In vitro antimicrobial and antibiofilm screening of eighteen Iranian medicinal plants.

BACKGROUND: Natural products are one of the best candidates for controlling drug-resistant pathogens, the advantages of which include low production costs and low side effects. In this study, as potential antimicrobials, the anti-bacterial and antibiofilm activities of several Iranian native medicinal plants were screened. METHODS: The antibacterial/antifungal and anti-biofilm activities of 18 medicinal plants including Reseda lutea L., Nepeta sintenisii Bunge., Stachys turcomanica Trautv., Stachys lavandulifolia Vahl, Diarthron antoninae (Pobed.) Kit Tan., Ziziphora clinopodioides Lam., Euphorbia kopetdaghi Prokh, Euphorbia serpens Kunth., Hymenocrater calycinus Benth., Scutellaria pinnatifida A.Ham., Viola tricolor L., Hypericum helianthemoides (Spach) Boiss., Hypericum scabrum L., Convolvulus lineatus L., Scabiosa rotata M.Bieb Greuter & Burdet, Delphinium semibarbatum Bien. Ex Boiss., Glycyrrhiza triphylla Fisch. & C.A.Mey., and Ziziphus jujuba Mill., against two Gram-positive bacteria, Staphylococcus aureus, Bacillus cereus, as well as two Gram-negative bacteria, Pseudomonas aeruginosa, Escherichia coli; and Candida albicans as a fungal strain, were evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values of the extracts against tested microorganisms were reported and we investigated their effect on the biofilm inhibition of Pseudomonas aeruginosa PAO1, Staphylococcus epidermis, Staphylococcus aureus and Streptococcus mutans. In addition, the effect of the extracts on the eradication of the biofilms of these bacteria was evaluated. RESULTS: In this study, H. scabrum was found to exhibit potentially significant activity against Gram-positive bacteria with the MIC range of 6.25-25 µg/mL. This extract also showed a significant effect on inhibiting the biofilm of S. aureus, S. mutans, and S. epidermidis and eradicating the biofilm of S. epidermidis DSMZ 3270. In addition, Hymenocrater calycinus root extract had moderate antibacterial activity against B. cereus with the MIC and MBC 62.5 µg/mL, respectively. CONCLUSIONS: The results of this study showed that the root extracts of two plants, Hypericum scabrum and Hymenocrater calycinus, had antimicrobial and anti-biofilm effects. Based on the observed anti-biofilm effects, these two plants may be considered in future studies to find responsible antimicrobial compounds.

Maternal Vertical Microbial Transmission During Skin-to-Skin Care.

BACKGROUND: Skin-to-skin (STS) care may contribute to mother-to-infant vertical microbial transmission by enriching the preterm infant's microbiome. PURPOSE: The purpose of this observational study was to define the impact of increased STS care duration on vertical microbial transmission and consequently modulate oral and intestinal microbial balance. METHODS: Postpartum women and their preterm infants, 31 to 34 weeks' gestation (n = 25), were recruited for this study. Using 16S rRNA sequencing, we compared α- and ß-diversity with the Shannon and Chao indexes and nonmetric multidimensional scaling, respectively, and relative abundance of microbial communities, which refers to the percentage of specific organisms in a community, from mother's chest skin, preterm infant's oral cavity, and preterm infant's stool samples. Effects of STS care on vertical transmission were determined by comparing oral and stool microbial population of preterm infants who received low exposure (<40 minutes) with that of preterm infants who received high exposure (>60 minutes). RESULTS: Microbial composition, diversity, and relative abundance were different across the 3 sites. Oral microbial richness was less and stool richness was greater among the preterm infants in the high STS care group. Oral and intestinal microbial diversity and composition were different between the groups, with the relative abundance of Gemella and Aggregatibacter genera and Lachnospiraceae family significantly greater in the stool of the high STS care group. IMPLICATIONS FOR PRACTICE: Results suggest that STS care may be an effective method to enhance microbial communities among preterm infants.

Maternal stress during the third trimester of pregnancy and the neonatal microbiome.

OBJECTIVES: Preliminary research suggests that maternal prenatal stress may alter the development of the fetal microbiome and resulting microbial composition after birth. However, the findings of existing studies are mixed and inconclusive. The purpose of this exploratory study was to assess whether maternal stress during pregnancy is associated with the overall number and diversity of various microbial species in the infant gut microbiome or the abundance of specific bacterial taxa. METHODS: Fifty-one women were recruited during their third trimester of pregnancy. The women completed a demographic questionnaire and Cohen's Perceived Stress Scale at recruitment. A stool sample was collected from their neonate at one month of age. Data on potential confounders, such as gestational age and mode of delivery, were extracted from medical records to control for their effects. 16s rRNA gene sequencing was used to identify the diversity and abundance of microbial species, along with multiple linear regression models to examine the effects of prenatal stress on microbial diversity. We employed negative binomial generalized linear models to test for differential expression of various microbial taxa among infants exposed to prenatal stress and those not exposed to prenatal stress. RESULTS: More severe symptoms of prenatal stress were associated with a greater diversity of microbial species in the gut microbiome of neonates (ß = .30, p = .025). Certain microbial taxa, such as Lactobacillus and Bifidobacterium, were enriched among infants exposed to greater maternal stress in utero, while others, such as Bacteroides and Enterobacteriaceae, were depleted in contrast to infants exposed to less stress. CONCLUSIONS: Findings suggest that mild to moderate stress exposure in utero could be associated with a microbial environment in early life that is more optimally prepared to thrive in a stressful postnatal environment. Adaptation of gut microbiota under conditions of stress may involve upregulation of bacterial species, including certain protective microorganisms (e.g. Bifidobacterium), as well as downregulation of potential pathogens (e.g. Bacteroides) via epigenetic or other processes within the fetal/neonatal gut-brain axis. However, further research is needed to understand the trajectory of microbial diversity and composition as infant development proceeds and the ways in which both the structure and function of the neonatal microbiome may mediate the relationship between prenatal stress and health outcomes over time. These studies may eventually yield microbial markers and gene pathways that are biosignatures of risk or resilience and inform targets for probiotics or other therapies in utero or during the postnatal period.

A National Survey of Neonatal Nurses' Knowledge, Beliefs, and Practices of Antibiotic Stewardship.

BACKGROUND: In the neonatal intensive care unit, implementation of antibiotic stewardship programs has been challenging, especially for staff nurses. PURPOSE: To identify neonatal nurses' knowledge and attitudes toward antibiotic stewardship programs in neonatal intensive care units. METHODS: This was a descriptive survey study to assess knowledge, attitudes, and beliefs of neonatal nurses related to antibiotic stewardship. The survey consisted of 23 questions, 6 of which were open-ended. The questions evaluated perceptions of general understanding of antibiotic stewardship, administration of antibiotics, information and perspective about antibiotic use, antibiotic resistance, and availability and usage of resources and education related to antibiotics. The survey was posted online for about 3 months on the Web site of a professional organization of neonatal nurses. RESULTS: Of the 78 neonatal nurses who responded to the survey, 39% were very familiar with the term antibiotic stewardship . The majority of participants did not question the treating provider about the choice, route, or dose of antibiotics. The majority also agreed that more education is needed to achieve the goal of incorporating principles of antibiotic stewardship more fully into practice in the neonatal intensive care unit. IMPLICATIONS FOR PRACTICE: Results suggest that although most nurses are familiar with the term antibiotic stewardship , they would like to have more education on the appropriate use of antibiotics. IMPLICATIONS FOR RESEARCH: Further studies are needed to identify nurse involvement in applying the principles of antibiotic stewardship programs while working with the vulnerable population of preterm infants.

Antimicrobial Stewardship Programs in Preterm Infants: Encouraging Staff Nurse Engagement.

In NICUs, antibiotics are the most frequently prescribed medications. Misuse or overuse of antibiotics may lead to resistant species and other life-threatening complications and untoward effects. Antimicrobial stewardship programs-coordinated programs that promote the appropriate use of antimicrobials (including antibiotics)-have reduced unnecessary medication administration, costs, readmissions, complications, and mortality rates related to antimicrobial agents, predominantly among adult patients in many hospitals. At the same time, however, implementation of antimicrobial stewardship programs among preterm infants has been challenging, especially for staff nurses in NICUs. This article provides an overview of the literature addressing the concept of stewardship, outlines core elements of antibiotic stewardship programs from the Centers for Disease Control and Prevention, and examines strategies for nursing implementation in NICUs focusing on preterm infants.

Distinct visual resolution supports aperture shaping in natural and pantomime-grasping.

Pantomime-grasping is a "simulated" motor response wherein an individual grasps to an area dissociated from a physical target. The task has been used in the apraxia literature as a proxy for natural grasping (i.e., physically grasping a target); however, it is important to recognize that the task's decoupled spatial relations between stimulus and response renders the top-down processing of target features (e.g., size) that accumulating evidence has shown to be mediated by visual information functionally distinct from natural grasping. Here, we examined whether the visual information supporting pantomime-grasps exhibits a visual resolution power commensurate with natural grasps. Participants were presented with a target and nontarget that differed in size below the perceptual threshold (i.e., 0.5 mm or ∼1.3%) and were asked to make a perceptual judgment about the target (i.e., "smaller" or "larger" than the nontarget) before and after completing natural and pantomime-grasps. Results showed that perceptual judgments "before" and "after" natural and pantomime-grasps did not reliably distinguish between target and nontarget. Natural grasp peak grip apertures (PGAs) scaled to target size and were comparable for "before" and "after" perceptual judgment trials-a result indicating that haptic feedback from physically grasping the target did not "boost" perceptual accuracy. Most notably, pantomime-grasp PGAs were insensitive to target size; that is, responses elicited a visual resolution power less than natural grasps. These results provide convergent evidence that pantomime-grasps are mediated by the same visual information as obligatory perceptions and do not provide a proxy for natural grasps. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A summary statistical representation influences perceptions but not visually or memory-guided grasping.

A statistical summary representation (SSR) is a phenomenon wherein a target property (e.g., size) is encoded based on the average of the stimulus-set to which it belongs. An SSR has been demonstrated in obligatory judgment tasks; however, to our knowledge no work has examined whether it influences grasps to 3D targets. Here, participants completed a method of adjustment task, and visually and memory-guided grasps in conditions wherein differently sized 3D targets (widths: 20, 30 and 40 mm; height and depth = 10 mm) were presented with equal frequency (i.e., control) and when the smallest (i.e., 20-mm: small-target) and largest (i.e., 40-mm: large-target) targets were presented five times as often as the other targets in the stimulus-set. In the method of adjustment task, responses for the small- and large-target weighting conditions were smaller and larger than the control condition, respectively. In other words, an SSR biased perceptions in the direction of the most frequently presented target in the stimulus-set - a result consistent with the view that perceptions are supported by relative visual information laid down by the ventral visual pathway. In contrast, grip apertures were refractory to target-weighting and was a finding independent of the presence (i.e., visually guided) or absence (i.e., memory-guided) of visual feedback. Furthermore, two one-sided tests showed that peak grip apertures for the different target weighting conditions were within an equivalence boundary. Accordingly, an SSR does not influence 3D grasps and is a finding adding to a growing literature reporting that actions are supported by the absolute visuomotor networks of the dorsal visual pathway.

Association of Occupational Distress and Sleep-Related Impairment in Physicians With Unsolicited Patient Complaints.

OBJECTIVE: To study the relationship between occupational distress and sleep-related impairment in physicians and unsolicited patient complaints. PARTICIPANTS AND METHODS: We used deidentified data from an academic medical center's physician survey administered in April and May of 2013 to perform a retrospective cohort study. Third-party stewards of the identifiable information regarding unsolicited patient complaints from January 1, 2013, through December 31, 2016, matched these data with corresponding physicians' occupational distress data. Unsolicited patient complaints were used to calculate the Patient Advocacy Reporting System (PARS) score, a validated predictor of malpractice litigation risk and clinical outcomes. Physicians were grouped into 1 of 3 PARS risk categories based on previously defined thresholds: low risk (score of 0), intermediate risk (score of 1-12), or high risk (score ≥13). RESULTS: Each 1-point increase in burnout and sleep-related impairment, on a 5-point scale, was associated with a 69% (odds ratio [OR], 1.69; 95% CI, 1.12-2.54) and 49% (OR, 1.49; 95% CI, 1.08-2.05) increased odds of being in the next higher PARS risk category, respectively, averaged across all 4 years. Professional fulfillment was a protective factor, associated with fewer unsolicited patient complaints. Each 1-point decrease in professional fulfillment was associated with a 68% (OR, 1.68; 95% CI, 1.16-2.44) increased odds of being in the next higher PARS risk category. The effect of depression on PARS risk category was not significant (OR, 1.33; 95% CI, 0.84-2.10). CONCLUSION: Findings from this research suggest that occupational distress and sleep-related impairment in physicians are associated with unsolicited patient complaints.

Organizational strategies to reduce physician burnout and improve professional fulfillment.

Burnout is highly prevalent among physicians and has been associated with negative outcomes for physicians, patients, staff, and health-care organizations. Reducing physician burnout and increasing physician well-being is a priority. Systematic reviews suggest that organization-based interventions are more effective in reducing physician burnout than interventions targeted at individual physicians. This consensus review by leaders in the field across multiple institutions presents emerging trends and exemplary evidence-based strategies to improve professional fulfillment and reduce physician burnout using Stanford's tripartite model of physician professional fulfillment as an organizing framework: practice efficiency, culture, and personal resilience to support physician well-being. These strategies include leadership traits, latitude of control and autonomy, collegiality, diversity, teamwork, top-of-license workflows, electronic health record (EHR) usability, peer support, confidential mental health services, work-life integration and reducing barriers to practicing a healthy lifestyle. The review concludes with evidence-based recommendations on establishing an effective physician wellness program.

Self-valuation: Attending to the Most Important Instrument in the Practice of Medicine.

OBJECTIVE: To measure self-valuation, involving constructive prioritization of personal well-being and a growth mindset perspective that seeks to learn and improve as the primary response to errors, in physicians and evaluate its relationship with burnout and sleep-related impairment. METHODS: We analyzed cross-sectional survey data collected between July 1, 2016, and October 31, 2017, from 5 academic medical centers in the United States. All faculty and medical-staff physicians at participating organizations were invited to participate. The self-valuation scale included 4 items measured on a 5-point (0-4) Likert scale (summative score range, 0-16). The self-valuation scale was developed and pilot tested in a sample of 250 physicians before inclusion in the multisite wellness survey, which also included validated measures of burnout and sleep-related impairment. RESULTS: Of the 6189 physicians invited to participate, 3899 responded (response rate, 63.0%). Each 1-point score increase in self-valuation was associated with -1.10 point lower burnout score (95% CI, -1.16 to -1.05; standardized ß=-0.53; P<.001) and 0.81 point lower sleep-related impairment score (95% CI, -0.85 to -0.76; standardized ß=-0.47; P<.001), adjusting for sex and medical specialty. Women had lower self-valuation (Cohen d=0.30) and higher burnout (Cohen d=0.22) than men. Lower self-valuation scores in women accounted for most of the sex difference in burnout. CONCLUSION: Low self-valuation among physicians is associated with burnout and sleep-related impairment. Further research is warranted to develop and test interventions that increase self-valuation as a mechanism to improve physician well-being.

Production optimization, characterization and gene expression of pullulan from a new strain of Aureobasidium pullulans.

In this study, a new yeast-like fungal was obtained from leaf surfaces collected from Kheyroodkenar forest, Mazandaran, Iran. The properties of this strain, such as morphology, DNA molecular, and product showed that it is related to Aureobasidium pullulans family and named A. pullulans MG271838. The pullulan production conditions by this strain were optimized using a Box-Behnken design. The results showed that the optimum production yield (37.55 ±â€¯0.45 g/l) was obtained in pH of 6.76, sucrose concentration of 6%w/v and yeast extract concentration of 0.2%w/v. The pullulan had a concentration-dependent flow behavior, amorphous structure based on XRD pattern and high thermal stability (decomposition temperature of 300 °C). Also, the chemical structure of pullulan was confirmed by FTIR spectroscopy. In addition, there was a direct relationship between pullulan yield and the gene expression of fks, pgm and ugp as the most important genes in pullulan production.

Estimating institutional physician turnover attributable to self-reported burnout and associated financial burden: a case study.

BACKGROUND: Awareness of the economic cost of physician attrition due to burnout in academic medical centers may help motivate organizational level efforts to improve physician wellbeing and reduce turnover. Our objectives are: 1) to use a recent longitudinal data as a case example to examine the associations between physician self-reported burnout, intent to leave (ITL) and actual turnover within two years, and 2) to estimate the cost of physician turnover attributable to burnout. METHODS: We used de-identified data from 472 physicians who completed a quality improvement survey conducted in 2013 at two Stanford University affiliated hospitals to assess physician wellness. To maintain the confidentially of survey responders, potentially identifiable demographic variables were not used in this analysis. A third party custodian of the data compiled turnover data in 2015 using medical staff roster. We used logistic regression to adjust for potentially confounding factors. RESULTS: At baseline, 26% of physicians reported experiencing burnout and 28% reported ITL within the next 2 years. Two years later, 13% of surveyed physicians had actually left. Those who reported ITL were more than three times as likely to have left. Physicians who reported experiencing burnout were more than twice as likely to have left the institution within the two-year period (Relative Risk (RR) = 2.1; 95% CI = 1.3-3.3). After adjusting for surgical specialty, work hour categories, sleep-related impairment, anxiety, and depression in a logistic regression model, physicians who experienced burnout in 2013 had 168% higher odds (Odds Ratio = 2.68, 95% CI: 1.34-5.38) of leaving Stanford by 2015 compared to those who did not experience burnout. The estimated two-year recruitment cost incurred due to departure attributable to burnout was between $15,544,000 and $55,506,000. Risk of ITL attributable to burnout was 3.7 times risk of actual turnover attributable to burnout. CONCLUSIONS: Institutions interested in the economic cost of turnover attributable to burnout can readily calculate this parameter using survey data linked to a subsequent indicator of departure from the institution. ITL data in cross-sectional studies can also be used with an adjustment factor to correct for overestimation of risk of intent to leave attributable to burnout.

A Brief Instrument to Assess Both Burnout and Professional Fulfillment in Physicians: Reliability and Validity, Including Correlation with Self-Reported Medical Errors, in a Sample of Resident and Practicing Physicians.

OBJECTIVE: The objective of this study was to evaluate the performance of the Professional Fulfillment Index (PFI), a 16-item instrument to assess physicians' professional fulfillment and burnout, designed for sensitivity to change attributable to interventions or other factors affecting physician well-being. METHODS: A sample of 250 physicians completed the PFI, a measure of self-reported medical errors, and previously validated measures including the Maslach Burnout Inventory (MBI), a one-item burnout measure, the World Health Organization's abbreviated quality of life assessment (WHOQOL-BREF), and PROMIS short-form depression, anxiety, and sleep-related impairment scales. Between 2 and 3 weeks later, 227 (91%) repeated the PFI and the sleep-related impairment scale. RESULTS: Principal components analysis justified PFI subscales for professional fulfillment, work exhaustion, and interpersonal disengagement. Test-retest reliability estimates were 0.82 for professional fulfillment (α = 0.91), 0.80 for work exhaustion (α = 0.86), 0.71 for interpersonal disengagement (α = 0.92), and 0.80 for overall burnout (α = 0.92). PFI burnout measures correlated highly (r ≥ 0.50) with their closest related MBI equivalents. Cohen's d effect size differences in self-reported medical errors for high versus low burnout classified using the PFI and the MBI were 0.55 and 0.44, respectively. PFI scales correlated in expected directions with sleep-related impairment, depression, anxiety, and WHOQOL-BREF scores. PFI scales demonstrated sufficient sensitivity to detect expected effects of a two-point (range 8-40) change in sleep-related impairment. CONCLUSIONS: PFI scales have good performance characteristics including sensitivity to change and offer a novel contribution by assessing professional fulfillment in addition to burnout.

Improving bone health in men with prostate cancer receiving androgen deprivation therapy: Results of a randomized phase 2 trial.

BACKGROUND: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care. METHODS: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy outcomes included guideline-appropriate calcium and vitamin D use and bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints included recruitment, retention, satisfaction, contamination, and outcome capture. The main analysis used logistic regression with a 1-sided P of .10. The trial is registered at ClinicalTrials.gov (identifier NCT02043236). RESULTS: A total of 119 men were recruited. The BHP+BHCC strategy was associated with a greater percentage of men undergoing a BMD test compared with the usual-care group (78% vs 36%; P<.001). BMD ordering also was found to be increased with the BHP+FP strategy (58% vs 36%; P = .047). Both strategies were associated with higher percentages of patients using calcium and vitamin D, but only the BHP+FP arm was statistically significant (P = .039). No men were detected to be at high fracture risk. All but one feasibility endpoint was met. CONCLUSIONS: Educational strategies to improve bone health care appear feasible and are associated with improved BMD ordering in men receiving ADT. Cancer 2018;124:1132-40. © 2017 American Cancer Society.

Leptin and leptin-receptor polymorphisms in fertile and infertile men.

The association of leptin (LEP) -2548G/A and/or leptin receptor (LEPR) Gln223Arg polymorphisms with male infertility and plasma FSH, LH, and testosterone (T) levels was examined. The genotypes and allele frequency distributions of LEP -2548G/A and LEPR Gln223Arg polymorphisms were investigated in 150 fertile and 150 infertile men by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Also, plasma levels of FSH, LH, and T were measured using commercial ELISA kits. Frequencies of AA, AG and GG genotypes of LEP-2548G/A polymorphism were statistically different in fertile and infertile men (p=0.012). The AG genotype showed a protective effect which could decrease risk of male infertility about 3 fold (p = 0.004). We did not observe any differences in frequencies of LEPR Gln223Arg alleles and genotypes between groups (p > 0.05). Sperm counts from infertile men with the AG and GG genotypes of the LEP polymorphism were significantly higher than AA genotype (p<0.05). Moreover, infertile men who carried the RR genotype of LEPR showed a statistically higher percentage of sperm with progressive motility than individuals with other genotypes (p = 0.004). There was no correlation between different combinations of LEP and LEPR genotypes and LH, FSH, and T levels (p > 0.05). Our study suggests that the LEP -2548G/A polymorphism may play a role in male fertility and the AG genotype may have a protective effect through increasing sperm counts. The distribution of genotypes of LEP -2548G/A polymorphism are different in fertile and infertile males and may be a useful tool in evaluation of male infertility. ABBREVIATIONS: LEP: leptin; LEPR: leptin receptor; T: testosterone; FSH: follicle-stimulating hormone; LH: luteinizing hormone.

Running on empty: a review of nutrition and physicians' well-being.

Resident and physician burnout is a complex issue. Adequate nutrition and hydration play important roles in the maintenance of health and well-being of all individuals. Given the high prevalence of burnout in physicians, we believe that in addition to issues related to heavy workload, structure and length of shifts, the current status of physicians' nutrition and hydration and their effects on their work performance and well-being should also be addressed. In this review, we summarise the current evidence on the potential effects of nutrition and hydration on physicians' occupational well-being and performance, identify gaps and discuss opportunities to address nutrition as one of the important means of improving physicians' well-being.

Vitamin K and musculoskeletal health in postmenopausal women.

Aside from its important role in blood clotting, vitamin K is an important dietary factor in regulating bone and cartilage mineralization. The vitamin K requirements to maintain musculoskeletal health may be more than the current recommendations and subclinical vitamin K deficiency may be involved in the pathogenesis of osteoporosis and osteoarthritis. Observational studies suggest that diets low in vitamin K are associated with increased risk of fractures and osteoarthritis in older adults. However, so far randomized controlled trials of vitamin K supplementation in Caucasian populations have not shown clinically significant improvements in bone mineral density at major skeletal sites. Supplementation with vitamin K may reduce the risk of fractures, but this conclusion comes from clinical trials with methodological limitations. At this time, only one randomized controlled trial has examined the effect of vitamin K supplementation on radiographic hand osteoarthritis and found no overall effect. Large well-designed randomized controlled trials are needed to compare the efficacies of vitamin K1 and K2 on fractures and osteoarthritis among older adults. In summary, currently there is not enough evidence to recommend the use of vitamin K supplements for the prevention of bone loss, fractures, or osteoarthritis in postmenopausal women.

Vitamin K and bone health.

Vitamin K has been purported to play an important role in bone health. It is required for the gamma-carboxylation of osteocalcin (the most abundant noncollagenous protein in bone), making osteocalcin functional. There are 2 main forms (vitamin K1 and vitamin K2), and they come from different sources and have different biological activities. Epidemiologic studies suggest a diet high in vitamin K is associated with a lower risk of hip fractures in aging men and women. However, randomized controlled trials of vitamin K1 or K2 supplementation in white populations did not increase bone mineral density at major skeletal sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures, but the trials that examined fractures as an outcome have methodological limitations. Large well-designed trials are needed to compare the efficacies of vitamin K1 and K2 on fractures. We conclude that currently there is not enough evidence to recommend the routine use of vitamin K supplements for the prevention of osteoporosis and fractures in postmenopausal women.

Bladder preservation for localized muscle-invasive bladder cancer: the survival impact of local utilization rates of definitive radiotherapy.

PURPOSE: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. METHODS AND MATERIALS: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. RESULTS: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). CONCLUSIONS: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued research into bladder preservation strategies and suggest that definitive radiotherapy represents a viable initial treatment strategy for those who wish to attempt to preserve their native bladder.