Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass

A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. INTRODUCTION: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. MATERIALS AND METHODS: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. RESULTS: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). CONCLUSIONS: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies

BACKGROUND: Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. OBJECTIVES: To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. RESULTS: Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. CONCLUSION: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.

Prognostic importance of anaemia in HIV type-1-infected patients starting antiretroviral therapy: collaborative analysis of prospective cohort studies

BACKGROUND: In HIV type-1-infected patients starting highly active antiretroviral therapy (HAART), the prognostic value of haemoglobin when starting HAART, and of changes in haemoglobin levels, are not well defined. METHODS: We combined data from 10 prospective studies of 12,100 previously untreated individuals (25% women). A total of 4,222 patients (35%) were anaemic: 131 patients (1.1%) had severe (<8.0 g/dl), 1,120 (9%) had moderate (male 8.0-<11.0 g/dl and female 8.0- < 10.0 g/dl) and 2,971 (25%) had mild (male 11.0- < 13.0 g/ dl and female 10.0- < 12.0 g/dl) anaemia. We separately analysed progression to AIDS or death from baseline and from 6 months using Weibull models, adjusting for CD4+ T-cell count, age, sex and other variables. RESULTS: During 48,420 person-years of follow-up 1,448 patients developed at least one AIDS event and 857 patients died. Anaemia at baseline was independently associated with higher mortality: the adjusted hazard ratio (95% confidence interval) for mild anaemia was 1.42 (1.17-1.73), for moderate anaemia 2.56 (2.07-3.18) and for severe anaemia 5.26 (3.55-7.81). Corresponding figures for progression to AIDS were 1.60 (1.37-1.86), 2.00 (1.66-2.40) and 2.24 (1.46-3.42). At 6 months the prevalence of anaemia declined to 26%. Baseline anaemia continued to predict mortality (and to a lesser extent progression to AIDS) in patients with normal haemoglobin or mild anaemia at 6 months. CONCLUSIONS: Anaemia at the start of HAART is an important factor for short- and long-term prognosis, including in patients whose haemoglobin levels improved or normalized during the first 6 months of HAART.

Long-term cardiovascular and non-cardiovascular mortality in women and men with type 1 and type 2 diabetes mellitus: a 30-year follow-up in Switzerland

While studies from other countries have shown an excess mortality in diabetic individuals when compared with the general population, comparable long-term data is not available for Switzerland.

Gender differences in cardiac rehabilitation outcomes: do women benefit equally in psychological health?

BACKGROUND: Psychological factors are important in the etiology and prognosis of coronary heart disease (CHD). Cardiac rehabilitation (CR) aims to reduce psychological distress, besides other somatic risk factors. Studies have shown that CR is effective in reducing psychological distress, but little is known about gender-specific outcome differences. Our objective was to examine whether women and men benefit equally from outpatient CR in terms of reduction in psychological distress and whether women show more impaired psychological health at baseline of CR than do men. METHODS: We enrolled 441 CHD patients (mean age 58+/-11 years, 79.8% men) who underwent a 12-week outpatient CR program. Psychological dimensions, namely, anxiety, depression, vital exhaustion, social inhibition, and negative affect, were assessed at baseline and post-CR. Multivariate analysis of variance (MANOVA), controlling for age, disease severity, and exercise capacity, was applied to test for gender-specific differences at baseline and change between baseline and post-CR. In addition, gender-specific effect sizes were calculated for the change on psychological dimensions. RESULTS: Women and men did not differ on any psychological measure at baseline of CR. The effect sizes show small to moderate treatment effects on the psychological dimensions assessed. Gender had a significant impact on change on the dimensions vital exhaustion (F=5.040(df=1), p<0.05) and social inhibition (F=5.74(df=1), p<0.05). Women showed larger change on social inhibition and smaller change on vital exhaustion than men. CONCLUSIONS: Women and men do not differ in the extent of psychological distress at baseline of CR, which could be explained also by the exclusion of highly distressed women from treatment. CR is less effective among women with regard to vital exhaustion and more effective with regard to social inhibition compared with men in a sample of low distressed patients.

Real-time quantitative PCR to determine chlamydial load in men and women in a community setting

We used a PCR method to quantify the loads of Chlamydia trachomatis organisms in self-collected urine and vulvovaginal swab (VVS) samples from 93 women and 30 men participating in the Chlamydia Screening Studies Project, a community-based study of individuals not seeking health care. For women, self-collected VVS had a higher mean chlamydial load (10,405 organisms/ml; 95% confidence interval [95% CI], 5,167 to 21,163 organisms/ml) than did first-void urines (FVU) (503 organisms/ml; 95% CI, 250 to 1,022 organisms/ml; P < 0.001). Chlamydial loads in female and male self-collected FVU specimens were similar (P = 0.634). The mean chlamydial load in FVU specimens decreased with increasing age in females and males. There was no strong statistical evidence of differences in chlamydial load in repeat male and female FVU specimens taken when patients attended for treatment a median of 23.5 (range, 14 to 62) and 28 (range, 13 to 132) days later, respectively, or in VVS taken a median of 35 (range, 14 to 217) days later. In this study, chlamydial load values for infected persons in the community who were not seeking treatment were lower than those published in other studies involving symptomatic patients attending clinical settings. This might have implications for estimates of the infectiousness of chlamydia. The results of this study provide a scientific rationale for preferring VVS to FVU specimens from women.

In search of optimal compression therapy for venous leg ulcers: a meta-analysis of studies comparing diverse [corrected] bandages with specifically designed stockings

OBJECTIVE: In search of an optimal compression therapy for venous leg ulcers, a systematic review and meta-analysis was performed of randomized controlled trials (RCT) comparing compression systems based on stockings (MCS) with divers bandages. METHODS: RCT were retrieved from six sources and reviewed independently. The primary endpoint, completion of healing within a defined time frame, and the secondary endpoints, time to healing, and pain were entered into a meta-analysis using the tools of the Cochrane Collaboration. Additional subjective endpoints were summarized. RESULTS: Eight RCT (published 1985-2008) fulfilled the predefined criteria. Data presentation was adequate and showed moderate heterogeneity. The studies included 692 patients (21-178/study, mean age 61 years, 56% women). Analyzed were 688 ulcerated legs, present for 1 week to 9 years, sizing 1 to 210 cm(2). The observation period ranged from 12 to 78 weeks. Patient and ulcer characteristics were evenly distributed in three studies, favored the stocking groups in four, and the bandage group in one. Data on the pressure exerted by stockings and bandages were reported in seven and two studies, amounting to 31-56 and 27-49 mm Hg, respectively. The proportion of ulcers healed was greater with stockings than with bandages (62.7% vs 46.6%; P < .00001). The average time to healing (seven studies, 535 patients) was 3 weeks shorter with stockings (P = .0002). In no study performed bandages better than MCS. Pain was assessed in three studies (219 patients) revealing an important advantage of stockings (P < .0001). Other subjective parameters and issues of nursing revealed an advantage of MCS as well. CONCLUSIONS: Leg compression with stockings is clearly better than compression with bandages, has a positive impact on pain, and is easier to use.

Zidovudine impairs immunological recovery on first-line antiretroviral therapy: collaborative analysis of cohort studies in southern Africa

OBJECTIVES Zidovudine (ZDV) is recommended for first-line antiretroviral therapy (ART) in resource-limited settings. ZDV may, however, lead to anemia and impaired immunological response. We compared CD4+ cell counts over 5 years between patients starting ART with and without ZDV in southern Africa. DESIGN Cohort study. METHODS Patients aged at least 16 years who started first-line ART in South Africa, Botswana, Zambia, or Lesotho were included. We used linear mixed-effect models to compare CD4+ cell count trajectories between patients on ZDV-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4+ cell count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4+ cell count and hemoglobin level, age, sex, type of regimen, viral load monitoring, and calendar year. RESULTS A total of 72,597 patients starting ART, including 19,758 (27.2%) on ZDV, were analyzed. Patients on ZDV had higher CD4+ cell counts (150 vs.128 cells/μl) and hemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be women than those on other regimens. Adjusted differences in CD4+ cell counts between regimens containing and not containing ZDV were -16 cells/μl [95% confidence interval (CI) -18 to -14] at 1 year and -56 cells/μl (95% CI -59 to -52) at 5 years. Impaired immunological recovery was more likely with ZDV compared to other regimens (odds ratio 1.40, 95% CI 1.22-1.61). CONCLUSION In southern Africa, ZDV is associated with inferior immunological recovery compared to other backbones. Replacing ZDV with another nucleoside reverse transcriptase inhibitor could avoid unnecessary switches to second-line ART.

Disparities in bone density measurement history and osteoporosis medication utilisation in Swiss women: results from the Swiss Health Survey 2007

BACKGROUND Although factors associated with the utilisation of bone density measurement (BDM) and osteoporosis treatment have been regularly assessed in the US and Canada, they have not been effectively analysed in European countries. This study assessed factors associated with the utilisation of BDM and osteoporosis medication (OM) in Switzerland. METHODS The Swiss Health Survey 2007 data included self-reported information on BDM and OM for women aged 40 years and older who were living in private households. Multivariable logistic regression analysis was used to identify sociodemographic, socioeconomic, healthcare-related and osteoporosis risk factors associated with BDM and OM utilisation. RESULTS The lifetime prevalence of BDM was 25.6% (95% CI: 24.3-26.9%) for women aged 40 years and older. BDM utilisation was associated with most sociodemographic factors, all the socioeconomic and healthcare-related factors, and with major osteoporosis risk factors analysed. The prevalence of current OM was 7.8% (95% CI: 7.0-8.6%) and it was associated with some sociodemographic and most healthcare-related factors but only with one socioeconomic factor. CONCLUSIONS In Swiss women, ever having had a BDM and current OM were low and utilisation disparities exist according to sociodemographic, socioeconomic and healthcare-related factors. This might foster further health inequalities. The reasons for these findings should be addressed in further studies of the elderly women, including those living in institutions.

Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies

BACKGROUND Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. METHODS AND FINDINGS Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. CONCLUSIONS South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.

Differential regulation of human 3β-hydroxysteroid dehydrogenase type 2 for steroid hormone biosynthesis by starvation and cyclic AMP stimulation: studies in the human adrenal NCI-H295R cell model

Human steroid biosynthesis depends on a specifically regulated cascade of enzymes including 3β-hydroxysteroid dehydrogenases (HSD3Bs). Type 2 HSD3B catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone and androstenedione in the human adrenal cortex and the gonads but the exact regulation of this enzyme is unknown. Therefore, specific downregulation of HSD3B2 at adrenarche around age 6-8 years and characteristic upregulation of HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI-H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77 site is crucial for hormonal stimulation with cAMP. In fact, these three transcription factors together were able to transactivate the HSD3B2 promoter in placental JEG3 cells which normally do not express HSD3B2. By contrast, epigenetic mechanisms such as methylation and acetylation seem not involved in controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects on HSD3B2 when comparing short (acute) versus long-term (chronic) stimulation. Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to regulation at co-factor or substrate level or posttranslational modification of the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased HSD3B2 expression through transcriptional regulation. Although PKA and MAPK pathways are obvious candidates for possibly transmitting the cAMP signal to HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream signaling of cAMP. However, both signaling pathways were clearly regulating HSD3B2 expression.

How women and men are addressed in job advertisements

Research has shown that gender references in job advertisements play an important role for gender (in)equality in personnel selection. In advertisements gender is referred to in different ways, for instance, by using grammatically masculine and feminine human nouns (e.g., German Mechaniker/Mechanikerin 'mechanic, masc./fem.'), by mentioning typically feminine or typically masculine traits (e.g., kind and friendly versus determined and independent) as well as by showing pictures of women and men. The present study addresses the questions which forms of gender references occur in job advertisements, how these forms are distributed across different lines of business and across different countries. We collected job advertisements published online in four countries with different rankings of gender equality (i.e., Switzerland, Austria, Poland, and Czech Republic; World Economic Forum, 2011). We randomly selected 100 advertisements per country from four lines of business that are characterized by different proportions of female and male employees: (1) steels/metals, (2) science, (3) restaurants/food services, and (4) health care. The advertisements were analyzed with regard to the linguistic form of the job title and of the remaining text as well as reference to gender-typical traits. We also examined indicators of job status and other information (e.g., equal opportunity policies) which might be related to the use of gender references in job advertisements. The results show that, in general, gender-fair language occurs much more often in job ads from Switzerland and Austria than in those from Poland and the Czech Republic, where job titles are mostly masculine. While exclusive use of feminine forms are almost never used in Switzerland and Austria, they are more frequently used in Poland and Czech Republic. In general, gender-fair forms are more common when there are many women in a line of business, whereas more masculine forms are used where the proportion of women is low. In Switzerland and Austria, masculine forms are mostly combined with the supplement m/f to indicate that both women and men are addressed. The present data provide a sound basis for future studies on gender references in job advertisements. Furthermore it sheds a light on how companies comply with national guidelines of gender equality.

Language as a barrier and facilitator for women's career progress

Purpose When applying for leadership positions or acting as leaders, women are still perceived with a ‘lack of fit’, thus hired less likely and evaluated less favorably than their male counterparts. In many languages, different language forms can be used to refer to both women and men: masculine forms (e.g., CEO in German: ‘Geschäftsführer’) and alternative forms (e.g., feminine‐masculine word pairs, CEO in German ‘Geschäftsführerin/Geschäftsführer’). We assumed that the use of masculine forms endorses the ‘lack of fit’ for women in leadership, whereas alternative forms reduce it. Design/Methodology Two studies tested the hypotheses by manipulating language forms (masculine forms vs. alternative forms) and gender of the target to hire/evaluate (female vs. male). Results The results indicated as predicted that masculine forms lead to the ‘lack of fit’ for women in the leadership context, whereas alternative forms reduce it. Women were less likely to be employed for leadership positions (Study 1) and evaluated less favorably as leaders (Study 2) than their male counterparts with masculine forms. However, with alternative forms no differences in employment decisions and evaluations of women and men were found. Limitations These two studies were conducted with student‐samples. Further research is needed to replicate effects with relevant samples as HRmanagers and to investigate underlying mechanisms. Research/Practical Implications Organizations may use alternative forms instead of masculine forms in job advertisements for leadership positions to overcome barriers for women in leadership. Originality/Value These are the first studies in testing the effects of language forms in the leader selection and evaluation.

Gender-fair language in the context of leadership: Preventing the lack of fit for women

Women are still underrepresented in leadership due to a perceived a ‘lack of fit’. Thus, women are hired less likely, evaluated unfavorably or are less willing to take over a leadership role than their male counterparts. Because gender-fair language (e.g., feminine-masculine word pairs, German: ‘Geschäftsführerin/Geschäftsführer’, CEO, fem./CEO, masc.) leads to a higher mental inclusion of women compared to generic masculine forms (German: ‘Geschäftsführer’, CEO,masc.), we argue that masculine forms endorse the ‘lack of fit’ for women in leadership, whereas gender-fair language reduces it. Three studies support our assumption. Masculine forms led to a ‘lack of fit’ for women in leader selection: they were hired less likely (Study 1) and evaluated less favorably (Study 2) than their male counterparts. Moreover, women showed less willingness to apply when masculine forms were used in the advertisement for a leadership position. Contrary, no such gender-bias was obtained in case of gender-fair language.