International society of sports nutrition position stand: nutritional concerns of the female athlete.

Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Female athletes have unique and unpredictable hormone profiles, which influence their physiology and nutritional needs across their lifespan. To understand how perturbations in these hormones affect the individual, we recommend that female athletes of reproductive age should track their hormonal status (natural, hormone driven) against training and recovery to determine their individual patterns and needs and peri and post-menopausal athletes should track against training and recovery metrics to determine the individuals' unique patterns. 2. The primary nutritional consideration for all athletes, and in particular, female athletes, should be achieving adequate energy intake to meet their energy requirements and to achieve an optimal energy availability (EA); with a focus on the timing of meals in relation to exercise to improve training adaptations, performance, and athlete health. 3. Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent, therefore we recommend first ensuring athletes meet their carbohydrate needs across all phases of the menstrual cycle. Secondly, tailoring carbohydrate intake to hormonal status with an emphasis on greater carbohydrate intake and availability during the active pill weeks of oral contraceptive users and during the luteal phase of the menstrual cycle where there is a greater effect of sex hormone suppression on gluconogenesis output during exercise. 4. Based upon the limited research available, we recommend that pre-menopausal, eumenorrheic, and oral contraceptives using female athletes should aim to consume a source of high-quality protein as close to beginning and/or after completion of exercise as possible to reduce exercise-induced amino acid oxidative losses and initiate muscle protein remodeling and repair at a dose of 0.32-0.38 g·kg-1. For eumenorrheic women, ingestion during the luteal phase should aim for the upper end of the range due to the catabolic actions of progesterone and greater need for amino acids. 5. Close to the beginning and/or after completion of exercise, peri- and post-menopausal athletes should aim for a bolus of high EAA-containing (~10 g) intact protein sources or supplements to overcome anabolic resistance. 6. Daily protein intake should fall within the mid- to upper ranges of current sport nutrition guidelines (1.4-2.2 g·kg-1·day-1) for women at all stages of menstrual function (pre-, peri-, post-menopausal, and contraceptive users) with protein doses evenly distributed, every 3-4 h, across the day. Eumenorrheic athletes in the luteal phase and peri/post-menopausal athletes, regardless of sport, should aim for the upper end of the range. 7. Female sex hormones affect fluid dynamics and electrolyte handling. A greater predisposition to hyponatremia occurs in times of elevated progesterone, and in menopausal women, who are slower to excrete water. Additionally, females have less absolute and relative fluid available to lose via sweating than males, making the physiological consequences of fluid loss more severe, particularly in the luteal phase. 8. Evidence for sex-specific supplementation is lacking due to the paucity of female-specific research and any differential effects in females. Caffeine, iron, and creatine have the most evidence for use in females. Both iron and creatine are highly efficacious for female athletes. Creatine supplementation of 3 to 5 g per day is recommended for the mechanistic support of creatine supplementation with regard to muscle protein kinetics, growth factors, satellite cells, myogenic transcription factors, glycogen and calcium regulation, oxidative stress, and inflammation. Post-menopausal females benefit from bone health, mental health, and skeletal muscle size and function when consuming higher doses of creatine (0.3 g·kg-1·d-1). 9. To foster and promote high-quality research investigations involving female athletes, researchers are first encouraged to stop excluding females unless the primary endpoints are directly influenced by sex-specific mechanisms. In all investigative scenarios, researchers across the globe are encouraged to inquire and report upon more detailed information surrounding the athlete's hormonal status, including menstrual status (days since menses, length of period, duration of cycle, etc.) and/or hormonal contraceptive details and/or menopausal status.

Factors associated with falls in older adults: A secondary analysis of a 12-month randomized controlled trial.

PURPOSE: While identifying older adults at risk for falls is important, fall prediction models have had limited success, in part because of a poor understanding of which physical function measures to include. The purpose of this secondary analysis was to determine physical function measures that are associated with future falls in older adults. METHODS: In a 12-month trial comparing Vitamin D3 supplementation versus placebo on neuromuscular function, 124 older adults completed physical function measures at baseline, including the Short Physical Performance Battery (SPPB), Timed Up and Go, tests of leg strength and power, standing balance on a force plate with firm and foam surfaces, and walking over an instrumented walkway. Falls were recorded with monthly diaries over 12 months and categorized as no falls vs. one or more falls. Univariate and multivariable logistic regression adjusting for demographics, treatment assignment, depression, and prescription medications were conducted to examine the association between each physical function measure and future falls. Models were additionally adjusted for fall history. RESULTS: 61 participants sustained one or more falls. In univariate analysis, white race, depression, fall history, SPPB, and postural stability on foam were significantly associated with future falls. In multivariable analysis, fall history (OR (95% CI): 3.20 (1.42-7.43)), SPPB (0.80 (0.62-1.01)), and postural stability on foam (3.01 (1.18, 8.45)) were each significantly associated with future falls. After adjusting for fall history, only postural stability on foam was significantly associated with falls. CONCLUSIONS: When developing fall prediction models, fall history, the SPPB, and postural stability when standing on foam should be considered.

Marjoram extract prevents ischemia reperfusion-induced myocardial damage and exerts anti-contractile effects in aorta segments of male wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marjoram (Origanum majorana L.) is an herb traditionally used as a medicine in different countries, as Morocco and Iran, because of its beneficial cardiovascular effects. Some studies suggest that these effects are due, at least in part, to the presence of phenolic compounds such as rosmarinic acid (RA) and luteolin. AIM OF THE STUDY: To analyze the possible cardiprotective effects of a marjoram extract (ME) reducing myocardial damage after coronary ischemia-reperfusion (IR) and its possible antihypertensive effects reducing the response of aorta segments to the vasoconstrictors noradrenaline (NA) and endothelin-1 (ET-1). MATERIALS AND METHODS: Male Wistar rats (300g) were used. After sacrifice, the heart was immediately removed and mounted in a perfusion system (Langendorff). The aorta was carefully dissected and cut in 2 mm segments to perform vascular reactivity experiments. RESULTS: In the heart, ME perfusion after IR reduced heart rate and prevented IR-induced decrease of cardiac contractility, possibly through vasodilation of coronary arteries and through the upregulation of antioxidant markers in the myocardium that led to reduced apoptosis of cardiomyocytes. In the aorta, ME decreased the vasoconstrictor response to NA and ET-1 and exerted a potent anti-inflammatory and antioxidant effect. Neither RA nor 6-hydroxi-luteolin-O-glucoside, major compounds of this ME, were effective in improving cardiac contractility after IR or attenuating vasoconstriction to NA and ET-1 in aorta segments. CONCLUSION: In conclusion, ME reduces the myocardial damage induced by IR and the contractile response to vasoconstrictors in the aorta. Thus, it may be useful for the treatment of cardiovascular diseases such as myocardial infarction and hypertension.

Reducing Antacid Use in a Level IV NICU: A QI Project to Reduce Morbidity.

INTRODUCTION: Gastroesophageal reflux is a physiologic occurrence in infants. Clinicians caring for neonates use histamine-2 receptor antagonists (H2As) or proton pump inhibitors (PPIs) for symptomatic reflux, apnea/bradycardia/desaturations, or irritability. Recent studies have shown that there is an increased incidence of infection, fracture, and mortality in neonates who receive antacids. METHODS: A multidisciplinary team aimed to decrease nonindicated antacid use in the NICU by 50% by April 2019. Outcome measures include the median number of inappropriate antacid prescriptions and patient-days on acid-suppressants. Interventions include education regarding use and risks of antacids, development of a list of indications deemed "appropriate" for starting an H2A or PPI, mandatory discussion on rounds when considering antacids, documentation of treatment goal, and indication, and an automatic drop-off in the electronic medical record. RESULTS: Baseline data (June-December 2017) showed 19 prescriptions of H2As or PPIs. Of those, 10 orders were deemed "inappropriate," according to our indicated uses. There were 407 total patient-days of medication-use (median: 51 patient-days). After the implementation of the interventions (October 2018-May 2019), there were 11 prescriptions of antacid medications, 3 of which were deemed "inappropriate." There were 206 total days of medication-use (median: 18.5 patient-days). CONCLUSIONS: A multidisciplinary agreement on indications for antacid use in neonates stimulates discussion and creates more purposeful use. Overall, we successfully decreased nonindicated antacid prescriptions in the NICU. For the next steps, we hope to educate physicians on the risks of antacid use and reduce prescriptions in other areas of the hospital and the outpatient setting.

The "Warrior" COMT Val/Met Genotype Occurs in Greater Frequencies in Mixed Martial Arts Fighters Relative to Controls.

A functional single-nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene (rs4680) is a gene variant that has been shown to predict the ability to maintain cognitive agility during combat and competition. Critically, COMT Met (low-activity; high dopamine) allele carriers outperform Val (high-activity; low dopamine) homozygotes on a variety of cognitive tasks. However, the relationship between genotype and cognitive performance appears to reverse under stressful conditions. Stress increases pre-frontal cortex dopamine (PFC DA) levels, and Met allele carriers (with higher DA) show performance deficits relative to Val allele carriers. This pattern reflects the inverted U-shaped function of DA activity where too little (Val allele) or too much (Met allele carriers under stress) DA is associated with poor cognitive performance. The Val allele advantage for stress resiliency is referred to as the COMT "warrior/ worrier" model. In line with this model, we predicted that elite level mixed martial arts (MMA) fighters would be more likely than athlete controls to carry the GG (warrior) genotype compared to an athlete group and a non-athlete group. Based on findings in our previous studies, we also assessed the stress biomarkers cortisol and salivary alpha-amylase (sAA). There was an overall significant difference in genotype frequencies between groups (p =0.01) and the MMA group showed a significantly greater GG (warrior) genotype frequency than the non-athlete control group (p = 0.003). There was not a significant group x genotype interaction for the cortisol or sAA; however, the non-athlete GG group had significantly higher cortisol than the A/- group (p = 0.038). Combined, our findings suggest that the "warrior" genotype may play a participation role in combat sports.

Massage as a mechanotherapy promotes skeletal muscle protein and ribosomal turnover but does not mitigate muscle atrophy during disuse in adult rats.

AIM: Interventions that decrease atrophy during disuse are desperately needed to maintain muscle mass. We recently found that massage as a mechanotherapy can improve muscle regrowth following disuse atrophy. Therefore, we aimed to determine if massage has similar anabolic effects when applied during normal weight bearing conditions (WB) or during atrophy induced by hindlimb suspension (HS) in adult rats. METHODS: Adult (10 months) male Fischer344-Brown Norway rats underwent either hindlimb suspension (HS, n = 8) or normal WB (WB, n = 8) for 7 days. Massage was applied using cyclic compressive loading (CCL) in WB (WBM, n = 9) or HS rats (HSM, n = 9) and included four 30-minute bouts of CCL applied to gastrocnemius muscle every other day. RESULTS: Massage had no effect on any anabolic parameter measured under WB conditions (WBM). In contrast, massage during HS (HSM) stimulated protein turnover, but did not mitigate muscle atrophy. Atrophy from HS was caused by both lowered protein synthesis and higher degradation. HS and HSM had lowered total RNA compared with WB and this was the result of significantly higher ribosome degradation in HS that was attenuated in HSM, without differences in ribosomal biogenesis. Also, massage increased protein turnover in the non-massaged contralateral limb during HS. Finally, we determined that total RNA degradation primarily dictates loss of muscle ribosomal content during disuse atrophy. CONCLUSION: We conclude that massage is an effective mechanotherapy to impact protein turnover during muscle disuse in both the massaged and non-massaged contralateral muscle, but it does not attenuate the loss of muscle mass.

A Prospective Study Evaluating the Effects of a Nutritional Supplement Intervention on Cognition, Mood States, and Mental Performance in Video Gamers.

Cognitive function is critical for successful prolonged performance in eSports. This double-blind placebo-controlled study examined the effect of an inositol-enhanced arginine silicate oral supplement on cognitive performance and energy in eSports athletes. Sixty healthy men and women who spent 5 or more hours a week playing video games were randomly assigned to take supplement or placebo for 7 days. On day 1 and 7, before and 15 min after dosing, subjects completed the Trail Making Test (TMT), Parts A and B; Stroop Test; and Profile of Mood States (POMS) questionnaire, and then played a video game for 60 min. Immediately after, cognitive tests were repeated. Self-reported energy levels increased, anger decreased, and TMT-B test errors decreased in the supplement group compared to placebo (p < 0.05). Fatigue, TMT-B time, and TMT B-A score improved in the supplement group compared to baseline (p < 0.05). After 60 min of gaming, supplementation decreased Stroop Test errors and TMT-A time (p < 0.05). Adverse events were minimal and not different between groups. These data appear to support the use of the studies product (nooLVL®) in eSports gamers looking to improve their accuracy, decision making, and reaction time during gaming.

Supercritical anti-solvent fractionation for improving antioxidant and anti-inflammatory activities of an Achillea millefolium L. extract.

Achillea millefolium L. is a plant widely used in traditional medicine. Nowadays, there is a growing concern about the study of its bioactive properties in order to develop food and nutraceutical formulations. Supercritical anti-solvent fractionation (SAF) of an A. millefollium extract was carried out to improve its antioxidant and anti-inflammatory activities. A selective precipitation of phenolic compounds was achieved in the precipitation vessel fractions, which presented an antioxidant activity twice than original extract, especially when fractionation was carried out at 10 MPa. The main phenolic components identified in this fraction were luteolin-7-O-glucoside, 3,5-dicaffeoylquinic acid, 6-hidroxyluteolin-7-O-glucoside and apigenin-7-O-glucoside. However, separator fractions presented higher anti-inflammatory activity than precipitation vessel ones, particularly at 15 MPa. This fact could be related to separator fractions enrichment in anti-inflammatory compounds, mainly camphor, artemisia ketone and borneol. Therefore, SAF produced a concentration of antioxidant and anti-inflammatory compounds that could be used as high-added valued ingredients.

A Recurrent BRCA2 Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico.

Breast cancer is the most common cause of cancer diagnosis in women and is responsible for considerable mortality among the women of Puerto Rico. However, there are few studies in Puerto Rico on the genetic factors influencing risk. To determine the contribution of pathogenic mutations in BRCA1 and BRCA2, we sequenced these genes in 302 cases from two separate medical centers, who were not selected for age of onset or family history. We identified nine cases that are carriers of pathogenic germline mutation. This represents 2.9% of unselected cases and 5.6% of women meeting National Comprehensive Cancer Network (NCCN) criteria for BRCA testing. All of the identified pathogenic mutations were in the BRCA2 gene and the most common mutation is the p.Glu1308Ter (E1308X) mutation in BRCA2 found in eight out of nine cases, representing 89% of the pathogenic carriers. The E1308X mutation has been identified in breast and ovarian cancer families in Spain, and analysis of flanking DNA polymorphisms shows that all E1308X carriers occur on the same haplotype. This is consistent with BRCA2 E1308X being a founder mutation for the Puerto Rican population. These results will contribute to better inform genetic screening and counseling of breast and ovarian cancer cases in Puerto Rico and Puerto Rican populations in mainland United States.

No Evidence for the Pathogenicity of the BRCA2 c.6937 + 594T>G Deep Intronic Variant: A Case-Control Analysis.

BACKGROUND: The role of deep intronic variants in hereditary cancer susceptibility has been largely understudied. Previously, the BRCA2 c.6937 + 594T>G variant has been shown to preferentially promote the inclusion of a 95 nucleotide cryptic exon and to introduce a premature termination codon. Our objective was to further assess the pathogenicity of the BRCA2 c.6937 + 594T>G deep intronic variant. PATIENTS AND METHODS: We examined the association between BRCA2 c.6937 + 594T>G and breast cancer (BC) risk in 464 BC cases and 497 noncancer controls from Puerto Rico. RESULTS: The overall frequency of the G allele was 2.1% in this population. There was no association between the TG/GG genotypes and BC risk in the uncorrected model and after correcting for confounders. There was only one carrier of the GG genotype. This individual did not have personal or family history of cancer and did not meet the National Comprehensive Cancer Network criteria for hereditary cancer genetic testing. CONCLUSIONS: Although previous work has demonstrated that the BRCA2 c.6937 + 594T>G variant affects splicing, this association study does not support a pathogenic role for the BRCA2 c.6937 + 594T>G intronic variant in breast and ovarian cancer syndrome susceptibility. Furthermore, it emphasizes the need to take into account multiple diverse populations in association studies for the assessment of variant pathogenicity.

Immunosuppressive agents in adult kidney transplantation in the National Health Service: a model-based economic evaluation.

BACKGROUND: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. METHODS: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime. A total of 16 different regimens were modelled to assess the cost-effectiveness of basiliximab and rabbit anti-thymocyte globulin (rabbit ATG) as induction agents (with no antibody induction as a comparator) and immediate-release tacrolimus, prolonged-release tacrolimus, mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept as maintenance agents (with ciclosporin and azathioprine as comparators). Graft survival was extrapolated from acute rejection rates, graft function and post-transplant diabetes rates, all estimated at 12 months post-transplantation. National Health Service (NHS) and personal social services costs were included. Cost-effectiveness thresholds of £20 000 and £30 000 per quality-adjusted life year were used. RESULTS: Basiliximab was predicted to be more effective and less costly than rabbit ATG and induction without antibodies. Immediate-release tacrolimus and mycophenolate mofetil were cost-effective as maintenance therapies. Other therapies were either more expensive and less effective or would only be cost-effective if a threshold in excess of £100 000 per quality-adjusted life year were used. CONCLUSIONS: A regimen comprising induction with basiliximab, followed by maintenance therapy with immediate-release tacrolimus and mycophenolate mofetil, is likely to be effective for uncomplicated adult kidney transplant patients and a cost-effective use of NHS resources.

Influence of Nrf2 activators on subcellular skeletal muscle protein and DNA synthesis rates after 6 weeks of milk protein feeding in older adults.

In older adults, chronic oxidative and inflammatory stresses are associated with an impaired increase in skeletal muscle protein synthesis after acute anabolic stimuli. Conjugated linoleic acid (CLA) and Protandim have been shown to activate nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor for the antioxidant response element and anti-inflammatory pathways. This study tested the hypothesis that compared to a placebo control (CON), CLA and Protandim would increase skeletal muscle subcellular protein (myofibrillar, mitochondrial, cytoplasmic) and DNA synthesis in older adults after 6 weeks of milk protein feeding. CLA decreased oxidative stress and skeletal muscle oxidative damage with a trend to increase messenger RNA (mRNA) expression of a Nrf2 target, NAD(P)H dehydrogenase quinone 1 (NQO1). However, CLA did not influence other Nrf2 targets (heme oxygenase-1 (HO-1), glutathione peroxidase 1 (Gpx1)) or protein or DNA synthesis. Conversely, Protandim increased HO-1 protein content but not the mRNA expression of downstream Nrf2 targets, oxidative stress, or skeletal muscle oxidative damage. Rates of myofibrillar protein synthesis were maintained despite lower mitochondrial and cytoplasmic protein syntheses after Protandim versus CON. Similarly, DNA synthesis was non-significantly lower after Protandim compared to CON. After Protandim, the ratio of protein to DNA synthesis tended to be greater in the myofibrillar fraction and maintained in the mitochondrial and cytoplasmic fractions, emphasizing the importance of measuring both protein and DNA synthesis to gain insight into proteostasis. Overall, these data suggest that Protandim may enhance proteostatic mechanisms of skeletal muscle contractile proteins after 6 weeks of milk protein feeding in older adults.

Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy.

UNLABELLED: Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. IMPORTANCE: The emergence and spread of multidrug-resistant M. tuberculosis are a major threat to global public health. Linezolid is an oxazolidinone that is licensed for human use and has demonstrated potent activity against multidrug-resistant M. tuberculosis. However, long-term use of linezolid has shown to be toxic in patients, often resulting in thrombocytopenia. We examined therapeutic linezolid regimens in an in vitro model to characterize the exposure-toxicity relationship. The antibacterial activity against M. tuberculosis was also assessed for these regimens, including the amplification or suppression of resistant mutant subpopulations by the chosen regimen. Higher exposures of linezolid resulted in greater antibacterial activity, but with more toxicity and, for some regimens, increased resistant mutant subpopulation amplification, illustrating the trade-off between activity and toxicity. These findings can provide valuable insight for designing optimal dosage regimens for linezolid that are part of the long combination courses used to treat multidrug-resistant M. tuberculosis.

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile.

Effect of home blood pressure telemonitoring and pharmacist management on blood pressure control: a cluster randomized clinical trial.

IMPORTANCE: Only about half of patients with high blood pressure (BP) in the United States have their BP controlled. Practical, robust, and sustainable models are needed to improve BP control in patients with uncontrolled hypertension. OBJECTIVES: To determine whether an intervention combining home BP telemonitoring with pharmacist case management improves BP control compared with usual care and to determine whether BP control is maintained after the intervention is stopped. DESIGN, SETTING, AND PATIENTS: A cluster randomized clinical trial of 450 adults with uncontrolled BP recruited from 14,692 patients with electronic medical records across 16 primary care clinics in an integrated health system in Minneapolis-St Paul, Minnesota, with 12 months of intervention and 6 months of postintervention follow-up. INTERVENTIONS: Eight clinics were randomized to provide usual care to patients (n = 222) and 8 clinics were randomized to provide a telemonitoring intervention (n = 228). Intervention patients received home BP telemonitors and transmitted BP data to pharmacists who adjusted antihypertensive therapy accordingly. MAIN OUTCOMES AND MEASURES: Control of systolic BP to less than 140 mm Hg and diastolic BP to less than 90 mm Hg (<130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 and 12 months. Secondary outcomes were change in BP, patient satisfaction, and BP control at 18 months (6 months after intervention stopped). RESULTS: At baseline, enrollees were 45% women, 82% white, mean (SD) age was 61.1 (12.0) years, and mean systolic BP was 148 mm Hg and diastolic BP was 85 mm Hg. Blood pressure was controlled at both 6 and 12 months in 57.2% (95% CI, 44.8% to 68.7%) of patients in the telemonitoring intervention group vs 30.0% (95% CI, 23.2% to 37.8%) of patients in the usual care group (P = .001). At 18 months (6 months of postintervention follow-up), BP was controlled in 71.8% (95% CI, 65.0% to 77.8%) of patients in the telemonitoring intervention group vs 57.1% (95% CI, 51.5% to 62.6%) of patients in the usual care group (P = .003). Compared with the usual care group, systolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months (-10.7 mm Hg [95% CI, -14.3 to -7.3 mm Hg]; P<.001), at 12 months (-9.7 mm Hg [95% CI, -13.4 to -6.0 mm Hg]; P<.001), and at 18 months (-6.6 mm Hg [95% CI, -10.7 to -2.5 mm Hg]; P = .004). Compared with the usual care group, diastolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months (-6.0 mm Hg [95% CI, -8.6 to -3.4 mm Hg]; P<.001), at 12 months (-5.1 mm Hg [95% CI, -7.4 to -2.8 mm Hg]; P<.001), and at 18 months (-3.0 mm Hg [95% CI, -6.3 to 0.3 mm Hg]; P = .07). CONCLUSIONS AND RELEVANCE: Home BP telemonitoring and pharmacist case management achieved better BP control compared with usual care during 12 months of intervention that persisted during 6 months of postintervention follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00781365.

Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

BACKGROUND: Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies. METHODS: We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels. RESULTS: A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89). CONCLUSIONS: Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates.

Preclinical assessment of comfort and secure fit of thermobrachytherapy surface applicator (TBSA) on volunteer subjects.

A thermobrachytherapy surface applicator (TBSA) was developed for simultaneous heat and brachytherapy treatment of chest wall (CW) recurrence of breast cancer. The ability to comfortably secure the applicator over the upper torso relative to the CW target throughout treatment is assessed on volunteers. Male and postmastectomy female volunteers were enrolled to evaluate applicator secure fit to CW. Female subjects with intact breast were also enrolled to assess the ability to treat challenging cases. Magnetic resonance (MR) images of volunteers wearing a TBSA over the upper torso were acquired once every 15 minutes for 90 minutes. Applicator displacement over this time period required for treatment preplanning and delivery was assessed using MR visible markers. Applicator comfort and tolerability were assessed using a questionnaire. Probability estimates of applicator displacements were used to investigate dosimetric impact for the worst-case variation in radiation source-to-skin distance for 5 and 10 mm deep targets spread 17 × 13 cm on a torso phantom. Average and median displacements along lateral and radial directions were less than 1.2 mm over 90 minutes for all volunteers. Maximum lateral and radial displacements were measured to be less than 1 and 1.5 mm, respectively, for all CW volunteers and less than 2 mm for intact breast volunteers, excluding outliers. No complaint of pain or discomfort was reported. Phantom treatment planning for the maximum displacement of 2 mm indicated < 10% increase in skin dose with < 5% loss of homogeneity index (HI) for -2 mm uniform HDR source displacement. For +2 mm uniform displacement, skin dose decreased and HI increased by 20%. The volunteer study demonstrated that such large and uniform displacements should be rare for CW subjects, and the measured variation is expected to be low for multifraction conformal brachytherapy treatment.

Sex, drugs, bugs, and age: rational selection of empirical therapy for outpatient urinary tract infection in an era of extensive antimicrobial resistance.

BACKGROUND: Optimal empirical therapy of urinary tract infection requires accurate knowledge of local susceptibility patterns, which may vary with organism and patient characteristics. METHODS: Among 9,798 consecutive, non-duplicate, community-source urine isolates from ambulatory patients > 13 years old, from clinical laboratory and an academic medical center in Curitiba, Brazil (May 1st to December 1st, 2009), susceptibility data for ampicillin, nitrofurantoin, trimethoprim-sulfamethoxazole, gentamicin, fluoroquinolones, and ceftriaxone/cefotaxime were compared with organism and patient gender and age. RESULTS: The female-to-male ratio decreased with age, from 28.1 (among 20-29 year-olds) to 3.3 (among > 80 year-olds). Overall, susceptibility prevalence varied widely by drug class, from unacceptably low levels (53.5% and 61.1%: ampicillin and trimethoprimsulfamethoxazole) to acceptable but suboptimal levels (81.2% to 91.7%: fluoroquinolones, ceftriaxone, nitrofurantoin, and gentamicin). E. coli isolates exhibited higher susceptibility rates than other isolates, from 3-4% higher (fluoroquinolones, gentamicin) to > 30% (nitrofurantoin, ceftriaxone). Males exhibited lower susceptibility rates than females. Within each gender, susceptibility declined with increasing age. For females, only nitrofurantoin and gentamicin were suitable for empirical therapy (> 80% susceptibility) across all age cohorts; fluoroquinolones were suitable only through age 60, and ceftriaxone only through age 80. For males, only gentamicin yielded > 80% susceptibility in any age cohort. CONCLUSION: Few suitable empirical treatment options for community-source urinary tract infection were identified for women aged over 60 years or males of any age. Empirical therapy recommendations must consider the patient's demographic characteristics. Site-specific, age and gender-stratified susceptibility surveillance involving all uropathogens is needed.

Sex, drugs, bugs, and age: rational selection of empirical therapy for outpatient urinary tract infection in an era of extensive antimicrobial resistance

BACKGROUND: Optimal empirical therapy of urinary tract infection requires accurate knowledge of local susceptibility patterns, which may vary with organism and patient characteristics. METHODS: Among 9,798 consecutive, non-duplicate, community-source urine isolates from ambulatory patients > 13 years old, from clinical laboratory and an academic medical center in Curitiba, Brazil (May 1st to December 1st, 2009), susceptibility data for ampicillin, nitrofurantoin, trimethoprim-sulfamethoxazole, gentamicin, fluoroquinolones, and ceftriaxone/cefotaxime were compared with organism and patient gender and age. RESULTS: The female-to-male ratio decreased with age, from 28.1 (among 20-29 year-olds) to 3.3 (among > 80 year-olds). Overall, susceptibility prevalence varied widely by drug class, from unacceptably low levels (53.5% and 61.1%: ampicillin and trimethoprimsulfamethoxazole) to acceptable but suboptimal levels (81.2% to 91.7%: fluoroquinolones, ceftriaxone, nitrofurantoin, and gentamicin). E. coli isolates exhibited higher susceptibility rates than other isolates, from 3-4% higher (fluoroquinolones, gentamicin) to > 30% (nitrofurantoin, ceftriaxone). Males exhibited lower susceptibility rates than females. Within each gender, susceptibility declined with increasing age. For females, only nitrofurantoin and gentamicin were suitable for empirical therapy (> 80% susceptibility) across all age cohorts; fluoroquinolones were suitable only through age 60, and ceftriaxone only through age 80. For males, only gentamicin yielded > 80% susceptibility in any age cohort. CONCLUSION: Few suitable empirical treatment options for community-source urinary tract infection were identified for women aged over 60 years or males of any age. Empirical therapy recommendations must consider the patient's demographic characteristics. Site-specific, age and gender-stratified susceptibility surveillance involving all uropathogens is needed.

Bodybuilding, energy, and weight-loss supplements are associated with deployment and physical activity in U.S. military personnel.

PURPOSE: The characteristics of U.S. military personnel who use dietary supplements have not been well described. This study aimed to determine whether deployment experience and physical activity were associated with the use of bodybuilding, energy, or weight-loss supplement among U.S. military personnel. METHODS: Self-reported data from active-duty, Reserve, and National Guard participants of the Millennium Cohort Study collected from 2007-2008 (n = 106,698) on supplement use, physical activity, and other behavioral data were linked with deployment and demographic data. We used multivariable logistic regression sex-stratified models to compare the adjusted odds of each type of supplement use among those with deployment experience in support of operations in Iraq or Afghanistan and those engaged in aerobic or strength-training activities. RESULTS: Overall, 46.7% of participants reported using at least one type of supplement, and 22.0% reported using multiple supplements. Male deployers were more likely to use bodybuilding supplements, whereas female deployers were more likely to use weight-loss supplements. Physically active and younger subjects reported all types of supplement use. Men and women reporting 5 or less hours of sleep per night were more likely to use energy supplements. CONCLUSIONS: The high prevalence of supplement use and important characteristics found to be associated with their use, including deployment, physical activity, and suboptimal sleep, suggest focus areas for future research and adverse event monitoring.