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Summary: Healthcare associated infections (HCAI) are a prevalent preventable cause of morbidity and mortality. Improving hand hygiene adherence is important for HCAI prevention. In this feasibility study, the objective was to determine if a humanoid robot could act as a novel single reminder intervention to improve hand hygiene adherence in a hospital setting. DAVE, a social humanoid robot, improved hand hygiene adherence at the entrance to a tertiary hospital and outpatient department, which was low at baseline, by 29%. DAVE shows promise as a novel intervention to improve hand hygiene adherence.

Turf toe is often described as an athletic injury commonly affecting football players on artificial turf. However, any trauma resulting in hyperextension of the first metatarsophalangeal joint (MTP) can disrupt the plantar capsular structures. Left untreated these injuries can result in prolonged pain and dysfunction of the foot. There is a paucity of literature discussing the surgical treatment of grade III turf toe injuries in the professional athletic population and at the community level. This case presents the diagnosis, surgical technique, and rehabilitation of a patient with a grade III turf toe injury after a traumatic hyperextension injury. This report illustrates the novel two incision technique with suture button fixation for a grade III turf toe injury.

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.

Small-molecule BET bromodomain inhibitors (BETis) are actively being pursued in clinical trials for the treatment of a variety of cancers, but the mechanisms of resistance to BETis remain poorly understood. Using a mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BETi treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi JQ1. Through application of multiplexed inhibitor beads (MIBs) and mass spectrometry, we demonstrate that BETi resistance is mediated by adaptive kinome reprogramming, where activation of compensatory pro-survival kinase networks overcomes BET protein inhibition. Furthermore, drug combinations blocking these kinases may prevent or delay the development of drug resistance and enhance the efficacy of BETi therapy.

Complement activation plays a critical role in controlling inflammatory responses. To assess the role of complement during ovarian cancer progression, we crossed two strains of mice with genetic complement deficiencies with transgenic mice that develop epithelial ovarian cancer (TgMISIIR-TAg). TgMISIIR-TAg mice fully or partially deficient for complement factor 3 (C3) (Tg+C3KO and Tg+C3HET, respectively) or fully deficient for complement factor C5a receptor (C5aR) (Tg+C5aRKO) develop either no ovarian tumors or tumors that were small and poorly vascularized compared to wild-type littermates (Tg+C3WT, Tg+C5aRWT). The percentage of tumor infiltrating immune cells in Tg+C3HET tumors compared to Tg+C3WT controls was either similar (macrophages, B cells, myeloid-derived suppressor cells), elevated (effector T cells), or decreased (regulatory T cells). Regardless of these ratios, cytokine production by immune cells taken from Tg+C3HET tumors was reduced on stimulation compared to Tg+C3WT controls. Interestingly, CD31+ endothelial cell (EC) function in angiogenesis was significantly impaired in both C3KO and C5aRKO mice. Further, using the C5aR antagonist PMX53, tube formation of ECs was shown to be C5a-dependent, possibly through interactions with the VEGF165 but not VEGF121 isoform. Finally, the mouse VEGF164 transcript was underexpressed in C3KO livers compare to C3WT livers. Thus, we conclude that complement inhibition blocks tumor outgrowth by altering EC function and VEGF165 expression.

Most patients with epithelial ovarian cancer (EOC) experience drug-resistant disease recurrence. Identification of new treatments is a high priority, and preclinical studies in mouse models of EOC may expedite this goal. We previously developed methods for magnetic resonance imaging (MRI) for tumor detection and quantification in a transgenic mouse model of EOC. The goal of this study was to determine whether three-dimensional (3D) fluorescence molecular tomography (FMT) and fluorescent molecular imaging probes could be effectively used for in vivo detection of ovarian tumors and response to therapy. Ovarian tumor-bearing TgMISIIR-TAg mice injected with fluorescent probes were subjected to MRI and FMT. Tumor-specific probe retention was identified in vivo by alignment of the 3D data sets, confirmed by ex vivo fluorescent imaging and correlated with histopathologic findings. Mice were treated with standard chemotherapy, and changes in fluorescent probe binding were detected by MRI and FMT. Ovarian tumors were detected using probes specific for cathepsin proteases, matrix metalloproteinases (MMPs), and integrin αvβ3. Cathepsin and integrin αvβ3 probe activation and retention correlated strongly with tumor volume. MMP probe activation was readily detected in tumors but correlated less strongly with tumor volume. Tumor regression associated with response to therapy was detected and quantified by serial MRI and FMT. These results demonstrate the feasibility and sensitivity of FMT for detection and quantification of tumor-associated biologic targets in ovarian tumors and support the translational utility of molecular imaging to assess functional response to therapy in mouse models of EOC.

Our goal was to further define the role of LPL gene polymorphisms in coronary heart disease (CHD) risk. We determined the frequencies of three LPL polymorphisms (D9N, N291S, and S447X) in 899 men from the Veterans Affairs HDL Intervention Trial (VA-HIT), a study that examined the potential benefits of increasing HDL with gemfibrozil in men with established CHD and low high density lipoprotein cholesterol (HDL-C; ≤40 mg/dl), and compared them with those of men without CHD from the Framingham Offspring Study (FOS). In VA-HIT, genotype frequencies for LPL D9N, N291S, and S447X were 5.3, 4.5, and 13.0%, respectively. These values differed from those for men in FOS having an HDL-C of >40, who had corresponding values of 3.2% (P = 0.06), 1.5% (P < 0.01), and 18.2% (P < 0.01). On gemfibrozil, carriers of the LPL N9 allele in VA-HIT had lower levels of large LDL (−32%; P < 0.01) but higher levels of small, dense LDL (+59%; P < 0.003) than did noncarriers. Consequently, mean LDL particle diameter was smaller in LPL N9 carriers than in noncarriers (20.14 ± 0.87 vs. 20.63 ± 0.80 nm; P < 0.003).In men with low HDL-C and CHD: 1) the LPL N9 and S291 alleles are more frequent than in CHD-free men with normal HDL-C, whereas the X447 allele is less frequent, and 2) the LPL N9 allele is associated with the LDL subclass response to gemfibrozil.

Previous studies have demonstrated frequent allelic losses of distal chromosome 11q in ovarian carcinomas. The tumor suppressor gene(s) presumably targeted by these losses have not yet been identified. PPP2R1B is a candidate tumor suppressor gene at 11q23 that has recently been shown to be mutated in a subset of colorectal and lung cancers. We evaluated 5 ovarian carcinoma cell lines and 27 primary ovarian carcinomas for allelic losses of 11q23 and for mutations in the open reading frame of PPP2R1B. We also evaluated the primary tumors for allelic losses at 17p13, another chromosomal region frequently affected by losses of heterozygosity (LOH) in ovarian cancers. 11q23 and 17p13 allelic losses were identified in 25% and 74% of the carcinomas, respectively. No mutations within PPP2R1Bcoding sequences were found. These findings indicate that mutations of the PPP2R1B gene are infrequent in ovarian cancer and that deletions affecting the distal portion of chromosome 11q in ovarian cancer likely target inactivation of other genes.

Introduction: With the implementation of low-dose computed tomography (LDCT) screening, multiple pulmonary tumor nodules (MPTN) are diagnosed with increasing frequency and the selection of surgical treatments versus systemic therapies has become challenging on a daily basis in clinical practice. In the presence of multiple carcinomas, especially adenocarcinomas, pathologically determined to be of pulmonary origin, the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is important for staging, management, and prognostication., Methods: We systemically reviewed various means that aid in the differentiation between SPLCs and IPMs explored by histopathologic evaluation and molecular profiling, the latter includes DNA microsatellite analysis, array comparative genomic hybridization, TP53 and oncogenic driver mutation testing and, more recently, with promising effectiveness, next-generation sequencing (NGS) comprising small- or large-scale multi-gene panels., Results: Comprehensive histologic evaluation may suffice to differentiate between SPLCs and IPMs. However, molecular profiling using larger-scale NGS typically provides superior discriminatory power, allowing for more accurate classification. Based on the literature review and expert opinions, we proposed a combined 4-step histologic and molecular classification algorithm for addressing MPTN of adenocarcinoma histology that encourages a multidisciplinary approach. It is also noteworthy that new technologies combining machine learning and digital pathology may develop into valuable diagnostic tools for distinguishing SPLCs from IPMs in the future., Conclusions: Although histopathologic evaluation is often adequate to differentiate SPLCs from IPMs, molecular profiling should be performed when possible, especially in cases with tumors exhibiting similar morphology. This manuscript summarized the previous efforts in resolving the current challenges and highlighted the recent progress in the differentiation methods and algorithms used in categorizing multiple lung adenocarcinomas into SPLCs or IPMs, which are becoming more and more critical in precision lung cancer management., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research., Methods: In this second phase of the initiative, metadata and screening CT scans from two time points were collected from 100 screening participants in seven countries. An automated deep learning AI lung segmentation algorithm, automated quantitative emphysema metrics, and a quantitative lung nodule volume measurement algorithm were run on these scans., Results: A total of 1394 CTs were collected from 697 participants. The LAV950 quantitative emphysema metric was found to be potentially useful in distinguishing lung cancer from benign cases using a combined slice thickness more than or equal to 2.5 mm. Lung nodule volume change measurements had better sensitivity and specificity for classifying malignant from benign lung nodules when applied to solid lung nodules from high-quality CT scans., Conclusions: These initial experiments revealed that ELIC can support deep learning AI and quantitative imaging analyses on diverse and globally distributed cloud-based data sets., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Low-dose computed tomography (LDCT) screening for lung cancer substantially reduces mortality from lung cancer, as revealed in randomized controlled trials and meta-analyses. This review is based on the ninth CT screening symposium of the International Association for the Study of Lung Cancer, which focuses on the major themes pertinent to the successful global implementation of LDCT screening and develops a strategy to further the implementation of lung cancer screening globally. These recommendations provide a 5-year roadmap to advance the implementation of LDCT screening globally, including the following: (1) establish universal screening program quality indicators; (2) establish evidence-based criteria to identify individuals who have never smoked but are at high-risk of developing lung cancer; (3) develop recommendations for incidentally detected lung nodule tracking and management protocols to complement programmatic lung cancer screening; (4) Integrate artificial intelligence and biomarkers to increase the prediction of malignancy in suspicious CT screen-detected lesions; and (5) standardize high-quality performance artificial intelligence protocols that lead to substantial reductions in costs, resource utilization and radiologist reporting time; (6) personalize CT screening intervals on the basis of an individual's lung cancer risk; (7) develop evidence to support clinical management and cost-effectiveness of other identified abnormalities on a lung cancer screening CT; (8) develop publicly accessible, easy-to-use geospatial tools to plan and monitor equitable access to screening services; and (9) establish a global shared education resource for lung cancer screening CT to ensure high-quality reading and reporting., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria., Methods: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion., Results: Unanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76-0.92) and 0.86 (95% CI: 0.79-0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96-1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89-0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma., Conclusions: Our study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The second leading cause of lung cancer is air pollution. Air pollution and smoking are synergistic. Air pollution can worsen lung cancer survival., Methods: The Early Detection and Screening Committee of the International Association for the Study of Lung Cancer formed a working group to better understand issues in air pollution and lung cancer. These included identification of air pollutants, their measurement, and proposed mechanisms of carcinogenesis. The burden of disease and the underlying epidemiologic evidence linking air pollution to lung cancer in individuals who never and ever smoked were summarized to quantify the problem, assess risk prediction models, and develop recommended actions., Results: The number of estimated attributable lung cancer deaths has increased by nearly 30% since 2007 as smoking has decreased and air pollution has increased. In 2013, the International Agency for Research on Cancer classified outdoor air pollution and particulate matter with aerodynamic diameter less than 2.5 microns in outdoor air pollution as carcinogenic to humans (International Agency for Research on Cancer group 1) and as a cause of lung cancer. Lung cancer risk models reviewed do not include air pollution. Estimation of cumulative exposure to air pollution exposure is complex which poses major challenges with accurately collecting long-term exposure to ambient air pollution for incorporation into risk prediction models in clinical practice., Conclusions: Worldwide air pollution levels vary widely, and the exposed populations also differ. Advocacy to lower sources of exposure is important. Health care can lower its environmental footprint, becoming more sustainable and resilient. The International Association for the Study of Lung Cancer community can engage broadly on this topic., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Immunotherapy including immune checkpoint inhibitors (ICIs) has become the backbone of treatment for most lung cancers with advanced or metastatic disease. In addition, they have increasingly been used for early stage tumors in neoadjuvant and adjuvant settings. Unfortunately, however, only a subset of patients experiences meaningful response to ICIs. Although programmed death-ligand 1 (PD-L1) protein expression by immunohistochemistry (IHC) has played a role as the principal predictive biomarker for immunotherapy, its performance may not be optimal, and it suffers multiple practical issues with different companion diagnostic assays approved. Similarly, tumor mutational burden (TMB) has multiple technical issues as a predictive biomarker for ICIs. Now, ongoing research on tumor- and host immune-specific factors has identified immunotherapy biomarkers that may provide better response and prognosis prediction, in particular in a multimodal approach. This review by the International Association for the Study of Lung Cancer Pathology Committee provides an overview of various immunotherapy biomarkers, including updated data on PD-L1 IHC and TMB, and assessments of neoantigens, genetic and epigenetic signatures, immune microenvironment by IHC and transcriptomics, and microbiome and pathologic response to neoadjuvant immunotherapies. The aim of this review is to underline the efficacy of new individual or combined predictive biomarkers beyond PD-L1 IHC and TMB., (Copyright © 2022 International Association for the Study of Lung Cancer. All rights reserved.)

This article was originally published under standard licence, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the paper have been modified accordingly.

Introduction: The impact of the Affordable Care Act (ACA) on the utilization of the emergency department (ED) for periapical abscess (PA) is unknown. The objectives of this study were to provide nationwide estimates of hospital-based ED visits with PA and to examine the effect of the ACA on the use of EDs for PAs., Methods: We performed a retrospective analysis of the Nationwide Emergency Department Sample (NEDS) for 2008 to 2014. All ED visits with a diagnosis of PA were selected. The International Classification of Diseases, Ninth Revision-Clinical Modification code was used to identify PA. Patient- and hospital-level characteristics were examined. Descriptive statistics were used to summarize the data., Results: From 2008 to 2014, a total of 3,505,633 ED visits for PA occurred. The proportion of ED visits with PA significantly increased over the study period (from 460,260 in 2008 to 545,693 in 2014). Medicaid was the primary payer (30.3%) and more than 40% were uninsured. Mean charge per PA-related ED visit was $1080.50 and total PA-related ED charge across the United States was $3.4 billion. Among those hospitalized following PA-related ED visits, mean hospitalization charges were $34,245 and total hospitalization charges were $5.7 billion., Conclusion: Oral health continues to be overlooked in health care. A large proportion of ED visits with PA were made by those covered by Medicaid and uninsured. The passing of the ACA has not reduced the number of ED visits with PA., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Human type-2 CD8 + T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8 + CRTH2 + (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D 2 (PGD 2 ) and cysteinyl leukotriene E 4 (LTE 4 ) are also increased in the airways of the same group of patients. In vitro PGD 2 and LTE 4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

Background: Breast cancer accounts for 7% of female cancer deaths, usually attributable to metastasis. While surgery is a mainstay of treatment, perioperative interventions may influence risk of metastasis during breast tumour resection. Amide local anaesthetics influence cancer cell biology via numerous mechanisms in vitro, but in vivo data is lacking. We aimed to test the hypothesis that perioperative lidocaine reduces pulmonary metastasis after inhalation and i.v. anaesthesia in the 4T1 murine breast cancer model., Methods: 4T1 Cancer cells were injected into the mammary fat-pad of immunocompetent BALB/c female mice. After 7 days, the resultant tumour was excised under either sevoflurane or ketamine/xylazine anaesthesia with or without perioperative i.v. lidocaine (1.5 mg kg -1 bolus followed by 25 min infusion 2 mg kg -1 h -1 ). Fourteen days post-surgery, posthumous lung and liver specimens were examined for metastasis. Pro-inflammatory and pro-metastatic cytokines were profiled in post-mortem serum from a small number of the mice., Results: Primary tumour diameter was similar between groups. Lidocaine reduced lung metastatic colony count vs sevoflurane alone; median (inter-quartile range) 0 (0-2) compared with 22.5 (0-481), P=0.02 and reduced the proportion of animals with pulmonary metastasis (28.5% compared with 52.5%, P=0.04). In mice receiving ketamine-xylazine, lidocaine did not decrease the overall colony count: 60 (26-123) compared with 23.5 (0-225), P=0.43, but increased the proportion of animals with pulmonary metastasis (100% compared with 50%, P<0.01). Post-mortem serum analysis demonstrated reduced pro-inflammatory and angiogenic cytokine expression in animals without metastasis which received lidocaine with sevoflurane., Conclusions: In this 4T1 murine model of breast cancer, lidocaine decreased pulmonary metastasis when combined with sevoflurane anaesthesia, perhaps via anti-inflammatory and anti-angiogenic effects. It had no such effect in mice given ketamine anaesthesia., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Intraoperative identification of pulmonary nodules, particularly small lesions, can be challenging. We hypothesize that folate receptor-targeted intraoperative molecular imagining can be safe and improve localization of pulmonary nodules during resection., Methods: Twenty subjects with biopsy-proven pulmonary adenocarcinomas were enrolled in a phase I clinical trial to test the safety and feasibility of OTL38, a novel folate receptor-α (FRα) targeted optical contrast agent. During resection, tumors were imaged in situ and ex vivo and fluorescence was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemistry was utilized to quantify FRα expression. A multivariate analysis using clinical and tumor data was performed to determine variables impacting tumor fluorescence., Results: Of the 20 subjects, three grade I adverse events were observed: all transient nausea/abdominal pain. All symptoms resolved after completing the infusion. Sixteen of 20 subjects (80%) had tumors with in situ fluorescence with a mean tumor-to-background fluorescence level of 2.9 (interquartile range, 2.1 to 4.2). The remaining 4 subjects' tumors fluoresced ex vivo. In situ fluorescence was dependent on depth from the pleural surface. Four subcentimeter nodules not identified on preoperative imaging were detected with intraoperative imaging., Conclusions: This phase I trial provides preliminary evidence suggesting that folate receptor-targeted molecular imaging with OTL38 is safe, with tolerable grade I toxicity. These data also suggest that OTL38 accumulates in known lung cancers and may improve identification of synchronous malignancies. Our group is initiating a five-center, phase II study to better understand the clinical implications of intraoperative molecular imaging using OTL38., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The increasing rate of e-prescribing is associated with a significant number of unclaimed prescriptions. The costs of unclaimed e-prescriptions could create an unwanted burden on community pharmacy practices. The objective of this study was to calculate the rate and costs of filled but unclaimed e-prescriptions at an independent pharmacy., Methods: This study was performed at a rural independent pharmacy in a Midwestern state. The rate and costs of the unclaimed e-prescriptions were determined by collecting information about all unclaimed e-prescriptions for a 6-month period from August 2013 to January 2014. The costs of unclaimed prescriptions included those expenses incurred to prepare the prescription, contact the patient, and return the unclaimed prescription to inventory. Two sensitivity analyses were conducted., Results: The total cost of 147 unclaimed e-prescriptions equaled $3,677.70 for the study period. Thus, the monthly cost of unclaimed e-prescriptions was $612.92 and the average cost of each unclaimed prescription was $25.02. The sensitivity analyses showed that using a technician to perform prescription return tasks reduced average costs to $19.33 and that using a state Medicaid cost of dispensing resulted in average costs of $18.54 per prescription. The rate of unclaimed e-prescriptions was 0.82%., Conclusion: The percentage of unclaimed e-prescriptions in this pharmacy was less than 1%. In addition to increased cost, unclaimed e-prescriptions add inefficiency to the work flow of the pharmacy staff, which can limit the time that they are available for performing revenue-generating activities. Adjustments to work flow and insurer policies could help to reduce the burden of unclaimed e-prescriptions., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The impact of anti-tuberculosis treatment with and without antiretroviral therapy (ART) on standardized interferon gamma release assay (IGRA) readouts has been studied inadequately in high-burden countries., Methods: The QuantiFERON-TB Gold In-Tube (QFT-GIT) test was used to evaluate interferon gamma (IFN-γ) responses longitudinally (0, 3, 6, and 12 months post initiation of tuberculosis (TB)-HIV co-treatment or ART alone) in 82 HIV-infected patients., Results: Of the 65 evaluable participants, 30 were co-infected on ART, 17 were co-infected but not on ART, and 18 were HIV-infected alone and on ART. In HIV-infected and HIV-TB-infected patients on ART, IFN-γ responses increased, whilst they decreased in those not on ART. However, baseline, month 3, and month 6 IFN-γ responses, irrespective of ART, did not differ in TB-HIV co-infected patients who culture-converted compared to those who did not (1.25 vs. 1.05, p=0.5 at baseline; 3.76 vs. 1.15, p=0.2 for month 3; 0.06 vs. 0.7, p=0.3 for month 6). IFN-γ levels did not correlate with the magnitude of sputum bacillary load, smear status, or liquid culture time-to-positivity., Conclusion: As IGRAs do not correlate with 2- or 6-month culture conversion or with markers of bacillary burden, they are unlikely to be useful for the prognostication of treatment outcome in co-infected patients., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The standard spinal preparation of bupivacaine contains a high concentration of glucose (80 mg ml(-1)). However, the addition of only a small amount of glucose (8 mg ml(-1)) to plain solutions of bupivacaine results in a solution which, although no more than marginally hyperbaric, produces a more predictable block when used for spinal anaesthesia in non-pregnant patients. However, bupivacaine 5 mg ml(-1) in glucose 8 mg ml(-1) has a density [1.00164 (SD 0.00008) at 37 degrees C] which is relatively greater than that of the cerebrospinal fluid (CSF) of the pregnant patient at term (1.0003 at 37 degrees C) because CSF density decreases during pregnancy. Therefore, a double-blind, randomized, controlled study was carried out to compare intrathecal bupivacaine (glucose 8 mg ml(-1)) with bupivacaine (glucose 80 mg ml(-1)) in 40 pregnant patients at term. Although there was no difference between groups in onset of sensory block, dose of ephedrine or patient satisfaction, patients receiving bupivacaine (5 mg ml(-1)) with glucose (8 mg ml(-1)) had persistently higher sensory blocks between 60 and 120 min after intrathecal injection, suggesting that the spread of spinal solutions in the pregnant patient at term is not dependent on density.

Two groups of 12 patients had a sciatic nerve block performed with 20 ml of either ropivacaine 7.5 mg ml(-1) or bupivacaine 5 mg ml(-1). There was no statistically significant difference in the mean time to onset of complete anaesthesia of the foot or to first request for post-operative analgesia. The quality of the block was the same in each group. Although there was no statistically significant difference in the mean time to peak plasma concentrations the mean peak concentration of ropivacaine was significantly higher than that of bupivacaine. There were no signs of systemic local anaesthetic toxicity in any patient in either group.

Aims: To investigate rates of dental caries and periodontal disease, available dental services and resources and perceived needs in a rural South African community., Design: A cross-sectional field study including situational analysis and focus group discussions., Setting: KwaZulu/Natal, South Africa., Participants: A total of 520 children, adolescents and adults., Methods: WHO caries scores and periodontal CPI score were determined through clinical examinations in five age groups, 5-6 years, 12 y, 15 y, 35-54 y, 55 y+. Focus groups included ten 15-year-old children and ten adults., Results: Caries prevalences and (mean scores) were 5-6 y 64% (dmft 3.0), 12 y 24% (DMFT 0.4), 15 y 27% (DMFT 0.8), 35-54 69% (DFT 2.6) and 55 y+ 80% (DFT 2.7). Most caries was untreated and where present, treatment had been extraction. Dental caries rates were low and except for 5-6 y were within WHO targets for the year 2000. Periodontal disease prevalence was high but would respond to improved oral hygiene. Knowledge of oral health was rudimentary., Conclusions: A district-wide oral health promotion programme is required preceded by research to define effective health education messages. Access to simple but effective preventive and curative services would seem reasonable. In view of the lack of resources ART is suggested as caries treatment.

Recent studies from our laboratory have shown that methyl palmoxirate (MEP), an inhibitor of mitochondrial beta-oxidation of long chain fatty acids, can be used to increase incorporation of radiolabeled palmitic acid into brain lipids and reduce beta-oxidation of the fatty acid. Thus, MEP allows the use of carbon labeled palmitate for studying brain lipid metabolism in animals and humans by quantitative autoradiography or positron emission tomography (PET). As it is essential to pretreat human subjects with an acute dose of MEP prior to intravenous injection of [1-11C]palmitate for PET scanning, this study was undertaken to determine the plasma elimination half-life of MEP in rats and human subjects and to provide insight about the drug's absorption and metabolism. A gas chromatographic method was developed to measure MEP in body fluids. Following oral administration of MEP to rats (2.5 and 10 mg/kg) and to humans, the unmetabolized drug could not be detected in plasma or urine (sensitivity of detection was 1 ng). However, when MEP was injected intravenously (10 mg/kg) in rats, a peak initial concentration could be measured in plasma (7.7 microg/mL), the clearance of the drug from plasma was rapid (t1/2 = 0.6 min), which indicates that MEP readily enters tissue lipid pools or is metabolized like long-chain fatty acids. As no adverse experience occured in the 11 human subjects studied, oral administration of a single dose of MEP was safe under the conditions of this study and may be used to increase the incorporation of positron labeled palmitic acid for studying brain lipid metabolism in vivo by PET.