The noncosmopolitanism paradigm of freshwater zooplankton: insights from the global phylogeography of the predatory cladoceran Polyphemus pediculus (Linnaeus, 1761) (Crustacea, Onychopoda).

A major question in our understanding of eukaryotic biodiversity is whether small bodied taxa have cosmopolitan distributions or consist of geographically localized cryptic taxa. Here, we explore the global phylogeography of the freshwater cladoceran Polyphemus pediculus (Linnaeus, 1761) (Crustacea, Onychopoda) using two mitochondrial genes, cytochrome c oxidase subunit I and 16s ribosomal RNA, and one nuclear marker, 18s ribosomal RNA. The results of neighbour-joining and Bayesian phylogenetic analyses reveal an exceptionally pronounced genetic structure at both inter- and intra-continental scales. The presence of well-supported, deeply divergent phylogroups across the Holarctic suggests that P. pediculus represents an assemblage of at least nine, largely allopatric cryptic species. Interestingly, all phylogenetic analyses support the reciprocal paraphyly of Nearctic and Palaearctic clades. Bayesian inference of ancestral distributions suggests that P. pediculus originated in North America or East Asia and that European lineages of Polyphemus were established by subsequent intercontinental dispersal events from North America. Japan and the Russian Far East harbour exceptionally high levels of genetic diversity at both regional and local scales. In contrast, little genetic subdivision is apparent across the formerly glaciated regions of Europe and North America, areas that historical demographic analyses suggest that were recolonized just 5500-24 000 years ago.

Risk factors for red cell transfusion in adults undergoing coronary artery bypass surgery: a systematic review.

BACKGROUND AND OBJECTIVE: Identifying factors that can predict adults at high risk of receiving red blood cell transfusion during coronary artery bypass graft (CABG) surgery may aid in more efficient blood banking practices and may tailor blood conservation strategies for these adult patients. The objective was to identify clinical factors associated with increased red cell transfusion in adults undergoing CABG surgery. METHODS: A systematic review of the MEDLINE and HealthSTAR databases from 1966 to December 2005 was conducted. Citations containing the medical subject heading or textwords 'coronary artery bypass graft', 'CABG' and 'cardiovascular surgery' were combined with the medical subject headings or textwords 'transfusion' and 'blood transfusion'. RESULTS: A total of 2461 abstracts were retrieved. Twenty-one studies met the inclusion/exclusion criteria. Transfusion rates ranged from 7 to 97%. Several variables were identified that were associated with increased red cell transfusion rates including older age, female sex, low haemoglobin concentration or haematocrit value, renal insufficiency and urgent/emergent surgery. The strongest risk factor was the urgency of surgery (urgent or emergent surgery), which was associated with a 4x to 8x increase in transfusion rates compared to elective surgery. Increasing age and female sex increased the likelihood of transfusion by 1x to 3x and 2x, respectively. CONCLUSIONS: Increasing patient age, female sex, lower preoperative haemoglobin levels, as well as the urgency of the CABG surgery were associated with higher transfusion rates. Identifying risk factors for transfusion may allow for targeted use of blood conservation strategies, improved efficiency in blood utilization and informing adults at risk of transfusion.

Macrogeographic patterns of breeding system diversity in the Daphnia pulex group from the United States and Mexico.

Studies on the biogeographical patterning of reproductive systems promise to extend understanding of the factors which modulate breeding system transitions. Two closely allied cladoceran crustaceans, Daphnia pulex and D. pulicaria, show varied modes of reproduction, with populations reproducing by either cyclic or obligate parthenogenesis. Prior studies have provided a detailed understanding of their breeding system diversity in the polar and cold temperate regions of North America. The present investigation extends this analysis, characterizing breeding systems and clonal diversity at sites throughout the United States and Mexico. Genotypic diversity in these southern areas was high, but only diploids were detected, indicating that polyploids are restricted to the north. F(1) hybrids and their two parental species were present in most areas, although their frequencies varied geographically. Hybrids invariably reproduced by obligate asexuality, but both parental taxa showed regional shifts in their breeding system. The complexity of these latter patterns suggests that they reflect the interplay of historical factors and selection.

Ultrasonographic appearance of splenic disease in 101 cats.

The sonographic findings in 101 cats with splenic abnormalities are presented. Diagnosis was made by ultrasound-guided fine needle aspirate or fine-needle biopsy (n = 91), ultrasound-guided core biopsy (n = 1), surgical core biopsy (n = 1), or necropsy (n = 10). Two cats had more than one diagnostic procedure (fine needle aspirate and necropsy or core biopsy and necropsy). The splenic abnormalities included lymphosarcoma (n = 30), mast cell tumor (n = 27), extramedullary hematopoiesis and/or lymphoid hyperplasia (n = 27), epithelial tumors (n = 6), mesenchymal tumors (n = 4), malignant histiocytosis (n = 2), myeloproliferative disease (n = 2), pyogranulomatous inflammation (n = 2), erythroleukemia (n = 1), eosinophilic syndrome (n = 1), hematoma (n = 1), and granulomatous splenitis (n = 1). Three cats had more than one splenic abnormality (mast cell tumor and metastatic carcinoma, pyogranulomatous inflammation and lymphoid hyperplasia, histiocytic lymphosarcoma, and lymphoid hyperplasia). Pathognomonic changes were not seen for any of the diseases.

What is the quality of drug therapy clinical practice guidelines in Canada?

BACKGROUND: The Canadian Medical Association maintains a national online database of clinical practice guidelines developed, endorsed or reviewed by Canadian organizations within 5 years of the current date. This study was designed to identify and describe guidelines in the database that make recommendations related to the use of drug therapy, and to assess their quality using a standardized guideline appraisal instrument. METHODS: Drug therapy guidelines in the database were identified with the use of search terms and hand searching. Descriptive information about the developers, endorsement by other organizations, publication status, disease and drug focus was abstracted. Each guideline was independently assessed by 3 appraisers (a physician, a pharmacist and a methodologist) with the use of the Appraisal Instrument for Clinical Guidelines. Conditions were classified according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems. RESULTS: We identified 217 drug therapy guidelines produced or reviewed from 1994 to 1998. Guideline developers included national organizations (47.0%), paragovernment organizations (39.6%) and professional associations (30.9%); 31.3% of the guidelines were published, and 10.6% stated drug company sponsorship. The most common conditions addressed by the guidelines were infections and parasitic diseases (39.6%), neoplasms (11.5%) and diseases of the circulatory system (11.5%). Drugs most commonly cited were anti-infective agents (42.9%), antiviral agents (15.2%) and cardiovascular drugs (16.1%). Eleven organizations produced 176 (81.1%) of the guidelines. In all, 14.7% of the guidelines met half or more of the 20 items assessing rigour of guideline development on the appraisal instrument (mean quality score 30.0% [95% confidence interval (CI) 27.5%-32.6%]), 61.8% met half or more of the 12 items assessing guideline context and content (mean score 57.0% [95% CI 54.6%-59.3%]), and none met half or more of the 5 items assessing guideline application (mean score 5.6% [95% CI 4.7%-6.5%]). Overall, 64.6% of the guidelines were recommended with modification by at least 2 of the 3 appraisers, 9.2% were recommended without change, and 26.3% were not recommended. The quality of the guidelines assessed varied significantly by developer, publication status and drug company sponsorship. No substantial improvement in guideline quality was observed over the 5-year study period. INTERPRETATION: Developers of Canadian drug therapy guidelines are producing guidelines that are often perceived to be clinically useful to physicians and pharmacists, although the methods (or the description of the methods) by which they are developed need to be more rigorous and thorough.

Red blood cell transfusion strategies.

Although the hemoglobin level of 100 g/L has been used for many years as the allogeneic red blood cell (RBC) transfusion trigger, current evidence indicates that for most patients a more restrictive transfusion strategy is at least as effective as and possibly superior to a liberal transfusion strategy. Moreover, the available data indicate that the use of smaller volumes of allogeneic RBCs may be associated with decreased risk of morbidity and mortality. Thus several recent studies indicate that the use of more restrictive triggers than 100 g/L does not appear to adversely affect patient outcomes. Indeed, the majority of recently published RBC transfusion guidelines recommend a more conservative and cautious approach to allogeneic RBC transfusion practice, primarily to reduce the risk of transfusion-related adverse effects. However, the available transfusion trigger studies do not provide sufficient data to allow the claim that the improved outcomes observed are the sole result of the transfusion strategy used. It is possible that the results are the consequence of effects yet to be defined clearly. Additional studies will be necessary to determine the effects of RBC storage time and the presence of allogeneic leukocytes in allogeneic RBC transfusion practice. Nonetheless, the available data, together with detailed information about alternatives to blood product transfusions, will enable physicians to improve outcomes in transfused patients.

Bioethics for clinicians: 23. Disclosure of medical error.

Adverse events and medical errors are not uncommon. In this article we review the literature on such events and discuss the ethical, legal and practical aspects of whether and how they should be disclosed to patients. Ethics, professional policy and the law, as well as the relevant empirical literature, suggest that timely and candid disclosure should be standard practice. Candour about error may lessen, rather than increase, the medicolegal liability of the health care professionals and may help to alleviate the patient's concerns. Guidelines for disclosure to patients, and their families if necessary, are proposed.

Disclosure of adverse events and errors in healthcare: an ethical perspective.

Adverse events and medical errors affecting patient care are recognised internationally as major problems in medicine. The failure of health care professionals and health institutes to address this problem has threatened to undermine public confidence in the health care system as a whole. Less focus has been directed at the ethical issues raised by negative outcomes of care, specifically the issue of disclosure. Efforts to prevent negative outcomes of care must be supplemented by policies of increased honesty and openness with patients and their families about adverse incidents. Disclosure should be made easier, not riskier, for healthcare practitioners so clinicians can learn from mistakes and improve patient care. Ethical guidelines for error disclosure must distinguish between disciplinary action and reporting of adverse incidents. Disclosure of negative outcomes requires tact and good communication skills. Healthcare institutions should provide training for the clinicians in this area, if necessary. As a general rule, patients should be informed of unexpected adverse incidents as soon as possible. Medical staff should be rewarded for adverse event reporting and protected from institutional retaliation on account of errors made in health care.

Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa.

We developed a rapid in vitro antibiotic susceptibility test to screen double- and triple-antibiotic combinations for bactericidal activity against 75 multiresistant Pseudomonas aeruginosa isolates referred from 44 cystic fibrosis (CF) patients. When used alone, the most effective intravenous antibiotic, meropenem, was bactericidal against only 44% of the isolates. High-dose tobramycin (200 microg/ml; concentrations achievable by aerosol administration) was bactericidal against 72% of isolates. Adding a second antibiotic significantly improved bactericidal activity. The most effective double-antibiotic combinations contained high-dose tobramycin plus meropenem, piperacillin/tazobactam, or ciprofloxacin, and were bactericidal against 88 to 94% of the isolates. Excluding high-dose tobramycin, the most effective intravenous double-antibiotic combinations contained meropenem plus ciprofloxacin, tobramycin (4 microg/ml), or cefipime, and were bactericidal against 85%, 71%, and 70% of isolates, respectively. Adding a third antibiotic did not significantly improve inhibition in vitro. We conclude that double-antibiotic combinations containing meropenem or high-dose tobramycin show the best bactericidal activity in vitro against multiresistant strains of P. aeruginosa. Addition of a third antibiotic to these double-antibiotic combinations may be unnecessary.

Intubation and mechanical ventilation for COPD: development of an instrument to elicit patient preferences.

BACKGROUND: Whether to simply provide palliative care or to intubate and use mechanical ventilation (MV) in a patient with severe COPD in acute respiratory failure is a difficult decision. The outcome of MV cannot be accurately predicted. Some patients cannot be weaned from the ventilator; those who are weaned often return to chronic severe respiratory disability. It is important that patients participate in this decision, but assistance is required. To address these issues, we developed and pilot-tested an aid to assist patients with MV decisions. METHODS: A scenario-based decision aid was developed consisting of an audiocassette and a booklet describing intubation and MV and its possible outcomes. We used a probability tradeoff technique to elicit the patients' preferences and a decisional conflict scale to evaluate satisfaction. RESULTS: With the assistance of the decision aid, all patients (10 men and 10 women) reached a decision. Two men and all 10 women declined MV. Mean decisional conflict was low (2.2 of a possible 5; SD, 0.9). At 1 year, only two patients (11%) had changed their decision. The agreement between physicians and patients was 65%; between next-of-kin and patients, there was uniform disagreement. CONCLUSION: With the decision aid, stable decisions were made with satisfaction and confidence. Proxy decisions were incongruent, especially when made by family members. The strong gender effect should be further investigated. We suggest that the COPD decision aid be further tested in a community clinical setting.

The modulation of DNA content: proximate causes and ultimate consequences.

The forces responsible for modulating the large-scale features of the genome remain one of the most difficult issues confronting evolutionary biology. Although diversity in chromosomal architecture, nucleotide composition, and genome size has been well documented, there is little understanding of either the evolutionary origins or impact of much of this variation. The 80,000-fold divergence in genome sizes among eukaryotes represents perhaps the greatest challenge for genomic holists. Although some researchers continue to characterize much variation in genome size as a mere by-product of an intragenomic selfish DNA "free-for-all" there is increasing evidence for the primacy of selection in molding genome sizes via impacts on cell size and division rates. Moreover, processes inducing quantum or doubling series variation in gametic or somatic genome sizes are common. These abrupt shifts have broad effects on phenotypic attributes at both cellular and organismal levels and may play an important role in explaining episodes of rapid-or even saltational-character state evolution.

The rural health care workforce implications of practice guideline implementation.

BACKGROUND: Rural health care workforce forecasting has not included adjustments for predictable changes in practice patterns, such as the introduction of practice guidelines. PURPOSE: To estimate the impact of a practice guideline for a single health condition on the needs of a rural health professional workforce. METHODS: The current care of a cohort of rural Medicare recipients with diabetes mellitus was compared with the care recommended by a diabetes practice guideline. The additional tests and visits that were needed to comply with the guideline were translated into additional hours of physician services and total physician full-time equivalents. RESULTS: The implementation of a practice guideline for Medicare recipients with diabetes in rural Minnesota would require over 30,000 additional hours of primary care physician services and over 5,000 additional hours of eye care professionals' time per year. This additional need represents a 1.3% to 2.4% increase in the number of primary care physicians and a 1.0% to 6.6% increase in the number of eye-care clinicians in a state in which the rural medical provider to population ratios already meet some recommended workforce projections. CONCLUSIONS: The implementation of practice guidelines could result in an increased need for rural health care physicians or other providers. That increase, caused by guideline implementation, should be accounted for in future rural health care workforce predictions.

The development of indications for the preoperative use of recombinant erythropoietin.

OBJECTIVE: To develop indications for the preoperative use of recombinant erythropoietin (rHuEPO) alone and in conjunction with preoperative autologous donation (PAD). DESIGN: A 2-round modified Delphi-consensus process. PARTICIPANTS: Nine physicians representing multiple clinical specialties, practice environments and geographic locations. METHOD: From evidence tables and a literature summary (MEDLINE database from January 1985 to August 1996) provided and using the RAND-UCLA appropriateness method, the physicians developed 264 indications for the preoperative use of rHuEPO by permuting 7 clinical factors (age, history of transfusion or antibody incompatibility, hemoglobin level, anemia of chronic disease, expected blood loss, presence of cardiovascular or cardiopulmonary disease and patient anxiety). These indications were rated on a 9-point appropriateness scale. Median scores and measures of agreement were determined. OUTCOME MEASURES: The significance of cost constraints or cost and blood supply constraints and the impact of each clinical factor on the ratings as judged by statistical analysis. RESULTS: Of the 264 indications, 54% were rated appropriate, 18% uncertain and 28% inappropriate. Expected blood loss had the greatest impact on the ratings (high expected blood loss had a 5.9 point more appropriate rating on the 9-point scale than low expected blood loss [p < 0.0001]). Preoperative hemoglobin level also significantly influenced the ratings (p < 0.0001). Compared with the clinical context, the ratings under the cost constraint were 1.0 less appropriate (p < 0.0001) for rHuEPO alone and 1.2 less appropriate for rHuEPO and PAD (p < 0.0001). The ratings for patients with moderate expected blood loss were significantly influenced by the cost constraint (less appropriate). CONCLUSIONS: Expected blood loss and preoperative hemoglobin level were the best indicators of rHuEPO appropriateness. Different contexts modify the appropriateness ratings of an expensive drug like rHuEPO.

Directed termination PCR: a one-step approach to mutation detection.

We describe a novel PCR-based method that allows the generation of nested termination fragments by integrating both selective DNA amplification and directed chain termination into a single PCR reaction. These termination fragments can be examined for sequence variation in either denaturing or non-denaturing polyacrylamide gels. This method provides a one-step and highly effective approach for the detection of both insertions/deletions and single base pair substitutions in sequences up to 1 kb in length.

Adult height and incidence of cancer in male physicians (United States).

Adult height has been found in some but not all studies to be associated positively with overall cancer incidence as well as several site-specific cancers. The Physicians' Health Study (PHS), a randomized trial of beta-carotene and aspirin in the primary prevention of cancer and cardiovascular disease in men, provided an opportunity to examine the association between height and total malignant neoplasms (excluding non-melanoma skin cancer), as well as site-specific cancers including prostate, colorectal, and lung cancer. The PHS is comprised of 22,071 US male physicians in the United States, a population homogeneous for adult socioeconomic status, aged 40 to 84 years in 1982. Participants were classified into five height categories at study entry. After an average follow-up of over 12 years, there were 2,566 cases of incident total malignant neoplasms, including 1,047 prostate, 341 colorectal, and 170 lung cancer cases. Height was associated positively with both total malignant neoplasms and prostate cancer. Compared with men in the shortest category (<67 inches), relative risks and 95 percent confidence intervals (CI) for total malignant neoplasms for men whose height (in inches) was 68-69, 70-71, 72, and 73+ were, respectively: 1.13 (CI = 0.99-1.28), 1.15 (CI = 1.02-1.30), 1.29 (CI = 1.12-1.49), and 1.21 (CI = 1.05-1.39), P trend 0.001, adjusted for age, randomized treatment assignments, body mass index (wt/ht2), cigarette smoking, alcohol use, and exercise frequency. For prostate cancer, the corresponding RR values were 1.23 (CI = 1.00-1.51), 1.26 (CI = 1.04-1.54), 1.59 (CI = 1.27-1.98), and 1.26 (CI = 1.00-1.59), P trend 0.005. For colorectal cancer, in some but not all height categories compared with the shortest, there were elevated RRs without a significant linear trend: RR = 1.51 (CI = 1.06-2.14), 1.14 (CI = 0.80-1.62), 1.19 (CI = 0.79-1.80), and 1.53 (CI = 1.04-2.25), P trend 0.23. In contrast, there was no evidence of an association of height with lung cancer. These data indicate a positive association between height and risk of total malignant neoplasms, as well as of prostate cancer and, possibly, colorectal cancer.

Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials.

OBJECTIVE: To examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. DATA SOURCES: We conducted a computerized literature search from 1985 through 1995 to identify all published trials testing statin drugs. The Cholesterol and Recurrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. TRIAL SELECTION: Criteria for inclusion of randomized trials in the overview were (1) statin drugs alone used to reduce lipid levels rather than multifactorial interventions including another type of cholesterol-lowering drug and (2) inclusion of data on deaths and/or strokes. DATA EXTRACTION: Data were extracted by 2 researchers, and only minor discrepancies, which were easily resolved by discussion, occurred. Principal investigators of the trials and their funding agencies were also contacted to secure any relevant data not included in the published reports. DATA SYNTHESIS: A total of 16 individual trials including approximately 29 000 subjects treated and followed up an average of 3.3 years were included in the overview. The average reductions in total and low-density lipoprotein cholesterol achieved were large-22% and 30%, respectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deaths occurred. Those assigned to statin drugs experienced significant reductions in risks of stroke of 29% (95% confidence interval [CI], 14%-41%) as well as total mortality of 22% (95% CI, 12%-31%), which was attributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI, 0.75-1.14). There was also no significant increase in risk of cancer (RR, 1.03; 95% CI, 0.90-1.17). CONCLUSION: This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence.

Description and evaluation of the vallecula sign: a new radiologic sign in the diagnosis of adult epiglottitis.

STUDY OBJECTIVE: To describe and prospectively evaluate a new radiologic sign with the potential to increase the diagnostic accuracy of soft-tissue radiography of the neck in the identification of adult epiglottitis. METHODS: We conducted a prospective, before-and-after blinded study at two tertiary care institutions. A convenience sample of four staff emergency physicians, three otolaryngology residents, four radiology residents, and four senior medical students volunteered to participate. We assembled 26 soft-tissue radiographs of the neck from consecutive patients ED with the diagnosis of epiglottitis made on the basic of direct visualization. Twenty-six control radiographs were identified from ED patients who were being evaluated for the presence of foreign bodies or minor cervical trauma. We then randomly mixed the two sets of radiographs. Participants were asked to identify epiglottis among the 52 randomly sequenced radiographs. A standardized 5-minute tutorial on the vallecula sign was presented to all participants after the first interpretation. We then asked the participants to make a second interpretation of the 52 radiographs without knowledge of correct answers from the initial evaluation. RESULTS: The participants accurately classified 80.5% of all radiographs reviewed before the tutorial and 98.8% after the tutorial (P < .0001). Similarly, sensitivity improved from 78.5% to 98.2% (P < .0001) and specificity improved from 82.8% to 99.5% (P < .0001). We found no significant differences in performance characteristics among the different types of participants. CONCLUSION: We have described a new radiographic sign that improves the diagnostic accuracy of soft-tissue radiography of the neck. If reproduced in prospective studies, the absence of the vallecula sign on radiography might obviate the need for routine use of direct visualization as an initial screen.