Price changes and within-class competition of cancer drugs in the USA and Europe: a comparative analysis.

BACKGROUND: Cancer drugs are a major component of pharmaceutical spending in the USA and Europe. The number of approved cancer drugs continues to increase. More new drugs with overlapping mechanisms of action and similar approved indications might be expected to decrease prices within drug classes. We compared patterns of price changes for cancer drugs within the same class in the USA and in two European countries (Germany and Switzerland) with national mechanisms for drug price negotiation. METHODS: For this comparative analysis, we identified cancer drugs approved for the treatment of solid cancers in the USA and Europe (Germany and Switzerland) between Jan 1, 2009, and Dec 31, 2020, using the US Food and Drug Administration's Drugs@FDA database and the European Medicines Agency's publicly available database. We considered cancer drugs as within-class competitors if they were approved for the same indication and had the same biological mechanism. We calculated monthly treatment prices for each drug, median price changes at launch and over time, and differences within and across drug classes. European price data were converted to US dollars by applying the exchange rates on Dec 1, 2020, and prices were adjusted for inflation. Median changes in the drugs' monthly treatment prices at 2 and 4 years after market entry across and within drug classes were also assessed. For the USA, correlations in relative price changes between all pairs of drugs within and across drug classes were calculated with Spearman's rank correlation. FINDINGS: Our study cohort comprised 12 drug classes covering nine indications. With the exception of one drug, increasing prices were observed within and across all drug classes in the USA (median 6·07% [range -3·60 to 33·83] 2 years after market entry, and 15·31% [-4·15 to 54·64] 4 years after market entry). By contrast, in Europe, prices generally decreased over time or did not increase more than inflation (2 years after market entry: -21·01% [range -50·72 to 12·71] in Germany and -1·48% [-26·81 to 1·69] in Switzerland; 4 years after market entry: -25·54% [-51·81 to 11·63] in Germany and -13·02% [-43·83 to 18·31] in Switzerland). In the USA, most prices changes within and across drug classes occurred at the end and beginning of the year (ie, from Dec 1 to Jan 31). In the USA, correlation for price changes was r=0·29 (SD 0·36) for within-class drugs and r=0·28 (0·36) for drugs across drug classes. INTERPRETATION: Competition within classes of cancer drugs generally did not constrain rising prices in the USA. Price negotiations, as practised in Germany or Switzerland, could help address the high prices of cancer drugs in the USA. FUNDING: Swiss Cancer Research Foundation (Krebsforschung Schweiz), Swiss National Science Foundation, and Arnold Ventures.

Occurrence and aetiology of subclinical mastitis in water buffalo in Bangladesh.

Subclinical mastitis (SCM) in water buffalo is a production disease associated with decreased milk yield and impaired milk quality and safety. Water buffalo is an important livestock species in Bangladesh, but information about the occurrence and aetiology of SCM in this species is scarce. A cross-sectional study was conducted as part of the Udder Health Bangladesh Programme to (i) determine the occurrence of SCM and bulk milk somatic cell count (SCC) in water buffalo in Bangladesh, (ii) identify pathogens causing SCM and (iii) evaluate penicillin resistance in isolated staphylococci strains. Sixteen buffalo farms in the Bagerhat and Noakhali regions of Bangladesh were selected for study and a bulk milk sample was collected from each farm. In addition, 299 udder quarter milk samples were collected from 76 animals. The bulk milk samples were assessed by direct SCC and the quarter milk samples by California mastitis test (CMT). The occurrence of SCM calculated at quarter and animal level was 42.5 and 81.6%, respectively. Milk samples from 108 CMT-positive quarters in 48 animals and 38 randomly selected CMT-negative quarters in 24 animals were investigated using bacteriological culture. Estimated mean bulk milk SCC was 195 000 cells/ml milk (range 47 000- 587 000 cells/ml milk). On culture, estimated quarter-level intramammary infection (IMI) was 40.4%. The identity of isolated bacteria was confirmed by MALDI-TOF mass spectrometry. Non-aureus staphylococci (NAS) were the most common pathogens (24.7%) and, among 36 NAS tested, 36.1% were resistant to penicillin. Thus there was high occurrence of SCM on the study farms, with relatively high penicillin resistance in NAS. Further studies are needed to identify underlying risk factors and develop an udder health control strategy for water buffalo in Bangladesh.

Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy.

BACKGROUND: Epigenetic variation has been linked to several human diseases. Proliferative diabetic retinopathy (PDR) is a major cause of vision loss in subjects with diabetes. However, studies examining the association between PDR and the genome-wide DNA methylation pattern are lacking. Our aim was to identify epigenetic modifications that associate with and predict PDR in subjects with type 1 diabetes (T1D). METHODS: DNA methylation was analyzed genome-wide in 485,577 sites in blood from cases with PDR (n = 28), controls (n = 30), and in a prospective cohort (n = 7). False discovery rate analysis was used to correct the data for multiple testing. Study participants with T1D diagnosed before 30 years of age and insulin treatment within 1 year from diagnosis were selected based on 1) subjects classified as having PDR (cases) and 2) subjects with T1D who had had diabetes for at least 10 years when blood DNA was sampled and classified as having no/mild diabetic retinopathy also after an 8.7-year follow-up (controls). DNA methylation was also analyzed in a prospective cohort including seven subjects with T1D who had no/mild diabetic retinopathy when blood samples were taken, but who developed PDR within 6.3 years (converters). The retinopathy level was classified by fundus photography. RESULTS: We identified differential DNA methylation of 349 CpG sites representing 233 unique genes including TNF, CHI3L1 (also known as YKL-40), CHN2, GIPR, GLRA1, GPX1, AHRR, and BCOR in cases with PDR compared with controls. The majority of these sites (79 %) showed decreased DNA methylation in cases with PDR. The Natural Killer cell-mediated cytotoxicity pathway was found to be significantly (P = 0.006) enriched among differentially methylated genes in cases with PDR. We also identified differential DNA methylation of 28 CpG sites representing 17 genes (e.g. AHRR, GIPR, GLRA1, and BCOR) with P <0.05 in the prospective cohort, which is more than expected by chance (P = 0.0096). CONCLUSIONS: Subjects with T1D and PDR exhibit altered DNA methylation patterns in blood. Some of these epigenetic changes may predict the development of PDR, suggesting that DNA methylation may be used as a prospective marker of PDR.

Incorporating parasite data in population structure studies of South African sardine Sardinops sagax.

A multidisciplinary approach has been applied to examine the population structure of sardine Sardinops sagax off South Africa, where this species supports significant fisheries and is also of ecological and eco-tourism importance. Observations of discontinuous sardine distribution patterns, discrete spawning grounds and significant spatial differences in a variety of phenotypic characteristics have suggested the existence of discrete western, southern and eastern sardine sub-populations or stocks. The use of parasites as biological tags to elucidate sardine population structure has recently been investigated, and strong spatial gradients around South Africa in the prevalence, mean infection intensity and mean abundance of a digenean 'tetracotyle' type metacercarial endoparasite considered to be of the genus Cardiocephaloides and found in the humours of fish eyes support and have proved particularly convincing evidence for the sardine multiple stock hypothesis. A discontinuous distribution in the occurrence of another parasite, the coccidean Eimeria sardinae found in fish testes, has provided additional but weaker evidence of discrete stocks. These results have contributed to a changed understanding of the population structure of South African sardine and have significant implications for management of the fisheries for this species.

Role of pattern, regularity, and silent intervals in auditory stream segregation based on inter-aural time differences.

Tone triplets separated by a pause (ABA_) are a popular tone-repetition pattern to study auditory stream segregation. Such triplets produce a galloping rhythm when integrated, but isochronous rhythms when segregated. Other patterns lacking a pause may produce less-prominent rhythmic differences but stronger streaming. Here, we evaluated whether this difference is readily explained by the presence of the pause and potentially associated with the reduction of adaptation, or whether there is contribution of tone pattern per se. Sequences with repetitive ABA_ and ABAA patterns were presented in magnetoencephalography. A and B tones were separated by differences in inter-aural time differences (ΔITD). Results showed that the stronger streaming of ABAA was associated with a more prominent release from the adaptation of the P(1)m in auditory cortex. We further compared behavioral streaming responses for patterns with and without pauses, and varied the position of the pause and pattern regularity. Results showed a major effect of the pauses' presence, but no prominent effects of tone pattern or pattern regularity. These results make a case for the existence of an early, primitive streaming mechanism that does not require an analysis of the tone pattern at later stages suggested by predictive-coding models of auditory streaming. The results are better explained by the simpler population-separation model and stress the previously observed role of neural adaptation for streaming perception.

Cardiovascular disease in relation to diabetes status in immigrants from the Middle East compared to native Swedes: a cross-sectional study.

BACKGROUND: Type 2 diabetes is highly prevalent in immigrants to Sweden from Iraq, but the prevalence of cardiovascular disease (CVD) and its risk factors are not known. In this survey we aimed to compare the prevalence of CVD and CVD-associated risk factors between a population born in Iraq and individuals born in Sweden. METHODS: This population-based, cross-sectional study comprised 1,365 Iraqi immigrants and 739 Swedes (age 30-75 years) residing in the same socioeconomic area in Malmö, Sweden. Blood tests were performed and socio-demography and lifestyles were characterized. To investigate potential differences in CVD, odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by multivariate logistic regression analysis with adjustment for metabolic, lifestyle and psychosocial risk factors for CVD. Outcome measures were odds of CVD. RESULTS: There were no differences in self-reported prevalence of CVD between Iraqi- and Swedish-born individuals (4.0 vs. 5.5%, OR 0.9, 95% CI 0.4-1.8). However, the prevalence of type 2 diabetes was higher in Iraqi compared to Swedish participants (8.4 vs. 3.3%, OR = 4.2, 95% CI 2.6-6.7). Moreover, among individuals with type 2 diabetes, Iraqis had a higher prevalence of CVD (22.8 vs. 8.0%, OR = 4.2, 95% CI 0.9-20.0), after adjustment for age and sex. By contrast, among those without diabetes, immigrants from Iraq had a lower prevalence of CVD than Swedes (2.2 vs. 5.5%, OR = 0.6, 95% CI 0.3-0.9).Type 2 diabetes was an independent risk factor for CVD in Iraqis only (OR = 6.8, 95% CI 2.8-16.2). This was confirmed by an interaction between country of birth and diabetes (p = 0.010). In addition, in Iraqis, type 2 diabetes contributed to CVD risk to a higher extent than history of hypertension (standardized OR 1.5 vs. 1.4). CONCLUSIONS: This survey indicates that the odds of CVD in immigrants from Iraq are highly dependent on the presence or absence of type 2 diabetes and that type 2 diabetes contributes with higher odds of CVD in Iraqi immigrants compared to native Swedes. Our study suggests that CVD prevention in immigrants from the Middle East would benefit from prevention of type 2 diabetes.

What (If Anything) is Wrong with High-Frequency Trading?

This essay examines three potential arguments against high-frequency trading and offers a qualified critique of the practice. In concrete terms, it examines a variant of high-frequency trading that is all about speed-low-latency trading-in light of moral issues surrounding arbitrage, information asymmetries, and systemic risk. The essay focuses on low-latency trading and the role of speed because it also aims to show that the commonly made assumption that speed in financial markets is morally neutral is wrong. For instance, speed is a necessary condition for low-latency trading's potential to cause harm in "flash crashes." On the other hand, it also plays a crucial role in a Lockean defense against low-latency trading being wasteful developed in this essay. Finally, this essay discusses the implications of these findings for related high-frequency trading techniques like futures arbitrage or latency arbitrage-as well as for an argument as to why quote stuffing is wrong. Overall, the qualifications offered in this essay act as a counterbalance to overblown claims about trading at high speeds being wrong.

Comparison of Uptake and Prices of Biosimilars in the US, Germany, and Switzerland.

Importance: Biologics account for a substantial proportion of health care expenditures. Their costs have been projected to reach US $452 billion in global spending by 2022. Given recent expiration of patent protection of biologics, a shift toward greater follow-on competition among biosimilars would be expected that would allow greater uptake and lower drug costs. Objective: To assess uptake and prices of biosimilars in the US compared with 2 European countries (Germany and Switzerland) with national mechanisms for drug price negotiation. Design, Setting, and Participants: In this cohort study, biologics and biosimilars that were approved in the US, Germany, and Switzerland until August 2020 were identified. Prices and sales data were extracted from public and commercial databases for the years 2011 to 2020. Data were analyzed from August 1, 2021, to February 28, 2022. Main Outcomes and Measures: Descriptive statistics were used to show temporal trends in the uptake of biosimilars and relative prices compared with those of reference products (ie, biologic agents) for each country. Descriptive analysis was also performed to compare the uptake of biosimilars between the 3 countries limited to biologics that have biosimilars on the market in all countries. To test if biosimilar awareness in each country increased over the last decade, a linear least squares regression was applied. Results: The study cohort included 15 biosimilars and 6 biologics for the US, 52 biosimilars and 15 biologics for Germany, and 28 biosimilars and 13 biologics for Switzerland. Uptake of biosimilars increased over time in all countries. On average, the biosimilar market share at launch was highest in Germany; however, it increased at the fastest rate in the US. Monthly treatment costs of biosimilars in the US were a median of 1.94 (IQR, 1.78-2.44) and 2.74 (IQR, 1.91-3.46) higher than corresponding costs in Germany and Switzerland, respectively. Conclusions and Relevance: The findings of this cohort study suggest that more biosimilars have been marketed in Germany and Switzerland than in the US. Policies that counter anticompetitive practices in the US could allow biosimilars to enter the market sooner and could also lower health care costs with improved access. Awareness of biosimilars should be promoted to increase uptake of biosimilars globally.

Nuclear factor of activated T cells regulates osteopontin expression in arterial smooth muscle in response to diabetes-induced hyperglycemia.

OBJECTIVE: Hyperglycemia is a recognized risk factor for cardiovascular disease in diabetes. Recently, we reported that high glucose activates the Ca(2+)/calcineurin-dependent transcription factor nuclear factor of activated T cells (NFAT) in arteries ex vivo. Here, we sought to determine whether hyperglycemia activates NFAT in vivo and whether this leads to vascular complications. METHODS AND RESULTS: An intraperitoneal glucose-tolerance test in mice increased NFATc3 nuclear accumulation in vascular smooth muscle. Streptozotocin-induced diabetes resulted in increased NFATc3 transcriptional activity in arteries of NFAT-luciferase transgenic mice. Two NFAT-responsive sequences in the osteopontin (OPN) promoter were identified. This proinflammatory cytokine has been shown to exacerbate atherosclerosis and restenosis. Activation of NFAT resulted in increased OPN mRNA and protein in native arteries. Glucose-induced OPN expression was prevented by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. The calcineurin inhibitor cyclosporin A or the novel NFAT blocker A-285222 prevented glucose-induced OPN expression. Furthermore, diabetes resulted in higher OPN expression, which was significantly decreased by in vivo treatment with A-285222 for 4 weeks or prevented in arteries from NFATc3(-/-) mice. CONCLUSIONS: These results identify a glucose-sensitive transcription pathway in vivo, revealing a novel molecular mechanism that may underlie vascular complications of diabetes.

High prevalence of type 2 diabetes in Iraqi and Swedish residents in a deprived Swedish neighbourhood--a population based study.

BACKGROUND: Immigrants from the Middle-East are at high risk of developing type 2 diabetes (T2D). The aim of the present survey was to measure, in a single deprived neighbourhood, the prevalence rates of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D in residents originating from Iraq and to compare them to those in residents born in Sweden. An additional aim was to identify metabolic, lifestyle and socioeconomic risk factors associated with IFG/IGT and T2D in these residents. METHODS: The study was conducted February 1'st to March 31'st 2010. Men and women aged 45 to 65 years of Swedish or Iraqi origin, living in the neighbourhood of Rosengård, Malmö, Sweden, were randomly selected from the census register. Each participant signed a written informed consent form, underwent a physical examination and an oral glucose tolerance test (OGTT), provided blood samples and filled in a questionnaire. A total of 175 subjects participated (Swedish origin n = 79, Iraqi origin n = 96), reflecting an overall response rate of almost 60%. RESULTS: In total, 21.9% and 19.0% of the Iraqi and Swedish participants, respectively, suffered from T2D, while 24.0% of the Iraqi participants and 25.3% of the Swedish participants had IFG/IGT. There were no significant differences in prevalence rates relating to country of origin.Obesity (BMI ≥30 kg/m2) and sedentary leisure time physical activity were highly prevalent in both groups, while a family history of diabetes was more prevalent in participants from Iraq (49.2%) than in those from Sweden (22.8%) (p = 0.001).Being obese or having a sedentary leisure time were, independently associated with T2D (OR 5.43 (95% CI 2.10-14.02) and 2.89 (95% CI 1.03-8.10) respectively), while economic difficulties were independently associated with IFG/IGT (OR 2.55 (95% CI 1.06-6.15)) after adjustment for the confounding effects of other common risk factors for T2D. CONCLUSIONS: This study reveals a high prevalence of T2D, independently of country of origin (Iraq or Sweden), in a socially vulnerable area and additionally presents a risk factor profile that is markedly different from that of Sweden in general.

Patients' access to drugs with rebates in Switzerland - Empirical analysis and policy implications for drug pricing in Europe.

BACKGROUND: Many European countries introduced (confidential) rebates in the past years. Authorities and manufacturers argue that this strategy allows reduction of spending on high-cost drugs, and quick access of innovative drugs. We evaluated these arguments using Switzerland as an example, one of the last countries with transparent rebates. METHODS: We identified all drugs granted rebates in Switzerland and all new drugs without rebates between January 2012 and October 2020. We assessed the amount of introduced drugs with and without rebates over time, clinical benefit of drugs with rebates, and duration between approval and price determination. FINDINGS: Our study cohort included 51 drugs with rebates, the majority were cancer drugs (32; 63%). 15/51 (29%) had high clinical benefit, 25/51 (49%) low benefit and for 11/51 (22%) benefit could not be assessed. The number of drugs with rebates increased in recent years. Time duration between approval and price determination was 302 days in median for drugs with and 106 days for drugs without rebates. INTERPRETATION: Drugs with rebates may hamper access to drugs and lead to overpayment. Improving transparency on actual drug prices and stronger cooperation between countries could help national authorities to make better informed pricing decisions, and improve access of innovative drugs to patients. FUNDING: This study was partially funded by the Swiss Cancer Research Foundation (Krebsforschung Schweiz) and the Swiss National Foundation (SNF).

Tumor necrosis factor-alpha does not mediate diabetes-induced vascular inflammation in mice.

OBJECTIVE: Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines of evidence have implicated the cytokine tumor necrosis factor (TNF) alpha as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF alpha in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE-/- mice. METHODS AND RESULTS: Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries 150 m in diameter as well as the macrophage accumulation in aortic root atherosclerotic plaques in apoE-/- mice. A more pronounced vascular inflammatory response was observed in diabetic TNF alpha-deficient apoE-/- mice. These mice were also characterized by increased accumulation of IgG and IgM autoantibodies in atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque formation in apoE-competent TNF alpha -/- mice, whereas no such effects were observed in C57BL/6 wild-type mice. CONCLUSIONS: The present findings suggest that TNF alpha does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF alpha. These effects are partly attributable to a direct antiinflammatory role of TNF alpha, but may also reflect a defective development of the immune system in these mice.

Coeliac disease-specific tissue transglutaminase autoantibodies are associated with osteoporosis and related fractures in middle-aged women.

OBJECTIVE: To investigate whether the serological marker for coeliac disease, tissue transglutaminase autoantibody (tTGAb), is associated with decreased bone mass density (BMD) and increased frequency of fractures in middle-aged women screened for osteoporosis. MATERIAL AND METHODS: The study comprised 6480 women (mean age 56 years, range 50-64) who answered a number of questionnaires and who underwent dual X-ray absorptiometry of the wrist bone. Serum samples were analysed for tTGAb using radioligand binding assays. A tTGAb level of >4 U/ml was used to determine a positive value and a level of >17 U/ml was used as an alternative discrimination of high levels. RESULTS: A tTGAb level >4 U/ml was found among 90/6480 (1.4%) women and correlated with lower BMD (multiple linear regression coefficient -382.1; 95% CI = - 673.6-90.7, p=0.011) and with fracture frequency (r=0.18, p=0.023). The 59 women with tTGAb levels >or=17 U/ml had a lower BMD (0.41+/-0.08 g/cm(2) versus 0.44+/-0.08 g/cm(2), p=0.001) and a lower T-score (-1.40+/-1.28 versus -0.90+/-1.40, p=0.003) as well as a higher prevalence of osteoporosis (13.4% versus 6.5%, p=0.008) compared with the remaining 6421 women with tTGAb levels <17 U/ml. Furthermore, fracture frequency was more pronounced in women with tTGAb levels >or=17 U/ml, among whom 19/59 (32.2%) had fractures during the study period compared with 1204/6421 (18.8%) among women with tTGAb levels <17 U/ml (p=0.009). CONCLUSIONS: High levels of tTGAb indicating coeliac disease are associated with lower BMD and higher fracture frequency in women between 50 and 64 years of age. Osteometry is therefore warranted in middle-aged women detected with tTGAb.

Inflammatory activity increases with haemoglobin A1c in patients with acute coronary syndrome.

OBJECTIVE: To study the relationship between inflammation, diabetes and HbA(1)c levels in patients with acute coronary syndrome (ACS). DESIGN: Single-centre cross-sectional study comprising 688 consecutive patients with ACS (108 with diabetes) and 341 with stable coronary artery disease (SCAD) (51 with diabetes). High-sensitive C-reactive protein (hsCRP), albumin and fibrinogen concentrations, erythrocyte sedimentation rates (ESR) and leukocyte counts were measured. RESULTS: hsCRP, fibrinogen and ESR levels were higher and albumin lower in ACS patients. ESR was higher, albumin lower and hsCRP borderline significantly higher (p=0.053) in ACS patient with diabetes compared to those without. All inflammatory markers were associated with HbA(1)c in all 688 ACS patients as well as in 540 non-diabetic ACS patients with normal HbA(1)c. In multivariate analyses, all inflammatory markers were independently associated with HbA(1)c in the entire ACS group, regardless of diabetes being present or not. When non-diabetic ACS patients were analyzed separately, only ESR and leukocyte counts were independently correlated with HbA(1)c. CONCLUSIONS: Patients with ACS had increased inflammatory activity, which increased with HbA(1)c levels in patients who neither had a history of diabetes nor HbA(1)c above normal, and was further exaggerated in the presence of diabetes.

The aldose reductase inhibitor fidarestat suppresses ischemia-reperfusion-induced inflammatory response in rat retina.

Recent studies suggest that increased aldose reductase (AR) activity plays an important role in ischemia-reperfusion injury in the retina. The mechanisms are not completely understood, but may be linked to inflammation. In the present study, we investigated whether the AR inhibitor fidarestat suppressed the retinal inflammatory response induced by ischemia-reperfusion in a rat model. The inflammatory response was manifested by increased gene expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 (ICAM-1) as well as elevated protein levels of soluble ICAM-1. This response was partially suppressed by the AR inhibitor fidarestat. The findings may reveal beneficial effects of AR inhibition on retinal inflammation associated with ischemia-reperfusion and are in agreement with recent developments in pharmacological research suggesting that pathological conditions other than diabetes may benefit from AR inhibitors.

Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery.

BACKGROUND: Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown. METHODS: The prospective, controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched, conventionally treated obese control subjects. We now report follow-up data for subjects (mean age, 48 years; mean body-mass index, 41) who had been enrolled for at least 2 years (4047 subjects) or 10 years (1703 subjects) before the analysis (January 1, 2004). The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years. RESULTS: After two years, the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group (P<0.001). After 10 years, the weight had increased by 1.6 percent and decreased by 16.1 percent, respectively (P<0.001). Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period. Two- and 10-year rates of recovery from diabetes, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, hypertension, and hyperuricemia were more favorable in the surgery group than in the control group, whereas recovery from hypercholesterolemia did not differ between the groups. The surgery group had lower 2- and 10-year incidence rates of diabetes, hypertriglyceridemia, and hyperuricemia than the control group; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable. CONCLUSIONS: As compared with conventional therapy, bariatric surgery appears to be a viable option for the treatment of severe obesity, resulting in long-term weight loss, improved lifestyle, and, except for hypercholesterolemia, amelioration in risk factors that were elevated at baseline.

Blood pressure in middle-aged women: are androgens involved? A population-based study of Swedish women: the Women's Health in the Lund Area study.

OBJECTIVE: To assess the prevalence of hypertension and use of antihypertensive drug therapy in relation to menopausal status and to delineate perceived associations between androgens and blood pressure in perimenopausal women. METHODS: A population-based sample of women aged 50-59 (n = 6893). Women were divided into three groups according to their hormonal status: premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy. RESULT: In the premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy groups, the prevalence of high blood pressure (>/= 140 mmHg systolic or >/= 90 mmHg diastolic) was 43.9, 49.9 and 45.8%, respectively. In women with normal blood pressure, adjusting for age, body mass index and smoking, there were negative associations between serum testosterone and systolic blood pressure in the total sample (P < 0.01) and the postmenopausal without hormone therapy group (P < 0.05). In women using antihypertensive drug therapy with a blood pressure of at least 140/90 mmHg, positive associations were found between serum testosterone and systolic blood pressure in the total series (P < 0.05) and in the postmenopausal without hormone therapy group (P < 0.05). CONCLUSION: Abnormal blood pressure is common in middle-aged women regardless of hormonal status. Our findings suggest that testosterone could have a dual influence on blood pressure in perimenopausal women.

Insulin resistance and self-rated symptoms of depression in Swedish women with risk factors for diabetes: the Women's Health in the Lund Area study.

Previous studies have suggested that depression increases the risk for diabetes and that this may be mediated through insulin resistance. The study aimed to analyze if self-rated symptoms of depression are related to insulin resistance among middle-aged and older Swedish women with features of the metabolic syndrome and being at risk for type 2 diabetes mellitus. We analyzed data from 1047 Swedish women aged 50 to 64 years without a history of diabetes and living in the southern part of Sweden. A variable self-rated symptoms of depression (SRSD) was defined by using the Gothenburg Quality of Life instrument. We estimated odds ratios (ORs) to determine whether or not SRSD was associated with the homeostasis model assessment of insulin resistance. The variable SRSD was not associated with insulin resistance. However, it was positively associated with waist-hip ratio (OR, 1.95; 95% confidence interval, 1.28-3.00) and negatively associated with physical exercise (OR, 1.29; 95% confidence interval, 0.99-1.68) after multivariate adjustment. In conclusion, lifestyle factors such as physical inactivity and abdominal obesity, but not insulin resistance, seem to be related to self-rated symptoms of depression in women with risk factors for diabetes mellitus. The relationship between insulin resistance and major depression needs to be further examined.

Health hazards in middle-aged women with cardiovascular disease: a case-control study of swedish women. the women's health in the Lund area (WHILA) study.

OBJECTIVE: To delineate the health profile in middle-aged women with cardiovascular disease (CVD). METHODS: The Women's Health in the Lund Area (WHILA) project covered all women born 1935-1945 (n = 10,766) living in the Lund area; 6917 (64.2%) women completed a generic questionnaire and underwent physical and laboratory assessments. Of the 6917 women, 6416 were postmenopausal women, of whom 104 had CVD. For each woman with CVD, two controls were selected and matched for age, smoking habits, body mass index (BMI), waist/hip ratio (WHR), low-density lipoprotein cholesterol (LDL-C), high-density liproprotein cholesterol (HDL-C), diastolic blood pressure and hormonal status. RESULTS: One hundred four women (1.6%) reported CVD. Forty-nine had a myocardial infarction (MI), 49 had a stroke, and 6 women had both events; 71.4% were postmenopausal, with never use of hormone therapy (HT) (PM0), and 28.6% were postmenopausal with ever use of HT (PMT). Compared with the control group, serum androstendione was lower (p = 0.004) in the case group, and menopausal estradiol (E(2)) values were less frequent (p = 0.037) in cases from the PM0 group. Among psychological and somatic symptoms, nervousness (p < 0.05), difficulty relaxing, crying easily, visual disturbance (p

Obese women and the relation between cardiovascular risk profile and hormone therapy, glucose tolerance, and psychosocial conditions.

OBJECTIVE: To evaluate the relation between cardiovascular disease (CVD) risk factors and hormone therapy, serum hormone levels, glucose tolerance, and psychosocial and psychological conditions in subjectively healthy obese female subjects. RESEARCH DESIGN AND METHODS: The study included 606 women, aged 50-64 years, with BMI 30-40 kg/m(2) and no history of cardiovascular or other severe diseases. One group with a CVD risk profile (n = 473) (i.e., cholesterol >7.0 mmol/l, HDL cholesterol <1.2 mmol/l, triglycerides >2.0 mmol/l, systolic or diastolic blood pressure >140/90 mmHg, or waist-to-hip ratio >0.85) was compared with women without such risk (n = 133). Steroid hormones, leptin, insulin, and oral glucose tolerance tests (OGTTs) were analyzed. A subgroup of women with baseline impaired glucose tolerance (IGT) completed a 2.5-year follow-up OGTT. RESULTS: Fewer obese postmenopausal women with CVD risk had ever used hormone therapy (odds ratio 0.24 [95% CI 0.07-0.75]), after multivariate adjustments. Furthermore, women with CVD risk had a higher testosterone index (1.07 [1.01-1.13]) and more had insulin resistance (1.04 [1.00-1.08]) and IGT (2.92 [1.50-5.69]), while OGTT was similar at follow-up. No differences were observed regarding family history or lifestyle, except that fewer women with CVD risk consumed fruits, boiled vegetables, or whole-grain cereals. More women with CVD risk lived alone (3.26 [1.28-8.31]) and had more mental problems (1.16 [1.05-1.28]). CONCLUSIONS: Previously healthy obese women with a CVD risk profile seemed to have a high risk of diabetes, as well as psychosocial or psychological problems. Hormone therapy was associated with reduced CVD risk. Obesity's growing burden on society makes it more important to further target individuals that are at greatest risk of future health hazards.