To examine opioid prescribing patterns after general surgery procedures and to estimate an ideal number of pills to prescribe.
Diversion of prescription opioids is a major contributor to the rising ...mortality from opioid overdoses. Data to inform surgeons on the optimal dose of opioids to prescribe after common general surgical procedures is lacking.
We evaluated 642 patients undergoing 5 outpatient procedures: partial mastectomy (PM), partial mastectomy with sentinel lymph node biopsy (PM SLNB), laparoscopic cholecystectomy (LC), laparoscopic inguinal hernia repair (LIH), and open inguinal hernia repair (IH). Postoperative opioid prescriptions and refill data were tabulated. A phone survey was conducted to determine the number of opioid pills taken.
There was a wide variation in the number of opioid pills prescribed to patients undergoing the same operation. The median number (and range) prescribed were: PM 20 (0-50), PM SLNB 20 (0-60), LC 30 (0-100), LIH 30 (15-70), and IH 30 (15-120). Only 28% of the prescribed pills were taken. This percentage varied by operation: PM 15%, PM SLNB 25%, LC 33%, LIH 15%, and IH 31%. Less than 2% of patients obtained refills.We identified the number of pills that would fully supply the opioid needs of 80% of patients undergoing each operation: PM 5, PM SLNB 10, LC 15, LIH 15, and IH 15. If this number were prescribed, the number of opioid initially prescribed would be 43% of the actual number prescribed.
There is wide variability in opioid prescriptions for common general surgery procedures. In many cases excess pills are prescribed. Using our ideal number, surgeons can adequately treat postoperative pain and markedly decrease the number of opioids prescribed.
The aim of this study was to determine whether an educational intervention was sufficient to decrease opioid prescribing after general surgical operations.
We recently analyzed opioid prescription ...and use for 5 common outpatient operations at our institution: partial mastectomy (PM), PM with sentinel lymph node biopsy (PM SLNB), laparoscopic cholecystectomy (LC), laparoscopic inguinal hernia repair (LIH), and open inguinal hernia repair (IH). We found that opioids were over-prescribed. We formulated guidelines for opioid prescribing that would halve the number of pills prescribed and also satisfy 80% of patients' opioid requirements.
We discussed our findings and opioid-prescribing guidelines with surgeons at our institution. We recommended that surgeons encourage patients to use a nonsteroidal anti-inflammatory drug (NSAID) and acetaminophen before using opioids. We then evaluated opioid prescriptions and use in 246 subsequent patients undergoing these same operations.
The mean number of opioid pills prescribed for each operation markedly decreased: PM 19.8 versus 5.1; PM SLNB 23.7 versus 9.6; LC 35.2 versus 19.4; LIH 33.8 versus 19.3, and IH 33.2 versus 18.3; all P < 0.0003. The total number of pills prescribed decreased by 53% when compared with the number that would have been prescribed before the educational intervention. Only 1 patient (0.4%) required a refill opioid prescription. Eighty-five percent of patients used either a NSAID or acetaminophen.
By defining postoperative opioid requirements through patient surveys and disseminating operation-specific guidelines for opioid prescribing to surgeons, we were able to decrease the number of opioids initially prescribed by more than half. Decreased initial opioid prescriptions did not result in increased opioid refill prescriptions.
Phylogenomic studies based on multi-locus sequence data sets are usually characterized by partial taxon coverage, in which sequences for some loci are missing for some taxa. The impact of missing ...data has been widely studied in phylogenetics, but it has proven difficult to distinguish effects due to error in tree reconstruction from effects due to missing data per se. We approach this problem using a explicitly phylogenomic criterion of success, decisiveness, which refers to whether the pattern of taxon coverage allows for uniquely defining a single tree for all taxa.
We establish theoretical bounds on the impact of missing data on decisiveness. Results are derived for two contexts: a fixed taxon coverage pattern, such as that observed from an already assembled data set, and a randomly generated pattern derived from a process of sampling new data, such as might be observed in an ongoing comparative genomics sequencing project. Lower bounds on how many loci are needed for decisiveness are derived for the former case, and both lower and upper bounds for the latter. When data are not decisive for all trees, we estimate the probability of decisiveness and the chances that a given edge in the tree will be distinguishable. Theoretical results are illustrated using several empirical examples constructed by mining sequence databases, genomic libraries such as ESTs and BACs, and complete genome sequences.
Partial taxon coverage among loci can limit phylogenomic inference by making it impossible to distinguish among multiple alternative trees. However, even though lack of decisiveness is typical of many sparse phylogenomic data sets, it is often still possible to distinguish a large fraction of edges in the tree.
Aortic dissection is the most common acute emergency condition of the aorta and often has a fatal outcome. Outcome is determined by the type and extent of dissection and the presence of associated ...complications (eg, cerebral sequelae, aortic branch involvement, pericardial involvement, and visceral involvement), with early diagnosis and treatment being essential for improved prognosis. Aortic dissections are classified on the basis of the site of the intimal tear according to the Stanford classification system. Type A aortic dissection involves the ascending thoracic aorta and may extend into the descending aorta, whereas in a type B dissection the intimal tear is located distal to the left subclavian artery. Type A dissection typically requires urgent surgical intervention, whereas type B dissection can often be treated medically. Modern multidetector computed tomography (CT) is a fast, widely available imaging modality with high sensitivity and specificity. Multidetector CT allows the early recognition and characterization of aortic dissection as well as determination of the presence of any associated complications, findings that are essential for optimizing treatment and improving clinical outcomes.
Terraces in Phylogenetic Tree Space Sanderson, Michael J.; McMahon, Michelle M.; Steel, Mike
Science (American Association for the Advancement of Science),
07/2011, Letnik:
333, Številka:
6041
Journal Article
Recenzirano
A key step in assembling the tree of life is the construction of species-rich phylogenies from multilocus—but often incomplete—sequence data sets. We describe previously unknown structure in the ...landscape of solutions to the tree reconstruction problem, comprising sometimes vast "terraces" of trees with identical quality, arranged on islands of phylogenetically similar trees. Phylogenetic ambiguity within a terrace can be characterized efficiently and then ameliorated by new algorithms for obtaining a terrace's maximum-agreement subtree or by identifying the smallest set of new targets for additional sequencing. Algorithms to find optimal trees or estimate Bayesian posterior tree distributions may need to navigate strategically in the neighborhood of large terraces in tree space.
Abstract
Reconstructing accurate historical relationships within a species poses numerous challenges, not least in many plant groups in which gene flow is high enough to extend well beyond species ...boundaries. Nonetheless, the extent of tree-like history within a species is an empirical question on which it is now possible to bring large amounts of genome sequence to bear. We assess phylogenetic structure across the geographic range of the saguaro cactus, an emblematic member of Cactaceae, a clade known for extensive hybridization and porous species boundaries. Using 200 Gb of whole genome resequencing data from 20 individuals sampled from 10 localities, we assembled two data sets comprising 150,000 biallelic single nucleotide polymorphisms (SNPs) from protein coding sequences. From these, we inferred within-species trees and evaluated their significance and robustness using five qualitatively different inference methods. Despite the low sequence diversity, large census population sizes, and presence of wide-ranging pollen and seed dispersal agents, phylogenetic trees were well resolved and highly consistent across both data sets and all methods. We inferred that the most likely root, based on marginal likelihood comparisons, is to the east and south of the region of highest genetic diversity, which lies along the coast of the Gulf of California in Sonora, Mexico. Together with striking decreases in marginal likelihood found to the north, this supports hypotheses that saguaro’s current range reflects postglacial expansion from the refugia in the south of its range. We conclude with observations about practical and theoretical issues raised by phylogenomic data sets within species, in which SNP-based methods must be used rather than gene tree methods that are widely used when sequence divergence is higher. These include computational scalability, inference of gene flow, and proper assessment of statistical support in the presence of linkage effects. Phylogenomics; phylogeography; rooting; Sonoran Desert.
A comprehensive phylogeny of papilionoid legumes was inferred from sequences of 2228 taxa in GenBank release 147. A semiautomated analysis pipeline was constructed to download, parse, assemble, ...align, combine, and build trees from a pool of 11,881 sequences. Initial steps included all-against-all BLAST similarity searches coupled with assembly, using a novel strategy for building length-homogeneous primary sequence clusters. This was followed by a combination of global and local alignment protocols to build larger secondary clusters of locally aligned sequences, thus taking into account the dramatic differences in length of the heterogeneous coding and noncoding sequence data present in GenBank. Next, clusters were checked for the presence of duplicate genes and other potentially misleading sequences and examined for combinability with other clusters on the basis of taxon overlap. Finally, two supermatrices were constructed: a “sparse” matrix based on the primary clusters alone (1794 taxa × 53,977 characters), and a somewhat more “dense” matrix based on the secondary clusters (2228 taxa × 33,168 characters). Both matrices were very sparse, with 95% of their cells containing gaps or question marks. These were subjected to extensive heuristic parsimony analyses using deterministic and stochastic heuristics, including bootstrap analyses. A “reduced consensus” bootstrap analysis was also performed to detect cryptic signal in a subtree of the data set corresponding to a “backbone” phylogeny proposed in previous studies. Overall, the dense supermatrix appeared to provide much more satisfying results, indicated by better resolution of the bootstrap tree, excellent agreement with the backbone papilionoid tree in the reduced bootstrap consensus analysis, few problematic large polytomies in the strict consensus, and less fragmentation of conventionally recognized genera. Nevertheless, at lower taxonomic levels several problems were identified and diagnosed. A large number of methodological issues in supermatrix construction at this scale are discussed, including detection of annotation errors in GenBank sequences; the shortage of effective algorithms and software for local multiple sequence alignment; the difficulty of overcoming effects of fragmentation of data into nearly disjoint blocks in sparse supermatrices; and the lack of informative tools to assess confidence limits in very large trees.
Few clades of plants have proven as difficult to classify as cacti. One explanation may be an unusually high level of convergent and parallel evolution (homoplasy). To evaluate support for this ...phylogenetic hypothesis at the molecular level, we sequenced the genomes of four cacti in the especially problematic tribe Pachycereeae, which contains most of the large columnar cacti of Mexico and adjacent areas, including the iconic saguaro cactus (Carnegiea gigantea) of the Sonoran Desert. We assembled a high-coverage draft genome for saguaro and lower coverage genomes for three other genera of tribe Pachycereeae (Pachycereus, Lophocereus, and Stenocereus) and a more distant outgroup cactus, Pereskia. We used these to construct 4,436 orthologous gene alignments. Species tree inference consistently returned the same phylogeny, but gene tree discordance was high: 37% of gene trees having at least 90% bootstrap support conflicted with the species tree. Evidently, discordance is a product of long generation times and moderately large effective population sizes, leading to extensive incomplete lineage sorting (ILS). In the best supported gene trees, 58% of apparent homoplasy at amino sites in the species tree is due to gene tree-species tree discordance rather than parallel substitutions in the gene trees themselves, a phenomenon termed “hemiplasy.” The high rate of genomic hemiplasy may contribute to apparent parallelisms in phenotypic traits, which could confound understanding of species relationships and character evolution in cacti.
Comprehensively sampled phylogenetic trees provide the most compelling foundations for strong inferences in comparative evolutionary biology. Mismatches are common, however, between the taxa for ...which comparative data are available and the taxa sampled by published phylogenetic analyses. Moreover, many published phylogenies are gene trees, which cannot always be adapted immediately for species level comparisons because of discordance, gene duplication, and other confounding biological processes. A new database, STBase, lets comparative biologists quickly retrieve species level phylogenetic hypotheses in response to a query list of species names. The database consists of 1 million single- and multi-locus data sets, each with a confidence set of 1000 putative species trees, computed from GenBank sequence data for 413,000 eukaryotic taxa. Two bodies of theoretical work are leveraged to aid in the assembly of multi-locus concatenated data sets for species tree construction. First, multiply labeled gene trees are pruned to conflict-free singly-labeled species-level trees that can be combined between loci. Second, impacts of missing data in multi-locus data sets are ameliorated by assembling only decisive data sets. Data sets overlapping with the user's query are ranked using a scheme that depends on user-provided weights for tree quality and for taxonomic overlap of the tree with the query. Retrieval times are independent of the size of the database, typically a few seconds. Tree quality is assessed by a real-time evaluation of bootstrap support on just the overlapping subtree. Associated sequence alignments, tree files and metadata can be downloaded for subsequent analysis. STBase provides a tool for comparative biologists interested in exploiting the most relevant sequence data available for the taxa of interest. It may also serve as a prototype for future species tree oriented databases and as a resource for assembly of larger species phylogenies from precomputed trees.
Most studies inferring species phylogenies use sequences from single copy genes or sets of orthologs culled from gene families. For taxa such as plants, with very high levels of gene duplication in ...their nuclear genomes, this has limited the exploitation of nuclear sequences for phylogenetic studies, such as those available in large EST libraries. One rarely used method of inference, gene tree parsimony, can infer species trees from gene families undergoing duplication and loss, but its performance has not been evaluated at a phylogenomic scale for EST data in plants.
A gene tree parsimony analysis based on EST data was undertaken for six angiosperm model species and Pinus, an outgroup. Although a large fraction of the tentative consensus sequences obtained from the TIGR database of ESTs was assembled into homologous clusters too small to be phylogenetically informative, some 557 clusters contained promising levels of information. Based on maximum likelihood estimates of the gene trees obtained from these clusters, gene tree parsimony correctly inferred the accepted species tree with strong statistical support. A slight variant of this species tree was obtained when maximum parsimony was used to infer the individual gene trees instead.
Despite the complexity of the EST data and the relatively small fraction eventually used in inferring a species tree, the gene tree parsimony method performed well in the face of very high apparent rates of duplication.
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