Outpatient Pharmacy Prescriptions During the First Year Following Serious Combat Injury: A Retrospective Analysis.

INTRODUCTION: Limited research has analyzed the full range of outpatient medication prescription activity following serious combat injury. The objectives of this study were to describe (1) outpatient medication prescriptions and refills during the first 12 months after serious combat injury, (2) longitudinal changes in medication prescriptions during the first-year postinjury, and (3) patient characteristics associated with outpatient prescriptions. MATERIALS AND METHODS: This was a retrospective analysis of existing health and pharmacy data for a random sample of U.S. service members who sustained serious combat injuries in the Iraq and Afghanistan conflicts, 2010-2013 (n = 381). Serious injury was defined by an Injury Severity Score (ISS) of 9 or greater. These patients typically participate in military rehabilitation programs (eg, amputation care) where prescription medications are essential. Data sources were the Expeditionary Medical Encounter Database for injury-specific data, the Pharmacy Data Transaction Service for outpatient medication prescriptions and refills, and the Military Health System Data Repository for diagnostic codes of pain and psychological disorders. Military trauma nurses reviewed casualty records to identify types of injuries. Using the American Hospital Formulary Service Pharmacologic-Therapeutic Classification system, clinicians identified 13 categories of prescription medications (eg, opioid, psychotherapeutic, immunologic) for analysis. Multivariable negative binomial and logistic regression analyses evaluated significant associations between independent variables (eg, blast injury, traumatic brain injury [TBI], ISS, limb amputation, diagnoses of chronic pain, or psychological disorders) and prescription measures (ie, number or category of medication prescriptions). We also describe longitudinal changes in prescription activity postinjury across consecutive quarterly intervals (91 days) during the first-year postinjury. RESULTS: During the first-year postinjury, patients averaged 61 outpatient prescriptions, including all initial prescriptions and refills. They averaged eight different categories of medications, primarily opioid, immunologic, gastrointestinal/genitourinary, central nervous system (CNS), nonopioid analgesic, and psychotherapeutic medications (representing 82% of prescriptions) during the first year. Prescription activity generally declined across quarters. There was still substantial prescription activity during the fourth quarter, as 79% of patients had at least one prescription. From 39 to 49% of patients had fourth-quarter prescriptions for opioid, CNS, or psychotherapeutic medications. Longitudinally, we found that 24-34% of patients had an opioid, CNS, or psychotherapeutic prescription during each of the final three quarters. In multivariable analysis, ISS, limb amputation (particularly bilateral amputation), and diagnoses of chronic pain and post-traumatic stress disorder (PTSD) were associated with significantly higher counts of individual and multiple medication prescriptions. TBI was associated with significantly lower numbers of prescriptions for certain medications. CONCLUSIONS: This is one of the first studies to provide a systematic analysis of outpatient medication prescriptions following serious combat injury. The results indicate substantial prescription activity from multiple medication categories throughout the first-year postinjury. Diagnoses of chronic pain, PTSD, and limb amputation and ISS were associated with significantly higher counts of prescriptions overall and more prescription medication categories. This study provides initial evidence to better understand medication prescription activity following serious combat injury. The results inform future research on medication prescription practices and planning for rehabilitation.

Clinic Use at the Departments of Defense and Veterans Affairs Following Combat Related Amputations.

INTRODUCTION: Little population-based research has described the transition from Department of Defense (DoD) to Department of Veterans Affairs (VA) healthcare following combat related amputations. The objectives were to describe (1) to what extent patients used either DoD only facilities, both DoD and VA facilities, or VA only facilities during the first 5 years postinjury, (2) which specific clinics were used and (3) clinic use among patients with different levels of amputation (upper versus lower), and among patients with early or late amputation. MATERIALS AND METHODS: This was a retrospective analysis of health data extracted from the expeditionary medical encounter database (EMED) and national DoD and VA databases. Patients were 649 US service members who sustained a single major limb amputation following injuries in the Iraq and Afghanistan conflicts, 2001-2008. We compared yearly DoD and VA clinic use by patient groups with different levels of amputation (upper limb: above versus below elbow or lower limb: above versus below knee), different timing of amputation (early: within 90 days postinjury versus late: more than 90 days postinjury), military component (Active Duty versus National Guard/Reserve) and race (White versus Black). For all groups, we calculated the percentage of patients using: (1) DoD only, (2) both DoD and VA or 3) VA only clinics during each of postinjury years 1 through 5. We also calculated the percentage of patients who used specific clinics (e.g., social work, prosthetics, mental health) during each postinjury year. RESULTS: During postinjury year 1, over 98% of patients used DoD only or both DoD and VA clinics. Most individuals (70% to 78%) used both DoD and VA clinics during postinjury year 1. Use of VA only clinics increased gradually between postinjury year 2 (15% to 30% of patient groups) and year 5 (75% to 88%). This gradual transition to use of VA only clinics was seen consistently across patient groups with different anatomical levels or timing of amputation, military component or race. Patients with lower levels of amputation (versus higher levels) and individuals with early amputations (versus late) transitioned earlier to VA only care. Overall, clinic use was high as 91% to 100% of all patient groups used one or more clinics (DoD or VA) during each of the first 5 years. For specific clinics, most patients used DoD facilities related to rehabilitation (physical therapy, prosthetics) or transitional care (social work) particularly during postinjury year 1. Use of most VA clinics studied (social work, primary care, prosthetics, mental health) showed a modest increase primarily after postinjury year 1 and remained stable through postinjury year 5. The results indicated apparent underuse of psychiatric/mental health and prosthetics between postinjury year 1 and 2. CONCLUSIONS: The present study indicated a gradual transition from DoD to VA only healthcare which extended across 5 years following combat related amputations. Patients with lower levels of amputation or early amputation generally transitioned earlier to VA only healthcare. These results can inform medical planning to support a timely and clinically effective transition from DoD to VA healthcare.

Retrospective study of cardiovascular disease risk factors among a cohort of combat veterans with lower limb amputation.

INTRODUCTION: Previous studies have shown that veterans with lower limb amputation have a higher risk for cardiovascular disease (CVD) compared with population-based controls. American veterans who have served in Iraq and Afghanistan with lower limb amputation may be at a similarly higher risk. PATIENTS AND METHODS: The Navel Health Research Center (NHRC) maintains the Expeditionary Medical Encounter Database (EMED) of military personnel who have sustained combat limb amputation or serious limb injury during the conflicts in Iraq and Afghanistan. Department of Veterans Affairs data from 2003 to April 2015 was used to analyze CVD risk factors in this cohort. Veterans with either unilateral (n=442) or bilateral (n=146) lower limb amputation were compared to those with serious lower limb trauma without amputation (n=184). Multivariate regression was used to measure associations between lower limb amputation and CVD risk factors over an average of 8 years of follow-up. Outcomes included mean arterial pressure (MAP), low-density lipoprotein, high-density lipoprotein (HDL), and serum triglycerides (TG). RESULTS: Compared with the limb injury group, those with unilateral lower limb amputation had significantly lower HDL (p<0.05) and higher TG (p<0.05). Those with bilateral lower limb amputation had significantly higher MAP (p<0.05), lower HDL (p<0.01), and higher TG (p<0.001). The prevalence of metabolic syndrome, defined as type 2 diabetes or a constellation of blood pressure and lipid changes consistent with metabolic syndrome, was 8.7%, 14.9%, and 21.9% for limb injury, unilateral amputation, and bilateral amputation groups, respectively. Veterans with bilateral lower limb amputation had a 2.25-increased odds ratio (95% confidence interval 1.19-5.05) of type 2 diabetes or blood pressure and lipid changes consistent with metabolic syndrome compared to those with limb injury. CONCLUSIONS: Results suggest that veterans with lower limb amputation have a higher risk for metabolic syndrome. Primary care interventions to manage weight, blood pressure, and lipid levels are fundamental in order to reduce cardiac risk in this relatively young cohort.

Tracking temporal shifts in area, biomes, and pollinators in the radiation of Salvia (sages) across continents: leveraging anchored hybrid enrichment and targeted sequence data.

PREMISE OF THE STUDY: A key question in evolutionary biology is why some clades are more successful by being widespread geographically, biome diverse, or species-rich. To extend understanding of how shifts in area, biomes, and pollinators impact diversification in plants, we examined the relationships of these shifts to diversification across the mega-genus Salvia. METHODS: A chronogram was developed from a supermatrix of anchored hybrid enrichment genomic data and targeted sequence data for over 500 of the nearly 1000 Salvia species. Ancestral areas and biomes were reconstructed using BioGeoBEARS. Pollinator guilds were scored, ancestral pollinators determined, shifts in pollinator guilds identified, and rates of pollinator switches compared. KEY RESULTS: A well-resolved phylogenetic backbone of Salvia and updated subgeneric designations are presented. Salvia originated in Southwest Asia in the Oligocene and subsequently dispersed worldwide. Biome shifts are frequent from a likely ancestral lineage utilizing broadleaf and/or coniferous forests and/or arid shrublands. None of the four species diversification shifts are correlated to shifts in biomes. Shifts in pollination system are not correlated to species diversification shifts, except for one hummingbird shift that precedes a major shift in diversification near the crown of New World subgen. Calosphace. Multiple reversals back to bee pollination occurred within this hummingbird clade. CONCLUSIONS: Salvia diversified extensively in different continents, biomes, and with both bee and bird pollinators. The lack of tight correlation of area, biome, and most pollinator shifts to the four documented species diversification shifts points to other important drivers of speciation in Salvia.

A Retrospective Comparison of Five-Year Health Outcomes Following Upper Limb Amputation and Serious Upper Limb Injury in the Iraq and Afghanistan Conflicts.

BACKGROUND: Limited population-based research has described long-term health outcomes following combat-related upper limb amputation. OBJECTIVE: To compare health outcomes following upper limb amputation with outcomes following serious upper limb injury during the first 5 years postinjury. DESIGN: Retrospective cohort. SETTING: Departments of Defense (DoD) and Veterans Affairs (VA) inpatient and outpatient health care facilities. PARTICIPANTS: Three-hundred eighteen U.S. Service Members. METHODS: Patients sustained an above elbow (AE, n = 51) or below elbow (BE, n = 80) amputation or serious arm injury without amputation (NO AMP, n = 187) in the Iraq or Afghanistan conflicts, 2001 through 2008. Injuries were coded by trauma nurses. Outcomes came from DoD and VA health databases. MAIN OUTCOME MEASUREMENTS: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes. RESULTS: Most patients were injured by blast weaponry causing serious to severe injuries. All groups had a high prevalence of physical and psychological health diagnoses. The prevalence for nearly all wound complications and many physical and psychological disorders decreased substantially after postinjury year 1. The prevalence of posttraumatic stress disorder, however, increased significantly from postinjury year 1 (20%) to 3 (36%). Pain and psychological disorders ranged from 69% to 90% of patients during postinjury year 1 and remained relatively high even postinjury during year 5 (37%-53%). After adjusting for covariates, the AE group had significantly higher odds for some physical and psychological diagnoses (eg, deep vein thrombosis/pulmonary embolism, cervical pain, osteoarthritis, obesity, and mood and adjustment disorders) relative to the BE or NO AMP groups. BE patients had significantly lower odds for osteomyelitis, and AE and BE patients had lower odds for fracture nonunion and joint disorders versus NO AMP. CONCLUSIONS: The results identify similarities and differences in clinical outcomes following combat-related upper limb amputation versus serious arm injury and can inform medical planning to improve rehabilitation programs and outcomes for these patients. LEVEL OF EVIDENCE: III.

Correction: A Comparison of Four-Year Health Outcomes following Combat Amputation and Limb Salvage.

[This corrects the article DOI: 10.1371/journal.pone.0170569.].

A Comparison of Four-Year Health Outcomes following Combat Amputation and Limb Salvage.

Little research has described the long-term health outcomes of patients who had combat-related amputations or leg-threatening injuries. We conducted retrospective analysis of Department of Defense and Department of Veterans Affairs health data for lower extremity combat-injured patients with (1) unilateral amputation within 90 days postinjury (early amputation, n = 440), (2) unilateral amputation more than 90 days postinjury (late amputation, n = 78), or (3) leg-threatening injuries without amputation (limb salvage, n = 107). Patient medical records were analyzed for four years postinjury. After adjusting for group differences, early amputation was generally associated with a lower or similar prevalence for adverse physical and psychological diagnoses (e.g., pain, osteoarthritis, posttraumatic stress disorder) versus late amputation and/or limb salvage. By contrast, early amputation was associated with an increased likelihood of osteoporosis during the first year postinjury. The prevalence of posttraumatic stress disorder increased for all patient groups over four years postinjury, particularly in the second year. The different clinical outcomes among combat extremity injured patients treated with early amputation, late amputation, or limb salvage highlight their different healthcare requirements. These findings can inform and optimize the specific treatment pathways that address the physical and psychological healthcare needs of such patients over time.

Venous thromboembolism after traumatic amputation: an analysis of 366 combat casualties.

BACKGROUND: We sought to determine the incidence, risk factors, and time course for deep vein thrombosis and pulmonary embolism (DVT/PE) after combat-related major limb amputations. METHODS: Patients with amputation in Iraq or Afghanistan from 2009 through 2011 were eligible. Details of postinjury care, date of diagnosis of DVT/PE, and injury specific data were collected. Military databases and chart reviews were used. RESULTS: In 366 patients, 103 (28%) had DVT/PE; PE was diagnosed in 59 (16%) and DVT in 59 (16%). Most DVT (69%) and PE (66%) occurred within 10 days. Increasing ventilator days (odds ratio [OR], 1.97; 95% CI, 1.16 to 3.37) and units of blood transfused (OR, 1.72; 95% CI, 1.11 to 2.68) were associated with DVT. Increasing units of fresh-frozen plasma were associated with PE (OR, 1.31; 95% CI, 1.10 to 1.55). CONCLUSIONS: The incidence of DVT/PE is high after combat-related amputation. Most DVT/PE occur early and prophylaxis is indicated.

Rehabilitation and multiple limb amputations: A clinical report of patients injured in combat.

This clinical report describes the outpatient rehabilitation program for patients with multiple limb amputations enrolled in the Comprehensive Combat and Complex Casualty Care facility at the Naval Medical Center San Diego. Injury-specific data for 29 of these patients wounded by blast weaponry in Afghanistan in 2010 or 2011 were captured by the Expeditionary Medical Encounter Database at the Naval Health Research Center and were reviewed for this report. Their median Injury Severity Score was 27 (N = 29; range, 11-54). Patients averaged seven moderate to serious injuries (Abbreviated Injury Scale scores ≥2), including multiple injuries to lower limbs and injuries to the torso and/or upper limbs. All patients received care from numerous clinics, particularly physical therapy during the first 6 mo postinjury. Clinic use generally declined after the first 6 mo with the exception of prosthetic devices and repairs. The clinical team implemented the Mayo-Portland Adaptability Inventory, 4th Revision (MPAI-4) to assess functioning at outpatient program initiation and discharge (n = 23). At program discharge, most patients had improved scores for the MPAI-4 items assessing mobility, pain, and transportation, but not employment. Case reports described rehabilitation for two patients with triple amputations and illustrated multispecialty care and contrasting solutions for limb prostheses.

Lower-limb amputation and effect of posttraumatic stress disorder on Department of Veterans Affairs outpatient cost trends.

Department of Veterans Affairs (VA) outpatient costs were analyzed for combat Veterans injured in Iraq and Afghanistan from 2001 to 2008. Patients had serious lower-limb injuries (n = 170) or unilateral (n = 460) or bilateral (n = 153) lower-limb amputation(s). Total costs over the follow-up period (2003 to 2012) and annual costs were analyzed. Unadjusted mean costs per year in 2012 U.S. dollars were $7,200, $14,700 and $18,700 for limb injuries and unilateral and bilateral lower-limb amputation(s), respectively (p < 0.001). Multivariate modeling indicated that annual cost declined after the first year in the VA for Veterans with limb injuries (p < 0.001, repeated measures). In contrast, annual costs doubled after 3-5 years with unilateral (p < 0.001) and bilateral amputation(s) (p < 0.001). Among amputees, prosthetics comprised more than 50% of outpatient cost; unadjusted mean cost per year for prosthetics was 7-9 times higher in comparison with Veterans with limb injuries. Amputation status was associated with an adjusted 3.12-fold increase in mean prosthetic cost per year (p < 0.001, generalized linear model). In addition, posttraumatic stress disorder (PTSD) was associated with increased prosthetic cost by amputation status (p < 0.001) and increased psychiatric and pharmacy costs (both p < 0.001). Results indicate relatively high and sustained outpatient costs driven by prosthetics following amputation. Finally, PTSD affected cost for multiple domains of health, highlighting the importance of accurate diagnosis, treatment, and support for PTSD.

Glasgow Coma Scale scores, early opioids, and 4-year psychological outcomes among combat amputees.

Morphine and fentanyl are frequently used for analgesia after trauma, but there is debate over the advantages and disadvantages of these opioids. Among combat amputees, intravenous (IV) morphine (vs IV fentanyl) after injury was associated with reduced likelihood of posttraumatic stress disorder (PTSD). The previous results were based on military health diagnoses over 2 yr postinjury. The present study followed psychological diagnoses of patients with amputation for 4 yr using military and Department of Veterans Affairs health data. In-theater combat casualty records (n = 145) documented Glasgow Coma Scale (GCS) scores and/or morphine, fentanyl, or no opioid treatment within hours of injury. We found that (1) GCS scores were not significantly associated with PTSD; (2) longitudinal modeling using four (yearly) time points showed significantly reduced odds of PTSD for patients treated with morphine (vs fentanyl) across years (adjusted odds ratio = 0.40; 95% confidence interval = 0.17­0.94); (3) reduced PTSD prevalence for morphine (vs IV fentanyl; morphine = 25%, fentanyl = 59%, p < 0.05) was significant, specifically among patients with traumatic brain injury during the first 2 yr postinjury; and (4) PTSD prevalence, but not other disorders (e.g., mood), increased between year 1 (PTSD = 18%) and years 2 through 4 postinjury (PTSD range = 30%­32%).

Glasgow Coma Scores, early opioids, and posttraumatic stress disorder among combat amputees.

A recent study found that combat amputees had a reduced prevalence of posttraumatic stress disorder (PTSD) compared with nonamputees with serious extremity injuries. We hypothesized that an extended period of impaired consciousness or early treatment with morphine could prevent consolidation of traumatic memory and the development of PTSD. To examine this hypothesis, we retrospectively reviewed 258 combat casualty records from the Iraq or Afghanistan conflicts from 2001-2008 in the Expeditionary Medical Encounter Database, including medications and Glasgow Coma Scale (GCS) scores recorded at in-theater facilities within hours of the index injury. All patients sustained amputations from injuries. Psychological diagnoses were extracted from medical records for 24 months postinjury. None of 20 patients (0%) with GCS scores of 12 or lower had PTSD compared to 20% of patients with GCS scores of 12 or greater who did have PTSD. For patients with traumatic brain injury, those treated with intravenous morphine within hours of injury had a significantly lower prevalence of PTSD (6.3%) and mood disorders (15.6%) compared to patients treated with fentanyl only (prevalence of PTSD = 41.2%, prevalence of mood disorder = 47.1%). GCS scores and morphine and fentanyl treatments were not significantly associated with adjustment, anxiety, or substance abuse disorders.

A comparison of health outcomes for combat amputee and limb salvage patients injured in Iraq and Afghanistan wars.

BACKGROUND: Treatment of military combatants who sustain leg-threatening injuries remains one of the leading challenges for military providers. The present study provides systematic health outcome data to inform decisions on the definitive surgical treatment, namely amputation versus limb salvage, for the most serious leg injuries. METHODS: This was a retrospective analysis of health records for patients who sustained serious lower-extremity injuries in the Iraq and Afghanistan conflicts, 2001 to 2008. Patients had (1) amputation during the first 90 days after injury (early amputees, n = 587), (2) amputation more than 90 days after injury (late amputees, n = 84), or (3) leg-threatening injuries without amputation (limb salvage [LS], n = 117). Injury data and health outcomes were followed up to 24 months. RESULTS: After adjusting for group differences, early amputees and LS patients had similar rates for most physical complications. Early amputees had significantly reduced rates of psychological diagnoses (posttraumatic stress disorder, substance abuse) and received more outpatient care, particularly psychological, compared with LS patients. Late amputees had significantly higher rates of many mental and physical health diagnoses, including prolonged infections and pain issues, compared with early amputees or LS patients. CONCLUSION: Early amputation was associated with reduced rates of adverse health outcomes relative to late amputation or LS in the short term. Most evident was that late amputees had the poorest physical and psychological outcomes. These findings can inform health care providers of the differing clinical consequences of early amputation and LS. These results indicate the need for separate health care pathways for early and late amputees and LS patients.

Phylogeny of New World Salvia subgenus Calosphace (Lamiaceae) based on cpDNA (psbA-trnH) and nrDNA (ITS) sequence data.

Salvia subgenus Calosphace (Lamiaceae) is economically and ethnomedicinally significant and comprised of more than 500 species. Although strongly supported as monophyletic, it has received no comprehensive systematic research since the initial establishment of 91 taxonomic sections in 1939. Representative taxa of 73 sections of Calosphace were sampled to investigate the phylogenetic relationships and identify major lineages using chloroplast (intergenic spacer psbA-trnH) and nuclear ribosomal DNA (internal transcribed spacer). Phylogenetic analysis of the combined data sets established monophyly of seven sections (Blakea, Corrugatae, Erythrostachys, Hastatae, Incarnatae, Microsphace, and Sigmoideae) and four major lineages (S. axillaris, "Hastatae clade", "Uliginosae clade", and "core Calosphace"). Sections spanning two or more centers of diversity are not supported by our results; rather, supported relationships exhibit significant geographic structure. Mexico is supported as the geographic origin of Calosphace, and no more than seven dispersal events to South America are required to account for current disjunct distributions.

Angiosperm phylogeny: 17 genes, 640 taxa.

PREMISE OF THE STUDY: Recent analyses employing up to five genes have provided numerous insights into angiosperm phylogeny, but many relationships have remained unresolved or poorly supported. In the hope of improving our understanding of angiosperm phylogeny, we expanded sampling of taxa and genes beyond previous analyses. METHODS: We conducted two primary analyses based on 640 species representing 330 families. The first included 25260 aligned base pairs (bp) from 17 genes (representing all three plant genomes, i.e., nucleus, plastid, and mitochondrion). The second included 19846 aligned bp from 13 genes (representing only the nucleus and plastid). KEY RESULTS: Many important questions of deep-level relationships in the nonmonocot angiosperms have now been resolved with strong support. Amborellaceae, Nymphaeales, and Austrobaileyales are successive sisters to the remaining angiosperms (Mesangiospermae), which are resolved into Chloranthales + Magnoliidae as sister to Monocotyledoneae + [Ceratophyllaceae + Eudicotyledoneae]. Eudicotyledoneae contains a basal grade subtending Gunneridae. Within Gunneridae, Gunnerales are sister to the remainder (Pentapetalae), which comprises (1) Superrosidae, consisting of Rosidae (including Vitaceae) and Saxifragales; and (2) Superasteridae, comprising Berberidopsidales, Santalales, Caryophyllales, Asteridae, and, based on this study, Dilleniaceae (although other recent analyses disagree with this placement). Within the major subclades of Pentapetalae, most deep-level relationships are resolved with strong support. CONCLUSIONS: Our analyses confirm that with large amounts of sequence data, most deep-level relationships within the angiosperms can be resolved. We anticipate that this well-resolved angiosperm tree will be of broad utility for many areas of biology, including physiology, ecology, paleobiology, and genomics.

Evolution and origins of the Mazatec hallucinogenic sage, Salvia divinorum (Lamiaceae): a molecular phylogenetic approach.

Salvia divinorum Epl. & Játiva-M. (Lamiaceae) is a potent hallucinogenic plant that is classified within Salvia subgenus Calosphace, section Dusenostachys, and hypothesized to be an interspecific hybrid. It is of ethnobotanical significance due to its employment in traditional healing ceremonies by the Mazatecs of Oaxaca, Mexico, and due to its unique pharmacology-a highly selective, non-nitrogenous, κ-opioid receptor agonist. In order to test its phylogenetic position and putative hybridity, we sequenced multiple DNA regions (ITS, trnL-trnF, and psbA-trnH) of 52 species-representing the major lineages of subgenus Calosphace-and six accessions of S. divinorum. Our molecular phylogenetic results suggest that S. divinorum should not be classified within Dusenostachys and that it is not a hybrid. Additionally, we determine that the closest known relative of this psychoactive Mexican sage is S. venulosa, a rare endemic of Colombia.

Evolution of secondary heads in Nassauviinae (Asteraceae, Mutisieae).

The evolution of the inflorescence head in Asteraceae is important in the diversification of this largest angiosperm family. The aggregation of heads into higher-order capitulescences (secondary heads or syncephalia) is considered evolutionarily advanced. The genera Moscharia, Nassauvia, Polyachyrus, and Triptilion of the subtribe Nassauviinae (Mutisieae) have syncephalia with differing degrees of capitula condensation. ITS and plastid trnL-trnF regions were analyzed separately and together using maximum parsimony and maximum likelihood to examine the evolution of syncephalia in the Nassauviinae. The four genera displaying syncephalia do not form a clade minus taxa without syncephalia, indicating that secondary heads in Nassauviinae have either convergently evolved twice in the subtribe (or, very unlikely) once with multiple reversions. Strong support was obtained for a sister relationship between Leucheria (without syncephalium) and Polyachyrus, and both sister to Moscharia. Nassauvia and Triptilion form a distinct clade but are sister to other genera, Perezia and Panphalea, without syncephalium. Previous hypotheses postulated the evolution from simple to more complex secondary heads. We show that the ancestor of Moscharia, Polyachyrus, and Leucheria, in a more arid habitat, had a complex type of secondary head, and loss of complexity occurred in response to a shift from arid to mesic conditions.

Does reducing your salt intake make you live longer?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether restricting dietary salt intake would provide protection from adverse cardiovascular events or mortality. Using the reported search, 462 papers were identified of which 14 papers represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and weaknesses were tabulated. We conclude that restricting sodium intake to levels below 6 g per day as most international guidelines such as those of the AHA, the US Dietary Guideline Committee and the Scientific Advisory Committee on Nutrition recommend, clearly reduces blood pressure and in turn may reduce the need for antihypertensives by as much as 30%. However, the ability of dietary sodium restriction to reduce the incidence of cardiovascular events is more controversial due to the lack of adequately powered randomised trials or observational studies conducted with sufficient rigour. Some of the largest studies such as NHANES and TOHP, which do demonstrate a significant benefit, report a 20-30% relative reduction in adverse events which, due to the low rate of these events in the studies equates to an absolute risk reduction over 10-20 years in the region of 2-3% for protection from adverse cardiovascular events from sodium dietary restriction.

Does enteric-coated aspirin result in a lower incidence of gastrointestinal complications compared to normal aspirin?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether enteric-coated aspirin results in a lower incidence of gastrointestinal complications compared to normal aspirin in CABG surgery. Using the reported search, 340 papers were identified. Nine papers represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, weaknesses, results and study comments were tabulated. Five randomised controlled trials of healthy volunteers undergoing endoscopy after a period of either enteric-coated aspirin or plain aspirin administration all demonstrated a clear reduction of gastric mucosal injury. However, these trials on healthy volunteers taking short-term aspirin have not been supported by clinical studies in older age-group adults taking lower doses of aspirin for long periods. No clinical benefits in terms of reduction of gastrointestinal bleeding or ulceration with enteric coating have, therefore, been successfully demonstrated, although the endoscopic studies show that potentially these benefits could exist.

Staminal evolution in the genus Salvia (Lamiaceae): molecular phylogenetic evidence for multiple origins of the staminal lever.

BACKGROUND AND AIMS: The genus Salvia has traditionally included any member of the tribe Mentheae (Lamiaceae) with only two stamens and with each stamen expressing an elongate connective. The recent demonstration of the non-monophyly of the genus presents interesting implications for staminal evolution in the tribe Mentheae. In the context of a molecular phylogeny, the staminal morphology of the various lineages of Salvia and related genera is characterized and an evolutionary interpretation of staminal variation within the tribe Mentheae is presented. METHODS: Two molecular analyses are presented in order to investigate phylogenetic relationships in the tribe Mentheae and the genus Salvia. The first presents a tribal survey of the Mentheae and the second concentrates on Salvia and related genera. Schematic sketches are presented for the staminal morphology of each major lineage of Salvia and related genera. KEY RESULTS: These analyses suggest an independent origin of the staminal elongate connective on at least three different occasions within the tribe Mentheae, each time with a distinct morphology. Each independent origin of the lever mechanism shows a similar progression of staminal change from slight elongation of the connective tissue separating two fertile thecae to abortion of the posterior thecae and fusion of adjacent posterior thecae. A monophyletic lineage within the Mentheae is characterized consisting of the genera Lepechinia, Melissa, Salvia, Dorystaechas, Meriandra, Zhumeria, Perovskia and Rosmarinus. CONCLUSIONS: Based on these results the following are characterized: (1) the independent origin of the staminal lever mechanism on at least three different occasions in Salvia, (2) that Salvia is clearly polyphyletic, with five other genera intercalated within it, and (3) staminal evolution has proceeded in different ways in each of the three lineages of Salvia but has resulted in remarkably similar staminal morphologies.