Using social media for patient-reported outcomes: A study of genital appearance and sexual function in adult bladder exstrophy patients.

INTRODUCTION: There have been few prior studies on patient-centered outcomes of adults with bladder exstrophy; those performed have been single institution reviews. In collaboration with the Association for the Bladder Exstrophy Communities (ABeC) - an international support network for patients and families living with bladder exstrophy - an anonymous social media survey was performed of patient-reported genital appearance and erectile function. OBJECTIVE: The study evaluated the Penile Perception Score (PPS) and the International Index of Erectile Function (IIEF-15) in adult men with bladder exstrophy. It was hypothesized that scores would be significantly lower than prior reported scores for men without the condition. STUDY DESIGN: After review by an anonymous patient advocate volunteer, the ABeC performed an anonymous online survey using social media. RESULTS: Adult men with bladder exstrophy reported PPS, and satisfaction with penile length and axis that were lower than prior published controls (n = 54, P < 0.05). Orgasmic function, sexual desire, and overall satisfaction were also lower (n = 46, P < 0.05). There was no difference in erectile function or intercourse satisfaction compared to controls. There was an association between PPS and erectile function, intercourse satisfaction, and overall satisfaction (P < 0.05) (Summary Fig.). Respondents identified urinary issues, genital appearance, and sexual function as the three main domains that warranted further research. CONCLUSION: This study found that PPS and IIEF-15 were low in adult men with bladder exstrophy, and worse perception of genital appearance was associated with worse sexual satisfaction. Social media is a novel tool for patient-centered outcomes research, and continued collaboration with patients and patient advocate groups is vital.

A Proton Pump Inhibitor in the Reformulation Setting: Bioequivalence and Potential Implications for Long-Term Safety.

Proton pump inhibitors (PPIs) have become known for both their therapeutic effect and good safety profile. An application was submitted to the US Food and Drug Administration for approval of a reformulated PPI product that failed bioequivalence testing, but was submitted on the basis of the long history of PPI use as a "surrogate" for equivalence. This review evaluates the safety data for PPIs, discuss variability of pharmacokinetic parameters of PPIs in the reformulation setting, and potential implications of those changes for long-term safety.

Evolutionary history of the Afro-Madagascan Ixora species (Rubiaceae): species diversification and distribution of key morphological traits inferred from dated molecular phylogenetic trees.

BACKGROUND AND AIMS: Previous work on the pantropical genus Ixora has revealed an Afro-Madagascan clade, but as yet no study has focused in detail on the evolutionary history and morphological trends in this group. Here the evolutionary history of Afro-Madagascan Ixora spp. (a clade of approx. 80 taxa) is investigated and the phylogenetic trees compared with several key morphological traits in taxa occurring in Madagascar. METHODS: Phylogenetic relationships of Afro-Madagascan Ixora are assessed using sequence data from four plastid regions (petD, rps16, rpoB-trnC and trnL-trnF) and nuclear ribosomal external transcribed spacer (ETS) and internal transcribed spacer (ITS) regions. The phylogenetic distribution of key morphological characters is assessed. Bayesian inference (implemented in BEAST) is used to estimate the temporal origin of Ixora based on fossil evidence. KEY RESULTS: Two separate lineages of Madagascan taxa are recovered, one of which is nested in a group of East African taxa. Divergence in Ixora is estimated to have commenced during the mid Miocene, with extensive cladogenesis occurring in the Afro-Madagascan clade during the Pliocene onwards. CONCLUSIONS: Both lineages of Madagascan Ixora exhibit morphological innovations that are rare throughout the rest of the genus, including a trend towards pauciflorous inflorescences and a trend towards extreme corolla tube length, suggesting that the same ecological and selective pressures are acting upon taxa from both Madagascan lineages. Novel ecological opportunities resulting from climate-induced habitat fragmentation and corolla tube length diversification are likely to have facilitated species radiation on Madagascar.

ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers.

Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this goal, we characterized the relevance of tumour necrosis factor-α-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types. In the present study, we analysed the expression profile of ADAM17 in a variety of normal and cancer cells of human origin and found that this protein is over-expressed on the surface of several types of cancer cells compared to the normal counterparts. Furthermore, we analysed the presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17 protein to specific T cells established from normal donors as well as ovarian cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is processed efficiently and presented by various cancer cells and not by normal cells. Tumour-specific T cell activation results in the secretion of both interferon-γ and granzyme B that can be blocked by HLA-A2 specific antibodies. Collectively, our data present evidence that ADAM17 can be a potential target antigen to devise novel immunotherapeutic strategies against ovarian, breast and prostate cancer.

Smoking rates and smoking cessation among individuals with multiple sclerosis.

PURPOSE: Adults with physical disabilities tend to smoke at higher rates than smokers in the general population. No study to date, however, has assessed smoking prevalence and cessation among individuals with multiple sclerosis (MS). Such information is critically needed because smoking is more deleterious for individuals with MS than for smokers without MS and increases MS risk. METHOD: Questionnaires were sent to 700 National Multiple Sclerosis Society Rhode Island Chapter members. RESULTS: Based on a 50% response rate, results demonstrated a 15.2% current smoker prevalence rate, which is lower than USA and Rhode Island general adult population averages. Individuals who smoked, however, tended to be heavy smokers, consuming 20 - 30 cigarettes daily, and had been smoking 10 years or longer. Smokers varied in their interest in quitting but seemed confident in their ability to do so. Respondents reported that it was difficult to quit because smoking was pleasurable; smoking was helpful in coping with boredom and with having MS; withdrawal symptoms were unpleasant; and treatment for tobacco dependence was expensive. CONCLUSIONS: Efficacious smoking cessation interventions for smokers with MS should be developed to address a critical health need for a population of highly nicotine-dependent smokers who face numerous obstacles to quitting.

Association between leisure time physical activity and markers of chronic inflammation related to coronary heart disease.

BACKGROUND: Some markers of chronic inflammation have been recognized as predictors of cardiovascular risk in apparently healthy subjects and in patients with coronary heart disease (CHD). High sensitivity C-reactive protein (CRP) appears to be the most useful marker in clinical settings. Several studies reported associations between inflammatory markers and other cardiovascular risk factors, such as age, obesity, cholesterol levels, the presence of diabetes mellitus, physical activity, social level and smoking habits. We focussed on the association between C-reactive protein, serum amyloid A (SAA), fibrinogen and leisure time physical activity (LTPA). METHODS: This report deals with the results observed in a sub-sample of the BELSTRESS study. 892 male subjects, free from clinical CHD and major ECG abnormalities, working in the same environment, aged 35-59 years, were selected. A questionnaire was used to estimate the level of leisure time physical activity. Associations between CRP, SAA, fibrinogen and leisure time physical activity were evaluated through univariate and multivariate methods. Subjects taking statins or other lipid lowering medication were excluded from the study. RESULTS: Regular leisure time physical activity is associated with reductions of several cardiovascular risk factors, such as body mass index (BMI), waist hip ratio and the lipid profile. Smokers and low educated subjects had a lower physical activity status. Age adjustment did not alter the means of inflammatory parameters according to the levels of leisure time physical activity. After correction for personal characteristics (BMI, current smoking status, educational level, presence of diabetes and alcohol consumption) no significant relation was found between leisure time physical activity and levels of inflammatory markers. The differences of CRP and fibrinogen according to the level of physical activity, found in bivariate analysis, seem to be explained by linked differences in BMI, or related to current smoking habits. Leisure time physical activity, as reported in this study, is not significantly related to C-reactive protein, serum amyloid A or fibrinogen levels, after correction for other cardiovascular risk factors. CONCLUSION: These data indicate that leisure time physical activity, as reported in our study, is not an independent predictor of C-reactive protein, serum amyloid A or fibrinogen levels. Possible interactions of physical activity and other cardiovascular risk factors might explain the (indirect) relation we found in the bivariate analysis.

Primary prevention of coronary heart disease in general practice: a cross sectional population study.

The aim of this study was to assess the interventions by general practitioners on cardiovascular risk factors among persons without a history of cardiovascular disease attending for a cardiovascular check-up. All inhabitants of three Belgian towns aged between 45 and 64 years were invited for a cardiovascular check-up and blood test. Of all the attending persons without a history of cardiovascular disease (n = 898), 51% received at least one prescription, diet or health advice: 28% for hyperlipidaemia, 23% for physical activity, 22% for caloric intake, 9% for blood sugar, 5% for blood pressure and 4% for smoking. Interventions on lipoproteins, blood sugar and smoking habits were significantly more often proposed to persons with a medium or high cardiovascular risk compared to those at low cardiovascular risk. For persons at low cardiovascular risk, therapeutic lifestyle changes are often not advised, and isolated risk factors often remain untreated.

Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations.

Folic acid is presently the mainstay of treatment for most subjects with elevated plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine, whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response to folic acid supplementation are characterized by considerable interindividual variation. The purpose of this study was to identify factors that contribute to heterogeneity in short-term responses to folic acid supplementation. The effects of folic acid supplementation (1 or 2 mg per day) for 3 wk on plasma homocyst(e)ine concentrations were assessed in 304 men and women. Overall, folic acid supplementation increased mean plasma folate 31.5 +/- 98.0 nmol/L and decreased mean plasma homocyst(e)ine concentrations 1.2 +/- 2.4 micromol/L. There was evidence of substantial interindividual variation in the homocyst(e)ine response from -18.5 to +7.1 micromol/L, including an increase in homocyst(e)ine in 20% of subjects (mean increase 1.5 +/- 1.4 micromol/L). Basal homocyst(e)ine, age, male gender, cigarette smoking, use of multivitamins, methylene tetrahydrofolate reductase, and cystathionine beta-synthase polymorphisms accounted for 47.6% of the interindividual variability in the change in homocyst(e)ine after folic acid supplementation, but about 50% of variability in response to folic acid was not explained by the variables we studied.

Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.

BACKGROUND: Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. METHODS AND RESULTS: Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997-1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985-1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985-1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years; P:<0.001) and more often female (32.1% versus 25.5%; P:<0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%; P:<0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction; P:<0.001), thrombotic (22.1% versus 11.3%; P:<0.001) or calcified (29.5% versus 10.8%; P:<0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985-1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%; P:<0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%; P:=0.001) than in the 1985-1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%; P:<0.001). CONCLUSIONS: Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985-1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Manpower in cardiology in Europe. The Cardiology Monospeciality Section of the UEMS.

This is the first systematic survey of cardiology manpower in Europe. Hitherto, there has been no published information on the number of cardiologists in the different European nations and whether it was growing or stable. Important differences in the number of cardiologists and trainees are observed, with the highest figures in Greece, Italy and France (more than 80/10(6)inhabitants) and the lowest in the Scandinavian nations, Austria, Germany and the U.K. (35 or less/10(6)inhabitants). This is partly due to different roles and the activities of the cardiologists in these countries as well as their capacity to undertake various cardiological procedures. Some comparisons with the U.S.A. and projections for the year 2000 are also made.

Corrected QT interval prolongation associated with intravenous haloperidol in acute coronary syndromes.

We report on three patients with acute coronary syndromes who developed QT interval prolongation associated with intravenous haloperidol use. One developed ventricular fibrillation. We also review 21 such patients from the literature. Haloperidol should be used with caution and QT intervals monitored closely in patients with coronary ischemia who may be prone to ventricular ectopy.

Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid.

Elevated total plasma homocysteine (tHcy) is an established risk factor for the development of vascular disease and neural tube defects. Total homocysteine levels can be lowered by folic acid supplements but individual response is highly variable. In this case-control study, involving 142 coronary artery disease (CAD) patients and 102 controls, we have typed six genetic polymorphisms in three homocysteine metabolizing genes and examined their relationship to the incidence of CAD, tHcy levels, and lowering of tHcy levels in response to folic acid supplementation. We found that two single nucleotide polymorphisms in the cystathionine beta synthase (CBS) gene, 699C --> T and 1080T --> C, are associated with decreased risk of CAD and increased responsiveness to the tHcy lowering effects of folic acid. Individuals homozygous for 699T were significantly underrepresented in CAD patients as compared to controls (4.9% vs 17.3%, P = 0.0015), as were individuals homozygous for the 1080C (29.6% vs 44.2%, P = 0.018). Additionally, 699T and 1080C homozygous individuals were the most responsive to folate supplementation. 699T homozygotes lowered tHcy levels 13.6% on average, compared to 4.8% lowering in 699C homozygotes (P = 0.009), while 1080C homozygotes lowered 12.9% compared to just 2.7% for 1080T homozygotes (P = 0.005). The two polymorphisms in CBS are third codon changes and would not be predicted to affect the underlying protein. However, there is strong linkage disequilibrium between these two positions, suggesting that they may also be linked to other as yet unidentified polymorphisms within the CBS gene. These observations suggest that specific CBS alleles are a risk factor for the development of vascular disease and that genetic information could be predictive of individual response to folic acid supplementation.

Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope.

AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.

Impact of second harmonic imaging on the determination of the global and regional left ventricular function by 2D echocardiography: a comparison with MIBI gated SPECT.

AIMS: To evaluate the impact of second harmonic (SH) compared to fundamental mode (FM) imaging on the echocardiographic determination of ejection fraction (EF) and wall motion score index (WMSI), using MIBI gated SPECT as an independent reference. METHODS: Sixty-two consecutive patients underwent an echocardiography study and a MIBI gated SPECT over 24 hours. EF was estimated visually (estimated-E) and was calculated with the Simpson biplane method (Tracing-T), for both FM and SH. WMSI was determined by two independent echo-readers blinded to the nuclear imaging results. The same segmentation and scoring system was used for WMSI determined by MIBI gated SPECT. RESULTS: The percentages of unscored segments because of suboptimal endocardial border detection were 19.5% (FM) and 9.0% (SH). The correlation coefficients (r) between SPECT-EF and echo-EF were: FM (E)=0.705, FM (T)=0.546, SH (E)=0.771, SH (T)=0.743. Agreement between SPECT-EF and echo-EF was acceptable for both imaging modalities (mean of the difference +/- 2 S.D.): -2.8 +/- 18.5 (FM) and -3.5 +/- 16.4 (SH). Correlation coefficients (r) between WMSI calculated by SPECT and by echo were 0.715 (FM) and 0.789 (SH). Agreement between SPECT-WMSI and echo-WMSI was good for all imaging modes but better with SH compared to FM: 0.12 +/- 0.91 (FM), 0.10 +/- 0.77 (SH). The interobserver correlation coefficients (r) for the WMSI were 0.939 (FM) and 0.996 (SH). The agreement between the two observers was better for SH compared to FM. The systematic differences (mean differences) were 0.21 (FM) and -0.01 (SH), and the random differences between both observers (2 S.D.) decreased from 1.55 (FM) to 0.29 (SH). CONCLUSIONS: The use of SH echocardiography decreases the number of unscored segments. This results in an important gain in correlation and agreement for EF determination between echo and SPECT, and in a considerable decline of the interobserver variability for the echo-determined WMSI. WMSI determined by MIBI gated SPECT correlated closely with the SH WMSI, and agreement between both methods was excellent.

Intravenous nitrates for pharmacological stimulation during head-up tilt testing in patients with suspected vasovagal syncope and healthy controls.

Nitrates may be used for pharmacological stimulation during tilt testing for the diagnosis of vasovagal syncope. In this study we assessed the diagnostic value of intravenous nitrates during tilt testing in patients with a typical history of vasovagal syncope. Twenty patients and 23 controls were tilted at 700 for a maximum duration of 30 minutes. After a 10-minute baseline supine phase, the test started with a continuous nitrate infusion at 1 microg/kg/min and increased every 5 minutes by 1 microg/kg/min, to a maximum of 6 microg/kg/min at the end of the test. The test was ended if the subjects developed a positive response (syncope or presyncope). Nineteen patients (95%) and 17 (74%) of the controls had a positive response. At test end sensitivity was 95%, but specificity was 26% and accuracy was 58%. Receiver operator characteristics (ROC) analysis revealed a maximum accuracy of 79% at 18 minutes, with a sensitivity of 80% and a specificity of 78%. Intravenous nitrates during tilt testing in patients with typical clinical criteria of vasovagal syncope is highly effective in provoking vasovagal syncope. Based on the ROC analysis, a maximum accuracy of 79% was attained at 18 minutes (at a dose of 4 microg/kg/min), suggesting a good diagnostic performance when tilt duration is limited to this point. A positive result requiring more than 18 minutes of stimulated tilting should be interpreted with caution, due to the accompanying considerable decrease of specificity.