Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome

Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), has recently been linked to obesity, insulin resistance syndromes such as polycystic ovary syndrome (PCOS), and an increased risk of cardiovascular disease. Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy. Twenty nonobese women [body mass index (BMI) /==" BORDER="0"> 27 kg/m(2)) with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months) or ethinyl estradiol (35 micro g)-cyproterone acetate (2 mg) oral contraceptive pills. The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [4.08 +/- 0.53 (SE) vs. 1.31 +/- 0.28 mg/liter; P < 0.001] and correlated to BMI and to a lesser extent waist-hip ratio, suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself. During metformin treatment, serum CRP levels decreased significantly from 3.08 +/- 0.7 mg/liter to 1.52 +/- 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects. In contrast, the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 +/- 0.68 mg/liter to 4.58 +/- 0.84 mg/liter (P < 0.001). Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear. The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.     

The association between normalising attributions and help-seeking for cancer alarm symptoms in the community: a cross-sectional survey

BackgroundAttribution of early symptoms to non-pathological factors such as age or diet (normalising) is often identified retrospectively by patients with cancer as an explanation for delay in presentation. However, there have been no community-based studies. We aimed to assess associations between normalising attributions and help-seeking in a community sample of patients reporting cancer alarm symptoms.MethodsA questionnaire was mailed to 4858 adults (≥50 years with no cancer diagnosis) through primary care, asking about symptom experience in the previous 3 months. Respondents were asked, within a longer symptom list, whether they had experienced any of ten cancer alarm symptoms in the previous 3 months. Follow-up questions addressed perceived cause (free text), with responses categorised into normalisation (age, external factors), non-cancer disease, psychological factors, cancer, or “don't know”. Blank responses were treated as missing and excluded from analyses. Respondents were asked whether they had consulted a doctor (yes or no).FindingsResponse rate was 35% (n=1724). Normalising was common for four symptoms: persistent cough or hoarseness (81/296, 27%), persistent change in bowel habit (88/216, 41%), persistent change in bladder habit (67/166, 40%), and change in the appearance of a mole (27/71, 38%). Age (ie, an effect of getting older) was a common attribution for all symptoms except persistent cough, which was often attributed to smoking. Change in diet was a common attribution for change in bowel habit, and sun exposure for change in a mole. Missing attribution data (n=280) ranged from 15% (n=53) for cough to 42% (n=51) for change in mole. Logistic regression showed that normalising attributions were associated with being less likely to having contacted a general practitioner for persistent cough (odds ratio 0·46, 95% CI 0·27–0·79), after controlling for demographic characteristics, and the same effect was observed across symptoms. No sex or socioeconomic differences in help-seeking were seen.InterpretationAttributing symptoms to normal everyday causes was associated with delayed help-seeking for four cancer alarm symptoms. Attributions such as smoking and sun exposure, which are themselves risk factors for cancer, were among the attributions that undermined help-seeking. The substantial proportion of missing data for the attribution item suggests some reluctance to complete open text responses. More research is needed into how people make help-seeking decisions.FundingThis work was supported by a Cancer Research UK Postdoctoral Fellowship grant (C33872/A13216) awarded to KLW.     

Validating abbreviated measures of effort-reward imbalance at work in European cohort studies: the IPD-Work consortium

Background

Effort-reward imbalance (ERI) is an established conceptualisation of work stress. Although a validated effort-reward questionnaire is available for public use, many epidemiological studies adopt shortened scales and proxy measures. To examine the agreement between different abbreviated measures and the original instrument, we compared different versions of the effort-reward scales available in 15 European cohort studies participating in the IPD-Work (Individual-participant-data meta-analysis in working populations) consortium.

Methods

Five of the 15 studies provide information on the original (‘complete’) scales measuring ‘effort’ and ‘reward’, whereas the 10 remaining studies used ‘partial’ scales. To compare different versions of the ERI scales, we analyse individual-level data from 31,790 participants from the five studies with complete scales.

Results

Pearson’s correlation between partial and complete scales was very high in case of ‘effort’ (where 2 out of 3 items were used) and very high or high in case of ‘reward’, if at least 4 items (out of 7) were included. Reward scales composed of 3 items revealed good to satisfactory agreement, and in one case, a reward scale consisting of 2 items only demonstrated a modest, but still acceptable degree of agreement. Sensitivity and specificity of a composite measure, the ratio of effort and reward, comparing partial versus complete scales ranged between 59–93 and 85–99 %, respectively. Complete and partial scales were strongly associated with poor self-rated health.

Conclusion

Our results support the notion that short proxy measures or partial versions of the original scales can be used to assess effort-reward imbalance.     

Association of adiponectin and leptin with relative telomere length in seven independent cohorts including 11,448 participants

Oxidative stress and inflammation are major contributors to accelerated age-related relative telomere length (RTL) shortening. Both conditions are strongly linked to leptin and adiponectin, the most prominent adipocyte-derived protein hormones. As high leptin levels and low levels of adiponectin have been implicated in inflammation, one expects adiponectin to be positively associated with RTL while leptin should be negatively associated. Within the ENGAGE consortium, we investigated the association of RTL with adiponectin and leptin in seven independent cohorts with a total of 11,448 participants. We performed partial correlation analysis on Z-transformed RTL and LN-transformed leptin/adiponectin, adjusting for age and sex. In extended models we adjusted for body mass index (BMI) and C-reactive protein (CRP). Adiponectin showed a borderline significant association with RTL. This appeared to be determined by a single study and when the outlier study was removed, this association disappeared. The association between RTL and leptin was highly significant (r = ?0.05; p = 1.81 × 10^?7). Additional adjustment for BMI or CRP did not change the results. Sex-stratified analysis revealed no difference between men and women. Our study suggests that high leptin levels are associated with short RTL.     

Nursing power as viewed by nursing professionals

Background: The concept of nursing power has not been extensively reported in the nursing literature. Power is an extremely abstract concept, making it difficult to define and study. However, when defined as the capacity to achieve goals, power becomes a significant resource in nursing. Aims: The aim of this study was to describe how nursing professionals perceive the level of nursing group power in public healthcare organizations. Additionally, the connections between the background variables and nursing group power were analysed. Methods: The participants in the study consisted of 289 Finnish nurses working in the specialist healthcare sector in Finland. The Sieloff‐King Assessment of Group Outcome Attainment within Organizations^© (SKAGOAO) instrument was utilized to assess the level of nursing group power within the selected organizations. Findings: According to the present study, nursing professionals rated the outcome attainment (mean, 1.93), as well as goals/outcome competency (mean, 2.24), as very good. The position of nursing (mean, 2.55) as part of the healthcare service system was considered fairly respected. The role of nursing (mean, 2.54) was also considered to be at a good level. As regards to the actualization of power or outcome attainment capacity, respondents gave the lowest ratings to controlling the effects of environmental forces (mean, 2.75), resources (mean, 3.48), communication competency (mean, 3.00) and group supervisor’s outcome attainment competency (mean, 2.87). Age, education, type of employment and work experience had an impact on how nursing group power was perceived. Conclusions: The results of the present study indicated that the nurses perceived the lowest levels of group power in relation to the subscales of controlling the effects of environmental forces, resources, communication competency and group supervisor’s outcome attainment competency.     

C-reactive protein-associated genetic variants and cancer risk: Findings from FINRISK 1992, FINRISK 1997 and Health 2000 studies

Background

Evidence from prospective observational studies suggests that elevated circulating C-reactive protein (CRP) concentrations are associated with cancer risk, but it is unclear whether this association is causal. In order to examine this, we investigated whether genetic variants that are associated with circulating CRP concentrations are associated with cancer risk.

Methods

We pooled data from three population-based prospective Finnish studies: FINRISK 1992 (n = 5289), FINRISK 1997 (n = 7160) and Health 2000 (n = 6299). Cancer cases were identified from cancer registrations. Thirteen CRP-associated SNPs, identified from genome-wide association studies, were genotyped. We examined the associations of the SNPs and cancer risk using Cox, probit and instrumented probit regression models.

Results

Compared to common allele homozygotes, individuals carrying one or two variant T alleles at rs1892534 had 1.05-fold (95% confidence interval (CI): 0.90, 1.23) and 1.2-fold (95% CI: 1.01, 1.42) increased overall cancer risk, respectively. Individuals with one or two variant A alleles at rs1169300 or rs2464196 had approximately 1.5- and 2-fold increased risk of lung cancer, respectively (p trend for both: 0.007). CRP SNPs were not associated with colorectal, prostate or breast cancer risk nor was CRP-associated with the probability of developing cancer in the instrumented probit analyses.

Conclusions

We found some evidence for an association of a small number of CRP-associated SNPs with the overall cancer risk and lung cancer risk. Our instrumental variable analyses provided no clear evidence for a causal association of CRP and cancer. These findings suggest that circulating CRP concentrations are unlikely to have a causal role in cancer.