Methods of Blood Pressure Measurement to Predict Hypertension-Related Cardiovascular Morbidity and Mortality.

PURPOSE OF REVIEW: As the evidence on different blood pressure phenotypes and their cardiovascular risks evolve, it is imperative to evaluate the reliability of office blood pressure (OBP), ambulatory blood pressure (ABP), and home blood pressure (HBP) measurements and their associations with cardiovascular morbidity and mortality. RECENT FINDINGS: HBP is more reliable in diagnosis of hypertension than OBP or ABP. HBP correlates better with left ventricular mass index (LVMI). Increasing systolic HBP is associated with a higher risk of all-cause mortality, cardiovascular mortality, and cardiovascular events. An elevated systolic ABP is also associated with a higher risk of cardiovascular events and mortality. ABP is a better predictor of cardiovascular events than OBP in diabetics. ABP and HBP furnish additional information beyond OBP. They correlate better with cardiovascular outcomes and are more helpful with monitoring therapy than OBP. Comparative effectiveness studies of all three methods associating with cardiovascular outcomes are warranted.

A Simulation-Based Workshop to Improve Residents' Collaborative Clinical Practice.

BACKGROUND: The Accreditation Council for Graduate Medical Education expects residents to attain competency in systems-based practice by advocating for quality patient care, working in interprofessional teams, and implementing system solutions to prevent errors. Diabetes in pregnancy was identified as an area for improvement through comprehensive interdisciplinary and interprofessional care. OBJECTIVE: An interdisciplinary and interprofessional workshop was created by 3 regional academic institutions to improve collaborative practice, clinical knowledge, and clinical judgment of residents. METHODS: A workshop consisting of 4 clinical simulation stations for ultrasound assessment, glycemic control, hyperglycemic emergencies, and macrosomia complications was designed to address gaps in quality of care. Workshop participants were residents from 6 programs and students in nursing, pharmacy, and sonography. Attitude and clinical knowledge were measured preworkshop and postworkshop, and at 3-month and 6- to 7-month follow-up. RESULTS: There were increases in average clinical knowledge scores across time points from residents: 56.4% preworkshop, 64.8% postworkshop, 66.0% at 3-month follow-up, and 68.1% at 6- to 7-month follow-up. Additionally, participants reported positive attitudes toward interprofessional education and indicated high overall satisfaction. CONCLUSIONS: Residents demonstrated improved knowledge and attitudes toward interprofessional training after participating in a large-scale simulation workshop focused on the care of patients with diabetes in pregnancy.

Evaluating Medical Students' Clinical Reasoning in Psychiatry Using Clinical and Basic Science Concepts Presented in Session-level Integration Sessions.

OBJECTIVE: The objective of this study was to evaluate improvement in clinical reasoning by preclinical medical students following participation in a clinical presentation curriculum that included both course and session-level integration of psychiatric and basic science concepts. A Script Concordance Test (SCT) for psychiatry was developed to assess differences in clinical reasoning in the students. METHODS: Pre- and post-integration session tests were used to evaluate clinical reasoning among second-year medical students (MSII) who attended three integration sessions. Scores were compared between experts and medical students, and the validity and reliability of the SCT for psychiatry was assessed. RESULTS: MSII scores improved 11% between the pre-and post-test (p < .001). There was no significant difference in scores between experts and MSII after attending the integration sessions. The SCT for psychiatry that was developed and used in this study provides reliable and valid results. CONCLUSION: The concepts included in the integration sessions for this study highlighted possibilities for helping novice learners elaborate causal networks with the intention of cultivate illness script formation and clinical reasoning. Additional studies in this area should be considered to further enhance understanding of the possible benefits of this curriculum model.

Energy output and in vitro biologic effects of an ionic toothbrush.

The Soladey™ toothbrush has a moisture-permeable titanium dioxide (TiO2) resin core in the replacement brush end of a handle activated by light conversion power cells. Purported to have an antibacterial effect and remove more plaque than an ordinary toothbrush, this study was undertaken to establish output measurements of the dry and wet TiO2 core of the toothbrush during typical illumination of the handle, then quantify lipid peroxidation in three distinct lipid-containing solutions, and bactericidal effects in a live bacterial suspension grown from suctioned oral secretions. METHODS: Within a range of illumination of the power cells in the handle, corresponding flow of electrons emitted from dry and wetted TiO2 cores was measured. The claim that an antibacterial effect can be attributed to generation of reactive oxygen-mediated lipid peroxidation of cell membranes was tested by exposing three lipid substrates to the light-activated ionic toothbrush tips for incremental periods of time. Products of lipid peroxidation were quantified using 3 commercially available assays, and bactericidal effects were assessed by scoring colony-forming units. RESULTS: Illumination of the handle generated quantifiable increases in electrons flowing from the wetted TiO2 core. Immersion of the TiO2 core end of illuminated toothbrush handles into lipid substrates showed linear effects of incremental exposure times on products of lipid peroxidation, but no evidence of a bactericidal effect occurring within 15 minutes. CONCLUSIONS: This validates capacity of the wetted current- activated TiO2 core to generate time-dependent lipid peroxides, particularly in the sonicated matrix containing disrupted cell membranes. Finding no time-dependent reduction in colony- forming units and less lipid peroxidation in a suspension of intact cells casts doubt that the ionic toothbrush has an immediate antibacterial effect while brushing teeth. If a toothbrush with a TiO2 core is self-disinfecting between uses, bactericidal effects requiring longer periods of exposure might still confer a hygienic advantage.

Randomized controlled trial of a TiO2 Semiconductor toothbrush on mild-to-moderate periodontitis..

UNLABELLED: The Soladey toothbrush (Shiken Corp., Osaka, Japan) is based on the principle that electrical induction will cause a wetted titanium dioxide semiconductor to emit electrons. The manufacturer claims that in addition to the established mechanical benefits of brushing, the flow of electrons from the brush head may disrupt ionic bonding of plaque, neutralize bacterial organic acids, and thus confer an advantage over a conventional toothbrush. AIM: Determine whether a TiO2 semiconductor-containing toothbrush confers an advantage over a conventional toothbrush in adult patients with mild-to-moderate gingivitis/periodontitis. MATERIALS and METHODS: Seventy-one patients with mild-to-moderate gingivitis/periodontitis were enrolled in this randomized, double-blind, placebo-controlled modified crossover trial that compared the Soladey-3 titanium dioxide semiconductor toothbrush (Shiken Corp., Osaka, Japan) to an otherwise identical toothbrush containing an inert resin core in place of the semiconductor. Changes in indices of gingivitis and periodontitis were the primary outcomes. RESULTS: Sixty-six patients completed the study. Relative to baseline, an almost two-fold increased gingival crevice fluid flow followed both active and control treatments was statistically significant. Relative to the inactive control device, the active Soladey-3 toothbrush had no clinically meaningful effects on selected markers of gingivitis/periodontitis. CONCLUSIONS: The active Soladey-3 toothbrush did not substantially impact selected markers of gingivitis/periodontitis by the end of a two-week treatment period in adult patients with mild-to-moderate disease. Both inactive (control) and active (TiO2 semi-conductor) versions of the Soladey toothbrushes significantly increased crevice fluid flow.

Discussing side effects of over-the-counter medicines: impact of adding percentage data.

OBJECTIVES: Discussing side effects with patients continues to be a difficult area of practice. Questions arise as to how many should be mentioned and which ones. The way such information is presented can affect drug-taking decisions. This study examined how over-the-counter (OTC) medicine users are influenced by numerical risk estimates of side effects. METHODS: As part of a larger study on patient decision-making, 30 participants aged over 50 years were asked to consider three OTC headache medicines. They responded to one of two headache scenarios, one with symptoms described as mild but common and the other severe but rare. Participants made their selection based on drug efficacy and side effects, at first not linked to occurrence rates and then with this information provided. KEY FINDINGS: Average age was 66.6 years and the majority were female. Most were currently using some form of drug therapy. Drug choices differed in relation to mild versus severe headache scenarios. A stronger preference for drug X (50% effective and two side effects) was evident when the headaches were mild, shifting to a more effective agent (but with more side effects) when more severe. Addition of occurrence rates to the side effects had the greatest effect within the severe headache scenario, where more participants opted for the most effective agent (drug Z at 100% effective but six side effects) upon seeing the numbers. Overall, however, most kept the same drug in spite of the numerical information. CONCLUSIONS: Inclusion of numerical data for side effects did not negatively influence potential OTC medicine users. For most, effectiveness and side effects were the concern before receiving the percentages, while effectiveness became more important when the frequency data seemed to instil a sense of reassurance.

Prevalence and duration of exercise induced albuminuria in healthy people.

PURPOSE: Vigorous exercise increases urine protein excretion. However, whether exercise increases urine albumin enough to reach the threshold for microalbuminuria (2.8 and 2.0 mg/mmol creatinine in women and men respectively) is uncertain. Furthermore, the duration of such albuminuria is unknown. We aimed to estimate the prevalence and duration of exercise induced microalbuminuria in normal healthy volunteers. METHODS: Thirty normal subjects provided a urine sample, then exercised to maximal heart rate, or exhaustion, using the standard Bruce Treadmill protocol. Further urine samples were collected within 15 min of completing exercise, and 24 and 48 hr later. Urine creatinine was measured by the Jaffé method and albumin via immunoturbidometry. RESULTS: Baseline urine albumin: creatinine ratio (A/C) was 0.5 +/- 0.3 (SD) in women (n=14) and 0.4 +/- 0.1 mg/mmol in men (n=16). Immediately after exercise A/C increased to 5.6 +/- 9.7 (in women) and 7.6 +/- 17.6 (in men). Twelve of 30 subjects reached the threshold for microalbuminuria and 2 that for macroalbuminuria. By 24 hr all had returned to baseline and there was no further change at 48 hours. CONCLUSIONS: A short period, 15-20 min, of maximal exercise leads to A/C ratios above the microalbuminuria threshold in a substantial proportion of normal subjects. Physicians should not measure urine albumin in patients who give a history of such activity in the past 24 hr.

Des-acyl ghrelin fragments evoke endothelium-dependent vasodilatation of rat mesenteric vascular bed via activation of potassium channels.

The mechanisms that subserve ghrelin-evoked vasodilatation have not been elucidated in previous studies. Changes in perfusion pressure evoked by ghrelin and its N-terminal fragments were examined ex vivo in phenylephrine-constricted perfused mesenteric vascular beds of male Sprague Dawley rats maintained at a constant flow rate. Both ghrelin (maximum effect [E(max)] 45%) and des-acyl ghrelin (E(max) 43%) evoked vasodilatation at concentrations between 10 pM and 1 nM, compared to acetylcholine (median effective concentration [EC(50)] 3 nM; E(max) 93%). Those responses were abolished in endothelium-denuded preparations, and in endothelium-intact preparations exposed to either calcium-activated potassium channel, or a depolarizing stimulus, or in the presence of a combination of either apamin and 1,2-chlorophenyl diphenylmethyl-1 H-pyrazole (triarylmethane-34 [TRAM-34]), or ouabain and barium. ATP-activated potassium channel blockade, or a combination of nitric oxide synthase and cyclooxygenase inhibition had no effect. The classical growth hormone secretagogue antagonist, [d-Lys(3)]-growth hormone-releasing peptide (10 nM), or several N-terminal fragments of des-acyl ghrelin, including the tripeptide glycine-serine-serine (G-S-S [1 nM]), showed endothelium-dependent vasodilatation like des-acyl ghrelin, while responses to glycine-serine or serine-serine were relatively lower. A higher concentration (100 muM) of l-serine, but not glycine, evoked vasodilatation of similar magnitude. The serine dense N-terminal sequence of des-acyl ghrelin mediates endothelium-dependent vasodilatation via activation of apamin+TRAM-34 sensitive small- and intermediate-conductance calcium-activated potassium channels present on the mesenteric endothelium. Thus, the vasodilator response to ghrelins in the perfused rat mesenteric vascular bed is not mediated by the classical growth hormone secretagogue receptor type 1a.

L-Serine lowers while glycine increases blood pressure in chronic L-NAME-treated and spontaneously hypertensive rats.

OBJECTIVE: To determine the acute hemodynamic effects of the nonessential amino acid, glycine, and its precursor, L-serine, in normotensive and hypertensive rats. METHODS: Changes in mean arterial pressure and heart rate evoked by comparable intravenously administered doses (0.3-3.0 mmol/kg) of L-serine, D-serine and glycine were examined in anaesthetized normotensive 14-week-old male Sprague-Dawley, Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats and WKY rats subjected to chronic nitric oxide synthase inhibition by treatment with NG nitro L-arginine methyl ester (0.7 mg/ml in drinking water for 5 days). RESULTS: L-Serine evoked a greater maximal fall in mean arterial pressure [L-serine vs. D-serine in Sprague-Dawley rats, mean +/- standard error of the mean values (mmHg): 30 +/- 3 vs. 20 +/- 5, P < 0.05; in control WKY rats: 46 +/- 3 vs. 30 +/- 4, P < 0.05; in NG nitro L-arginine methyl ester-treated WKY rats: 93 +/- 6 vs. 41 +/- 5, P < 0.01; in spontaneously hypertensive rats: 81 +/- 7 vs. 39 +/- 5 P < 0.01]. The effects of L-serine were significantly reduced in rats pretreated with a combination of apamin and charybdotoxin, inhibitors of the small conductance and intermediate conductance calcium-activated potassium (KCa) channels. Glycine elicited a dose-dependent fall in mean arterial pressure in normotensive WKY rats (25 +/- 4; P < 0.01) and evoked pressor responses in both spontaneously hypertensive rats (29 +/- 3; P < 0.01) and NG nitro L-arginine methyl ester-pretreated hypertensive WKY (39 +/- 5; P < 0.01) rats. Both the depressor and pressor responses to glycine were abolished by pretreatment with the N-methyl D-aspartate receptor antagonist, MK-801. CONCLUSION: The profound stereo-selective antihypertensive effect of L-serine is neither mediated nor mimicked by glycine. It does not require N-methyl D-aspartate receptor activation by glycine but likely involves activation of endothelial KCa channels. L-Serine is a potential antihypertensive agent.

The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training.

High doses of ibuprofen have been shown to inhibit muscle protein synthesis after a bout of resistance exercise. We determined the effect of a moderate dose of ibuprofen (400 mg x d(-1)) consumed on a daily basis after resistance training on muscle hypertrophy and strength. Twelve males and 6 females (approximately 24 years of age) trained their right and left biceps on alternate days (6 sets of 4-10 repetitions), 5 d x week(-1), for 6 weeks. In a counter-balanced, double-blind design, they were randomized to receive 400 mg x d(-1) ibuprofen immediately after training their left or right arm, and a placebo after training the opposite arm the following day. Before- and after-training muscle thickness of both biceps was measured using ultrasound and 1 repetition maximum (1 RM) arm curl strength was determined on both arms. Subjects rated their muscle soreness daily. There were time main effects for muscle thickness and strength (p < 0.01). Ibuprofen consumption had no effect on muscle hypertrophy (muscle thickness of biceps for arm receiving ibuprofen: pre 3.63 +/- 0.14, post 3.92 +/- 0.15 cm; and placebo: pre 3.62 +/- 0.15, post 3.90 +/- 0.15 cm) and strength (1 RM of arm receiving ibuprofen: pre 18.6 +/- 2.8, post 23.4 +/- 3.5 kg; and placebo: pre 18.8 +/- 2.8, post 22.8 +/- 3.4 kg). Muscle soreness was elevated during the first week of training only, but was not different between the ibuprofen and placebo arm. We conclude that a moderate dose of ibuprofen ingested after repeated resistance training sessions does not impair muscle hypertrophy or strength and does not affect ratings of muscle soreness.

Nitric oxide synthase inhibition promotes endothelium-dependent vasodilatation and the antihypertensive effect of L-serine.

L-serine is a precursor of central neurotransmitters. Its cardiovascular effects are largely unstudied. We compared the in vitro effects of L-serine and acetylcholine in phenylephrine-constricted third-order branches of mesenteric arterioles in the NO synthase inhibitor N(G)-nitro L-arginine methyl ester (L-NAME), pretreated hypertensive rats, and a control group of normotensive male Sprague-Dawley rats. The changes in mean arterial pressure and heart rate evoked by acute intravenous infusion of either L-serine (0.1 to 3.0 mmol/kg) or acetylcholine (0.1 to 10.0 nmol/kg) were determined in anesthetized rats. L-serine evoked concentration-dependent (10 to 200 micromol/L) vasodilatation in endothelium-intact but not in endothelium-denuded vessels. It was abolished by the inclusion of a combination of apamin (SK(Ca) channel inhibitor) and TRAM-34 (IK(Ca) channel inhibitor) or ouabain (Na(+) pump inhibitor) and Ba(2+) (K(ir) channel inhibitor) or when the vessels were constricted by potassium chloride. The maximal response to L-serine was higher in the L-NAME treatment group (control 20% versus L-NAME 40%) in relation to the maximal response to acetylcholine (control 93% versus L-NAME 79%). L-serine evoked a rapid, reversible, dose-dependent fall in mean arterial pressure without increasing heart rate and was more pronounced in L-NAME-treated rats (maximal response: >60 mm Hg) than in the control rats (maximal response: 25 mm Hg). This was inhibited (P<0.01) by apamin+charybdotoxin pretreatment. The in vitro and in vivo data confirm that L-serine promotes vasodilatation in resistance arterioles and evokes a greater fall in mean arterial pressure in NO synthase-inhibited hypertensive rats via activation of apamin and charybdotoxin/TRAM-34-sensitive K(Ca) channels present on the endothelium.

Field-test of a date-rape drug detection device.

Drink Safe Technology Version 1.2 is an inexpensive color-change reagent test marketed internationally for use by consumers in settings such as a night club to detect potentially incapacitating concentrations of gamma-hydroxybutyric acid (GHB) and ketamine in beverages. The objective of this study was to compare product performance in the laboratory and performance in the hands of consumers in the field. Product performance in the laboratory adhered to the protocol defined by the manufacturer. Product performance in the hands of consumers in field settings allowed browsing participants to pipette an aliquot of their own drinks into randomly coded vials containing authentic drugs, or pure water, so as to yield the same concentrations of GHB or ketamine specified in the manufacturer-defined protocol, or blanks. Consumers were to proceed according to the directions printed on the product, and to record their results on a card with a code corresponding with the vial to which they had added an aliquot of their beverage. Diagnostic performance was calculated using two-way analysis. In the laboratory, Drink Safe Technology Version 1.2 reliably detected GHB and ketamine at concentrations specified by the manufacturer's protocol. The reactive color change denoting a positive test for GHB was rapid, but a positive test for ketamine required substantially more time to resolve. Nonetheless, test accuracy following the manufacturer's protocol in the laboratory was 100%. In the field, based on 101 paired-test results recorded by consumers, the test efficiency was 65.1%, sensitivity 50%, and specificity 91.6%. The product performed much better in the laboratory than it did in the hand of consumers in the field. There seems to be considerable potential for consumers to misinterpret a test result. The potential for consumers to record a false-negative test result for a spiked drink is cause for concern.