Process, structural, and outcome quality indicators to support perioperative opioid stewardship: a rapid review.

Opioids are effective analgesics but can cause harm. Opioid stewardship is key to ensuring that opioids are used effectively and safely. There is no agreed set of quality indicators relating to the use of opioids perioperatively. This work is part of the Yorkshire Cancer Research Bowel Cancer Quality Improvement programme and aims to develop useful quality indicators for the improvement of care and patient outcomes at all stages of the perioperative journey.A rapid review was performed to identify original research and reviews in which quality indicators for perioperative opioid use are described. A data tool was developed to enable reliable and reproducible extraction of opioid quality indicators.A review of 628 abstracts and 118 full-text publications was undertaken. Opioid quality indicators were identified from 47 full-text publications. In total, 128 structure, process and outcome quality indicators were extracted. Duplicates were merged, with the final extraction of 24 discrete indicators. These indicators are based on five topics: patient education, clinician education, pre-operative optimization, procedure, and patient-specific prescribing and de-prescribing and opioid-related adverse drug events.The quality indicators are presented as a toolkit to contribute to practical opioid stewardship. Process indicators were most commonly identified and contribute most to quality improvement. Fewer quality indicators relating to intraoperative and immediate recovery stages of the patient journey were identified. An expert clinician panel will be convened to agree which of the quality indicators identified will be most valuable in our region for the management of patients undergoing surgery for bowel cancer.

Attack rates of Sirex noctilio and patterns of pine tree defenses and mortality in northern Patagonia.

Accidental and intentional global movement of species has increased the frequency of novel plant-insect interactions. In Patagonia, the European woodwasp, Sirex noctilio, has invaded commercial plantations of North American pines. We compared the patterns of resin defenses and S. noctilio-caused mortality at two mixed-species forests near San Carlos de Bariloche, Argentina. We observed lower levels of resin flow and higher levels of mortality in Pinus contorta compared with Pinus ponderosa. In general, S. noctilio attacked trees with lower resin compared with neighboring trees. Resin production in P. ponderosa was not related to growth rates, but for P. contorta, slower growing trees produced less resin than faster growing conspecifics. For all infested trees, attack density and number of drills (ovipositor probes) per attack did not vary with resin production. Most attacks resulted in one or two drills. Attack rates and drills/attack were basically uniform across the bole of the tree except for a decrease in both drills/attack and attack density in the upper portion of the crown, and an increase in the attack density for the bottom 10% of the tree. Planted pines in Patagonia grow faster than their counterparts in North America, and produce less resin, consistent with the growth-differentiation balance hypothesis. Limited resin defenses may help to explain the high susceptibility of P. contorta to woodwasps in Patagonia.

Temperature affects phenological synchrony in a tree-killing bark beetle.

Phenological synchrony can promote population growth in species with positive density dependence. Variation among life stages in the thermal thresholds for development can foster phenological synchrony under thermal regimes that include frequent occurrence of temperatures between developmental thresholds. The southern pine beetle is an insect with positive density dependence that has recently undergone important shifts in population abundance at the northern extremes of their distribution. We evaluated the hypothesis that cooler winter temperatures in their northern range cause a convergence of the population life stage structure that leads to synchrony in spring flight phenology. We used a combination of approaches. First, in situ laboratory experiments demonstrated a threshold temperature for pupation that was greater than was required for larval development; rearing larvae at lower temperatures increased the pooling of individuals at the end stage of larval development and synchrony in adult emergence. Second, a development rate model showed a similar convergence of the majority of the population at the end stage of larval development when brood experienced the cooler temperatures of the northern region, but not with temperatures from the southern region, or as a null model. Finally, field trapping of wild beetles showed greater synchrony in the pine forests of New Jersey than in the warmer, historically occupied forests of Georgia and Mississippi. Given these results, pine-dominated forests in the northern edge of the southern pine beetle's range may experience more frequent occurrence of outbreaks, due to the positive feedbacks associated with a synchronous spring emergence of this insect.

Uveal Effusion After Immune Checkpoint Inhibitor Therapy.

Importance: Immune checkpoint inhibitors, including antiprogrammed cell death protein-1 (anti-PD-1) and antiprogrammed cell death ligand-1 (anti-PD-L1) monoclonal antibodies, have recently been introduced as a promising new immunotherapy for solid cancers. The adverse effects typically include inflammation of the skin, endocrine, and gastrointestinal systems. Objective: To describe 3 patients who developed uveal effusion after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy. Design, Setting, and Participants: This case series was conducted in a university-based ocular oncology practice. The participants were a 68-year-old African American man with metastatic adenocarcinoma of the lung and 2 white men, aged 52 years and 85 years, with metastatic cutaneous melanoma; all were taking anti-PD-1 and anti-PD-L1 monoclonal antibody therapy. Main Outcomes and Measures: Ocular findings of 3 patients. Results: We identified 3 patients who developed uveal effusion within 1 to 2 months after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy. Uveal effusion resolved completely in 6 to 12 weeks after discontinuation of systemic therapy in 2 patients and persisted in 1 patient who continued the therapy. Conclusions and Relevance: Uveal effusion should be considered in patients taking anti-PD-1 and/or PD-L1 monoclonal antibody therapy. Because of the role of the PD-1 pathway in the inhibition of self-reactive T cells, PD-1 inhibition might lead to inflammation because of immune-related adverse effects.

Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy.

Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL); however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens. Peripheral blood samples from 21 patients with relapsed/refractory CLL in acalabrutinib phase I (100-400 mg/day) and II (100 mg BID) clinical trials were collected prior to and on days 8 and 28 after treatment initiation and evaluated for plasma chemokines, reverse phase protein array, immunoblotting and pseudoemperipolesis. The on-target pharmacodynamic profile of acalabrutinib in CLL lymphocytes was comparable to ibrutinib in measures of acalabrutinib-mediated changes in CCL3/CCL4 chemokine production, migration assays and changes in B-cell receptor signaling pathway proteins and other downstream survival proteins. Among several CLL-targeted agents, venetoclax, when combined with acalabrutinib, showed optimal complementary activity in vitro, ex vivo and in vivo in TCL-1 adoptive transfer mouse model system of CLL. These findings support selective targeting and combinatorial potential of acalabrutinib.

Caprine lentivirus in sheep milk and semen / Lentivírus caprino em leite e sêmen de ovinos

With the objective of detecting the presence of caprine lentivirus (CLV) in ewe milk and in ram semen, ten matrixes and four reproducers experimentally infected with CLV were used. Samples of ewe milk were collected during the four months of lactation, five collections per animal, totaling 50 samples. Regarding the rams, eight semen collections were made per animal, during one year of experimentation, totaling 32 samples. The milk and semen samples were submitted to DNA extraction and the nested polymerase chain reaction test (nPCR) to detect CLV proviral DNA. Eight (16%) of the milk samples were positive in nPCR originating from two ewes. Only one (3.12%) semen sample was positive. The amplification products were sequenced, and were confirmed to be a CLV genomic sequence. Thus, the presence of CLV proviral DNA in sheep milk and semen was demonstrated, confirming the feasibility of infection between species, and alerting to the risk of spreading infections.(AU)

Com o objetivo de detectar a presença do lentivírus caprino (LVC) no leite de ovelhas e no sêmen de carneiros, utilizaram-se 10 matrizes e quatro reprodutores infectados experimentalmente com o LVC. Foram coletadas amostras de leite das ovelhas durante os quatro meses de lactação, ocorrendo cinco coletas por animal, totalizando 50 amostras. Quanto aos carneiros, realizaram-se oito coletas de sêmen por animal, durante um ano de experimentação, totalizando 32 amostras. As amostras de leite e de sêmen foram submetidas à extração de DNA e à prova de reação em cadeia da polimerase do tipo nested (nPCR) visando à detecção de DNA proviral do LVC. Oito (16%) amostras de leite foram positivas na nPCR oriundas de duas ovelhas. Apenas uma (3,12%) amostra de sêmen apresentou positividade. Produtos da amplificação foram sequenciados, confirmando-se tratar de sequência genômica do LVC. Dessa forma, demonstrou-se a presença do DNA proviral do LVC em leite e sêmen de ovinos, confirmando a viabilidade da infecção entre espécies e, assim, alertando sobre o risco de que a infecção seja disseminada.(AU)

Population biology of the European woodwasp, Sirex noctilio, in Galicia, Spain.

Sirex noctilio Fabricius (Hymenoptera, Siricidae) is rare and rarely studied where it is native in Eurasia, but is a widespread pest of pines in the Southern Hemisphere. Here we report on the abundance, basic biology, host use patterns and natural enemies of native S. noctilio in Galicia, Spain. Most trees attacked by S. noctilio failed to produce any adult progeny: >90% of emergences came from <20% of the attacked trees. The highest reproduction was in Pinus pinaster, followed by Pinus sylvestris and Pinus radiata. The proportions of S. noctilio requiring 1, 2 or 3 years for development were 0.72: 0.24: 0.04. Delayed development could be an adaptation to avoid parasitic nematodes, which sterilized 41.5% adults with one year generation time but only 19% of adults with 2 years generation time. Hymenoptera parasitoids accounted for 20% mortality. Sex ratios were male biased at 1: 2.9. Body size and fecundity were highly variable and lower than previously reported from the Southern Hemisphere. On attacked trees, there were 5-20 attacks per standard log (18 dm2), with usually 1-3 drills per attack. Attack densities and drills per attack were higher in trees that subsequently died. The production of S. noctilio per log was positively related to total attacks, and negatively related to: (1) attack density, (2) incidence of blue stain from Ophiostoma fungi and (3) frequency of lesions in plant tissue around points of attack. A preliminary life table for S. noctilio in Galicia estimated effects on potential population growth rate from (in decreasing order of importance) host suitability, unequal sex ratio, parasitic nematodes and Hymenoptera parasitoids.

Signal diversification in Oecanthus tree crickets is shaped by energetic, morphometric, and acoustic trade-offs.

Physiology, physics, and ecological interactions can generate trade-offs within species, but may also shape divergence among species. We tested whether signal divergence in Oecanthus tree crickets is shaped by acoustic, energetic, and behavioral trade-offs. We found that species with faster pulse rates, produced by opening and closing wings up to twice as many times per second, did not have higher metabolic costs of calling. The relatively constant energetic cost across species is explained by trade-offs between the duration and repetition rate of acoustic signals-species with fewer stridulatory teeth closed their wings more frequently such that the number of teeth struck per second of calling and the resulting duty cycle were relatively constant across species. Further trade-offs were evident in relationships between signals and body size. Calling was relatively inexpensive for small males, permitting them to call for much of the night, but at low amplitude. Large males produced much louder calls, reaching up to four times more area, but the energetic costs increased substantially with increasing size and the time spent calling dropped to only 20% of the night. These trade-offs indicate that the trait combinations that arise in these species represent a limited subset of conceivable trait combinations.

Temperature alters the relative abundance and population growth rates of species within the Dendroctonus frontalis (Coleoptera: Curculionidae) community.

Temperature has strong effects on metabolic processes of individuals and demographics of populations, but effects on ecological communities are not well known. Many economically and ecologically important pest species have obligate associations with other organisms; therefore, effects of temperature on these species might be mediated by strong interactions. The southern pine beetle (Dendroctonus frontalis Zimmermann) harbors a rich community of phoretic mites and fungi that are linked by many strong direct and indirect interactions, providing multiple pathways for temperature to affect the system. We tested the effects of temperature on this community by manipulating communities within naturally infested sections of pine trees. Direct effects of temperature on component species were conspicuous and sometimes predictable based on single-species physiology, but there were also strong indirect effects of temperature via alteration of species interactions that could not have been predicted based on autecological temperature responses. Climatic variation, including directional warming, will likely influence ecological systems through direct physiological effects as well as indirect effects through species interactions.

Antinociceptive effect on mice of the hydroalcoholic fraction and (-) epicatechin obtained from Combretum leprosum Mart & Eich.

Previous studies on Combretum leprosum, a tree growing in the Northeastern states of Brazil, have shown antinociceptive effects of the ethanol extract of its leaves and bark, but studies examining its constituents are rare. The objective of this study was to evaluate the antinociceptive effect of the hydroalcoholic fraction (HF) of one of its constituents, the flavonoid (-) epicatechin (EPI), administered orally to mice (20-30 g) in models of chemical nociception, and the possible mechanisms involved. Different doses of HF (62.5 to 500 mg/kg) and EPI (12.5 to 50 mg/kg) were evaluated in models of abdominal writhing, glutamate, capsaicin, and formalin in animals pretreated with different antagonists: naloxone, ondansetron, yohimbine, ketanserin, pindolol, atropine, and caffeine in the abdominal writhing test. To determine the role of nitric oxide, the animals were pretreated with L-arginine (600 mg/kg, ip) in the glutamate test. The HF was effective (P < 0.05) in all protocols at different doses and EPI was effective in the abdominal writhing, capsaicin and glutamate tests (P < 0.05) at doses of 25 and 50 mg/kg. However, in the formalin test it was only effective in the second phase at a dose of 25 mg/kg. The antinociceptive effect of HF was inhibited when HF was associated with yohimbine (0.15 mg/kg), ketanserine (0.03 mg/kg), and L-arginine (600 mg/kg), but not with the other antagonists. HF and EPI were effective in models of chemical nociception, with the suggested participation of the adrenergic, serotonergic and nitrergic systems in the antinociceptive effect of HF.

Antinociceptive effect on mice of the hydroalcoholic fraction and (-) epicatechin obtained from Combretum leprosum Mart & Eich

Previous studies on Combretum leprosum, a tree growing in the Northeastern states of Brazil, have shown antinociceptive effects of the ethanol extract of its leaves and bark, but studies examining its constituents are rare. The objective of this study was to evaluate the antinociceptive effect of the hydroalcoholic fraction (HF) of one of its constituents, the flavonoid (-) epicatechin (EPI), administered orally to mice (20-30 g) in models of chemical nociception, and the possible mechanisms involved. Different doses of HF (62.5 to 500 mg/kg) and EPI (12.5 to 50 mg/kg) were evaluated in models of abdominal writhing, glutamate, capsaicin, and formalin in animals pretreated with different antagonists: naloxone, ondansetron, yohimbine, ketanserin, pindolol, atropine, and caffeine in the abdominal writhing test. To determine the role of nitric oxide, the animals were pretreated with L-arginine (600 mg/kg, ip) in the glutamate test. The HF was effective (P < 0.05) in all protocols at different doses and EPI was effective in the abdominal writhing, capsaicin and glutamate tests (P < 0.05) at doses of 25 and 50 mg/kg. However, in the formalin test it was only effective in the second phase at a dose of 25 mg/kg. The antinociceptive effect of HF was inhibited when HF was associated with yohimbine (0.15 mg/kg), ketanserine (0.03 mg/kg), and L-arginine (600 mg/kg), but not with the other antagonists. HF and EPI were effective in models of chemical nociception, with the suggested participation of the adrenergic, serotonergic and nitrergic systems in the antinociceptive effect of HF.

Isokinetic strength training of lower limb muscles following acquired brain injury.

PRIMARY OBJECTIVE: To investigate the effectiveness of isokinetic strength training of ankle and knee muscles in adults with chronic acquired brain injury (ABI). RESEARCH DESIGN: Series of single case studies. METHODS: Twelve people with ABI participated in a 2.5-week baseline, 12-week intervention and a 4-week follow-up phase. INTERVENTION: Concentric isokinetic exercise, twice a week, for plantarflexors (PFs), dorsiflexors (DFs), knee flexors (KFs) and knee extensors (KEs). OUTCOMES: Peak torque and power at 60 and 90° s⁻¹, PFs and KFs tone at 60° s⁻¹, gait speed and timed chair rises. RESULTS: For single case analyses strength improvements were noted in 11/12 participants' PFs, 5/12 participants' DFs and 7/12 participants' KEs and KFs. Gait speed improved in 8/12 participants and chair rise time improved in 7/12 participants. PFs tone increased in three participants, KFs tone increased in six participants and three participants reported knee pain. For group analyses, peak torque of PFs and KEs, fast gait speed and timed chair rises demonstrated improvement (p < 0.05). CONCLUSIONS: Isokinetic strength training may be effective to improve lower limb muscle strength; however, care needs to be taken in selecting suitable candidates as some individuals reported knee pain with this intensive programme.

An isokinetic muscle strengthening program for adults with an acquired brain injury leads to meaningful improvements in physical function.

PRIMARY OBJECTIVE: To investigate if an isokinetic strength training programme for leg muscles lead to personally meaningful changes in adults with an acquired brain injury (ABI). RESEARCH DESIGN: A qualitative exploratory design. METHODS: Twelve people with ABI participated in pre- and post-intervention face-to-face interviews with open ended questions. Data were initially analysed using a case study research approach exploring individuals experiences and then cross case analysis to determine common themes for the group. INTERVENTION: Twelve-week isokinetic strength training programme for ankle and knee muscles. OUTCOMES: Participants perceived changes. RESULTS: Thematic analysis determined four main themes arising from the interviews; occupation, vitality, sense of self and personal interactions. Participants reported reductions in impairments as a response to the exercise programme and these changes led to increased function and participation in activities they valued. Also marked improvements in vitality were reported as well as increases in self-esteem and general well-being for many participants. CONCLUSIONS: An isokinetic strength training programme resulted in improvements in motor skills and functional abilities that were meaningful for the participants.

Effect of homeopathic medicines on helminth parasitism and resistance of Haemonchus contortus infected sheep.

This study evaluated the effects of homeopathic treatment on control of Haemonchus contortus infection in sheep. Twenty lambs were randomized to three treatments: treated with the homeopathic medicines, Ferrum phosphoricum, Arsenicum album and Calcarea carbonica; treated with a conventional antihelminthic, doramectin, and an untreated control group. Fecal and blood samples were taken from each animal on days 18, 38 and 68 after start of treatment. A significant reduction in number of H. contortus larvae (p<0.01) was observed for animals in the homeopathic treatment group compared to the control group. Fecal egg counts showed negative correlation between haematocrit and haemoglobin concentrations in the homeopathic treatment group (p<0.01); however, the biochemical and immunological parameters showed better correlation, indicating that the homeopathic medicine improved vital functions. Daily weight gain in the homeopathic treatment group was superior to the control and to the antihelminthic groups, 31 and 6.5%, respectively. The cost benefit analysis confirmed that homeopathy group increases economic trend when compared with the other groups.

Effects of tree phytochemistry on the interactions among endophloedic fungi associated with the southern pine beetle.

We examined the interaction between host trees and fungi associated with a tree-killing bark beetle, Dendroctonus frontalis. We evaluated (1) the response of four Pinus species to fungal invasion and (2) the effects of plant secondary metabolites on primary growth of and secondary colonization of three consistent fungal associates. Two of these fungi, Entomocorticium sp. A and Ophiostoma ranaculosum, are obligate mutualists with D. frontalis, and the third associate is a blue-staining fungus, O. minus, that is commonly introduced by beetles and phoretic mites. O. minus negatively affects beetle larvae and in high abundance can impact D. frontalis population dynamics. Size of lesions formed and quantity of secondary metabolites produced in response to fungal inoculations varied significantly among Pinus species. However, monoterpene composition within infected tissue did not significantly vary across treatments. While all eight tested metabolites negatively affected the growth rate of O. minus, only 4-allylanisole, p-cymene, and terpinene reduced the growth of the mycangial fungi. Surprisingly, growth rates of mycangial fungi increased in the presence of several secondary metabolite volatiles. O. minus out-competed both mycangial fungi, but the presence of secondary metabolites altered the outcome slightly. O. ranaculosum out-performed E. sp. A in the presence of dominant conifer monoterpenes, such as alpha- and beta-pinene. Volatiles from the mycangial fungi, particularly E. sp. A, had a negative effect on O. minus growth. In general, phloem phytochemistry of particular Pinus species appeared to alter the relative growth and competitiveness of mutualistic and non-mutualistic fungi associated with D. frontalis. The outcome of interactions among these fungi likely has important consequences for the population dynamics of D. frontalis.

Effects of available water on growth and competition of southern pine beetle associated fungi.

Competitive, interactions among bark beetle associated fungi are potentially influenced by abiotic factors. Water potential, in particular, undergoes marked changes over the course of beetle colonization of tree hosts. To investigate the impact of water potential on competition among three southern pine beetle associated fungi, Ophiostoma minus, Entomocorticium sp. A and Ceratocystiopsis ranaculosus, we utilized artificial media with water potentials of 0, -5, -10, and -20 MPa. Growth of all three fungi, when grown alone, decreased on media with lower water potentials. Growth rates of all three fungi were likewise reduced in competition experiments. At -5 to -10 MPa, C. ranaculosus (a fungus with beneficial effects toward southern pine beetle) was nearly equal in competitive ability to O. minus (a fungus with antagonistic effects towards southern pine beetle). This was not true on control media, nor at other water potentials tested. The range of water potentials used in our assays was similar to the range of water potentials we measured in loblolly pines within a southern pine beetle infestation. This study indicates that water potential may alter the outcome of competitive interactions among bark beetle-associated fungi in ways that favour bark beetle success.

Linking breeding and wintering ranges of a migratory songbird using stable isotopes.

We used the natural abundance of stable isotopes (carbon and hydrogen) in the feathers of a neotropical migrant songbird to determine where birds from particular breeding areas spend the winter and the extent to which breeding populations mix in winter quarters. We show that most birds wintering on western Caribbean islands come from the northern portion of the species' North American breeding range, whereas those on more easterly islands are primarily from southern breeding areas. Although segregated by breeding latitude, birds within local wintering areas derive from a wide range of breeding longitudes, indicating considerable population mixing with respect to breeding longitude. These results are useful for assessing the effects of wintering habitat loss on breeding population abundances and for predicting whether the demographic consequences will be concentrated or diffuse.

Determination of DDT and its metabolites in cattle dip soil available in aqueous phase after remediation.

Soil taken from a former cattle tick dip site in NSW Australia, was remediated with a chemical leaching technology. The pre- and post-remediated soil (20g) was dispersed in water (100mL) and subjected to passive diffusion using polymeric membranes. The remediation reduced tDDT from 1174.3 microg/g to 102.9 microg/g (ash weight basis), which was further reduced to 43.2 microg/g with composting. The membranes accumulated 41.3 microg tDDT/g from the dip soil, 49.2 microg tDDT/g from the chemically leached soil and 3.1 microg tDDT/g from the leached composted soil. The chemical leaching removed over 90% of the tDDT, but released soil bound DDT, which was converted to DDE, while 2.99 microg/g was accumulated by the membranes from dip soil, 37.52 microg/g was accumulated from remediated soil. Composting, however, almost eliminated the availability for passive diffusion by the membranes from 50-60 microg/g in remediated soil to 3 -3.5 microg/g in composted soil. Variability studies of the membranes using eight replicates demonstrated that the accumulation by the membranes was reproducible with an average relative error of 20.3% for p,p'-DDT in soil type two, whilst the lowest average relative error for p,p'-DDE was 4.3%, suggesting that triplicate analyses will achieve acceptable accuracy.