Fractures in Thoroughbred racing and the potential for pre-race identification of horses at risk.

Risk rates for and predisposing factors to fractures occurring in Thoroughbred racing that have been published in peer reviewed journals are documented. The potential for currently available techniques to identify horses at increased risk for fracture is discussed on the bases of principles, practicalities, advantages, disadvantages and current data. All are reviewed in light of justifiable decision making and importance of fractures to horseracing's social license.

Arthroscopically guided lag screw fixation of subchondral bone cysts in the medial femoral condyle in Thoroughbred racehorses: description of technique and comparative results.

OBJECTIVE: To describe an arthroscopically guided technique for lag screw placement across subchondral bone cyst (SBC) in the medial femoral condyle (MFC) and to compare postoperative racing performance with corticosteroid injection and cyst debridement. STUDY DESIGN: Retrospective cohort study. ANIMALS: One hundred twenty-three horses with 134 MFC SBCs undergoing treatment at a single referral hospital in the UK between January, 2009, and December, 2020. METHODS: Sex, age, limb affected, radiographic cyst dimensions, preoperative and postoperative lameness, surgical technique (lag screw placement, cyst debridement, intralesional corticosteroid injection), and, where applicable, screw positioning were recorded retrospectively. A ratio was calculated using measurements from preoperative and postoperative radiographs. Outcome was assessed by resolution or improvement in lameness, reduction in cyst size, and starting one race after treatment. Outcome data was compared between treatment groups. RESULTS: Twenty-six of 45 (57.8%) horses that underwent transcondylar screw placement raced postoperatively, at a median of 403 days between surgery and first postoperative race. There was no difference between treatment groups with regard to racing or preoperative and postoperative lameness. Cysts treated with transcondylar screw placement had a greater reduction in cyst size and a reduced period of convalescence in comparison with those that underwent debridement; the results were similar to those treated by intralesional corticosteroid injection. CONCLUSION: Postoperative racing rates were similar for all techniques. Convalescence was reduced for lag screw placement and corticosteroid injection compared to debridement. CLINICAL SIGNIFICANCE: The arthroscopically guided technique results in radiographically consistent screw placement and cyst engagement and offers a viable alternative to other treatments.

Characterization of Virulence-Associated Traits in Mycoplasma penetrans Strains Acting as Likely Etiological Agents of Idiopathic Nongonococcal Urethritis.

Mycoplasma penetrans is an emerging pathogen with a reduced genome. This bacterium has only previously been cultured from individuals with chronic immunodeficiencies. Here we report the characteristics of 4 M. penetrans isolates from the urine of immunocompetent males with nongonococcal urethritis, in comparison with strain HF-2 from an immunocompromised patient. Several features exhibited distinct differences between these isolates and HF-2. Unlike HF-2, all 4 were resistant to azithromycin. They exhibited greater sialic acid-dependent binding to erythrocytes, gliding motility speed, and H2O2 production than HF-2. All new isolates produced thinner capsules than HF-2. Invasiveness varied, with some isolates being more invasive than HF-2 and some less invasive. Cytotoxicity to HeLa cells was similar to HF-2, and all strains could clear extracellular traps produced by innate immune cells. We conclude that subtle differences among M. penetrans strains may be critical for this organism to establish an infection in an otherwise healthy individual.

Predicting return to racing after repair of fractures of the metacarpal/metatarsal condyles in Thoroughbred racehorses.

OBJECTIVE: To identify prognostic factors for return to racing after lag screw repair of condylar fractures and develop a predictive model for return to racing. STUDY DESIGN: Retrospective cohort study. ANIMALS: A total of 356 horses referred to a single referral hospital in the UK with a third metacarpal/metatarsal condylar fracture between January 1999 and December 2018. METHODS: Age, sex, fracture site, fracture characteristics, surgery related variables and complications were retrieved from case records. Data were divided into two sets for model training and model validation. Univariable analyses were performed, and predictors were selected in a stepwise fashion for inclusion in the multivariable logistic regression model. Sensitivity and specificity were evaluated using the second dataset. RESULTS: Older horses, fillies, fractures of forelimbs, complex, complete, displaced or propagating fractures and concurrent proximal sesamoid bone fracture were negatively associated with return to racing. Colts and geldings were 3 and 4 times more likely to race than fillies, respectively. Horses with hindlimb, incomplete or nonpropagating fractures were 4, 5 and 4 times more likely to race than those with a forelimb, complete or propagating fracture, respectively. Using a predicted probability cut-off threshold of 0.5, a predictive model was created within one dataset (sensitivity = 84%, specificity = 50.5%) and applied to another (sensitivity = 83.1%, specificity = 24.0%). CONCLUSION: Negative prognostic factors were identified and led to a predictive model with acceptable sensitivity and specificity in the tested population. CLINICAL SIGNIFICANCE: The results provide proof of concept for the model in the reported population and justify further validation in different populations of horses.

Biallelic SYNE2 Missense Mutations Leading to Nesprin-2 Giant Hypo-Expression Are Associated with Intellectual Disability and Autism.

Autism spectrum disorder (ASD) is a group of neurological and developmental disabilities characterised by clinical and genetic heterogeneity. The current study aimed to expand ASD genotyping by investigating potential associations with SYNE2 mutations. Specifically, the disease-causing variants of SYNE2 in 410 trios manifesting neurodevelopmental disorders using whole-exome sequencing were explored. The consequences of the identified variants were studied at the transcript level using quantitative polymerase chain reaction (qPCR). For validation, immunofluorescence and immunoblotting were performed to analyse mutational effects at the protein level. The compound heterozygous variants of SYNE2 (NM_182914.3:c.2483T>G; p.(Val828Gly) and NM_182914.3:c.2362G>A; p.(Glu788Lys)) were identified in a 4.5-year-old male, clinically diagnosed with autism spectrum disorder, developmental delay and intellectual disability. Both variants reside within the nesprin-2 giant spectrin repeat (SR5) domain and are predicted to be highly damaging using in silico tools. Specifically, a significant reduction of nesprin-2 giant protein levels is revealed in patient cells. SYNE2 transcription and the nuclear envelope localisation of the mutant proteins was however unaffected as compared to parental control cells. Collectively, these data provide novel insights into the cardinal role of the nesprin-2 giant in neurodevelopment and suggest that the biallelic hypomorphic SYNE2 mutations may be a new cause of intellectual disability and ASD.

Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro.

Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment. Current epidermal models fail to consider the effects of culturing keratinocytes on plastic prior to setting up three-dimensional cultures, so the impact of this non-physiological exposure on epidermal assembly is largely overlooked. In this study, primary keratinocytes cultured on plastic were compared with those grown on 4, 8, and 50 kPa stiff biomimetic hydrogels that have similar mechanical properties to skin. Our data show that keratinocytes cultured on biomimetic hydrogels exhibited major changes in cellular architecture, cell density, nuclear biomechanics, and mechanoprotein expression, such as specific Linker of Nucleoskeleton and Cytoskeleton (LINC) complex constituents. Mechanical conditioning of keratinocytes on 50 kPa biomimetic hydrogels improved the thickness and organisation of 3D epidermal models. In summary, the current study demonstrates that the effects of extracellular mechanics on keratinocyte cell biology are significant and therefore should be harnessed in skin research to ensure the successful production of physiologically relevant skin models.

Beyond question wording: How survey design and administration shape estimates of disability.

BACKGROUND: Between 2008 and 2014, annual estimates of disability prevalence among U.S. adults varied somewhat across federal surveys that use a standardized measure of disability, but trends over-time were relatively stable and consistent. In 2014, however, estimates of disability from the Survey of Income and Program Participation (SIPP) increased markedly relative to previous years and were much higher than disability estimates from other federal surveys. OBJECTIVE: To examine why disability prevalence among adults aged 40 and older substantially increased in the first wave of the 2014 SIPP Panel. METHODS: We consider three factors that may have contributed to the rise in disability: data processing, context effects linked to question order, and sampling. To do so, we compare estimates with and without survey weights and imputed data, analyze supplemental disability-related data collected among SIPP participants, and employ decomposition analysis to assess what proportion of the increase in disability can be attributed to changes in sample composition. RESULTS: We find evidence that differences in sample composition contributed to the observed rise in disability prevalence in SIPP between 2011 and 2014. There is less evidence that weighting and imputation or context effects played a role. CONCLUSIONS: Previous studies emphasize differences in operationalization and conceptualization of disability as the major factor driving discrepancies in disability estimates. This study suggests that other factors related to survey design and administration may influence disability measurement. Such aspects of surveys, like question order and sampling, may be difficult to standardize, leading to meaningful cross-survey differences in disability estimates.

Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core.

The Mediator complex plays an essential and multi-faceted role in regulation of RNA polymerase II transcription in all eukaryotes. Structural analysis of yeast Mediator has provided an understanding of the conserved core of the complex and its interaction with RNA polymerase II but failed to reveal the structure of the Tail module that contains most subunits targeted by activators and repressors. Here we present a molecular model of mammalian (Mus musculus) Mediator, derived from a 4.0 Å resolution cryo-EM map of the complex. The mammalian Mediator structure reveals that the previously unresolved Tail module, which includes a number of metazoan specific subunits, interacts extensively with core Mediator and has the potential to influence its conformation and interactions.

A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers.

While Mediator plays a key role in eukaryotic transcription, little is known about its mechanism of action. This study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-EM) to dissect the function and structure of mammalian Mediator (mMED). Deletion analyses in B, T, and embryonic stem cells (ESC) identified a core of essential subunits required for Pol II recruitment genome-wide. Conversely, loss of non-essential subunits mostly affects promoters linked to multiple enhancers. Contrary to current models, however, mMED and Pol II are dispensable to physically tether regulatory DNA, a topological activity requiring architectural proteins. Cryo-EM analysis revealed a conserved core, with non-essential subunits increasing structural complexity of the tail module, a primary transcription factor target. Changes in tail structure markedly increase Pol II and kinase module interactions. We propose that Mediator's structural pliability enables it to integrate and transmit regulatory signals and act as a functional, rather than an architectural bridge, between promoters and enhancers.

Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial.

BACKGROUND: Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone. METHODS: In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA1c) concentration of 7·5% or higher (≥58 mmol/mol) and 11% or lower (≤97 mmol/mol), and had been using the same insulin regimen for the previous 3 months. Exclusion criteria included body-mass index of 45 kg/m2 or higher; severe cardiac, hepatic, or renal impairment; and more than two severe hypoglycaemic events in the past year. Eligible participants were randomly assigned (1:1), with randomisation blocked within each site, to either d-Nav and health-care professional support (intervention group) or health-care professional support alone (control group). Both groups were contacted seven times (three face-to-face and four phone visits) during 6 months of follow-up. The primary objective was to compare average change in HbA1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycaemic events. The primary objective and safety were assessed in the intention-to-treat population. We used Student's t test to assess the primary outcome for statistical significance. This study was registered with ClinicalTrials.gov, number NCT02424500. FINDINGS: Between Feb 2, 2015, and March 17, 2017, 236 patients were screened for eligibility, of whom 181 (77%) were enrolled and randomly assigned to the intervention (n=93) and control (n=88) groups. At baseline, mean HbA1c was 8·7% (SD 0·8; 72 mmol/mol [SD 8·8]) in the intervention group and 8·5% (SD 0·8; 69 mmol/mol [SD 8·8]) in the control group. The mean decrease in HbA1c from baseline to 6 months was 1·0% (SD 1·0; 11 mmol/mol [SD 11]) in the intervention group, and 0·3% (SD 0·9; 3·3 mmol/mol [9·9]) in the control group (p<0·0001). The frequency of hypoglycaemic events per month was similar between the groups (0·29 events per month [SD 0·48] in the intervention group vs 0·29 [SD 1·12] in the control group; p=0·96). INTERPRETATION: The combination of automated insulin titration guidance with support from health-care professionals offers superior glycaemic control compared with support from health-care professionals alone. Such a solution facilitated safe and effective insulin titration in a large group of patients with type 2 diabetes, and now needs to be evaluated across large health-care systems to confirm these findings and study cost-effectiveness. FUNDING: US National Institutes of Health, National Institute of Digestive and Kidney Diseases.

Baseline Knowledge of Potential Pet Toxins among the US General Public.

In 2014, the American Society for the Prevention of Cruelty toAnimals Animal Poison Control Center fielded more than 167,000cases of potential nonhuman animal toxicosis. Concomitantly, thereremain limited free and reputable veterinary toxicology resourcesavailable for companion-animal (pet) caregivers (owners) seekingassistance and advice about potentially harmful exposures inanimals. The objective of this study was to assess pet toxicantknowledge among a representative sample of Americans andgauge the need for additional toxicology resources. The studyinvolved a survey designed to capture participants' ability to identifypotential animal toxicants and what resource they would use ifan accidental toxic ingestion occurred. Participants were ableto correctly identify 52% of potential pet toxins. Women, olderparticipants and participants from the South expressed moreconcern about each potential pet poison. Approximately halfof participants indicated they would consult a veterinarian andwhereas most others indicated they would search the Internet formore information about pet toxicology. The findings suggest moreveterinary poisoning education is needed for pet owners to be ableto accurately distinguish potential pet toxicants from nontoxicants.

Pharmacists' Knowledge of Veterinary Pharmacotherapy and the Impact of an Educational Intervention.

Background: To date, there is very limited data regarding pharmacists' preparedness to handle animal prescriptions. No previous studies exist examining the impact of a veterinary-pharmacy-focused educational intervention. Objective: To assess pharmacists' baseline knowledge of veterinary pharmacotherapy, as relevant to their professional responsibilities, and assess the impact of a piloted educational program. Methods: Two studies were conducted. The first study involved a statewide assessment of pharmacists' knowledge of veterinary pharmacotherapy; the second study assessed the impact of an educational intervention to improve pharmacists' veterinary pharmacotherapy knowledge base. Participants in the pilot study were assessed via pretest and posttest. Results: The statewide sample of participants (n = 602) received a mean score of 5.9 (SD = 2.6) on a 17-item questionnaire. There were no discernible differences in participants' knowledge based on the subject matter of the question (pathophysiology, dosing, counseling, compounding, legality, and toxicology). Using the same 17-item questionnaire, pilot study participants (n = 60) received a mean score of 5.2 (SD = 2.4) on the pretest and 16.6 (SD = 0.7) on the posttest. Conclusion: The findings of this study suggest that a substantial portion of pharmacists lack the knowledge needed to process and dispense the veterinary prescriptions most commonly encountered in community pharmacies. Furthermore, this study shows that implementation of an educational intervention can increase pharmacists' knowledge of core concepts necessary to safely care for animal patients.

Baseline knowledge of potential pet toxins: a survey of pharmacists

Background: Consumer expenditures on their family pets are rapidly increasing, part of which can be attributed to prescription and OTC medications. In turn, community pharmacies are seeking and receiving an increased number of prescriptions for animals. Community pharmacists’ ability to safely care for animal patients is relatively unexplored. Human medications, their normal dosing and even medication excipients could be lethal in some animal patients. Objective: The overarching objective of this study was to assess pharmacists’ baseline knowledge of potential pet poisons. Methods: The sample consisted of licensed pharmacists registered with the North Carolina Board of Pharmacy. The Pet Toxins Survey (PTS), a survey consisting of 25 potential pet toxins, was administered during October and November 2015. Analyses consisted of calculating descriptive statics (including graphical summaries to test for normality), and inferential statistics (two-tailed t-tests and ANOVAs) to compare responses across demographic variables. Results: A 6.3% response rate was obtained. After selecting either a dog or a cat to establish a frame of reference, participants in this study were able to correctly identify 15 of the 25 listed items as toxic to a pet (60% accuracy). Participants did not express adequate concern for the ingestion of several potential toxins. This includes potential excipients found in medication formulations such as xylitol, tea tree oil and caffeine. Female participants and those age 50 years and older were more likely to indicate concern for each potential toxin. There was no significant difference observed in responses based on the pharmacists’ work setting. Conclusions: The findings of this investigation suggest that pharmacists are deficient in their understanding of veterinary toxicology. Given the rise of community pharmacists caring for animal patients, it’s paramount that pharmacists be able to confidently distinguish potential pet toxins from non-toxins. It is also important that pharmacists receive a better understanding of what exposures require immediate action and what action should be taken (AU)

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Baseline knowledge of potential pet toxins: a survey of pharmacists.

BACKGROUND: Consumer expenditures on their family pets are rapidly increasing, part of which can be attributed to prescription and OTC medications. In turn, community pharmacies are seeking and receiving an increased number of prescriptions for animals. Community pharmacists' ability to safely care for animal patients is relatively unexplored. Human medications, their normal dosing and even medication excipients could be lethal in some animal patients. OBJECTIVE: The overarching objective of this study was to assess pharmacists' baseline knowledge of potential pet poisons. METHODS: The sample consisted of licensed pharmacists registered with the North Carolina Board of Pharmacy. The Pet Toxins Survey (PTS), a survey consisting of 25 potential pet toxins, was administered during October and November 2015. Analyses consisted of calculating descriptive statics (including graphical summaries to test for normality), and inferential statistics (two-tailed t-tests and ANOVAs) to compare responses across demographic variables. RESULTS: A 6.3% response rate was obtained. After selecting either a dog or a cat to establish a frame of reference, participants in this study were able to correctly identify 15 of the 25 listed items as toxic to a pet (60% accuracy). Participants did not express adequate concern for the ingestion of several potential toxins. This includes potential excipients found in medication formulations such as xylitol, tea tree oil and caffeine. Female participants and those age 50 years and older were more likely to indicate concern for each potential toxin. There was no significant difference observed in responses based on the pharmacists' work setting. CONCLUSIONS: The findings of this investigation suggest that pharmacists are deficient in their understanding of veterinary toxicology. Given the rise of community pharmacists caring for animal patients, it's paramount that pharmacists be able to confidently distinguish potential pet toxins from non-toxins. It is also important that pharmacists receive a better understanding of what exposures require immediate action and what action should be taken.

Epigenetic Control of Apolipoprotein E Expression Mediates Gender-Specific Hematopoietic Regulation.

Epigenetic alterations play a central role in the control of normal and malignant blood cell development. We demonstrate here that expression of a truncated DNA methyltransferase 3B isoform DNMT3B7, which has been shown to alter cellular epigenetic patterns, decreases the overall number of hematopoietic stem and progenitor cells (HSPCs), and markedly diminishes blood cell reconstitution within the female hormonal microenvironment. Gene expression profiling of HSPCs isolated from DNMT3B7 transgenic embryos identified Apolipoprotein E (Apoe) as overexpressed. The CpG island controlling Apoe expression had lower levels of modified cytosines in DNMT3B7 transgenic HSPCs, corresponding with the observed increase in gene expression. Furthermore, we observed that spleens and bone marrows of female mice transplanted with DNMT3B7 transgenic HSPCs express very high levels of Apoe. Finally, the introduction of Apoe-overexpressing HSPCs into male recipients decreased bone marrow engraftment, recapitulating our original observations in female recipients. Our work reveals a dynamic interplay between the intrinsic epigenetic changes in HSPCs and extrinsic endocrine factors acting on these cells to regulate the efficiency of HSPC engraftment and reconstitution. We have identified a novel mechanism by which gender-specific hormones modulate HSPC function, which could serve as a target for augmenting hematopoiesis in cases with limited HSC functionality.

Many women undergoing fertility treatment make poor lifestyle choices that may affect treatment outcome.

STUDY QUESTION: What are the lifestyle choices and dietary aspects of women about to undergo fertility treatment in New Zealand? SUMMARY ANSWER: A considerable proportion of women about to undergo fertility treatment make poor lifestyle choices, including the consumption of alcohol and caffeine. WHAT IS KNOWN ALREADY: Women undergoing fertility treatment are highly motivated to achieve pregnancy, but there are relatively few published data on their lifestyle, lifestyle changes or dietary aspects. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of 250 women aged 20-43 years, taking place between March 2010 and August 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women about to undergo IVF or ICSI treatment in two large fertility clinics in Auckland and Hamilton, New Zealand. Lifestyle and dietary intake questionnaires were individually administered once to each participant 35 days (SD = 22) prior to fertility treatment initiation. Outcome measures included incidence of smoking, consumption of alcohol and caffeinated beverages, BMI, detailed intake of dietary supplements and fertility treatment success. Consumption of certain nutrient supplements was compared with the general female New Zealand population. MAIN RESULTS AND THE ROLE OF CHANCE: There were high rates of alcohol (50.8%) and caffeine (86.8%) consumption. Most women (82.8%) reported at least one lifestyle change in preparation for fertility treatment, but less than half of women who consumed alcohol regularly reduced their intake and 60% did not change consumption of caffeinated beverages. Similarly, the majority of women did not change their exercise levels (64.4%) or BMI (83.6%) ahead of fertility treatment. Coffee intake appeared unrelated to treatment outcome, but women who consumed caffeinated herbal tea (36.4% of the study population consumed green tea) had lower odds of becoming pregnant (odds ratio, OR 0.52; P = 0.041 versus those not consuming caffeinated herbal tea). Women who abstained from drinking or reduced alcohol intake had twice the odds of becoming pregnant than those who maintained their drinking habits prior to fertility treatment (OR 2.27; P = 0.049). While 93.2% of women took a folic acid supplement, 16.8% had an inadequate intake compared with the current New Zealand prenatal recommendation of 800 mcg/day. Women who held a university degree or higher qualification had twice the odds of becoming pregnant as women with lower levels of education (OR 2.08; P = 0.017), though this finding appeared to be unrelated to lifestyle or dietary habits. LIMITATIONS, REASONS FOR CAUTION: The study involved self-reported behaviours that might have been misrepresented by respondents. In addition, our questionnaires covered the period following the first clinical assessment but ∼5 weeks prior to fertility treatment initiation, so that we cannot ascertain whether dietary intakes and lifestyle choices persisted over the course of treatment itself. WIDER IMPLICATIONS OF THE FINDINGS: Many women about to undergo fertility treatment make poor lifestyle choices that may negatively affect their chances of becoming pregnant. These findings may be more widely applicable to other women attempting to become pregnant. Specific advice for women regarding healthy lifestyle choices while undergoing fertility treatment is warranted. STUDY FUNDING/COMPETING INTERESTS: A.A.G. received financial support from Abbott Nutrition Research & Development Asia-Pacific Center; J.C.P. is a shareholder of Fertility Associates; the other authors have no financial or non-financial conflicts of interest to disclose.

Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification.

An inpatient treatment and discharge planning protocol for alcohol dependence: efficacy in reducing 30-day readmissions and emergency department visits.

BACKGROUND: Alcohol dependence results in multiple hospital readmissions, but no discharge planning protocol has been studied to improve outcomes. The inpatient setting is a frequently missed opportunity to discuss treatment of alcohol dependence and initiate medication-assisted treatment, which is effective yet rarely utilized. AIM: Our aim was to implement and evaluate a discharge planning protocol for patients admitted with alcohol dependence. SETTING: The study took place at the San Francisco General Hospital (SFGH), a university-affiliated, large urban county hospital. PARTICIPANTS: Learner participants included Internal Medicine residents at the University of California, San Francisco (UCSF) who staff the teaching service at SFGH. Patient participants included inpatients with alcohol dependence admitted to the Internal Medicine teaching service. PROGRAM DESCRIPTION: We developed and implemented a discharge planning protocol for patients admitted with alcohol dependence that included eligibility assessment and initiation of medication-assisted treatment. PROGRAM EVALUATION: Rates of medication-assisted treatment increased from 0% to 64% (p value < 0.001). All-cause 30-day readmission rates to SFGH decreased from 23.4% to 8.2% (p value = 0.042). All-cause emergency department visits to SFGH within 30 days of discharge decreased from 18.8% to 6.1% (p value = 0.056). DISCUSSION: Through implementation of a discharge planning protocol by Internal Medicine residents for patients admitted with alcohol dependence, there was a statistically significant increase in medication-assisted treatment and a statistically significant decrease in both 30-day readmission rates and emergency department visits.

The pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets, and syrups in african HIV-infected children.

BACKGROUND: Guidelines recommend lopinavir/ritonavir (LPV/r) as first- and second-line therapy for young and older HIV-infected children, respectively. Available formulations have limitations making their widespread use complex. METHODS: An open-label comparative bioavailability (randomized crossover) study compared a novel twice-daily minitab sprinkle formulation (40 mg/10 mg, Cipla Pharmaceuticals) versus innovator syrup in HIV-infected Ugandan infants aged 3 to <12 months (cohort A) and children aged 1-4 years (cohort B) and versus Cipla tablets (100/25 mg) in children aged 4 to <13 years (cohort C). Twelve-hour intensive pharmacokinetic sampling after observed LPV/r intake (plus 2 nucleoside reverse transcriptase inhibitors) following World Health Organization 2010 dosing with food was performed 4 weeks after enrollment. Children then switched formulation; sampling was repeated at week 8. Acceptability data were also collected. RESULTS: Seventy-seven infants/children were included in cohort A (n = 19)/B (n = 26)/C (n = 32). Among 132 evaluable pharmacokinetic profiles, there were 13/21/25 within-child comparisons in cohort A/B/C. For minitabs versus syrup, geometric mean [95% confidence interval (CI)] AUC0-12h was 88.6 (66.7-117.6) versus 77.6 (49.5-121.5) h·mg/L in cohort A [geometric mean ratio (GMR) (90% CI) = 1.14 (0.71 to 1.85)] and 138.7 (118.2 to 162.6) versus 109.1 (93.7 to 127.1) h·mg/L in cohort B [GMR (90% CI) = 1.27 (1.10 to 1.46)]. For minitabs versus tablets, geometric mean (95% CI) AUC0-12h was 83.1 (66.7 to 103.5) versus 115.6 (103.0 to 129.7) h·mg/L; GMR (90% CI) = 0.72 (0.60 to 0.86). Subtherapeutic levels (<1.0 mg/L) occurred in 0 (0%)/2 (15%) minitabs/syrup in infants (P = 0.48), no children aged 1-4 years and 4 (16%)/1 (4%) minitabs/tablets (P = 0.35). About 13/17 (76%) and 19/26 (73%) caregivers of infants and children aged 1-4 years, respectively, chose to continue minitabs after week 8, mainly for convenience; only 7/29 (24%) older children (five <6 years) remained on minitabs. CONCLUSIONS: LPV/r exposure from minitabs was comparable with syrup, but lower than tablets, with no significant differences in subtherapeutic concentrations. Minitabs were more acceptable than syrups for younger children, but older children preferred tablets.