A Medium-Chain Fatty Acid Analogue Prevents Intestinal Failure-Associated Liver Disease in Preterm Yorkshire Piglets.

BACKGROUND & AIMS: At least 20%-30% of patients with intestinal failure receiving long-term parenteral nutrition will develop intestinal failure-associated liver disease (IFALD), for which there are few therapeutic options. SEFA-6179 is a first-in-class structurally engineered medium-chain fatty acid analogue that acts through GPR84, PPARα, and PPARγ agonism. We hypothesized that SEFA-6179 would prevent biochemical and histologic liver injury in a preterm piglet model of IFALD. METHODS: Preterm Yorkshire piglets were delivered by cesarean section, and parenteral nutrition was provided for 14 days via implanted central venous catheters. Animals were treated with either medium-chain triglyceride vehicle control or SEFA-6179. RESULTS: Compared to medium-chain triglyceride vehicle at day of life 15, SEFA-6179 prevented biochemical cholestasis (direct bilirubin: 1.9 vs <0.2 mg/dL, P = .01; total bilirubin: 2.7 vs 0.4 mg/dL, P = .02; gamma glutamyl transferase: 172 vs 30 U/L, P = .01). SEFA-6179 also prevented steatosis (45.6 vs 13.9 mg triglycerides/g liver tissue, P = .009), reduced bile duct proliferation (1.6% vs 0.5% area cytokeratin 7 positive, P = .009), and reduced fibrosis assessed by a masked pathologist (median Ishak score: 3 vs 1, P = 0.007). RNA sequencing of liver tissue demonstrated that SEFA-6179 broadly impacted inflammatory, metabolic, and fibrotic pathways, consistent with its in vitro receptor activity (GPR84/PPARα/PPARγ agonist). CONCLUSIONS: In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial.

Periodontal disease in patients with WHIM syndrome.

AIM: WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain-of-function (GOF) mutations in the chemokine receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome. MATERIALS AND METHODS: Twenty-two adult WHIM syndrome patients and 22 age- and gender-matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis. RESULTS: Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature-induced periodontitis. CONCLUSIONS: Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.

Short communication: Metabolic synthesis of vitamin D2 by the gut microbiome.

The origin of vitamin D2 in herbivorous animals was investigated in vivo in sheep and in bovine as well as mouse gastrointestinal tracts. A high concentration of 25-hydroxyvitamin D2 in blood plasma of sheep both in summer and winter appeared to be incompatible with the undetectable level of vitamin D2 in the pasture on which the sheep were grazing. Studies with bovine rumen contents from a cow grazing the same pasture as the sheep, demonstrated an increased concentration of vitamin D2 on anaerobic incubation in a 'Rusitec' artificial rumen, which was further enhanced when cellulose powder was added as a fermentation substrate. The colon contents of mice that were fed from weaning on a vitamin D-free diet were found to contain vitamin D2. The results of these comparative studies in 3 animal species indicated that vitamin D2 was being generated by microbial anaerobic metabolism in the gastrointestinal tract.

Animal sheltering: A scoping literature review grounded in institutional ethnography.

A diverse research literature now exists on the animals, staff and organisations involved in animal sheltering. We reviewed this research through the lens of institutional ethnography, a method of inquiry that focuses on the actual work that people do within institutions. The main topics, identified through a larger ethnographic study of animal sheltering, were: (i) research about shelter staff and officers; (ii) the relinquishment of animals to shelters; and (iii) animals' length of stay in shelters. After reviewing the literature, we held focus groups with shelter personnel to explore how their work experiences are or are not represented in the research. The review showed that stress caused by performing euthanasia has attracted much research, but the decision-making that leads to euthanasia, which may involve multiple staff and potential conflict, has received little attention. Research on 'compassion fatigue' has also tended to focus on euthanasia but a granular description about the practical and emotional work that personnel undertake that generates such fatigue is missing. Published research on both relinquishment and length of stay is dominated by metrics (questionnaires) and often relies upon shelter records, despite their limitations. Less research has examined the actual work processes involved in managing relinquishment as well as monitoring and reducing animals' length of stay. Institutional ethnography's focus on people's work activities can provide a different and more nuanced understanding of what is happening in animal sheltering and how it might better serve the needs of the animals and staff.

Using institutional ethnography to analyse animal sheltering and protection I: Animal protection work.

Animal protection laws exist at federal, provincial and municipal levels in Canada, with enforcement agencies relying largely upon citizens to report concerns. Existing research about animal protection law focuses on general approaches to enforcement and how legal terms function in the courts, but the actual work processes of animal law enforcement have received little study. We used institutional ethnography to explore the everyday work of Call Centre operators and Animal Protection Officers, and we map how this work is organised by laws and institutional polices. When receiving and responding to calls staff try to identify evidence of animal 'distress' as legally defined, because various interventions (writing orders, seizing animals) then become possible. However, many cases, such as animals living in deprived or isolated situations, fall short of constituting 'distress' and the legally mandated interventions cannot be used. Officers are also constrained by privacy and property law and by the need to record attempts to secure compliance in order to justify further action including obtaining search warrants. As a result, beneficial intervention can be delayed or prevented. Officers sometimes work strategically to advocate for animals when the available legal tools cannot resolve problems. Recommendations arising from this research include expanding the legal definition of 'distress' to better fit animals' needs, developing ways for officers to intervene in a broader range of situations, and more ethnographic research on enforcement work in jurisdictions with different legal systems to better understand how animal protection work is organised and constrained by laws and policies.

A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH.

BACKGROUND & AIMS: Although long-chain omega-3 fatty acids (LCn-3FAs) regulate inflammatory pathways of relevance to non-alcoholic steatohepatitis (NASH), their susceptibility to peroxidation may limit their therapeutic potential. We compared the metabolism of eicosapentaenoic acid (EPA) with an engineered EPA derivative (icosabutate) in human hepatocytes in vitro and their effects on hepatic glutathione metabolism, oxidised lipids, inflammation, and fibrosis in a dietary mouse model of NASH, and in patients prone to fatty liver disease. METHODS: Oxidation rates and cellular partitioning of EPA and icosabutate were compared in primary human hepatocytes. Comparative effects of delayed treatment with either low- (56 mg/kg) or high-dose (112 mg/kg) icosabutate were compared with EPA (91 mg/kg) or a glucagon-like peptide 1 receptor agonist in a choline-deficient (CD), L-amino acid-defined NASH mouse model. To assess the translational potential of these findings, effects on elevated liver enzymes and fibrosis-4 (FIB-4) score were assessed in overweight, hyperlipidaemic patients at an increased risk of NASH. RESULTS: In contrast to EPA, icosabutate resisted oxidation and incorporation into hepatocytes. Icosabutate also reduced inflammation and fibrosis in conjunction with a reversal of CD diet-induced changes in the hepatic lipidome. EPA had minimal effect on any parameter and even worsened fibrosis in association with depletion of hepatic glutathione. In dyslipidaemic patients at risk of NASH, icosabutate rapidly normalised elevated plasma ALT, GGT and AST and reduced FIB-4 in patients with elevated ALT and/or AST. CONCLUSION: Icosabutate does not accumulate in hepatocytes and confers beneficial effects on hepatic oxidative stress, inflammation and fibrosis in mice. In conjunction with reductions in markers of liver injury in hyperlipidaemic patients, these findings suggest that structural engineering of LCn-3FAs offers a novel approach for the treatment of NASH. LAY SUMMARY: Long-chain omega-3 fatty acids are involved in multiple pathways regulating hepatic inflammation and fibrosis, but their susceptibility to peroxidation and use as an energy source may limit their clinical efficacy. Herein, we show that a structurally modified omega-3 fatty acid, icosabutate, overcame these challenges and had markedly improved antifibrotic efficacy in a mouse model of non-alcoholic steatohepatitis. A hepatoprotective effect of icosabutate was also observed in patients with elevated circulating lipids, in whom it led to rapid reductions in markers of liver injury.

Ligand conjugate SAR and enhanced delivery in NHP.

N-Acetylgalactosamine (GalNAc) conjugated short interfering RNAs (siRNAs) are a leading RNA interference (RNAi) platform allowing targeted inhibition of disease-causing genes in hepatocytes. More than a decade of development has recently resulted in the first approvals for this class of drugs. While substantial effort has been made to improve nucleic acid modification patterns for better payload stability and efficacy, relatively little attention has been given to the GalNAc targeting ligand. In addition, the lack of an intrinsic endosomal release mechanism has limited potency. Here, we report a stepwise analysis of the structure activity relationships (SAR) of the components comprising these targeting ligands. We show that there is relatively little difference in biological performance between bi-, tri-, and tetravalent ligand structures while identifying other features that affect their biological activity more significantly. Further, we demonstrate that subcutaneous co-administration of a GalNAc-functionalized, pH responsive endosomal release agent markedly improved the activity and duration of effect for siRNA conjugates, without compromising tolerability, in non-human primates. These findings could address a significant bottleneck for future siRNA ligand conjugate development.

Dual targeting of hepatic fibrosis and atherogenesis by icosabutate, an engineered eicosapentaenoic acid derivative.

BACKGROUND & AIMS: While fibrosis stage predicts liver-associated mortality, cardiovascular disease (CVD) is still the major overall cause of mortality in patients with NASH. Novel NASH drugs should thus ideally reduce both liver fibrosis and CVD. Icosabutate is a semi-synthetic, liver-targeted eicosapentaenoic acid (EPA) derivative in clinical development for NASH. The primary aims of the current studies were to establish both the anti-fibrotic and anti-atherogenic efficacy of icosabutate in conjunction with changes in lipotoxic and atherogenic lipids in liver and plasma respectively. METHODS: The effects of icosabutate on fibrosis progression and lipotoxicity were investigated in amylin liver NASH (AMLN) diet (high fat, cholesterol and fructose) fed ob/ob mice with biopsy-confirmed steatohepatitis and fibrosis and compared with the activity of obeticholic acid. APOE*3Leiden.CETP mice, a translational model for hyperlipidaemia and atherosclerosis, were used to evaluate the mechanisms underlying the lipid-lowering effect of icosabutate and its effect on atherosclerosis. RESULTS: In AMLN ob/ob mice, icosabutate significantly reduced hepatic fibrosis and myofibroblast content in association with downregulation of the arachidonic acid cascade and a reduction in both hepatic oxidised phospholipids and apoptosis. In APOE*3Leiden.CETP mice, icosabutate reduced plasma cholesterol and TAG levels via increased hepatic uptake, upregulated hepatic lipid metabolism and downregulated inflammation pathways, and effectively decreased atherosclerosis development. CONCLUSIONS: Icosabutate, a structurally engineered EPA derivative, effectively attenuates both hepatic fibrosis and atherogenesis and offers an attractive therapeutic approach to both liver- and CV-related morbidity and mortality in NASH patients.

Financial incentives to Medicaid smokers for engaging tobacco quit line treatment: maximising return on investment.

BACKGROUND: Low-income smokers experience greater difficulty in quitting smoking than do other smokers. Providing financial incentives for treatment engagement increases smoking cessation success. This study models the cost-effectiveness of varying levels of financial incentives to maximise return on investment (ROI) for engaging low-income Medicaid recipients who smoke to take calls from a tobacco quit line. METHODS: Participants (N=1900) were recruited from May 2013 to June 2015 through quit line-based (n=980), clinic-based (n=444) or community-based referrals (n=476) into the Wisconsin Medicaid Quit Line Incentive project. Incentive (n=948) and control group participants (n=952) received $30 versus $0 per call, respectively, for taking up to five Wisconsin Tobacco Quit Line (WTQL) calls. Cost-effectiveness analyses estimated the incremental cost-effectiveness ratio for alternative financial incentives for engagement with WTQL calls. Probabilistic sensitivity analysis was employed to determine an optimal strategy for financial incentives to minimise the cost per individual who quit smoking. RESULTS: Using fixed payments, the incremental cost-effectiveness ratio of $2316 per smoker who quit in the randomised trial decreased to $2150 per smoker who quit when the incentives were modelled at $20 per each of five WTQL calls taken. Using variable payments, the minimal cost per additional smoker who quit was $2125 when incentives for the first four WTQL calls were set at $20, and the financial payment for the fifth WTQL call was set at $70. CONCLUSIONS: Modelling suggests that financial incentives in the amount of $20 per call for taking the first four quit line calls and $70 for taking a fifth quit line call maximise ROI to engage low-income smokers with evidence-based smoking cessation treatment.

Building capacity for injury prevention: a process evaluation of a replication of the Cardiff Violence Prevention Programme in the Southeastern USA.

OBJECTIVES: Violence is a major public health problem in the USA. In 2016, more than 1.6 million assault-related injuries were treated in US emergency departments (EDs). Unfortunately, information about the magnitude and patterns of violent incidents is often incomplete and underreported to law enforcement (LE). In an effort to identify more complete information on violence for the development of prevention programme, a cross-sectoral Cardiff Violence Prevention Programme (Cardiff Model) partnership was established at a large, urban ED with a level I trauma designation and local metropolitan LE agency in the Atlanta, Georgia metropolitan area. The Cardiff Model is a promising violence prevention approach that promotes combining injury data from hospitals and LE. The objective was to describe the Cardiff Model implementation and collaboration between hospital and LE partners. METHODS: The Cardiff Model was replicated in the USA. A process evaluation was conducted by reviewing project materials, nurse surveys and interviews and ED-LE records. RESULTS: Cardiff Model replication centred around four activities: (1) collaboration between the hospital and LE to form a community safety partnership locally called the US Injury Prevention Partnership; (2) building hospital capacity for data collection; (3) data aggregation and analysis and (4) developing and implementing violence prevention interventions based on the data. CONCLUSIONS: The Cardiff Model can be implemented in the USA for sustainable violent injury data surveillance and sharing. Key components include building a strong ED-LE partnership, communicating with each other and hospital staff, engaging in capacity building and sustainability planning.

Short communication: Condition of male dairy calves at auction markets.

Male dairy calves in North America are frequently marketed through live auctions. Calves have been observed in suboptimal condition both at auctions and upon arrival at calf-rearing facilities that supply the veal or dairy-beef industries. The objectives of this study were to describe the health of male dairy calves at a commercial auction in British Columbia, Canada, examine the relationships between calf price and condition, and use price data from other auctions to reflect more broadly on the variability in calf condition at auction markets. Price and breed were recorded for 1,624 male calves, and a sample of 355 calves was assessed using a standardized health exam and body weight estimation. Linear regression was used to assess which calf characteristics were associated with price. Prices for young dairy calves at auctions in 2 other provinces (Nova Scotia and Quebec) were compiled for comparison. Twenty percent of calves had at least one health abnormality; the most common was navel disease (12%), followed by ocular or nasal discharge (4%), a depressed (dull, unable, or unwilling to rise) attitude (2%), coughing (2%), and joint inflammation (1%). The mean (±SD) estimated body weight was 47 ± 8 kg with a range of 27 to 82 kg. Calves were sold for up to Can$370 (median Can$140), but 10.5% sold for Can$10 or less, and 2.8% were not sold at all. [The mean exchange rate over the course of this study (Oct. 2017 to Mar. 2018) was Can$1 = US$0.79.] Calves with a depressed attitude sold for lower prices than bright, alert calves. In addition, those with Brown Swiss or Jersey genetics sold for lower prices than those with Holstein genetics, and cross-bred calves with beef genetics sold for higher prices. During 2018, 62% of young dairy calves sold at the Nova Scotia auction and 18% of young Holstein calves sold in Quebec were classed as lower quality and sold for 23% and 40%, respectively, of the value of higher-quality calves. The results underline the need to develop solutions to reduce the risk of marketing calves in poor condition at auction markets.

Hot topic: Health and welfare challenges in the marketing of male dairy calves-Findings and consensus of an expert consultation.

A diverse group of Canadian experts was convened for a focused 2-d discussion on potential health and welfare problems associated with the marketing (i.e., transportation and sale) of male dairy calves. Written notes and audio recording were used to summarize the information provided on transport times and marketing practices. Content analysis was used to develop a consensus statement on concerns, possible solutions, and recommendations to improve male dairy calf marketing. The group noted that calves across all Canadian regions are commonly transported at 3 to 7 d of age and undergo transport for 12 to 24 h or longer depending on the location of their dairy farm of origin. Calves in some regions are marketed almost exclusively through auction markets, whereas others have more direct sales. A need was identified for better criteria for calf fitness for transport, maintaining farm biosecurity, reducing the use of antimicrobial therapy in calf production, and improving education for farmers and veterinarians on the importance of neonatal care for male dairy calves before transportation. Experts noted that major changes in male dairy calf marketing will be required to comply with amendments to the federal Health of Animals Regulations (Part XII) on animal transportation; collaborative effort will be needed to safeguard animal health and welfare as this transition is made.

Biomechanical analysis of the osseointegration of porous tantalum implants.

STATEMENT OF PROBLEM: Although implants containing porous tantalum undergo osseointegration, whether this material significantly alters new bone formation and improves implant stability during healing in comparison to titanium is unclear. PURPOSE: The purpose of this in vivo study was to determine the influence of the inclusion of porous tantalum into a dental implant on the biomechanical properties of the bone-implant interface and peri-implant bone which may contribute to secondary implant stability. MATERIAL AND METHODS: Threaded titanium implants with a porous tantalum midsection (Trabecular Metal Dental Implant; Zimmer Biomet) or without (Tapered Screw-Vent; Zimmer Biomet) were placed in rabbit tibiae and allowed to heal for 4, 8, or 12 weeks. The implants were evaluated by resonance frequency analysis and removed with surrounding bone for nanoindentation testing. Two-way ANOVA was used to determine the impact of implant type, bone region, and time on the outcomes implant stability quotient (ISQ), hardness, and elastic modulus (α=.05). RESULTS: Resonance frequency analysis found no significant difference in ISQ values between implant types at 4, 8, or 12 weeks, and ISQ values did not increase for either implant over time. Nanoindentation showed no significant differences in hardness or elastic modulus in newly formed bone adjacent to either implant type at any time point. CONCLUSIONS: The stiffness of the bone-implant interface was similar for threaded titanium implants with or without porous tantalum when placed in the rabbit tibia and allowed to heal for at least 4 weeks. The new peri-implant bone adjacent to dental implants containing porous tantalum showed no difference in nanomechanical properties to the new bone around implants comprised completely of threaded titanium at all healing time points.

Risk factors for poor health outcomes for male dairy calves undergoing transportation in western Canada.

The condition of 640 male dairy calves was recorded and their health deterioration, morbidity, and mortality evaluated after long-distance transport. Assessments included a health examination, weight estimation, and measure of failed transfer of passive immunity (FTPI). A McNemar Test and logistic regression analysis were used to evaluate the effects of pre-transport condition on subsequent health. Before transport, calf health and age at shipping varied between farms; overall, 17%, 8%, and 12% of calves had diarrhea, navel disease, and FTPI, respectively, and calves were transported at a median age of 5 days. In their first 2 weeks after transportation, 23% and 44% of calves were treated for diarrhea and bovine respiratory disease (BRD), respectively, and 4% died. Calves with navel disease, low body weight, and a depressed attitude at the farm of origin were more likely to experience negative health outcomes. Better health before transportation is needed to protect the subsequent health and welfare of young calves.

Facteurs de risque associés à un résultat de mauvaise santé pour des veaux laitiers mâles soumis à un transport dans l'ouest canadien. La condition de 640 veaux laitiers mâles fut enregistrée et la détérioration de leur santé, la morbidité et la mortalité évaluées après un transport de longue distance. Les évaluations incluaient un examen de santé, une estimation du poids et une mesure de l'échec du transfert d'immunité passive (FTPI). Un test de McNemar et une analyse de régression logistique furent utilisés pour évaluer les effets des conditions pré-transport sur la santé subséquente. Avant le transport, la santé des veaux et l'âge au moment de l'expédition variaient entre les fermes; globalement, 17 %, 8 % et 12 % des veaux avaient de la diarrhée, une pathologie de l'ombilic et FTPI, respectivement, et les veaux furent transportés à l'âge médian de 5 jours. Durant les deux premières semaines après le transport, 23 % et 44 % des veaux furent traités pour de la diarrhée et des problèmes respiratoires (BRD), respectivement, et 4 % sont décédés. Les veaux avec une pathologie à l'ombilic, un faible poids corporel et une attitude déprimée à la ferme d'origine étaient plus susceptibles d'avoir des conséquences négatives sur leur santé. Une meilleure santé avant le transport est nécessaire pour protéger la santé ultérieure et le bien-être des jeunes veaux.(Traduit par Dr Serge Messier).

Tracking Veterinary Students Who Aspire to Careers in Science.

The Cornell Leadership Program for Veterinary Students is an intensive 10-week learning experience intended to guide competitively selected scholars into careers in science and public health. It features independent research, vocational counseling, and student-directed learning modules. Program scholars are encouraged to objectively evaluate graduate training as preparation for careers promoted by the program. Prominence is given to experiential learning through research, participation in program enrichment modules, and inspirational experiences achieved through group meetings and individual interactions with established scientists. Program alumni are monitored to determine how the careers they pursue relate to their earlier-stated ambitions. In addition, subjective assessments are made of the quality of graduate training and its impact on alumni career paths. The influence of mentors, vocational counseling, and inspirational experiences on subsequent training is also subjectively assessed. Information is obtained from students' anonymous responses to questionnaires and recorded interviews. Program alumni are contacted annually to determine their current activities and career aspirations. The Leadership Program encourages program graduates to undertake careers in science and public health, yet an unanticipated number of alumni enter private veterinary practice. A factor relevant to that outcome is that many students destined for practice lack a definitive career plan. Persuading veterinary students to consider careers in research or public service is challenging but worth the effort. Critical to that connection is the need for veterinary students to objectively evaluate graduate training options because the vocations they follow appear to be strongly influenced by the experiences they choose.

Prosthesis Survival Rates and Prosthetic Complications of Implant-Supported Fixed Dental Prostheses in Partially Edentulous Patients.

PURPOSE: To determine the prevalence and distribution of prosthetic complications affecting implant-supported fixed dental prostheses (ISFDPs). MATERIALS AND METHODS: Subjects previously treated with one or more ISFDP(s) were identified from an electronic health record search and recalled for comprehensive clinical examination. Past prosthesis failures and complications were identified from the patient records while any existing complications, not previously recorded, were assessed during examination. ISFDP survival and failure rates were calculated with Kaplan-Meier curves and life table analysis, while regression Poisson analysis was used to identify associations between outcomes and possible patient- and prosthesis-based risk factors. RESULTS: Seventy-four subjects with 107 ISFDPs were enrolled in the study with a mean time between prosthesis delivery and exam of 3.14 years (range: 1.00-9.00 years). Four prostheses failed, resulting in a cumulative prosthesis survival rate of 96.26%. Prosthetic complications affected 48.59% of ISFDPs, the majority (94.87%) of them minor complications. Only the use of a nightguard was associated with a lower prevalence of prosthetic screw loosening (HR 0.11, 95% CI 0.02-0.59, p = 0.007) while no outcome differences were noted for other variables. Patient satisfaction was high regardless of presence or number of complications. CONCLUSIONS: ISFDPs demonstrated a high survival rate and overall high, patient-reported satisfaction. Minor prosthetic complications were common but were only significantly associated with nightguard use.

Peri-Implant Diseases and Biologic Complications at Implant-Supported Fixed Dental Prostheses in Partially Edentulous Patients.

PURPOSE: This is a single center, retrospective study to assess the prevalence of peri-implant disease and biologic complications in a cohort of partially edentulous subjects in relation to selected prosthetic factors. MATERIALS AND METHODS: Subjects previously treated with one or more implant-supported fixed dental prosthesis (ISFDPs) were recalled for a comprehensive examination. Clinical and radiographic records were taken and questionnaires were administered. The prevalence of implant failure, peri-implant disease and other biologic complications were correlated with selected prosthetic, clinical and patient-related factors using chi-square and multiple regression analyses. RESULTS: A convenience sample of 71 subjects with 100 prostheses supported by 222 dental implants were enrolled in the study. The mean follow-up time after prosthesis delivery was 3.3 ± 1.5 years (range of 1-9 years). The cumulative implant survival rate was 99.1%. Peri-implantitis was the most frequent major biologic complication (5% of implants), while the most frequent minor biologic complication was peri-implant mucositis (84.10% of implants). A diagnosis of peri-implant mucositis was more likely associated with cement-retained prostheses compared to screw-retained prostheses (OR 6.8, 95% CI 1.1-78.6, p = 0.045) and for short-span prostheses (≤3 prosthetic units) (OR 2.3, 95% CI 1.1-5.0, p = 0.034). Subject-reported quality of life measures were high regardless of the existence of major and/or minor complications, but decreased with increasing number of minor and total biologic complications. CONCLUSIONS: Peri-implant mucositis and other minor biologic complications were highly prevalent. The distribution of the observed complications differed based on the method of prosthesis retention and the number of prosthetic units replaced.

Paying Low-Income Smokers to Quit? The Cost-Effectiveness of Incentivizing Tobacco Quit Line Engagement for Medicaid Recipients Who Smoke.

OBJECTIVES: To determine the cost-effectiveness of an incentive-based stop-smoking intervention that paid Medicaid recipients who smoke to take calls from a tobacco quit line. METHODS: A cost-effectiveness analysis was conducted alongside a randomized controlled trial. The analysis was conducted from a health care systems perspective on the basis of costs and effectiveness over a 6-month follow-up. Participants (n = 1900) were recruited from May 2013 to June 2015 through quit line (n = 980), clinic-based (n = 444), or community-based (n = 476) referrals. Incentive group participants (n = 948) received $30 a call for taking up to five tobacco quit line calls and $40 for biochemically verified tobacco abstinence at 6 months. Control group participants (n = 952) did not receive financial incentives for taking quit line calls. Intervention resource costs included incentive payments to participants, counselor and administrative staff time, and smoking cessation medications. Smoking status at baseline and 6 months was determined for all study participants via carbon monoxide (CO) breath tests (abstinence: CO < 7 ppm). Cost-effectiveness analysis calculated the incremental cost-effectiveness ratio (ICER). RESULTS: Incentive treatment produced higher 6-month CO-confirmed 7-day point-prevalence abstinence than did the control treatment (21.6 vs. 13.8%; P < 0.001). The ICER of the financial incentives intervention was $2316 (95% confidence interval $1582-$4270) per additional person who quit. The study ICER compares favorably with other smoking treatments, such as varenicline combined with proactive telephone counseling, whose ICER has been estimated at $2600 per additional smoker who quits. CONCLUSIONS: Use of financial incentives to engage with tobacco quit line treatment is a cost-effective option to enhance smoking cessation rates for low-income smokers.

Bone response to porous tantalum implants in a gap-healing model.

OBJECTIVES: The objective of this study was to determine the relative osteogenic behavior of titanium implants with or without a porous tantalum modification when placed with a gap between the implant and existing bone. MATERIALS AND METHODS: A gap-healing model in the rabbit tibia was used for placement of titanium implants. Forty-eight rabbits received 96 implants, with 48 of the implants containing a porous tantalum middle section and the remaining 48 implants were composed of solid titanium. After 4, 8, and 12 weeks of healing, biomechanical stability was measured with removal torque testing, implant-adherent cells were isolated for analysis of osteogenic gene expression, and histomorphometric analysis was performed on sections of the implants and surrounding bone. RESULTS: Increased osteogenic activity at 4 weeks was demonstrated by upregulation of key osteogenic genes at implants containing porous tantalum which was accompanied by greater bone-implant contact at 4, 8, and 12 weeks and significantly greater removal torque at 8 and 12 weeks. CONCLUSIONS: Implants containing porous tantalum demonstrated increased peri-implant bone formation within this gap-healing model as shown by significant differences in biomechanical and histomorphometric outcomes. Such implants may represent an alternative to influence bone healing in surgical sites with an existing gap.

Perceptions of on-farm emergency slaughter for dairy cows in British Columbia.

Some jurisdictions permit on-farm emergency slaughter (OFES) as one end-of-life option for dairy cows and other animals that cannot be transported humanely but are deemed fit for human consumption. Anecdotal reports suggest that OFES is controversial among dairy industry professionals, but to date their perceptions of OFES have not been studied systematically. Twenty-five individual interviews and 3 focus groups with 40 dairy producers, veterinarians, and other professionals in British Columbia, Canada, revealed positive and negative perceptions of OFES influenced by (1) individual values, (2) the perceived operational legitimacy of OFES, and (3) concern over social responsibility and public perception of the dairy industry. Study participants valued cow welfare but were divided on whether OFES quickened or delayed death for injured animals. Views on the operational legitimacy of OFES varied because of different perceptions and concerns regarding regulatory, veterinary, and meat inspector oversight, a possible conflict of interest for veterinarians, and concerns over carcass hygiene and transport. Whereas many appreciated that OFES prevented transport of compromised cows, others saw OFES as merely a stopgap measure. Seven recommended actions could address concerns while retaining the benefits of OFES: (1) specifying precise timing parameters for OFES, (2) clarification of allowable cow conditions for OFES, (3) consultation with dairy industry professionals if OFES is to be expanded, (4) more proactive culling and the development of euthanasia protocols on farms, (5) the designation of veterinarians as the first point of contact in the OFES process, (6) veterinarian training on animal inspection and allowable conditions for OFES, and (7) the use of proper procedures and equipment during the OFES process to ensure food safety.