Health effects of reduced occupational sedentary behaviour in type 2 diabetes using a mobile health intervention: a study protocol for a 12-month randomized controlled trial-the ROSEBUD study.

BACKGROUND: Short-term trials conducted in adults with type 2 diabetes mellitus (T2DM) showed that reducing sedentary behaviour by performing regular short bouts of light-intensity physical activity enhances health. Moreover, support for reducing sedentary behaviour may be provided at a low cost via mobile health technology (mHealth). There are a wide range of mHealth solutions available including SMS text message reminders and activity trackers that monitor the physical activity level and notify the user of prolonged sitting periods. The aim of this study is to evaluate the effects of a mHealth intervention on sedentary behaviour and physical activity and the associated changes in health in adults with T2DM. METHODS: A dual-arm, 12-month, randomized controlled trial (RCT) will be conducted within a nationwide Swedish collaboration for diabetes research in primary health care. Individuals with T2DM (n = 142) and mainly sedentary work will be recruited across primary health care centres in five regions in Sweden. Participants will be randomized (1:1) into two groups. A mHealth intervention group who will receive an activity tracker wristband (Garmin Vivofit4), regular SMS text message reminders, and counselling with a diabetes specialist nurse, or a comparator group who will receive counselling with a diabetes specialist nurse only. The primary outcomes are device-measured total sitting time and total number of steps (activPAL3). The secondary outcomes are fatigue, health-related quality of life and musculoskeletal problems (self-reported questionnaires), number of sick leave days (diaries), diabetes medications (clinical record review) and cardiometabolic biomarkers including waist circumference, mean blood pressure, HbA1c, HDL-cholesterol and triglycerides. DISCUSSION: Successful interventions to increase physical activity among those with T2DM have been costly and long-term effectiveness remains uncertain. The use of mHealth technologies such as activity trackers and SMS text reminders may increase awareness of prolonged sedentary behaviour and encourage increase in regular physical activity. mHealth may, therefore, provide a valuable and novel tool to improve health outcomes and clinical management in those with T2DM. This 12-month RCT will evaluate longer-term effects of a mHealth intervention suitable for real-world primary health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04219800 . Registered on 7 January 2020.

Factor XIII activity at onset of labour and association with postpartum haemorrhage: an exploratory post-hoc study.

BACKGROUND: Platelets, fibrinogen and factor XIII (FXIII) are required to form a stable clot in case of haemorrhage. The aims of this study were to evaluate a possible association between FXIII activity at the onset of labour and postpartum haemorrhage (PPH), and to ascertain whether FXIII activity at labour onset differs from after delivery. METHODS: FXIII activity in 239 women with PPH (blood loss >1 L) and in 76 women without PPH was compared, as was activity before and after delivery in a third group of 80 women. RESULTS: FXIII activity at onset of labour was significantly lower in the PPH group compared with the control group (mean ±â€¯SD 0.98 ±â€¯0.20 vs 1.05 ±â€¯0.17 kIU/L; P=0.0006). The difference was significantly greater in subgroups having vaginal delivery with no oxytocin stimulation or uterine exploration (absolute difference 0.131; 95% CI 0.055 to 0.206), compared with a subgroup experiencing any complication (0.04; 95% CI -0.023 to 0.104; interaction P-value 0.098). There was a weak but statistically significant inverse correlation between FXIII and estimated blood loss (r=-0.25; P=0.030) in the control group but not the PPH group. There was no significant difference between FXIII activity at onset of labour and after delivery (mean ±â€¯SD 1.03 ±â€¯0.17 vs 1.04 ±â€¯0.19 kIU/L; P=0.093). CONCLUSIONS: At the onset of labour women with a subsequent PPH had significantly lower mean FXIII activity than that of women without PPH. This difference was small and within normal limits. FXIII activity did not change during normal delivery. The importance of FXIII during PPH requires study.

Association between bleeding tendency and health-related quality of life in carriers of moderate and severe haemophilia.

INTRODUCTION: Carriers of severe and moderate haemophilia A and B are expected to have approximately 50% of the normal level of factors VIII and IX. However, due to X chromosome inactivation in early embryonic life, factor levels can vary considerably. This can lead to increased bleeding tendency, which may in turn impact on health-related quality of life (HRQOL). AIM: The aim of this study was to assess HRQOL in carriers of severe and moderate haemophilia with and without increased bleeding tendency. METHODS: One hundred and twenty-four adult carriers and 90 controls were recruited. Bleeding tendency was evaluated using a structured bleeding assessment tool. HRQOL was measured by the short form 36 (SF-36) questionnaire. The SF-36 scores were compared with Swedish normative age-matched data and reported as Z scores. RESULTS: There was no significant difference between the whole groups of carriers and controls in the Z scores of the eight SF-36 domains. The mental component summary (MCS) was lower in carriers, compared with controls (P = 0.048). The subgroup of carriers with an increased bleeding tendency had significantly lower Z scores compared to controls regarding the General Health (P = 0.008), the Social Functioning (P = 0.040) and the Mental Health (P = 0.048) domains. The MCS was significantly lower in this carrier subgroup than in controls (P = 0.033). CONCLUSION: We conclude that the subgroup of carriers of haemophilia with increased bleeding tendency have impaired HRQOL. The SF-36 results indicate that this condition affects mental rather than physical health.

Fibrinogen plasma concentration before delivery is not associated with postpartum haemorrhage: a prospective observational study.

BACKGROUND: Low plasma fibrinogen concentration has been linked to postpartum haemorrhage. The primary aim of this study was to assess whether fibrinogen concentration at admission before labour is associated with severe postpartum haemorrhage. Secondary aims were to describe fibrinogen concentration before and after labour and to identify predictors for severe postpartum haemorrhage. METHODS: 1951 healthy women were included in a prospective observational study. Fibrinogen concentration was determined at admission to the labour ward and in a subgroup of women (n=80) also after the placenta was delivered. Bleeding volume postpartum was estimated by weighing surgical sponges and pads and by measuring collected blood. Predictors for severe postpartum haemorrhage (>1000 ml) were identified with bivariate and multivariate regression analyses. RESULTS: Mean fibrinogen concentration was 5.3 (SD 0.8) g litre(-) (1). Median estimated blood loss was 450 (range 70-4400) ml and 250 (12.8%) women bled >1000 ml. Fibrinogen concentration was not correlated with postpartum haemorrhage in the entire cohort (r(s)=0.003, P=0.90) or in any subgroup. Fibrinogen concentration was not associated with bleeding >1000 ml (odds ratio 1.01 (CI 95% 0.85-1.19), P=0.93) and did not differ significantly before and after delivery. Oxytocin stimulation, instrumental delivery, Caesarean section and exploration of uterus were identified as independent predictors of haemorrhage >1000 ml. CONCLUSIONS: Fibrinogen plasma concentration at admission before labour does not predict severe postpartum haemorrhage in a general obstetric population. Fibrinogen concentration does not decrease significantly during normal labour. Excessive postpartum bleeding is mainly as a result of obstetric complications.

Major obstetric haemorrhage: monitoring with thromboelastography, laboratory analyses or both?

BACKGROUND: Haemorrhage is a common cause of morbidity and mortality in the obstetric population. The aim of this study was to compare the use of thromboelastography and laboratory analyses to evaluate haemostasis during major obstetric haemorrhage. A secondary aim was to evaluate correlations between the results of thromboelastography, laboratory analyses and estimated blood loss. METHODS: Forty-five women with major obstetric haemorrhage and 49 women with blood loss <600 mL were included. The following thromboelastography analyses were performed: time to start of clotting (TEG-R), time to 20 mm of clot firmness (TEG-K), rate of clot growth (TEG-Angle), maximum amplitude of clot (TEG-MA) and lysis after 30 min (TEG-LY30). In addition, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin and D-dimer were measured. RESULTS: Thromboelastography variables reflecting clot stability and fibrinolysis were decreased in women with massive obstetric haemorrhage compared to women with normal bleeding, while clot initiation was accelerated. Laboratory analyses also showed impaired haemostasis with the most pronounced differences in platelet count, fibrinogen concentration and antithrombin activity. The strongest correlations existed between fibrinogen and TEG-MA and between estimated blood loss and TEG-MA, fibrinogen and antithrombin, respectively. CONCLUSIONS: Impaired haemostasis, demonstrated by thromboelastography and laboratory analyses, was found after an estimated blood loss of 2000 mL. Thromboelastography provides faster results than standard laboratory testing which is advantageous in the setting of on-going obstetric haemorrhage. However, laboratory analyses found greater differences in coagulation variables, which correlated better with estimated blood loss.

Feasibility of the FINDRISC questionnaire to identify individuals with impaired glucose tolerance in Swedish primary care. A cross-sectional population-based study.

AIM: To evaluate the performance of the FINDRISC questionnaire as a tool to recruit individuals with impaired glucose tolerance for lifestyle intervention programmes. METHODS: A cross-sectional population-based study in primary Health Care Centres in a middle-sized Swedish town. All 9734 individuals, aged 35-75 years, living within a defined area, were invited by mail to fill in and return the FINDRISC questionnaire. Participants with a risk score ≥ 15 (n = 525) were invited to perform an oral glucose tolerance test while those with known diabetes were excluded. RESULTS: In total, 5452 questionnaires (58%) were returned and revealed a mean risk-score of 8.5 ± 4.5 (mean ± SD). We found that 525 participants had a risk-score ≥ 15 and 302 (58%) were further examined with an oral glucose tolerance testing (OGTT). Among them we detected 11% with previously undiagnosed Type 2 diabetes, 16% with impaired glucose tolerance and 29% with impaired fasting glucose. A FINDRISC score ≥ 15 was associated with a positive predictive value of 55% for impaired glucose metabolism (impaired fasting glucose + impaired glucose tolerance + Type 2 diabetes) and of 16% for impaired glucose tolerance, respectively. The positive predictive value for impaired glucose tolerance did not increase to more than 17% when choosing the cut-point 17, while there was a significant increase in the positive predictive value for impaired glucose metabolism (70%). CONCLUSIONS: The FINDRISC questionnaire is a useful instrument for identification of individuals with impaired glucose metabolism but seems less effective for detection of individuals with impaired glucose tolerance. Strategies to find individuals with impaired glucose tolerance for implementation of lifestyle changes in primary care should therefore be developed further.

PP107. Cardiovascular parameters 40 years after hypertensive pregnancies.

INTRODUCTION: Epidemiological data indicate an increased cardiovascular risk in women with previous hypertensive pregnancies. There are few clinical investigations regarding the mechanisms that could mediate this increased risk. OBJECTIVES: The aim of the present study was to clarify if any deterioration in the cardiovascular, metabolic or neuroendocrine status is present in women 40 years after pregnancies complicated by hypertension. METHODS: Three hundred and nineteen women were invited to take part in a follow up investigation regarding cardiovascular regulation. One hundred and five women accepted to participate - 50 with previously hypertensive pregnancies (HTP) and 55 with normotensive pregnancies (NTP). Office and ambulatory blood pressure levels, central blood pressure and pulse wave velocity, echocardiographic measurements (RWT, LVMI, LA, LA-RA, diastolic function, strain) and P-glucose, HbA1c, S-leptin, S-hsCRP, P-renin, P-Noradrenaline and NT-proBNP were examined. Women who choose not to participate (n=214) were followed up with a questionnaire regarding their previous pregnancies and present cardiovascular health. RESULTS: The investigations did not reveal differences in any examined variables regarding blood pressure, echocardiographic parameters or blood analysis for metabolic and neurohumoral balance. Twenty-five individuals were diagnosed with hypertension in the HTP group (mean BP 145/86mmHg) and 17 subjects in the NTP group (mean BP 145/87mmHg). The questionnaire was answered by 79% of the participants and revealed that these women had an impaired cardiovascular health compared to the group investigated. CONCLUSION: Blood pressure, metabolic and neuroendocrine parameters are not permanently worsened in all women with previous hypertensive pregnancies. There exist disparities within the group of women with previous hypertensive pregnancies and there are women without obvious cardiovascular or metabolic dysfunction 40 years after the hypertensive manifestation during pregnancy.

Cardiovascular risk markers during treatment with estradiol and trimegestone or dydrogesterone.

OBJECTIVE: To study cardiovascular risk markers in women taking estradiol/trimegestone or estradiol/dydrogesterone. DESIGN: Multicenter, randomized, prospective, double-blind study of 184 healthy post-menopausal women randomized to 6 cycles of either estradiol (2mg)+trimegestone (0.5mg) (T-group) or estradiol (2mg)+dydrogesterone (10mg) (DYDR group). Cardiovascular risk markers were measured before, after cycle 1, 3 and 6 and at 4 weeks post-treatment. RESULTS: Fibrinogen was reduced in both groups but more markedly in the DYDR group. Factor VIIc activity levels decreased in both groups with a greater change in the T-group. Factor VII antigen was increased in both groups with a greater increase in the DYDR group. Factor VIIa was increased in the DYDR group only. Plasminogen levels were also increased in both groups with a greater increase in the T-group. There were no statistically significant changes in lipid variables between the different regimens. Changes in total cholesterol and LDL cholesterol were correlated positively with changes in factor VIIc in the DYDR group and negatively with changes in factor VIIc in the T-group. Trigemestone was associated with a better bleeding pattern. CONCLUSIONS: Trimegestone was associated with less procoagulant changes in factor VIIa and factor VIIc activity and larger decrease in PAI-1 activity compared with the dydrogesterone preparation. These results reflect less androgenic properties of the trimegestone preparation. The fibrinogen level and Lp(a) were more decreased during dydrogesterone treatment. Further investigation is required to clarify the relative importance of beneficial effects with respect to cardiovascular risk.

Medium- and short-chain dehydrogenase/reductase gene and protein families : Dual functions of alcohol dehydrogenase 3: implications with focus on formaldehyde dehydrogenase and S-nitrosoglutathione reductase activities.

Alcohol dehydrogenase 3 (ADH3) is highly conserved, ubiquitously expressed in mammals and involved in essential cellular pathways. A large active site pocket entails special substrate specificities: shortchain alcohols are poor substrates, while medium-chain alcohols and particularly the glutathione adducts S-hydroxymethylglutathione (HMGSH) and S-nitrosoglutathione (GSNO) are efficiently converted under concomitant use of NAD(+)/NADH. By oxidation of HMGSH, the spontaneous glutathione adduct of formaldehyde, ADH3 is implicated in the detoxification of formaldehyde. Through the GSNO reductase activity, ADH3 can affect the transnitrosation equilibrium between GSNO and S-nitrosated proteins, arguing for an important role in NO homeostasis. Recent findings suggest that ADH3-mediated GSNO reduction and subsequent product formation responds to redox states in terms of NADH availability and glutathione levels. Finally, a dual function of ADH3 is discussed in view of its potential implications for asthma.

A hydrogen-bonding network in mammalian sorbitol dehydrogenase stabilizes the tetrameric state and is essential for the catalytic power.

Subunit interaction in sorbitol dehydrogenase (SDH) has been studied with in vitro and in silico methods identifying a vital hydrogen-bonding network, which is strictly conserved among mammalian SDH proteins. Mutation of one of the residues in the hydrogen-bonding network, Tyr110Phe, abolished the enzymatic activity and destabilized the protein into tetramers, dimers and monomers as judged from gel filtration experiments at different temperatures compared to only tetramers for the wild-type protein below 307 K. The determined equilibrium constants revealed a large difference in Gibbs energy (8 kJ/mol) for the tetramer stability between wild-type SDH and the mutated form Tyr110Phe SDH. The results focus on a network of coupled hydrogen bonds in wild-type SDH that uphold the protein interface, which is specific and favorable to electrostatic, van der Waals and hydrogen-bond interactions between subunits, interactions that are crucial for the catalytic power of SDH.

Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism.

The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K(m) values ranged from 0.05 to 0.3 microM and k(cat) values from 2.3 to 17.6 min(-1), while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K(m) values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations.

Preanalytical conditions that affect coagulation testing, including hormonal status and therapy.

Preanalytical conditions, be they due to the individual's physiologic state or to exogenous factors, can affect coagulation factors, in either a transient or a persistent manner, and need to be considered in laboratory testing. These conditions include physical and mental stress, diurnal variation, hormone levels and posture at the time of blood drawing. While testing of these factors has not been exhaustive and some results are conflicting, guidelines for testing conditions can be given.

Inverse association between plasma homocysteine, sulphonylurea exposure and physical activity: a community-based sample of type 2 diabetes patients in the Skaraborg hypertension and diabetes project.

AIM: This study aimed to investigate levels of Homocysteine (tHcy) and folate in a population-based sample of patients with type 2 diabetes. In particular, the study explored modifiable determinants such as treatment for diabetes, life style, glucose control and kidney function. PATIENTS AND METHODS: In a community-based surveillance of patients with type 2 diabetes, 196 men and 191 women were consecutively identified in primary care and characterized by cardiovascular disease (CVD) risk factors focusing on components in the metabolic syndrome. For categorical associations plasma tHcy was dichotomized using the upper 10 percentiles of the distribution. RESULTS: Treatment with sulphonylurea was associated with lower serum levels of tHcy compared to those on diet alone. The association was confined to women [odds ratio 0.14; confidence interval 0.03-0.8] and remained significant when differences in factors related to the metabolic syndrome, life style and previous CVD were accounted for, but was lost when adjusted for HbA1c. There was an inverse dose-related association between physical activity and plasma levels of tHcy (men p = 0.006, women p = 0.034), and a positive association with serum levels of creatinine (men p = 0.004, women p < 0.001). CONCLUSIONS: The association with physical activity might be one contributing explanation for its well-known protective effect on cardiovascular disease. The over risk for vascular complications in diabetic patients with kidney disease may be partially explained by high levels of tHcy and should be further explored. Prospective studies are particularly needed on various treatment for type 2 diabetes and tHcy to explore possible implications for clinical procedures and for public health.

The oral direct thrombin inhibitor, ximelagatran, an alternative for anticoagulant treatment during the puerperium and lactation.

OBJECTIVE: To determine the excretion of the oral direct thrombin inhibitor (oral DTI), ximelagatran, and its active form, melagatran, in human milk, and to thus evaluate the potential exposure of breastfed infants to melagatran. DESIGN: An open, single dose, single centre study. SETTING: Department of Antenatal Care, Primary Health Care South Bohuslän and Institute for the Health of Women and Children, Göteborg University, Sweden. SAMPLE: Seven healthy Caucasian breastfeeding women who were at least two months postpartum were studied. METHODS: The concentrations of ximelagatran, its two intermediates, and melagatran were determined using liquid chromatography-mass spectrometry, with the limit of quantification of 2 nmol L(-1) for human milk and 10 nmol L(-1) for plasma concentrations. MAIN OUTCOME MEASURES: Concentrations of ximelagatran, its intermediates and melagatran were measured in breast milk over 72 hours, and in plasma over 12 hours, after a single oral 36 mg dose of ximelagatran. RESULTS: Neither ximelagatran nor its intermediates were detected in human breast milk. Only trace amounts of melagatran were detected. The mean cumulative amount of melagatran excreted into breast milk over the 72-hour period after dosing with oral ximelagatran was 0.00091% of the administered dose of ximelagatran. Ximelagatran was well tolerated, with no clinically relevant changes in laboratory variables or vital signs. CONCLUSIONS: Trace levels of melagatran are excreted in human breast milk following administration of the oral DTI ximelagatran. The exposure of breastfed infants to melagatran appears to be low and is therefore unlikely to be of clinical concern.

Fluticasone propionate aqueous nasal spray in pregnancy rhinitis.

Pregnancy rhinitis is a common condition with longstanding nasal congestion; troublesome for the mother, possibly also affecting the fetus. There is need for a safe, effective treatment. Nasal corticosteroids, indisputable in other types of rhinitis, have not been evaluated in pregnancy rhinitis. In this placebo-controlled, randomized, double-blind study with parallel groups, we evaluated the effect of 8 weeks of treatment with fluticasone propionate aqueous nasal spray in 53 women with pregnancy rhinitis. Daily symptom scores and nasal peak expiratory flow, as well as acoustic rhinometry before and after treatment, did not show any difference between the groups. Placebo resulted in 6/27 responders, compared with 5/26 for active treatment. There was no detectable influence on maternal cortisol as measured by morning S-cortisol and overnight 12-h-U-cortisol, or any difference in ultrasound measures of fetal growth or pregnancy outcome. Altogether, our study indicates no significant effects of the treatment described here.

Headache and associations with lifestyle among pupils in senior level elementary school.

OBJECTIVE: To investigate the prevalence of headache and its association with lifestyle among schoolchildren and to test an intervention programme. DESIGN: A cross-sectional survey of all pupils in the school who were asked to complete a questionnaire about headache and lifestyle factors. SETTING: School health care at an elementary school in Sweden. SUBJECTS: All 344 pupils aged 13-16 years, 170 girls and 174 boys, at senior level answered the questionnaire and were included in the study. MAIN OUTCOME MEASURES: Headache occurring at least once a week. RESULTS: Twenty-two percent had headache at least once a week. The problem was more common among girls than among boys; OR 1.6 (95%CI 1.3-2.1). In girls, headache was associated with smoking; OR 6.6 (CI 1.2-35.5), going to bed later than 11 p.m.; OR 4.4 (CI 1.1-18.0), headache in parents; OR 2.0 (CI 1.0-4.2), and few sports activities; OR 3.0 (CI 1.2-7.5). The only corresponding association in boys was with smoking; OR 12.0 (CI 1.5-101). Headache improved in pupils participating in the programme. CONCLUSIONS: Headache is a common health problem in schoolchildren of both sexes at senior level and shows strong associations with lifestyle factors in girls. Intervention seems to be efficient.