Early Attrition Research Articles

Treatment of infectious aortic disease with bovine pericardial tube grafts

Our aim was to evaluate the mid-term outcomes of bovine pericardial tube graft repair for infectious aortic disease in any aortic segment. Between May 2015 and July 2020, 45 patients were treated for infectious aortic disease of the native (n = 9) aorta or after (endo-)graft (n = 36) implantation with bovine pericardial tube grafts. Clinical, infectious details, outcomes and follow-up data were evaluated. All aortic segments underwent pericardial tube graft or bifurcational replacement: the aortic root (n = 12, 27%), ascending aorta (n = 18, 40%), aortic arch (n = 7, 16%), descending aorta (n = 5, 11%), thoraco-abdominal aorta (n = 6, 13%) and abdominal aorta (n = 18, 40%) including the iliac arteries (n = 14, 31%). Organ fistulation (n = 15, 33%) was the most common underlying pathology. Seven patients (16%) expired in-hospital secondary to ongoing sepsis (n = 5, 11%), respiratory failure (n = 1, 2%) and unknown cause (n = 1, 2%). A fungal infection was predictive for in-hospital mortality (P = 0.026, odds ratio: 19.470). After a median follow-up of 11 [first quartile: 2, third quartile 26] months, 9 additional patients (20%) expired and 1 patient developed a postoperative spondylodiscitis at the level of the aortic tube graft. Hence, freedom from proven aortic graft re-infection was 98%. Orthotopic aortic reconstruction using bovine pericardial tube grafts to treat infectious aortic disease is possible in any aortic segment. Organ fistulation is a frequently observed disease mechanism requiring concomitant treatment. Granted, the early attrition rate is substantial, but after the initial period, both survival and freedom from re-infection appear encouraging.

Investigation of early career teacher attrition and the impact of induction programs in Western Australia

This paper contributes to the limited knowledge about Australian early career teacher (ECT) attrition.The population studied included ECTs employed by the Department of Education Western Australia from 2004–2018.This quantitative study focused on ECT attrition rate and profiling ECTs who were likely to leave teaching, and used mixed-methods to investigate ECTs university preparation, intent to stay, resignation reasons and the combined supports received while employed.Study findings reinforced the need for a standardised definition and method of measuring attrition to enable comparisons, and provided information to optimise conditions in retaining ECTs. Ultimately, this will inform planning for teacher workforce supply and provide justification to continue the scale and scope of support for ECTs to address ECT attrition.

Attrition Bias in an Observational Study of Very Low-Energy Diet: A Cohort Study.

Obesity treatment is plagued by attrition. Estimates of attrition bias are needed. Thus, in this study, percent change from baseline BMI at 1, 2, and 3 years following enrollment in a 2-year weight management program using a very low-energy diet was calculated. Program data were supplemented with information from medical records. Attrition was classified as occurring early (<6 months), late (6-21 months), at program completion (22-28 months), and after program completion (>28 months). Stepwise multivariable regression examined attrition and other covariates. A total of 881 subjects had ≥3 years of follow-up. BMI decreased by a mean (SD) of 11.8 (9.2), 8.6 (9.3), and 5.2 (10.0) kg/m2 at 1, 2, and 3 years after enrollment, respectively. At year 1, every 10-kg/m2 increase in baseline BMI was associated with a 2% (95% CI: 1%-3%) decrease in BMI. Individuals with early attrition decreased their mean BMI by 13% (11%-15%) less than program completers and by 9% (7%-11%) at 2 years. At 3 years, there was no significant difference in BMI between individuals with early attrition and program completers. However, BMI decreased 5% (3%- 8%) more in individuals who extended participation compared with program completers. Reported outcomes of weight management programs must account for program attrition.

Abstract PO-123: Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases

Abstract Four decades of intense multinational efforts to improve outcomes for children and teenagers with osteosarcoma have failed. Today, we still treat patients with a regimen first developed in 1982. The same 35-40% of young people diagnosed with osteosarcoma die from their disease, almost always from complications related to lung metastasis. Believing that therapies targeting lung metastasis could dramatically improve outcomes, we have sought to understand the mechanisms that drive lung colonization in this disease. We previously found that interactions with lung epithelium cause osteosarcoma cells to produce IL6 and CXCL8 and that this activity is necessary for metastasis. Inhibiting IL6 and CXCL8 signaling prevents metastasis entirely in 85% of mice with osteosarcoma. While conducting these studies, we learned that individual tumor cells react differently to signals from lung epithelium. Nearly all the IL6 and CXCL8 produced by osteosarcoma cells come from a small subset of cells. Interactions with pulmonary epithelium cause this discrete subset of tumor cells to produce large quantities of inflammatory cytokines, become strongly p21+, and stop proliferating. Early metastatic lesions consist almost entirely of cells with this phenotype, positioning them to orchestrate the development of the metastatic niche. Thus, we call these hypo-proliferative, cytokine-producing cells that survive early attrition "anchor cells." In the initial stages of metastasis, anchor cells alter the surrounding lung tissue in ways that facilitate subsequent colonization by tumor cells with proliferating phenotypes ("growth cells"). Growth cells then divide to create expanding, clinically-relevant metastasis. Importantly, one can leverage the biology of these anchor cells to develop rational targeting strategies. Anchor cells exhibit profound sensitivity to known senolytic agents. Combining these with conventional therapies (which effectively target growth cells) can eradicate established metastatic lesions and prevent new metastases from forming. These novel findings fundamentally alter our understanding of osteosarcoma and metastasis biology and have direct implications for approaches to treatment. Citation Format: James B. Reinecke, John M. Hinckley, Amy C. Gross, Maren Cam, Sanjana Rajan, Ryan D. Roberts. Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-123.

Leukocyte telomere length is associated with iron overload in male adults with hereditary hemochromatosis.

Background: Hereditary hemochromatosis (HH) is a primary iron overload (IO) condition. Absolute telomere length (ATL) is a marker of cellular aging and DNA damage associated with chronic diseases and mortality.Aim: To evaluate the relationship between ATL and IO in patients with HH.Methods: Cross-sectional study including 25 patients with HH: 8 with IO and 17 without IO (ferritin < 300 ng/ml) and 25 healthy controls. Inclusion criteria were: age > 18 years, male sex and HH diagnosis. Patients with diabetes or other endocrine and autoimmune diseases were excluded. ATL was measured by real-time PCR.Results: HH patients with IO were older (P<0.001) and showed higher ferritin concentration (P<0.001). Patients with HH, disregarding the iron status, showed higher glucose and body mass index (BMI) than controls (both P<0.01). ATL was shorter in patients with IO than controls [with IO: 8 (6–14), without IO: 13 (9–20), and controls: 19 (15–25) kilobase pairs, P<0.01]; with a linear trend within groups (P for trend <0.01). Differences in ATL remained statistically significant after adjusting by age, BMI and glucose (P<0.05).Discussion: Patients with IO featured shorter ATL while patients without IO showed only mild alterations vs. controls. Screening for IO is encouraged to prevent iron-associated cellular damage and early telomere attrition.

Coping with recruiter stress: Hardiness, performance and well-being in US Army recruiters

ABSTRACT Recruiting for military service can be a highly stressful job, but it is one that is essential for success in the all-volunteer force. Military recruiters face a number of job stressors, including pressure to meet monthly production quotas, long work hours and time away from family. They also work in relative isolation, with limited work social support networks. These factors make recruiters vulnerable to burnout and early attrition. The present study examines psychological hardiness and active, problem focused coping as potential stress resilience resources in US Army recruiters. In a stratified random sample of N = 817 recruiters, hardiness was found to predict supervisor-rated performance and psychological well-being. Hardiness also interacted with problem focused coping to predict psychological well-being, suggesting a mediating role for coping. These results can be applied to help improve policy for selecting and training military recruiters.

Predictors of attrition from a weight loss program. A study of adult patients with obesity in a community setting

PurposeObesity unit attrition is frequent and contributes to treatment failure. Many studies evaluating attrition predictors were part of randomized trials, and different terminology and criteria were used in the engagement field. We aimed to investigate the factors potentially implicated in early (< 12 weeks) and late (> 12 weeks) attrition from an obesity unit in a community settingMethodsThis was a retrospective cohort study of 250 patients with obesity who were followed-up at our obesity unit. Our program included at least 6 meetings in 12 months. Sociodemographic and anthropometric data, and psychometric questionnaires were collected from all participants.ResultsOne-hundred thirty-four (53.6%) participants dropped out. Those individuals showed lower BMI, lower overall health status, and increased depression scores. In a multiple regression model, BMI (inversely; OR = 0.90; 95%CI 0.84–0.96) and depression score (directly, OR = 1.05; 1.00–1.10) were associated with attrition risk. Early dropouts (n = 47) had lower weights, smaller waist circumferences and worse mental health scores than late dropouts (n = 87) and more frequently lived alone. When compared to completers, early dropouts had lower weights, BMIs, waist circumferences, overall health and mental status scores, increased depression scores and percentage of individuals living alone. In a multiple regression, lower BMI (OR = 0.83; 0.75–0.92), lower mental status score (OR = 3.17; 1.17–8.59) and living alone (OR = 2.25; 1.02–4.97) were associated with early attrition risk.ConclusionLower BMI and increased depression score were associated with attrition. Early attrition was associated with lower weight, decreased mental well-being, and living alone. Individuals with these characteristics might need tailored approaches to enhance their engagement.Level of evidenceLevel V, retrospective descriptive study.

Mobile Health Apps in Pediatric Obesity Treatment: Process Outcomes From a Feasibility Study of a Multicomponent Intervention

BackgroundMulticomponent family interventions underline current best practice in childhood obesity treatment. Mobile health (mHealth) adjuncts that address eating and physical activity behaviors have shown promise in clinical studies.ObjectiveThis study aimed to describe process methods for applying an mHealth intervention to reduce the rate of eating and monitor physical activity among children with obesity.MethodsThe study protocol was designed to incorporate 2 mHealth apps as an adjunct to usual care treatment for obesity. Children and adolescents (aged 9-16 years) with obesity (BMI ≥98th centile) were recruited in person from a weight management service at a tertiary health care center in the Republic of Ireland. Eligible participants and their parents received information leaflets, and informed consent and assent were signed. Participants completed 2 weeks of baseline testing, including behavioral and quality of life questionnaires, anthropometry, rate of eating by Mandolean, and physical activity level using a smart watch and the myBigO smartphone app. Thereafter, participants were randomized to the (1) intervention (usual clinical care+Mandolean training to reduce the rate of eating) or (2) control (usual clinical care) groups. Gender and age group (9.0-12.9 years and 13.0-16.9 years) stratifications were applied. At the end of a 4-week treatment period, participants repeated the 2-week testing period. Process evaluation measures included recruitment, study retention, fidelity parameters, acceptability, and user satisfaction.ResultsA total of 20 participants were enrolled in the study. A web-based randomization system assigned 8 participants to the intervention group and 12 participants to the control group. Attrition rates were higher among the participants in the intervention group (5/8, 63%) than those in the control group (3/12, 25%). Intervention participants undertook a median of 1.0 training meal using Mandolean (25th centile 0, 75th centile 9.3), which represented 19.2% of planned intervention exposure. Only 50% (9/18) of participants with smart watches logged physical activity data. Significant differences in psychosocial profile were observed at baseline between the groups. The Child Behavior Checklist (CBCL) mean total score was 71.7 (SD 3.1) in the intervention group vs 57.6 (SD 6.6) in the control group, t-test P<.001, and also different among those who completed the planned protocol compared with those who withdrew early (CBCL mean total score 59.0, SD 9.3, vs 67.9, SD 5.6, respectively; t-test P=.04).ConclusionsA high early attrition rate was a key barrier to full study implementation. Perceived task burden in combination with behavioral issues may have contributed to attrition. Low exposure to the experimental intervention was explained by poor acceptability of Mandolean as a home-based tool for treatment. Self-monitoring using myBigO and the smartwatch was acceptable among this cohort. Further technical and usability studies are needed to improve adherence in our patient group in the tertiary setting.

TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model.

Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using the blood-and-muscle model, indicate that higher early life LTL attrition, as estimated by the ratio between LTL and skeletal muscle telomere length (MTL), rather than short LTL at conception, as estimated by MTL, should be responsible of the ASCVD-LTL connection. We combined LTL and MTL measurements and SNPs profiling in 402 individuals to determine if 15 SNPs classically described as associated with short LTL at adult age were rather responsible for higher LTL attrition during early life than for shorter LTL at birth. Two of these SNPs (rs12696304 and rs10936599) were associated with LTL in our cohort (p = 0.027 and p = 0.025, respectively). These SNPs, both located on the TERC gene, were associated with the LTL/MTL ratio (p = 0.007 and p = 0.037, respectively), but not with MTL (p = 0.78 and p = 0.32 respectively). These results suggest that SNPs located on genes coding for telomere maintenance proteins may contribute to a higher LTL attrition during the highly replicative first years of life and have an impact later on the development of ASCVD.

Handheld ultrasound in training - The future is getting smaller!

Traditional ultrasound teaching is normally delivered using large, costly and often quite advanced cart-based systems. These carts are often large systems on wheels, usually limited to the departments that own them i.e. clinics, wards or radiology. Portability has been further improved by the development of laptop style systems, which are easier to wheel in-between patients/departments. In our experience and anecdotally, many of these systems can be intimidating to the novice and can lead to early attrition or poor uptake of ultrasound into clinical practice. Carts can also restrict the amount of training deliverable to practitioners, as they are limited in number due to cost and can take quite some time to boot up, reducing convenience. This dogma is being progressively changed with the advent of smaller handheld devices, some clearly within the financial grasps of most practitioners, and even to the point of medical schools offering students their own personal device.1,2 This relative inexpensiveness can lead to the purchase of these devices for novelty and convenience, over need. Obvious caution is needed in these circumstances, but with increased ease of purchase, better availability and inbuilt simplicity, ultrasound learning can be seamlessly integrated into day-to-day practice. This review discusses how one of the most disruptive innovations in modern medicine is changing ultrasound from a classic imaging modality to become integrated as the fifth pillar of clinical examination, and how these new devices can serve as springboards to more advanced ultrasound training. In fact, within what has become a bigger area of clinical examination, things are getting smaller.

Sociocognitive factors associated with lifestyle intervention attrition after successful weight loss among participants with prediabetes-The PREVIEW study.

Major risk factors for type 2 diabetes are lifestyle choices such as lack of physical activity (PA) and poor diet. Many individuals either do not take part or struggle to complete interventions supporting lifestyle changes. Demographic and theory-based sociocognitive factors associated with PREVIEW intervention attrition after successful weight loss were examined. Participants (1,856) who started the weight maintenance phase after completion of low-energy diet were retrospectively divided into three clusters depending on the point they left the trial. Discriminant analysis examined which demographic and theory-based sociocognitive variables were associated with cluster membership. Most of the participants were women and well-educated. Two discriminant functions were calculated (χ2 (24)=247.0, p≥.05, d=0.78). The demographic variables, such as age and ethnicity, and the social cognitive variable outcome expectancies on the other side were associated with cluster membership. Older age, Caucasian ethnicity, and fewer expected disadvantages of PA were associated with high success. The discriminant model gave insight into some factors associated with early attrition. For practitioners planning interventions it underlines the necessity to take extra attention to younger participants and to those being afraid that being physically active causes unpleasant ramifications.

Sarcopenic Obesity Predicts Early Attrition in Treatment-Seeking Patients with Obesity: A Longitudinal Pilot Study.

Attrition is a major cause of failure in obesity treatment, which is still not fully understood. The identification of factors related to this outcome is of clinical relevance. We aimed to assess the relationship between sarcopenic obesity (SO) and early attrition. Early attrition was assessed at six months, and two groups of patients were selected from a large cohort of participants with overweight or obesity enrolled at the Outpatient Clinic of the Department of Nutrition and Dietetics at Beirut Arab University (Lebanon). Body composition was measured using a bioimpedance analyser (Tanita BC-418) and participants at baseline were categorized as having or not having SO. The “dropout group” included 72 participants (cases) compared to 31 participants (controls) in the “completer group”, with the former displaying a higher prevalence of SO than the latter (51.0% vs. 25.8%; p = 0.016). In the same direction, Poisson regression analysis showed that SO increased the relative risk of dropout by nearly 150% (RR = 1.45; 95% CI = 1.10–1.89; p = 0.007) after adjustment for age, gender, body mass index (BMI), age at first dieting, sedentary habits and weight-loss expectation. In conclusion, in a “real-world” outpatient clinical setting, the presence of SO at baseline increases the risk of dropout at six months. New directions of future research should be focused on identifying new strategies to reduce the attrition rate in this population.

The Association between Trauma History, Trauma-Related Psychopathology and Treatment Completion at an Adolescent Inpatient Substance Abuse Treatment Center in Turkey

Some adolescents are at great risk for early attrition from inpatient substance abuse treatment. We aimed to examine the effect of sociodemographic features, substance use patterns, childhood traumas and trauma-related psychopathology on the completion of an adolescent substance abuse inpatient treatment program in order to acquire information about adapting treatment strategies to enhance patient retention. Our study included 105 adolescents who were referred with a diagnosis of substance use disorder to our Child and Adolescent Substance Abuse Treatment Center's inpatient treatment program in Istanbul, Turkey from February to December 2017. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, the Hamilton Depression Rating Scale, the Conners-Wells Adolescent Self Report Scale, the Childhood Trauma Questionnaire, the Childhood Abuse and Neglect Question List, the Dependency Profile Index-Practitioner Form and the Adolescent Dissociative Experiences Scale were administered to the study group. The treatment completion rate was 26.7%. The patients who did not complete the inpatient treatment program had more history of childhood emotional neglect and/or abuse. The most common type of psychosocial trauma was emotional neglect (34%). Early attrition from the inpatient treatment program was related to dissociative amnesia, more severe attention deficit hyperactivity disorder, depression and synthetic cannabinoids use (p < 0.05). Our findings indicate that childhood psychosocial trauma and related clinical characteristics were associated with attrition from the adolescent inpatient substance abuse treatment program. Substance abuse treatment programs should adopt early assessment tools to identify those at risk for early attrition from treatment and provide targeted interventions for them.

Prestige, Status, and Esteem and the Teacher Shortage

1,127 U.S. high school senior and college undergraduate perceptions of teaching&amp;rsquo;s prestige, status, and esteem were explored in this study. The population consisted of 302 high school seniors and 825 college undergraduates from the Midwestern region of the United States. The study included 51 statements where participants rated their perceptions of teaching&amp;rsquo;s prestige, status, and esteem on an 8-point Likert scale. The data was factor analyzed, and the results identified that the perceptions of teaching&amp;rsquo;s prestige consisted of financial and image perceptions. A descriptive analysis found that U.S. high school senior and college undergraduate perceptions of teaching&amp;rsquo;s financial component of prestige (M = 9.99, SD = 2.90) and esteem (M = 10.42, SD = 3.05) were more negative in comparison to status (M = 13.38, SD = 2.74).&#x0D; &#x0D; Bivariate correlation, Univariate, and hierarchal linear regression techniques measured the effects that the perceptions of teaching&amp;rsquo;s prestige, status, and esteem had on U.S. high school seniors and college undergraduate teaching considerations. The results indicated that the perceptions of teaching&amp;rsquo;s status may encourage U.S. high school seniors and college undergraduates to consider careers in teaching, but the perceptions of esteem may produce opposite effects. The results demonstrated that the perceptions of teaching&amp;rsquo;s esteem may discourage U.S. high school seniors and college undergraduates scoring in the upper deciles of the ACT (American College Testing) from considering teaching in the United States. The results indicated that the perceptions of esteem may also discourage U.S. urban female high school seniors and college undergraduates from considering the career. Finally, the results demonstrated the perceptions of teaching&amp;rsquo;s esteem and its interaction with the financial perceptions of teaching&amp;rsquo;s prestige may discourage U.S. aspiring teachers from the career. This result raises questions as to the &amp;ldquo;roots&amp;rdquo; of the early teacher attrition problem in the United States.

The impact of health on professional diver attrition.

Approximately 77% of professional divers leave the industry within five years of entry, for reasons that are uncertain. One possibility is that attrition is due to ill-health. The health of New Zealand occupational divers is surveyed by a comprehensive medical examination every five years and by a health questionnaire in the intervening years. Divers are thereby confirmed 'fit' annually. The aim of this study was to determine if divers quit the industry due to a health problem not identified by this health surveillance system. 601 divers who had left the industry within five years of entry medical examination ('quitters') were identified from a computerised database. One hundred and thirty-six who could be contacted were questioned about their principal reason for quitting. Comparison was made between the health data of all those defined as 'quitters' and a group of 436 'stayers' who have remained active in the industry for over 10 years. Health was the principal reason for abandoning a diving career for only 2.9% of quitters. The overwhelming majority (97.1%) quit because of dissatisfaction with aspects of the work, such as remuneration and reliability of employment. Besides gender, the only significant difference between the health data of quitters and stayers was that smoking was four times more prevalent among quitters. The key determinant of early attrition from the New Zealand professional diver workforce is industry-related rather than health-related. The current New Zealand diver health surveillance system detects the medical problems that cause divers to quit the industry.

2269-PUB: Early Attrition from a Randomized Lifestyle Modification Protocol

Assigned exercise and other lifestyle modification can alter the natural history of diabetic neuropathy, but adherence to lifestyle change protocols poses a challenge in a clinical trial setting. In particular, the commitment for participants to begin engagement with the assigned intervention is a critical juncture. The Activity for DiAbetic neuroPaThy (ADAPT) trial is an NIDDK sponsored two-center single blinded protocol that randomizes type 2 diabetic neuropathy patients for 18 months to either brief lifestyle counseling or a combination of monitored exercise, diet counseling and actigraphy driven anti-sedentary behavioral modification. 103 participants have consented, screened, and been found eligible for ADAPT. Of these, 20 dropped from the trial during baseline evaluation (n=3), randomization (n=1), or before the first intervention visit or 3-month follow-up (n=16). Of the 83 who have reached 3-month follow-up, only 7 participants have dropped from the study. The pattern of early attrition has differed at the two sites. At one site, early attrition was essentially equal between assigned groups. The second site 9 of those randomized to intervention and one assigned to control dropped before 3 months. At the second site, protocol changes to improve “hand-off” from the assessment to intervention coordinators, and marked reduction in time from randomization to first intervention visit has improved retention. Structured counseling to set expectations, reduce performance anxiety, and address disappointment with assignment to the less intensive arm has improved initial retention at both sites. Once familiar with the intervention process, most participants will continue with behavioral modification. Clinical trials utilizing patient-motivated lifestyle modification protocols should seek to minimize physical barriers to initial engagement, and focus counseling and motivational effort on the critical early trial period during which participants commit internally to the intervention process. Disclosure C. Revere: None. A. Smith: Consultant; Self; Alexion Pharmaceuticals, Inc., Disarm, Regenesis. P. Kluding: None. R.L. Marcus: None. M. Dimachkie: Research Support; Self; Viromed. F. Vivanco: None. S.C. Foster-Palmer: None. P.E. Hauer: None. A.B. Aperghis: None. M. Pasnoor: Advisory Panel; Self; Alexion Pharmaceuticals, Inc., Terumo BCT. Consultant; Self; Momenta Pharmaceuticals. A. Stonebraker: None. A.N. Hawks: None. L. Herbelin: None. J. Singleton: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases; National Center for Advancing Translational Sciences

Pharmacokinetics, tissue distribution, plasma protein binding, and metabolism study of mefunidone, a novel pirfenidone derivative.

Mefunidone (MFD), a novel derivation of pirfenidone (PFD), exhibits promising anti-renal fibrosis activity. To avoid early development failures and attrition in clinical phase 1, an evaluation of the preclinical pharmacokinetic (PK) properties of MFD was conducted in this study. The absolute bioavailability was evaluated in Sprague Dawley rats and cynomolgus monkeys, who received an intragastric or intravenous administration at the dose of 31.25mg/kg and 10mg/kg, respectively. Tissue distribution and plasma protein binding studies were performed to evaluate the distribution characteristics of MFD. The enzymes involved in the metabolism of MFD were assayed by calculating the inhibition rate using the in vitro incubation system of human liver microsomes. The metabolic pathway of MFD was also examined in the in vitro incubation system as well as in rats in vivo. The results revealed satisfactory absorption of MFD in vivo, with an absolute bioavailability of MFD in rats and monkeys of approximately 77.2% and 70.0%, respectively. MFD was rapidly distributed to all tissues and was highly concentrated in the kidney, which was the target organ of MFD. The plasma protein binding rates in rat, monkey, and human plasma were 36.40%-41.68%, 30.88%-63.92%, and 37.75%-57.77%, respectively. MFD was primarily metabolized by the enzymes CYP3A4, CYP2C9, and CYP2C8. The metabolic pathway of MFD is nitrogen demethylation of the pyridine ring of the MFD nucleus, hydroxylation of the aromatic ring, and demethylation of the piperazine ring. In conclusion, MFD exhibited good PK properties in the initial preclinical PK study. The results strongly support further research to investigate the potential of MFD as a clinical anti-renal fibrosis drug.

Individual and institutional characteristics associated with short tenures of deanships in academic nursing

The departures of chief academic administrators of nursing programs within a short tenure are likely to affect the operation of their institutions significantly. To help nursing schools improve recruitment and retention of chief academic administrators. We obtained deans' records from the membership database of the American Association of Colleges of Nursing (AACN) for 11 starting cohorts between 2001 and 2011 and matched the data with dean data collected in the AACN Annual Survey to retrieve additional information on individual and institutional characteristics. Bivariate and multivariate analyses were used to examine the association between a characteristic and short tenures (less than 5 years). We found that 41% of deanships have short tenures, and the figure increased from earlier cohorts to later cohorts in general. We did not find that first-time deans were more likely to experience a short tenure. However, we found in bivariate analyses that deans in newly created nursing programs have a higher likelihood of leaving deanships in less than 5 years. We also found in bivariate and multivariate analyses that an individual characteristic, age 60 or older, and three institutional attributes, deans with a title as Chair, Director, or Department Head, deans in nursing schools without a tenure system, and deans in baccalaureate or associate degree granting institutions are more likely to have a short tenure. In brief, our findings show that deans in smaller nursing programs are more likely than deans in larger nursing programs to experience a short tenure DISCUSSION: Our findings that deans in smaller programs and newly created programs are more likely to experience early attrition provide useful information to the nursing education community so more focused efforts can be made to improve the retention of chief academic administrators in nursing programs.

Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim.

Apoptosis of CD8 T cells is an essential mechanism that maintains immune system homeostasis, prevents autoimmunity, and reduces immunopathology. CD8 T cell death also occurs early during the response to both inflammation and costimulation blockade (CoB). In this article, we studied the effects of a combined deficiency of Fas (extrinsic pathway) and Bim (intrinsic pathway) on early T cell attrition in response to lymphocytic choriomeningitis virus infection and during CoB during transplantation. Loss of Fas and Bim function in Bcl2l11-/-Faslpr/lpr mice inhibited apoptosis of T cells and prevented the early T cell attrition resulting from lymphocytic choriomeningitis virus infection. Bcl2l11-/-Faslpr/lpr mice were also resistant to prolonged allograft survival induced by CoB targeting the CD40-CD154 pathway. These results demonstrate that both extrinsic and intrinsic apoptosis pathways function concurrently to regulate T cell homeostasis during the early stages of immune responses and allograft survival during CoB.

Characteristics and early clinical outcomes of key populations attending comprehensive community-based HIV care: Experiences from Nasarawa State, Nigeria.

BackgroundDespite a call for differentiated care, there are limited data from sub-Saharan Africa on comprehensive community-based HIV care for key populations (KP), including commercial sex workers (CSW), men who have sex with men (MSM), and people who inject drugs (PWID). In Nigeria, a programme was implemented that liaised with community-based organizations and offered HIV testing, same-day ART initiation, and ART follow-up to KP. Here we characterize KP and their partners enrolled on ART. Our objective is to assess the early treatment outcomes and to estimate predictors of attrition among KP.MethodThis is a retrospective cohort study of routinely collected data in a community-based HIV program for KP in Nasarawa state, Nigeria from August 2016 to November 2017. Variables of interest were socio-demographic, KP types, treatment outcomes, ART adherence, WHO stage, TB status and viral load. Summary statistics, logistic and Cox proportional hazard regression were used to describe the characteristics of KP and estimate predictors of attrition (patients either lost to follow-up (LTFU) or dead).ResultSeven hundred and ten (710) KP and their partners were enrolled into this study, 77.3% (549) of study participants were female and the median age was 30 years (IQR: 24–35). Respectively, 74.2%, 4.5%, 1.1% and 20% were FSW, MSM, PWID and their partners. Of 710 KP who started ART, 13.9% (99/710) discontinued after the first visit. After a median follow-up time of 7 months on ART 73.2% of patients were retained, 23.4% were LTFU, and 3.4% were dead. Lack of formal education (aHR 1.8; 95% CI 1.3–2.6) and unemployment (aHR 1.8; 95% CI 1.2–2.6) were significantly associated with attrition.ConclusionComprehensive community-based HIV care, including HIV testing and same-day ART is feasible. However, ART initiation on the same day of confirmatory HIV testing resulted in a high uptake of ART, but possibly inflated early attrition on ART. To mitigate early attrition among KP after same-day ART initiation, the psychosocial readiness of clients should be assessed better. We strongly recommend further studies to understand factors contributing to high attrition among the KP.