Overestimation of postischemic myocardial stunning on gated SPECT imaging: correlation with echocardiography.

BACKGROUND: Postischemic global and regional left ventricular (LV) dysfunction on stress-gated single photon emission computed tomography (SPECT) imaging is attributed widely to myocardial stunning. We sought to determine the specificity of gated SPECT for the detection of myocardial stunning after ischemic stress. METHODS AND RESULTS: Twenty-seven patients with an ischemic response to stress on dual-isotope exercise SPECT were enrolled prospectively. Transthoracic echocardiography was performed just before stress gated SPECT for assessment of regional wall motion and quantitative LV ejection fraction (LVEF). The 17 myocardial segments for each patient were scored for myocardial perfusion by stress gated SPECT, and regional wall motion by stress gated SPECT and echo. Of the 459 myocardial segments, 41% had perfusion defects, 15% had stress gated SPECT regional wall motion abnormality, 4.8% had poststress echo regional wall motion abnormality, and 3.9% had baseline regional wall motion abnormality. Overall, a stress gated SPECT regional wall motion abnormality had a sensitivity of 100% and a specificity of 89%. Among reversible perfusion defects of moderate severity or more, a stress gated SPECT regional wall motion abnormality had a specificity of 41% and a positive predictive value of 8%. Stress gated SPECT LVEF was similar to poststress echo LVEF for all patients, but significantly lower in patients with reversible perfusion defects of moderate severity or more. CONCLUSION: Post-stress gated SPECT imaging overestimates global and regional myocardial stunning. Caution should be exercised in interpreting poststress global or regional LV function on stress gated SPECT in scans with reversible ischemia.     

Let’s Get Physical: Sexual Orientation Disparities in Physical Activity,Sports Involvement,and Obesity Among a Population-Based Sample of Adolescents

Objectives. We examined sexual orientation disparities in physical activity, sports involvement, and obesity among a population-based adolescent sample.Methods. We analyzed data from the 2012 Dane County Youth Assessment for 13 933 students in grades 9 through 12 in 22 Wisconsin high schools. We conducted logistic regressions to examine sexual orientation disparities in physical activity, sports involvement, and body mass index among male and female adolescents.Results. When we accounted for several covariates, compared with heterosexual females, sexual minority females were less likely to participate in team sports (adjusted odds ratio [AOR] = 0.44; 95% confidence interval [CI] = 0.37, 0.53) and more likely to be overweight (AOR = 1.28; 95% CI = 1.02, 1.62) or obese (AOR = 1.88; 95% CI = 1.43, 2.48). Sexual minority males were less likely than heterosexual males to be physically active (AOR = 0.62; 95% CI = 0.46, 0.83) or to participate in team sports (AOR = 0.26; 95% CI = 0.20, 0.32), but the 2 groups did not differ in their risk of obesity.Conclusions. Sexual orientation health disparities in physical activity and obesity are evident during adolescence. Culturally affirming research, interventions, and policies are needed for sexual minority youths.Obesity is an increasing and serious health problem among adolescents.1,2 This is of major concern because obesity has many health and social consequences and it affects adolescents’ overall well-being.3,4 Obesity among adolescents also has a high likelihood of continuing into adulthood.5 Recent population-based and longitudinal research has demonstrated that there are disparities in obesity between sexual minority and heterosexual adolescents.6–8 Research has also documented sexual orientation disparities in physical activity and sports involvement in adolescence.9,10 Despite this increased attention, the overall empirical base remains limited, and findings also suggest some gender nuances that need further exploration. More population-based research is needed to investigate these disparities, consistent with federal health priorities.7,11There are sexual orientation–based disparities in physical activity and sports involvement among adolescents; however, there are mixed findings for females. One study reported that sexual minority females are less likely than heterosexual females to participate in moderate to vigorous physical activity and team sports,9 whereas another study found no such differences in physical activity.10 Findings are more consistent for sexual minority male adolescents, who are less likely than heterosexual males to engage in moderate to vigorous physical activity, to engage in recommended levels of physical activity, and to participate in team sports.9,10 More research is needed because of the paucity of studies and mixed results. This is especially important given that adolescents’ physical activity has been shown to relieve stress and protect against many mental and physical health conditions, including obesity,12,13 for which sexual minority adolescents are at greater risk.Research on sexual orientation disparities in obesity suggests that there are some gender nuances. Many studies have found that sexual minority female adolescents have higher risk of obesity than heterosexual females (e.g., higher body mass index [BMI], defined as weight in kilograms divided by the square of height in meters).6,8,10,14 These sexual orientation disparities in obesity among adolescent females parallel those among sexual minority adult women.15,16Findings of elevated obesity risk among sexual minority male adolescents are mixed. Some studies show that sexual minority males, specifically bisexual males, have higher odds of obesity than heterosexuals,14 whereas other studies have documented no differences.10 By contrast, some studies have found that heterosexual males have increases in BMI during adolescence compared with sexual minority males.6,8 These mixed findings for sexual minority males might be attributed to physical maturation and developmental changes in adolescence that some of the cross-sectional studies could not examine.10,14 Specifically, one study found that sexual minority males had higher obesity risk than heterosexual males in early adolescence, but their risk of obesity became lower than for heterosexual males later in adolescence.6 The authors postulated that, compared with heterosexual males, sexual minority males reach puberty maturation earlier in adolescence but make less substantial weight gains later in adolescence.6Sexual orientation health disparities have been explained through the minority stress model: sexual minority youths experience unique stressors and stigma related to their sexual identity (e.g., homophobic bullying), which lead to poorer health.17 Sexual minority adolescents might therefore be less likely to be physically active or involved in team sports because of potential minority stressors that they often experience at school, especially bias and heightened discrimination experienced in the context of sports or in their communities.18–20 More recently, the negative effects of minority stress and stigma on physical health disparities have been documented,21,22 including their effects on obesity for sexual minority women.23 However, the minority stress model is not sufficient in explaining how sexual minority adolescent females, but not males, are at greater risk for obesity compared with their heterosexual peers.Another potential explanation of these obesity disparities is related to cultural norms and sexual minority females’ experiences of internalizing ideals for femininity and appearance8 and sexual minority males’ ideals for muscularity and body image.24 For instance, compared with heterosexual women, sexual minority women are more likely to be satisfied with their bodies and attracted to women with greater body mass,25,26 whereas sexual minority men are less likely to be satisfied with their bodies compared with heterosexual men and are more likely to be attracted to muscular men.25,27 Therefore, these 2 groups might engage (or not engage) in differing body weight management and dieting behaviors compared with their heterosexual peers; concomitantly, these behaviors might render differing risks for obesity.Sexual minority adolescents’ lack of physical activity and sports involvement might be influenced by traditional gender norms associated with athleticism and sports, which has implications for their athletic self-esteem and involvement. For adolescent males, team sports are a means to define masculinity28; however, adolescent males often engage in homophobic banter to prove their masculinity and heterosexuality and to enforce traditional gender norms.29,30 Sexual prejudice is pervasive in athletic settings,19,20 making sports contexts unwelcoming and unsafe for many sexual minority males. Traditional feminine gender norms and homophobia also affect sexual minority females’ involvement in sports.31 However, sexual minority adolescent females have unique gendered experiences in relation to sports. Because women’s athleticism can be a stereotype for being a lesbian,32 sexual minority females might avoid sports involvement. Expecting or experiencing exclusion in sports settings might also affect sexual minority adolescents’ athletic self-esteem, consequently preventing them from engaging in future sports or physical activity.9 In fact, athletic self-esteem has been found to contribute to sexual orientation disparities in sports involvement and physical activity.9Emerging evidence of sexual orientation disparities in physical activity, sports involvement, and obesity among adolescents, in addition to potential gender nuances in these disparities, points to the need for more population-based research in this area. We therefore examined sexual orientation disparities among a large adolescent population-based sample and tested for gender differences. While accounting for variables commonly associated with physical activity and obesity among adolescents,4,33 we hypothesized that sexual minority adolescents would be less likely to report physical activity and sports involvement than would their heterosexual peers. We also hypothesized that sexual minority females would be at higher risk for being overweight and obese than their heterosexual peers. Because of mixed findings in existing sexual orientation disparities research among adolescent males, we hypothesized that sexual minority males would be at equal risk for being overweight and obese than their heterosexual male peers.     

Effect of tranexamic acid on platelet ADP during extracorporeal circulation

Seventeen adults received the antifibrinolytic drug tranexamic acid during cardiac surgery utilizing extracorporeal circulation (ECC). In 8 patients, drug administration began prior to skin incision (pre-ECC); infusions commenced after ECC and protamine administration in another 9 patients (post-ECC). Compared with the post-ECC group, the pre-ECC group exhibited less bleeding via mediastinal drains (420 vs. 655 mL/12 h median, P = 0.024), decreased frequency of the presence (greater than or equal to 10 micrograms/mL) of fibrin split products (P less than 0.05), and greater platelet dense granule content of adenosine diphosphate after surgery (15.47 vs. 4.05 nmoles/mg protein median, P = 0.021). Follow-up in vitro study of tranexamic acid inhibition of plasmin-induced platelet activation utilizing normal human platelet rich plasma and porcine plasmin revealed a 13-fold lower concentration of tranexamic acid for 50% inhibition when plasmin was preincubated with the drug (1.2 micrograms/mL, 95% CI = 1.13-1.60 micrograms/mL) compared to when platelet rich plasma was preincubated with the drug (16 micrograms/mL, 95% CI = 7.3-99. micrograms/mL). Plasmin inactivated with tranexamic acid retained its ability to inhibit thrombin-induced platelet activation, thus suggesting that tranexamic acid inhibits plasmin's catalytic activity and not its binding to platelets. Both clot lysis and platelet dysfunction may contribute to bleeding after ECC. Tranexamic acid blocks plasmin-induced partial platelet activation during ECC, thus preserving platelet function and promoting hemostasis after ECC.     

Otitis media in children. I. The systemic immune response to nontypable Hemophilus influenzae

Twenty-one infants experienced 29 episodes of otitis media with effusion caused by nontypable Hemophilus influenzae (NTHI) during 2 y of observation. Bactericidal antibody was detected in acute serum of 26% of the subjects at a mean titer of 0.8 +/- 0.3 (log2) and was observed in convalescent serum of all of the individuals at a mean titer of 4.0 +/- 0.3 (log2, P less than .001). The serum bactericidal antibody response was not age-dependent (r = .08, P greater than .05). Serum concentrations of bactericidal antibody remained stable for the entire observation period in 90% of the children. The presence of serum bactericidal antibody correlated significantly with a reduction in the number of bacteria present in the middle ear fluid (P less than .025). Eight children experienced a second episode of otitis media with effusion caused by a different serotype of NTHI. All those who lacked bactericidal antibody against the organism causing the second episode possessed bactericidal antibody against the first strain at the time of the second episode. These data suggest that the immune response to NTHI in otitis media with effusion is type-specific. The occurrence of second episodes of otitis media with effusion due to different strains of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of cross-protection.     

Guidelines for Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is common, costly, and clinically serious. Several national and international practice guidelines have been developed to promote more appropriate, cost-effective care for patients with CAP. This article compares and contrasts eight international practice guidelines for the management of CAP, describes the extent to which recommendations are reflected in practice, and proposes explanations for non-adherence to guidelines. We found consistency in recommendations across all the guidelines for the management of patients with CAP requiring intensive care. In this setting, all guidelines recommend chest radiography, sputum Gram stain and culture, blood cultures, testing for Legionella pneumophila, and timely administration of antibiotics active against both typical (i.e. Streptococcus pneumoniae, Hemophilus influenzae) and atypical organisms (i.e. Legionella spp., Mycoplasma pneumoniae, and Chlamydia pneumoniae). Recommendations for the management of the average inpatient with pneumonia were more variable, with the greatest differences between the North American and European guidelines. The North American guidelines (in contrast to European ones), recommended empiric treatment of typical and atypical organisms in all inpatients. There were also differences in policies regarding the necessity of chest radiography, sputum studies, and serologic testing. Some guidelines explicitly embrace the use of prediction rules to inform the decision to hospitalize, while others do not. Some of these admission decision algorithms focus on identifying low risk patients, while others are most concerned with high risk patients. There was also considerable variation in the specificity and operationalization of clinical criteria for switching from parenteral to oral antibiotics or judging appropriateness for discharge. Many recommendations for key management decisions tended to lack explicit, objective, and actionable criteria that could be easily implemented in real world practice. Review of the pneumonia literature revealed that physician performance of guideline-recommended best practices is often suboptimal. Administration of timely antibiotics (< or =8 hours of presentation) and use of first-line antibiotics occurred in 75-85% and 18-79% of cases, respectively. Collection of blood cultures within 24 hours of presentation and prior to administration of antibiotics was achieved in 69-83% and 63-82% of cases, respectively. Screening the eligibility of CAP patients for hospital-based pneumococcal and influenza vaccination occurred on average in 11 and 14% of hospitalizations, respectively, in the US. Lack of awareness of guidelines, conflicting advice among them, and lack of specific, objective, actionable recommendations most likely contribute to nonadherence to CAP guidelines. Increased attention to these factors will be needed if professional society practice guidelines are to fulfill their promise as tools for improving the quality and outcomes of care for patients with pneumonia.     

Physical therapy and mobility 2 and 6 months after hip fracture

OBJECTIVES: To examine the relationship between early physical therapy (PT), later therapy, and mobility 2 and 6 months after hip fracture. DESIGN: Prospective, multisite observational study. SETTING: Four hospitals in the New York City area. PARTICIPANTS: Four hundred forty-three hospitalized older patients discharged after surgery for hip fracture in 1997-98. MEASUREMENTS: Patient demographics, fracture type, comorbidities, dementia, number of new impairments at discharge, amount of PT between day of surgery and postoperative day (POD) 3, amount of therapy between POD4 and 8 weeks later, and prefracture, 2-, and 6-month mobility measured using the Functional Independence Measure. RESULTS: More PT immediately after hip fracture surgery was associated with significantly better locomotion 2 months later. Each additional session from the day of surgery through POD3 was associated with an increase of 0.4 points (P=.032) on the 14-point locomotion scale, but the positive relationship between early PT and mobility was attenuated by 6 months postfracture. There was no association between later therapy and 2- or 6-month mobility. CONCLUSION: PT immediately after hip fracture surgery is beneficial. The effects of later therapy on mobility were difficult to assess because of limitations of the data. Well-designed randomized, controlled trials of the effect of varying schedules and amounts of therapy on functional status after hip fracture would be informative.     

Inhibited apoptosis and drug resistance in acute myeloid leukaemia

Despite extensive investigation into mechanisms of drug resistance in acute myeloid leukaemia (AML), the aetiology of therapeutic resistance is unclear. We found that five leukaemia cell lines (K562, HL-60, CEM, CEM induced to overexpress bcl-2, and REH) displayed parallel sensitivity to four antileukaemia drugs with different mechanisms of action, with K562 generally being the least sensitive and REH being the most sensitive. The amount of spontaneous apoptosis in the cell lines after serum-free culture paralleled their drug sensitivity: K562 cells displayed the least apoptosis at 24 h (2.50 ± 0.24%) and REH the most (24.47 ± 8.22%). The extent of spontaneous apoptosis of leukaemic blasts from 39 patients with newly diagnosed de novo AML also correlated with the success of the intensive, infusional cytarabine-based induction therapy. There was a median of 19.5% (range 3.6–64%) apoptotic AML cells after 24 h of serum-free culture in patients who entered a complete remission compared with 4.2% (1.8–7.0%) apoptotic AML cells in patients who did not achieve a complete remission ( P  = 0.0007). Thus, inhibited apoptosis was associated with both in vitro and in vivo pan-resistance to antileukaemic chemotherapy. The cause of inhibited apoptosis in AML is probably a function of interactions among multiple signals that influence apoptosis. Assessment of spontaneous apoptosis may serve as an important prognostic factor for AML.