proximal colon. This study provides further evidence that dietary PUFA composition may play an important role in altering the microenvironment within the human colon.

Can Creatinine Height Index Predict Weaning and Survival Outcomes in Patients on Prolonged Mechanical Ventilation After Critical Illness?

OBJECTIVE: Malnutrition is common in chronic critically ill patients on prolonged mechanical ventilation (PMV) and may affect weaning. The creatinine height index (CHI), which reflects lean muscle mass, is regarded as the most accurate indicator of malnutrition. The objective of this study was to determine the impact of CHI in comparison with other traditional nutritional indices on successful weaning and survival in patients on PMV after critical illness. METHODS: Records of 167 patients on PMV following critical illness, admitted for weaning, were reviewed. Parameters studied included age, gender, body mass index (BMI), percentage ideal body weight (%IBW), total protein, albumin, prealbumin, hemoglobin (Hb), and cause of respiratory failure. Number successfully weaned and number discharged alive and time to wean and time to discharge alive were determined from records. The CHI was calculated from 24-hour urine creatinine using a standard formula. Unpaired 2-sample t test was performed to determine the association between the studied nutritional parameters and outcomes. Predictive value of studied parameters for successful weaning and survival was determined by multivariate logistic regression analysis to model dichotomous outcome of successful weaning and survival. RESULTS: Mean age was 68 ± 14 years, 49% were males, 64% were successfully weaned, and 65.8% survived. Total protein, Hb, and CHI had a significant impact on successful weaning. Weight, %IBW, BMI, and CHI had a significant effect on survival. Of all parameters, CHI was most strongly predictive of successful weaning and survival. CONCLUSIONS: The CHI is a strong predictor of successful weaning and survival in patients on PMV.

Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia.

PURPOSE: Clinicians use tamsulosin, an α1-adrenoceptor antagonist, to manage symptomatic benign prostatic hyperplasia (BPH). Because α1-adrenoceptors are also present in the brain, the potential exists for adverse effects on cognitive functions. We explored the association between tamsulosin use and dementia risk. METHODS: We used Medicare data (2006-2012) to conduct a cohort study among patients aged ≥65 years and diagnosed with BPH. Men taking tamsulosin (n = 253 136) were matched at a 1:1 ratio using propensity-scores to each of 6 comparison cohorts: patients who used no BPH-medication (n = 180 926), and patients who used the following alternative-BPH-medications: doxazosin (n = 28 581), terazosin (n = 23 858), alfuzosin (n = 17 934), dutasteride (n = 34 027), and finasteride (n = 38 767). Assessment began following the first fill of BPH-medication to identify incident dementia by ICD-9 diagnosis codes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for dementia using Cox proportional hazard regression for each of the 6 propensity-score-matched cohort-pairs. RESULTS: The median follow-up period for all cohorts was 19.8 months. After propensity-score matching, the tamsulosin cohort had an incidence of dementia of 31.3/1000 person-years compared with only 25.9/1000 person-years in the no-BPH-medication cohort. The risk of dementia was significantly higher in the tamsulosin cohort, when compared with the no-BPH-medication cohort (HR [95% CI]: 1.17 [1.14, 1.21]) and each of the alternative-BPH-medication cohorts: doxazosin (1.20 [1.12, 1.28]), terazosin (1.11 [1.04, 1.19]), alfuzosin (1.12 [1.03, 1.22]), dutasteride (1.26 [1.19, 1.34]), and finasteride (1.13 [1.07, 1.19]). The significance of these findings persisted in sensitivity analyses. CONCLUSION: Tamsulosin may increase the risk of dementia in older men with BPH.