S. pneumoniae infection remains a serious public health concern despite the availability of vaccines covering up to 23 of more than 94 known serotypes. The purpose of the present study was to monitor recent serotype distribution data. PubMed, EMBASE, Cochrane Reviews and Ingenta databases were searched. Serotype data covering invasive pneumococcal disease (IPD) and non-IPD were extracted from articles published from March 2014 to March 2015. Fifty-nine studies presented pneumococcal serotype prevalence by specific age categories. Most prevalent serotypes not covered by pneumococcal conjugate vaccines (PCV) were as follows: 15B, 22F, 15A, 23A among children under the age of 7 y with IPD; among adults with IPD: 22F, 11A, 10A, 38 in the 65y and older age group; 12F, 9N, 8 in the 50-64 year-old age group and 12F, 8, 6C, 16F in the 15-59 age group. Geographic variations in serotype distribution highlight the importance of monitoring evolving pneumococcal serotype prevalence after pneumococcal vaccine implementation.

BACKGROUND:Few studies have assessed the prevalence of mixed dyslipidemia (MD) and the effectiveness of lipid-modifying therapy (LMT) for the treatment of abnormal levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in Australian clinical practice.OBJECTIVE:To estimate the prevalence of MD in Australian patients undergoing LMT.METHODS:Patients 35 years of age and older undergoing LMT for ≥1 year were enrolled from nine general practice and cardiologist/endocrinologist outpatient clinics in Australia between April 2007 and May 2008. Lipid levels, including LDL-C, HDL-C and TG levels, were prospectively collected at the enrollment date and from patient records one year before LMT was initiated. Normal lipid levels were assessed according to Australian guidelines. Multivariate logistic regression was used to evaluate predictors of normal lipid level attainment.RESULTS:Of 297 patients (mean age 60.1 years; 43% male), the prevalence of MD before LMT was 61%; 93% of patients had elevated LDL-C levels, 17% had low HDL-C levels and 62% had elevated TG levels. Following LMT (98.3% statins), 31% of patients had MD. The prevalence of elevated LDL-C levels, low HDL-C levels and elevated TG levels were 44%, 21% and 42%, respectively. Baseline lipid levels were significant predictors of attainment of normal LDL-C levels (OR 0.42 [95% CI 0.27 to 0.63]) and TG levels (OR 0.26 [95% CI 0.16 to 0.45]).CONCLUSION:Among Australian patients primarily treated with statins, nearly one-third had MD despite LMT. LMT considerably improved LDL-C goal attainment; however, a large proportion of patients did not achieve normal HDL-C and TG levels. Patients may benefit from a more comprehensive approach to lipid management that treats all three lipid risk factors, as suggested in clinical guidelines.

BACKGROUND Prior studies have found inverse associations between high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I levels and cardiovascular disease (CVD). Whether this observation is consistent across low-density lipoprotein cholesterol (LDL-C) levels or total atherogenic particle burden (apolipoprotein B100) is less well-studied, particularly in women. OBJECTIVE To determine the association between HDL-C or apolipoprotein A-I level and CVD across a range of LDL-C and apolipoprotein B100 values. DESIGN Prospective cohort study. SETTING The Women's Health Study, a cohort of U.S. female health professionals. PARTICIPANTS 26,861 initially healthy women, aged 45 years or older at study entry (1992-1995), who were followed for a mean of approximately 11 years. MEASUREMENTS Baseline lipids were measured directly, and apolipoproteins were measured with immunoassays. Outcomes were incident total CVD (n = 929), coronary events (n = 602), and stroke (n = 319). RESULTS In multivariable analyses, HDL-C and apolipoprotein A-I levels were inversely associated with CVD and coronary events but not stroke. Adjusted coronary hazard ratios for decreasing quintiles of HDL-C were 1.00 (reference), 1.23 (95% CI, 0.85 to 1.78), 1.42 (CI, 0.98 to 2.06), 1.90 (CI, 1.33 to 2.71), and 2.19 (CI, 1.51 to 3.19) (P for linear trend < 0.001); corresponding hazard ratios for apolipoprotein A-I were 1.00 (reference), 0.98 (CI, 0.71 to 1.35), 1.02 (CI, 0.72 to 1.44), 1.37 (CI, 0.98 to 1.90), and 1.58 (CI, 1.14 to 2.20) (P for linear trend = 0.005). Consistent inverse associations were found for HDL-C with coronary events across a range of LDL-C values, including among women with low LDL-C levels. No associations were noted for HDL-C or apolipoprotein A-I among women with low apolipoprotein B100 values (<0.90 g/L). LIMITATION Participants were at low risk for CVD, the number of events in the lowest apolipoprotein B100 stratum was small, only a single baseline measurement was obtained, and residual confounding may have occurred. CONCLUSION Consistent inverse associations were found for HDL-C with incident coronary events among women with a range of LDL-C values. Among women with low total atherogenic particle burden (apolipoprotein B100 level <0.90 g/L), few events occurred and no associations were seen. PRIMARY FUNDING SOURCE Merck & Co. and the National Heart, Lung, and Blood Institute and National Cancer Institute, National Institutes of Health.

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease (CVD) and is the primary target of therapy (1). While LDL particles are the predominant circulating atherogenic lipoproteins, other triglyceride-rich lipoproteins such as very-low-density and intermediate-density lipoproteins have been implicated in atherogenesis (2). Apolipoprotein B100 reflects the total number of atherogenic lipoprotein particles that include not only LDL particles but also the triglyceride-rich very-low-density and intermediate-density lipoprotein particles, since all atherogenic particles carry an apolipoprotein B protein in a one-to-one fashion (2). By contrast, high-density-lipoprotein (HDL) particles do not carry apolipoprotein B100, but instead carry apolipoprotein A-1. Hence, apolipoprotein A-1 reflects the potentially anti-atherogenic HDL particles, although not in a one-to-one fashion, since each HDL particle may carry one or more apolipoprotein A-1 molecule. The inverse association between HDL cholesterol (HDL-C) and CVD is well-established (3–9). However, whether this inverse association of HDL-C with CVD remains across different levels of LDL-C is less well-studied, and the clinical significance of low HDL-C in patients with low LDL-C is presently debated. Among men, the inverse association of HDL-C with CVD was consistent across a range of LDL-C in several studies (4,6,10). Among women, particularly healthy women, there is a dearth of studies examining the association of HDL-C across a range of LDL-C (11). Similarly, while low concentrations of apolipoprotein A-1, the major protein carried by HDL particles, have been associated inversely with CVD (2), it is unclear whether apolipoprotein A-1 is inversely associated with CVD across a range of LDL-C. It is also unclear whether apolipoprotein A-1 or HDL-C are inversely associated with CVD when concentrations of apolipoprotein B100, i.e. total atherogenic particles (including the triglyceride-rich particles), are low. Therefore, we examined the associations of HDL-C and apolipoprotein A-1 with incident CVD, including coronary and stroke events, in apparently healthy women across a range of concentrations for LDL-C and apolipoprotein B100. Furthermore, since clinicians encounter women with very high HDL-C concentrations and it is unknown if these women are more protected against CVD, a secondary aim of this study was to determine whether extreme elevation of HDL-C occurring spontaneously in these women provided additional protection.

AIMS:To evaluate the single and joint associations of serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol with coronary heart disease (CHD) risk. METHODS:Study cohorts included 21,375 Finnish participants who were 25-74 years of age and free of CHD and stroke at baseline. RESULTS:During a median follow-up period of 10.8 years, 437 participants developed CHD. The sex- and multivariable-adjusted hazard ratios (HRs) of CHD at different levels of HDL cholesterol [<40 (reference), 40-49, 50-59, 60-69, and ≥ 70 mg/dL] were 1.00, 1.00, 0.74, 0.58, and 0.69 (p (trend) = 0.006), respectively. The sex- and multivariable-adjusted HRs of CHD at different levels of LDL cholesterol [<100 (reference), 100-129, 130-159, and ≥ 160 mg/dL] were 1.00, 1.25, 1.92, and 2.65 (p (trend) < 0.001), respectively. In joint analyses, a decreased trend in the incidence rate of CHD with an increasing HDL cholesterol level was consistent in people with any level of LDL cholesterol. Likewise, an increasing trend in incidence of CHD with an increase in the LDL cholesterol level was consistent in subjects with any level of HDL cholesterol. CONCLUSION:These results suggest an inverse association between HDL cholesterol and CHD risk and a direct association between LDL cholesterol and CHD risk, independent of other risk factors. The protective effect of HDL cholesterol on CHD risk is observed at all levels of LDL cholesterol.

Epidemiological studies have extensively evaluated the association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) risk. The objective of this systematic review was to enumerate the number of original prospective studies that showed a significant association between HDL-C and CVD risk and provided evidence of the consistency of this association across other lipid risk factors. A systematic MEDLINE literature search identified 53 prospective cohort and five nested case-control studies that provided multivariate assessments of the association between HDL-C and CVD risk. Among these 58 prospective studies, 31 studies found a significant inverse association between HDL-C and CVD risk for all CVD outcomes and subpopulations studied, whereas 17 studies found a significant association for some CVD outcomes and/or subpopulations assessed. The ratio of studies that found a significant association out of the total studies identified was similar across all CVD outcomes, although there was less evidence for stroke and atherosclerotic outcomes. Only seven studies tested for the consistency of this association across other lipid risk factors, of which six studies suggested that the association was consistent across other lipid levels. In conclusion, the association between HDL-C and CVD risk is significant and strong, although further evidence may be needed to establish whether this association is consistent across other lipid risk factors. Furthermore, uncertainties remain regarding the mechanism in which HDL-C exerts its effects, suggesting a need for further research focused on new methods for reliable measurement.

Reducing low-density lipoprotein (LDL) cholesterol with statins reduces cardiovascular risk, but the associations between increases in high-density lipoprotein (HDL) cholesterol and cardiovascular risk at different LDL levels have been less well characterized. To evaluate the associations between the I-year changes in HDL cholesterol and LDL cholesterol with lovastatin and subsequent acute major coronary events (AMCEs), we studied 2,928 patients in the lovastatin arm who were followed for 5.2 years in a post-hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). The percentage of HDL cholesterol increase and apolipoproteins at year 1 and the incidence of AMCEs thereafter were assessed stratified by the LDL cholesterol levels. With lovastatin, LDL cholesterol was reduced by 25% on average to 115 mg/dl at year 1, and HDL cholesterol increased 6.0%. Patients with both an increase in HDL cholesterol of >= 7.5% and LDL cholesterol of <115 mg/dl at year 1 had the lowest event rate (3.53/1,000 person-years; p = 0.028). Similar results were found for an increase in HDL cholesterol of >= 7.5% and a decrease in LDL cholesterol of >25%, as well as for apolipoproteins A-I and B. The 1-year percent increase in HDL cholesterol appeared to be associated with a reduction in AMCEs in subsequent follow-up (p = 0.07 with the percentage of HDL cholesterol increase analyzed continuously). Patients with an HDL cholesterol increase of >= 7.5% had an AMCE rate of 5.18 compared with 7.66/1,000 person-years in patients with a lower HDL cholesterol increase (p = 0.08). In conclusion, lovastatin therapy was associated with a greater risk reduction of AMCEs when LDL cholesterol was substantially reduced and the HDL cholesterol increased by >= 7.5%. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:829-834)

This study explored the functions of the signal transducers and activators of transcription 5a and 5b (referred to as Stat5 here) during different stages of mouse mammary gland development by using conditional gene inactivation. Mammary gland morphogenesis includes cell specification, proliferation and differentiation during pregnancy, cell survival and maintenance of differentiation throughout lactation, and cell death during involution. Stat5 is activated by prolactin, and its presence is mandatory for the proliferation and differentiation of mammary epithelium during pregnancy. To address the question of whether Stat5 is also necessary for the maintenance and survival of the differentiated epithelium, the two genes were deleted at different time points. The 110-kb Stat5 locus in the mouse was bracketed with loxP sites, and its deletion was accomplished by using two Cre-expressing transgenic lines. Loss of Stat5 prior to pregnancy prevented epithelial proliferation and differentiation. Deletion of Stat5 during pregnancy, after mammary epithelium had entered Stat5-mediated differentiation, resulted in premature cell death, indicating that at this stage epithelial cell proliferation, differentiation, and survival require Stat5.

ContextThe value of exercise testing in women has been questioned.ObjectiveTo determine the prognostic value of exercise testing in a population-based cohort of asymptomatic women followed up for 20 years.Design and SettingNear-maximal Bruce-protocol treadmill test data from the Lipid Research Clinics Prevalence Study (1972-1976) with follow-up through 1995.ParticipantsA total of 2994 asymptomatic North American women, aged 30 to 80 years, without known cardiovascular disease.Main Outcome MeasuresCardiovascular and all-cause mortality.ResultsThere were 427 (14%) deaths during 20 years of follow-up, of which 147 were due to cardiovascular causes. Low exercise capacity, low heart rate recovery (HRR), and not achieving target heart rate were independently associated with increased all-cause and cardiovascular mortality. There was no increased cardiovascular death risk for exercise-induced ST-segment depression (age-adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.57-1.80; P = .96). The age-adjusted hazard ratio for cardiovascular death for every metabolic equivalent (MET) decrement in exercise capacity was 1.20 (95% CI, 1.18-1.30; P<.001); for every 10 beats per minute decrement in HRR, the hazard ratio was 1.36 (95% CI, 1.19-1.55; P<.001). After adjusting for multiple other risk factors, women who were below the median for both exercise capacity and HRR had a 3.5-fold increased risk of cardiovascular death (95% CI, 1.57-7.86; P = .002) compared with those above the median for both variables. Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001).ConclusionThe prognostic value of exercise testing in asymptomatic women derives not from electrocardiographic ischemia but from fitness-related variables.

Obesity is a well‐known risk factor for postmenopausal breast cancer. In contrast, the relationship between obesity and stage of breast cancer at diagnosis is less clear. We hypothesized that increased breast size in obese women may delay discovery of breast tumors. Thus, the purpose of our study was to examine whether there is an association between body mass and stage of breast cancer at diagnosis using hospital medical records. Newly diagnosed breast cancer cases ( n = 966) in the Baltimore metropolitan area from 1991 to 1997 were included in our study. Patient information including age, ethnicity, weight, height and pathology data were obtained from hospital medical records. High body mass was significantly associated with late stage of breast cancer at diagnosis. Women who were obese (body mass index [BMI] ≥ 27.3) were more likely to be at an advanced stage at diagnosis compared with women with a BMI of < 27.3 (multivariate‐adjusted odds ratio [OR] 1.57, 95% confidence interval [CI] 1.15–2.14). The association between body mass and stage at diagnosis was stronger among women younger than 50 years (OR 2.34, 95% CI 1.34–4.08) compared with women 50 years or older (OR 1.30, 95% CI 0.89–1.91). Our study suggests that higher body mass is associated with advanced stage of breast cancer at diagnosis. This finding may be of considerable concern, given the increasing prevalence of obesity in women in the United States and the poor prognosis associated with late‐stage tumors. © 2001 Wiley‐Liss, Inc.