Drug-Related Hospital Visits and Admissions Associated with Laboratory or Physiologic Abnormalities—A Systematic-Review

Countless studies have demonstrated that many emergency-room visits and hospital admissions are drug-related and that a significant proportion of these drug-related visits (DRVs) are preventable. It has not been previously studied which DRVs could be prevented through enhanced monitoring of therapy. The objective of the study was to determine the incidence of DRVs attributed to laboratory or physiologic abnormalities. Three authors independently performed comprehensive searches in relevant health care databases using pre-determined search terms. Articles discussing DRV associated with poisoning, substance abuse, or studied among existing in-patient populations were excluded. Study country, year, sample, design, duration, DRV identification method, proportion of DRVs associated with laboratory or physiologic abnormalities and associated medications were extracted. The three authors independently assessed selected relevant articles according to the Strengthening the reporting of observational studies in epidemiology (STROBE) as applicable according to the studies'' methodology. The initial literature search yielded a total of 1,524 articles of which 30 articles meeting inclusion criteria and reporting sufficient laboratory or physiologic data were included in the overall analysis. Half employed prospective methodologies, which included both chart review and patient interview; however, the overwhelming majority of identified studies assessed only adverse drug reactions (ADRs) as a drug-related cause for DRV. The mean (range) prevalence of DRVs found in all studies was 15.4% (0.44%–66.7%) of which an association with laboratory or physiologic abnormalities could be attributed to a mean (range) of 29.4% (4.3%–78.1%) of cases. Most laboratory-associated DRVs could be linked to immunosuppressant, antineoplastic, anticoagulant and diabetes therapy, while physiologic-associated DRVs were attributed to cardiovascular therapies and NSAIDs. Significant proportions of laboratory and physiologic abnormalities contribute to DRVs and are consistently linked to specific drugs. These therapies are potential targets for enhanced medication monitoring initiatives to proactively avert potential DRVs.     

Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.     

Biochar,Bentonite and Zeolite Supplemented Feeding of Layer Chickens Alters Intestinal Microbiota and Reduces Campylobacter Load

A range of feed supplements, including antibiotics, have been commonly used in poultry production to improve health and productivity. Alternative methods are needed to suppress pathogen loads and maintain productivity. As an alternative to antibiotics use, we investigated the ability of biochar, bentonite and zeolite as separate 4% feed additives, to selectively remove pathogens without reducing microbial richness and diversity in the gut. Neither biochar, bentonite nor zeolite made any significant alterations to the overall richness and diversity of intestinal bacterial community. However, reduction of some bacterial species, including some potential pathogens was detected. The microbiota of bentonite fed animals were lacking all members of the order Campylobacterales. Specifically, the following operational taxonomic units (OTUs) were absent: an OTU 100% identical to Campylobacter jejuni; an OTU 99% identical to Helicobacter pullorum; multiple Gallibacterium anatis (>97%) related OTUs; Bacteroides dorei (99%) and Clostridium aldenense (95%) related OTUs. Biochar and zeolite treatments had similar but milder effects compared to bentonite. Zeolite amended feed was also associated with significant reduction in the phylum Proteobacteria. All three additives showed potential for the control of major poultry zoonotic pathogens.     

PpASCL,the Physcomitrella patens Anther-Specific Chalcone Synthase-Like Enzyme Implicated in Sporopollenin Biosynthesis,Is Needed for Integrity of the Moss Spore Wall and Spore Viability

Sporopollenin is the main constituent of the exine layer of spore and pollen walls. The anther-specific chalcone synthase-like (ASCL) enzyme of Physcomitrella patens, PpASCL, has previously been implicated in the biosynthesis of sporopollenin, the main constituent of exine and perine, the two outermost layers of the moss spore cell wall. We made targeted knockouts of the corresponding gene, PpASCL, and phenotypically characterized ascl sporophytes and spores at different developmental stages. Ascl plants developed normally until late in sporophytic development, when the spores produced were structurally aberrant and inviable. The development of the ascl spore cell wall appeared to be arrested early in microspore development, resulting in small, collapsed spores with altered surface morphology. The typical stratification of the spore cell wall was absent with only an abnormal perine recognisable above an amorphous layer possibly representing remnants of compromised intine and/or exine. Equivalent resistance of the spore walls of ascl mutants and the control strain to acetolysis suggests the presence of chemically inert, defective sporopollenin in the mutants. Anatomical abnormalities of late-stage ascl sporophytes include a persistent large columella and an air space incompletely filled with spores. Our results indicate that the evolutionarily conserved PpASCL gene is needed for proper construction of the spore wall and for normal maturation and viability of moss spores.     

Stress‐induced peak (but not resting) metabolism correlates with mating display intensity in male guppies

Recent empirical and conceptual papers have highlighted the potential for metabolism to act as a proximate mechanism for behavior that could explain animal personality (consistency over time). Under this hypothesis, individuals with consistently high levels of behavioral activity should also have high resting metabolic rate (RMR) as it can reflect capacity to process food and generate energy. We tested for the predicted positive covariance between RMR and three behaviors that differ in energy demands in 30 male guppies, using multivariate mixed models; we repeatedly measured their activity (10 times each), courtship displays (nine times), voracity (10 times), and metabolism (four‐times). Resting metabolic rate (measured overnight in respirometry trials) did not consistently differ among males, whereas initial peak metabolism measured during those same trials (R = 0.42), and all behaviors were repeatable (R = 0.33–0.51). RMR declined over time suggesting habituation to the protocol, whereas peak metabolism did not. Initial peak metabolism was negatively correlated with courtship display intensity, and voracity was positively correlated with activity, but all other among‐individual correlations were not significant. We conclude that RMR does not provide a proximate explanation for consistent individual differences in behavior in male guppies, and therefore the potential for independent evolution of these physiological and behavioral traits seems possible. Finally, we identify peak metabolism as a potential measure of the stress response to confinement, which highlights the value of considering various aspects of metabolic rates recording during respirometry trials.     

Emergence and accumulation of novel pathogens suppress an invasive species

Emerging pathogens are a growing threat to human health, agriculture and the diversity of ecological communities but may also help control problematic species. Here we investigated the diversity, distribution and consequences of emerging fungal pathogens infecting an aggressive invasive grass that is rapidly colonising habitats throughout the eastern USA. We document the recent emergence and accumulation over time of diverse pathogens that are members of a single fungal genus and represent multiple, recently described or undescribed species. We also show that experimental suppression of these pathogens increased host performance in the field, demonstrating the negative effects of emerging pathogens on invasive plants. Our results suggest that invasive species can facilitate pathogen emergence and amplification, raising concerns about movement of pathogens among agricultural, horticultural, and wild grasses. However, one possible benefit of pathogen accumulation is suppression of aggressive invaders over the long term, potentially abating their negative impacts on native communities.     

Outcomes associated with planned place of birth among women with low-risk pregnancies

Background:Previous studies have shown that planned home birth is associated with a decreased likelihood of intrapartum intervention with no difference in neonatal outcomes compared with planned hospital birth. The purpose of our study was to evaluate different birth settings by comparing neonatal mortality, morbidity and rates of birth interventions between planned home and planned hospital births in Ontario, Canada.Methods:We used a provincial database of all midwifery-booked pregnancies between 2006 and 2009 to compare women who planned home birth at the onset of labour to a matched cohort of women with low-risk pregnancies who had planned hospital births attended by midwives. We conducted subgroup analyses by parity. Our primary outcome was stillbirth, neonatal death (< 28 d) or serious morbidity (Apgar score < 4 at 5 min or resuscitation with positive pressure ventilation and cardiac compressions).Results:We compared 11 493 planned home births and 11 493 planned hospital births. The risk of our primary outcome did not differ significantly by planned place of birth (relative risk [RR] 1.03, 95% confidence interval [CI] 0.68–1.55). These findings held true for both nulliparous (RR 1.04, 95% CI 0.62–1.73) and multiparous women (RR 1.00, 95% CI 0.49–2.05). All intrapartum interventions were lower among planned home births.Interpretation:Compared with planned hospital birth, planned home birth attended by midwives in a jurisdiction where home birth is well-integrated into the health care system was not associated with a difference in serious adverse neonatal outcomes but was associated with fewer intrapartum interventions.In Ontario, Canada, the College of Midwives of Ontario has regulated midwifery since 1994, and increasing numbers of women with low obstetrical risk and their newborns receive care in a publicly funded, midwifery-led continuity of care model.¹ Midwives have admission and discharge privileges at their local hospitals and are able to consult or transfer care to other health care providers if required. In Ontario, midwives attend a small proportion of all births in the province (10%), and about 20% of the births they attend take place at home.² A comprehensive record is maintained for every woman and infant in a midwife’s care. Until 2009, this record was submitted to the provincial Ministry of Health and Long-term Care (MOHLTC) through the Ontario Midwifery Program to access reimbursement for care provided.In the last century, Western culture has come to view hospital birth as safer than home birth.³ Recently, however, the value of hospital birth for all women with low-risk pregnancies has come into question; it has been suggested that in the absence of benefit, a planned hospital birth for this population may increase the use of intrapartum interventions, including cesarean delivery.^4–7 Even though recent studies comparing planned home and hospital births have had moderate sample sizes, they are individually limited in their ability to report definitively on rare outcomes such as death. Owing to a lack of evidence from randomized controlled trials (RCTs) to show that restricting a woman’s freedom to choose a place of birth prevents harm, the authors of a 2012 Cochrane review of planned hospital versus planned home births concluded that home birth services with collaborative medical backup should be established and offered to women with low-risk pregnancies in all jurisdictions.⁸ This conclusion, along with findings from the large English Birthplace Cohort Study,⁴ may be what prompted the National Institute for Health and Care Excellence (NICE) in England to update its intrapartum care guidelines to recommend that, for women at low risk of birth-associated complications, home birth should be considered a generally safe option.⁹ With the paucity of information derived from RCTs,⁸ observational studies are essential to continue to inform and monitor maternal and infant outcomes for women at low obstetrical risk who plan home or hospital birth, and to continue to provide pregnant women with quality information about choice of birthplace.The primary purpose of this retrospective cohort study was to determine the risk of stillbirth or neonatal death or serious neonatal morbidity among women at low obstetrical risk whose deliveries were attended by midwives and who had planned a home birth at the onset of labour, compared with women at low obstetrical risk who planned a hospital birth at the onset of labour. In addition, we also compared the incidence of maternal death and morbidity, birth interventions and breastfeeding between planned home births and planned hospital births.     

Robust human body model injury prediction in simulated side impact crashes

This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments. Four injury metrics (head injury criterion, half deflection, thoracic trauma index and pelvic force) were used to calculate injury risk. Rib fracture prediction and lung strain metrics were also analysed. As hypothesized, bullet speed had the greatest effect on each injury measure. Injury risk was reduced when bullet location was further from the B-pillar or when the bullet angle was more oblique. Age had strong correlation to rib fractures frequency and lung strain severity. The injuries from a real-world crash were predicted using two different methods by (1) subsampling the injury predictors from the 12 best crush profile matching simulations and (2) using regression models. Both injury prediction methods successfully predicted the case occupant's low risk for pelvic injury, high risk for thoracic injury, rib fractures and high lung strains with tight confidence intervals. This parametric methodology was successfully used to explore crash parameter interactions and to robustly predict real-world injuries.