Coronary evaginations are associated with positive vessel remodelling and are nearly absent following implantation of newer-generation drug-eluting stents: an optical coherence tomography and intravascular ultrasound study

OBJECTIVES The purpose of this study was to assess the occurrence, predictors, and mechanisms of optical coherence tomography (OCT)-detected coronary evaginations following drug-eluting stent (DES) implantation. BACKGROUND Angiographic ectasias and aneurysms in stented segments have been associated with a risk of late stent thrombosis. Using OCT, some stented segments show coronary evaginations reminiscent of ectasias. METHODS Evaginations were defined as outward bulges in the luminal contour between struts. They were considered major evaginations (MEs) when extending ≥3 mm along the vessel length, with a depth ≥10% of the stent diameter. A total of 228 patients who had sirolimus (SES)-, paclitaxel-, biolimus-, everolimus (EES)-, or zotarolimus (ZES)-eluting stents implanted in 254 lesions, were analysed after 1, 2, or 5 years; and serial assessment using OCT and intravascular ultrasound (IVUS) was performed post-intervention and after 1 year in 42 patients. RESULTS Major evaginations occurred frequently at all time points in SES (∼26%) and were rarely seen in EES (3%) and ZES (2%, P = 0.003). Sirolimus-eluting stent implantation was the strongest independent predictor of ME [adjusted OR (95% CI) 9.1 (1.1-77.4), P = 0.008]. Malapposed and uncovered struts were more common in lesions with vs. without ME (77 vs. 25%, P < 0.001 and 95 vs. 20%, P < 0.001, respectively) as was thrombus [49 vs. 14%, OR 7.3 (95% CI: 1.7-31.2), P = 0.007]. Post-intervention intra-stent dissection and protrusion of the vessel wall into the lumen were associated with an increased risk of evagination at follow-up [OR (95% CI): 2.9 (1.8-4.9), P < 0.001 and 3.3 (1.6-6.9), P = 0.001, respectively]. In paired IVUS analyses, lesions with ME showed a larger increase in the external elastic membrane area (20% area change) compared with lesions without ME (5% area change, P < 0.001). CONCLUSION Optical coherence tomography-detected MEs are a specific morphological footprint of early-generation SES and are nearly absent in newer-generation ZES and EES. Evaginations appear to be related to vessel injury at baseline; are associated with positive vessel remodelling; and correlate with uncoverage, malapposition, and thrombus at follow-up.

The association between admission systolic blood pressure and mortality in significant traumatic brain injury: A multi-centre cohort study

INTRODUCTION Low systolic blood pressure (SBP) is an important secondary insult following traumatic brain injury (TBI), but its exact relationship with outcome is not well characterised. Although a SBP of <90mmHg represents the threshold for hypotension in consensus TBI treatment guidelines, recent studies suggest redefining hypotension at higher levels. This study therefore aimed to fully characterise the association between admission SBP and mortality to further inform resuscitation endpoints. METHODS We conducted a multicentre cohort study using data from the largest European trauma registry. Consecutive adult patients with AIS head scores >2 admitted directly to specialist neuroscience centres between 2005 and July 2012 were studied. Multilevel logistic regression models were developed to examine the association between admission SBP and 30 day inpatient mortality. Models were adjusted for confounders including age, severity of injury, and to account for differential quality of hospital care. RESULTS 5057 patients were included in complete case analyses. Admission SBP demonstrated a smooth u-shaped association with outcome in a bivariate analysis, with increasing mortality at both lower and higher values, and no evidence of any threshold effect. Adjusting for confounding slightly attenuated the association between mortality and SBP at levels <120mmHg, and abolished the relationship for higher SBP values. Case-mix adjusted odds of death were 1.5 times greater at <120mmHg, doubled at <100mmHg, tripled at <90mmHg, and six times greater at SBP<70mmHg, p<0.01. CONCLUSIONS These findings indicate that TBI studies should model SBP as a continuous variable and may suggest that current TBI treatment guidelines, using a cut-off for hypotension at SBP<90mmHg, should be reconsidered.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

[Cervical cancer screening in Switzerland - current practice and future challenges]

At the beginning of the 20th Century, cervical cancer was the leading cause of death from cancer in women. A marked decline in cervical cancer has been observed since the 1960s, in parallel with the introduction of the Papanicolau (Pap) test as a cytological screening method. Today, Pap smear screening is still the most widely used tool for cervical cancer prevention. Testing for human papillomavirus (HPV) in cervical specimens or a combination of Pap and HPV testing are also now available. In this article we compare current guidelines for cervical cancer screening in Switzerland with those in other European countries. In view of the opportunities offered by HPV testing and, since 2008, HPV vaccination, current guidelines for cervical cancer screening should be updated. Both the choice of screening tests and general organization of cervical cancer screening should be reviewed.

Social Factors Associated with Readiness for Sexual Activity in Adolescents: A Population-Based Cohort Study

Various factors are associated with sexual activity in adolescence and it is important to identify those that promote healthy and adaptive romantic and sexual development. The objectives of this study were to describe rates of early sexual intercourse (before 16 years) and sexual readiness in adolescence and to assess the extent to which these were social patterned. We prospectively studied nearly 5,000 15-year-olds from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Between 2006 and 2008, female and male participants answered a computer assisted interview about romantic and sexual behaviors in the last year. Predictors of sexual intercourse and readiness for sexual intercourse were examined across a range of sociodemographic measures. Overall, 17.7 % (95 % CI 16.7 %, 18.9 %) of participants reported having had sexual intercourse in the last year, with more girls than boys reporting sexual experience (risk ratio 1.30, 95 % CI 1.15, 1.47). Of these, one-third of both male and female were classed as unready because they were unwilling, lacking in autonomy, felt regret or had not used contraception. There was strong evidence of social patterning for sexual activity with higher rates for young people from poorer homes, with lower social class, and with younger, less educated mothers. In contrast, among 860 young people who had had sexual intercourse, there was no clear evidence of associations between social factors and sexual readiness. The lack of social patterning in sexual readiness supports the provision of comprehensive education to develop life skills for adolescents across all social groups.

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

AIMS Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with 'paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. METHODS AND RESULTS Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm(2) m(-2), stroke volume index ≤35 mL/m(2), ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm(2) m(-2), EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG 2006 ± 586 vs. LEF-LG 2216 ± 765 dyne s m(-5), P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG 6.9 ± 1.9 vs. LEF-LG 7.7 ± 2.5 mmHg mL(-1) m(-2), P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG 71.7% vs. LEF-LG 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). CONCLUSION TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar extent.

Classification and pharmacological treatment of preschool wheezing: changes since 2008.

Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.

Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.

Chlamydia prevalence in young attenders of rural and regional primary care services in Australia: a cross-sectional survey.

OBJECTIVE To estimate chlamydia prevalence among 16-29-year-olds attending general practice clinics in Australia. DESIGN, PARTICIPANTS AND SETTING A cross-sectional survey was conducted from May 2010 to December 2012. Sexually experienced 16-29-year-olds were recruited from 134 general practice clinics in 54 rural and regional towns in four states and in nine metropolitan clinics (consecutive patients were invited to participate). Participants completed a questionnaire and were tested for chlamydia. MAIN OUTCOME MEASURE Chlamydia prevalence. RESULTS Of 4284 participants, 197 tested positive for chlamydia (4.6%; 95% CI, 3.9%-5.3%). Prevalence was similar in men (5.2% [65/1257]; 95% CI, 3.9%-6.4%) and women (4.4% [132/3027]; 95% CI, 3.5%-5.2%) (P = 0.25) and high in those reporting genital symptoms or a partner with a sexually transmissible infection (STI) - 17.0% in men (8/47; 95% CI, 2.8%-31.2%); 9.5% in women (16/169; 95% CI, 5.1%-13.8%). Nearly three-quarters of cases (73.4% [130/177]) were diagnosed in asymptomatic patients attending for non-sexual health reasons, and 83.8% of all participants (3258/3890) had attended for non-sexual health reasons. Prevalence was slightly higher in participants from rural and regional areas (4.8% [179/3724]; 95% CI, 4.0%-5.6%) than those from metropolitan areas (3.1% [17/548]; 95% CI, 1.5%-4.7%) (P = 0.08). In multivariable analysis, increasing partner numbers in previous 12 months (adjusted odds ratio [AOR] for three or more partners, 5.11 [95% CI, 2.35-11.08]), chlamydia diagnosis in previous 12 months (AOR, 4.35 [95% CI, 1.52-12.41]) and inconsistent condom use with most recent partner (AOR, 2.90 [95% CI, 1.31-6.40]) were significantly associated with chlamydia in men. In women, increasing partner numbers in previous 12 months (AOR for two partners, 2.59 [95% CI, 1.59-4.23]; AOR for three or more partners, 3.58 [95% CI, 2.26-5.68]), chlamydia diagnosis in previous 12 months (AOR, 3.13 [95% CI, 1.62-6.06]) and age (AOR for 25-29-year-olds, 0.23 [95% CI, 0.12-0.44]) were associated with chlamydia. CONCLUSIONS Chlamydia prevalence is similar in young men and women attending general practice. Testing only those with genital symptoms or a partner with an STI would have missed three-quarters of cases. Most men and women are amenable to being tested in general practice, even in rural and regional areas.

Social relationship correlates of major depressive disorder and depressive symptoms in Switzerland: nationally representative cross sectional study

BACKGROUND The quality and quantity of social relationships are associated with depression but there is less evidence regarding which aspects of social relationship are most predictive. We evaluated the relative magnitude and independence of the association of four social relationship domains with major depressive disorder and depressive symptoms. METHODS We analyzed a cross-sectional telephone interview and postal survey of a probability sample of adults living in Switzerland (N = 12,286). Twelve-month major depressive disorder was assessed via structured interview over the telephone using the Composite International Diagnostic Interview (CIDI). The postal survey assessed depressive symptoms as well as variables representing emotional support, tangible support, social integration, and loneliness. RESULTS Each individual social relationship domain was associated with both outcome measures, but in multivariate models being lonely and perceiving unmet emotional support had the largest and most consistent associations across depression outcomes (incidence rate ratios ranging from 1.55-9.97 for loneliness and from 1.23-1.40 for unmet support, p's < 0.05). All social relationship domains except marital status were independently associated with depressive symptoms whereas only loneliness and unmet support were associated with depressive disorder. CONCLUSIONS Perceived quality and frequency of social relationships are associated with clinical depression and depressive symptoms across a wide adult age spectrum. This study extends prior work linking loneliness to depression by showing that a broad range of social relationship domains are associated with psychological well-being.

Measuring Consumer Satisfaction in Family Preservation Services: Identifying Instrument Domains

Measuring consumer satisfaction in the social services has become an important source of feedback for the improvement of service delivery. Consumer satisfaction has recently been incorporated into family preservation evaluation. This article reviews instruments used to measure consumer satisfaction in family preservation services and other related areas. Trends in current practice are examined and instrument dimensions are identified. Finally, some recommendations are made about the application of consumer satisfaction measurement in family preservation services.

Coronary artery disease severity and aortic stenosis: clinical outcomes according to SYNTAX score in patients undergoing transcatheter aortic valve implantation.

AIM The aim of this study was to evaluate whether coronary artery disease (CAD) severity exerts a gradient of risk in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS A total of 445 patients with severe AS undergoing TAVI were included into a prospective registry between 2007 and 2012. The preoperative SYNTAX score (SS) was determined from baseline coronary angiograms. In case of revascularization prior to TAVI, residual SS (rSS) was also determined. Clinical outcomes were compared between patients without CAD (n = 158), patients with low SS (0-22, n = 207), and patients with high SS (SS >22, n = 80). The pre-specified primary endpoint was the composite of cardiovascular death, stroke, or myocardial infarction (MI). At 1 year, CAD severity was associated with higher rates of the primary endpoint (no CAD: 12.5%, low SS: 16.1%, high SS: 29.6%; P = 0.016). This was driven by differences in cardiovascular mortality (no CAD: 8.6%, low SS: 13.6%, high SS: 20.4%; P = 0.029), whereas the risk of stroke (no CAD: 5.1%, low SS: 3.3%, high SS: 6.7%; P = 0.79) and MI (no CAD: 1.5%, low SS: 1.1%, high SS: 4.0%; P = 0.54) was similar across the three groups. Patients with high SS received less complete revascularization as indicated by a higher rSS (21.2 ± 12.0 vs. 4.0 ± 4.4, P < 0.001) compared with patients with low SS. High rSS tertile (>14) was associated with higher rates of the primary endpoint at 1 year (no CAD: 12.5%, low rSS: 16.5%, high rSS: 26.3%, P = 0.043). CONCLUSIONS Severity of CAD appears to be associated with impaired clinical outcomes at 1 year after TAVI. Patients with SS >22 receive less complete revascularization and have a higher risk of cardiovascular death, stroke, or MI than patients without CAD or low SS.

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms.The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data.In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child.Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland

Switzerland has a complex human immunodeficiency virus (HIV) epidemic involving several populations. We examined transmission of HIV type 1 (HIV-1) in a national cohort study. Latent class analysis was used to identify socioeconomic and behavioral groups among 6,027 patients enrolled in the Swiss HIV Cohort Study between 2000 and 2011. Phylogenetic analysis of sequence data, available for 4,013 patients, was used to identify transmission clusters. Concordance between sociobehavioral groups and transmission clusters was assessed in correlation and multiple correspondence analyses. A total of 2,696 patients were infected with subtype B, 203 with subtype C, 196 with subtype A, and 733 with recombinant subtypes (mainly CRF02_AG and CRF01_AE). Latent class analysis identified 8 patient groups. Most transmission clusters of subtype B were shared between groups of gay men (groups 1-3) or between the heterosexual groups "heterosexual people of lower socioeconomic position" (group 4) and "injection drug users" (group 8). Clusters linking homosexual and heterosexual groups were associated with "older heterosexual and gay people on welfare" (group 5). "Migrant women in heterosexual partnerships" (group 6) and "heterosexual migrants on welfare" (group 7) shared non-B clusters with groups 4 and 5. Combining approaches from social and molecular epidemiology can provide insights into HIV-1 transmission and inform the design of prevention strategies.