User-Centred Design of a Digital Care Plan for Patients and Professionals in Cross-Organisational Teams.

Care for patients with multimorbidity and long-term complex needs is costly and with demographic changes this group is growing. The research project Dignity Care addresses how to improve the care for this patient group by studying how a conceptual shared digital care plan for complex clinical pathways can guide and support cross-organisational care teams. This paper presents the user-centred design process for the digital care plan development. Panels of patients and health care professionals will participate in co-creation user workshops and simulation of complex patients' pathways. The main contribution from this work is recommendations for how to actively involve user groups in digital health development, applying a partly remote approach of user-centred design methodology during the Covid-19 pandemic.

How to Enhance Digital Support for Cross-Organisational Health Care Teams? A User-Based Explorative Study.

Health care service provision of individualised treatment to an ageing population prone to chronic conditions and multimorbidities is threatened. There is a need for digitally supported care, that is, (1) person-centred, (2) integrated, and (3) proactive. The research project 3P, Patients and Professionals in Productive Teams, aimed to validate and verify the prerequisites for health care systems run with patient-centred service models. This paper presents an explorative study of the digital support of a cross-organisational health care team in Norway, providing services to elderly frail people with multimorbidities in hospital discharge transition. Qualitative research methods were employed, with interviews and observations to map and evaluate the information flow and the digital support of collaborative work across organisations. The evaluation showed a lacking interoperability between the digital systems and a limited support for cross-organisational teamwork, causing raised manual efforts to maintain the information flow. Tools for coordination and planning across organisations were lacking. To enhance the situation, principles for a cloud-based health portal are proposed with a shared workspace, teamwork functionality for cross-organisational health care teams, and automatic back-end synchronisation of stored information. The main implications of this paper lie in the proposed principles which are transferable to a multitude of clinical contexts, where ad-hoc based access to shared medical information is of importance for decision-making and life-saving treatment.

Patient pathways as social drama: a qualitative study of cancer trajectories from the patient's perspective.

PURPOSE: The number of persons living with and beyond cancer is increasing. Such persons often have complex needs that last, and change, over time. The aim of this study is to get insights of lived experience of person diagnosed with colorectal cancer and to create an understanding of cancer trajectories as a dynamic process. This study thus explores Victor Turner's model of social drama in a cancer care context. METHOD: Turner suggests that crisis is a dynamic process structured by four phases: 1) breach of norm 2) crisis 3) redressive actions 4) reintegration or schism. The research team employed content analysis to explore material gathered through a series of qualitative interviews with nine Norwegian cancer patients over a period of one year. RESULTS: To the authors' knowledge, Turner's model has not earlier been applied to such materials. The results show that Turner's model of social drama is useful in achieving new and possibly important knowledge on illness trajectories from a lived experience perspective. CONCLUSIONS: The model of social drama may contribute to a deeper understanding of the processes patients are going through in long-term illness trajectories, demonstrating that illness is not a static matter.

"What matters to you?" A longitudinal qualitative study of Norwegian patients' perspectives on their pathways with colorectal cancer.

PURPOSE: Person-centred care (PCC) is a well-acknowledged goal throughout the western world both within the health care services sector and for the patients themselves. To be able to create a future health care system that includes improved PCC, we need more in-depth knowledge of what matters to patients, how "what matters" might change over time, and tentative descriptions of commonalities across patients' perspectives. The aim of this study is to contribute to this knowledge base. METHODS: We conducted a qualitative interview series over one year with nine Norwegian patients who were recently diagnosed with rectal cancer tumor-node-metastasis stage I-III. RESULTS: We found that: (1) patients have an initial focus on "biological goals" and conventional treatment; (2) pathways are unique and dynamic; (3) family and friends affected patient pathways positively with respect to meaningfulness and quality of life, but for some participants also negatively because there were heavy burdens of caretaking; (4) receiving help in the health care system depended on the patients' navigation skills; (5) pluralism in health-seeking behaviour was important in all patient pathways. CONCLUSION: Long lasting illness may be a dynamic and complex journey. These results represent some features of a pathway with cancer and are important because they contribute with knowledge about what matters most seen from the cancer patients' point of view.

The effectiveness and cost effectiveness of the PAtient-Centred Team (PACT) model: study protocol of a prospective matched control before-and-after study.

BACKGROUND: The present study protocol describes the evaluation of a comprehensive integrated care model implemented at two hospital sites at the University Hospital of North Norway (UNN). The PAtient Centred Team (PACT) model includes proactive, patient-centred interdisciplinary teams that aim to improve the continuum and quality of care of frail elderly patients and reduce health care costs. The main objectives of the evaluation are to analyse the effectiveness and cost effectiveness of using patient-centred teams as part of routine service provision for this patient group. The evaluation will analyse the effect on patient health and functional status, patient experiences and hospital utilisation, and it will conduct an economic evaluation. This paper describes the PACT model and the rationale for and design of the planned effectiveness and cost-effectiveness study. METHODS/DESIGN: This is a prospective, non-randomised matched control before-and-after intervention study. Patients in the intervention group will be recruited from the hospital sites that have implemented the PACT model. The controls will be recruited from two hospitals without the model. The control patients and the index patients will be matched according to sex, age and number of long-term conditions. The study aims to include 600 patients in each group, which will provide sufficient power to detect a clinical change in the primary outcome. The primary outcome is the physical dimension of the Short Form Health Survey (SF-36). Secondary outcomes are the Patient Generated Index (PGI), the Patient Activation Measure (PAM), the Patient Assessment of Chronic Illness Care (PACIC), hospitalisation and length of stay. The cost-effectiveness study takes a health provider perspective and calculates the cost per quality-adjusted life-years (QALYs) gained. The data will be collected at baseline, 6 and 12 months. The data will be analysed using techniques and models that recognise the lack of randomisation and the correlation of cost and effect data. DISCUSSION: The study results will provide knowledge about whether the integrated care model implemented at UNN improves the quality of care for the frail elderly with multiple conditions. The study will establish whether the PAC. T model improves health and functional status and is cost effective compared to the usual care for this patient group. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02541474.

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women.

PURPOSE: Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. METHODS: The data reported here come from the enrollment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. RESULTS: The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. CONCLUSIONS: Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.

Electronic symptom reporting between patient and provider for improved health care service quality: a systematic review of randomized controlled trials. part 1: state of the art.

BACKGROUND: Over the last two decades, the number of studies on electronic symptom reporting has increased greatly. However, the field is very heterogeneous: the choices of patient groups, health service innovations, and research targets seem to involve a broad range of foci. To move the field forward, it is necessary to build on work that has been done and direct further research to the areas holding most promise. Therefore, we conducted a comprehensive review of randomized controlled trials (RCTs) focusing on electronic communication between patient and provider to improve health care service quality, presented in two parts. Part 2 investigates the methodological quality and effects of the RCTs, and demonstrates some promising benefits of electronic symptom reporting. OBJECTIVE: To give a comprehensive overview of the most mature part of this emerging field regarding (1) patient groups, (2) health service innovations, and (3) research targets relevant to electronic symptom reporting. METHODS: We searched Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and IEEE Xplore for original studies presented in English-language articles published from 1990 to November 2011. Inclusion criteria were RCTs of interventions where patients or parents reported health information electronically to the health care system for health care purposes and were given feedback. RESULTS: Of 642 records identified, we included 32 articles representing 29 studies. The included articles were published from 2002, with 24 published during the last 5 years. The following five patient groups were represented: respiratory and lung diseases (12 studies), cancer (6), psychiatry (6), cardiovascular (3), and diabetes (1). In addition to these, 1 study had a mix of three groups. All included studies, except 1, focused on long-term conditions. We identified four categories of health service innovations: consultation support (7 studies), monitoring with clinician support (12), self-management with clinician support (9), and therapy (1). Most of the research (21/29, 72%) was conducted within four combinations: consultation support innovation in the cancer group (5/29, 17%), monitoring innovation in the respiratory and lung diseases group (8/29, 28%), and self-management innovations in psychiatry (4/29, 14%) and in the respiratory and lung diseases group (4/29, 14%). Research targets in the consultation support studies focused on increased patient centeredness, while monitoring and self-management mainly aimed at documenting health benefits. All except 1 study aiming for reduced health care costs were in the monitoring group. CONCLUSION: RCT-based research on electronic symptom reporting has developed enormously since 2002. Research including additional patient groups or new combinations of patient groups with the four identified health service innovations can be expected in the near future. We suggest that developing a generic model (not diagnosis specific) for electronic patient symptom reporting for long-term conditions may benefit the field.

Electronic symptom reporting between patient and provider for improved health care service quality: a systematic review of randomized controlled trials. part 2: methodological quality and effects.

BACKGROUND: We conducted in two parts a systematic review of randomized controlled trials (RCTs) on electronic symptom reporting between patients and providers to improve health care service quality. Part 1 reviewed the typology of patient groups, health service innovations, and research targets. Four innovation categories were identified: consultation support, monitoring with clinician support, self-management with clinician support, and therapy. OBJECTIVE: To assess the methodological quality of the RCTs, and summarize effects and benefits from the methodologically best studies. METHODS: We searched Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and IEEE Xplore for original studies presented in English-language articles between 1990 and November 2011. Risk of bias and feasibility were judged according to the Cochrane recommendation, and theoretical evidence and preclinical testing were evaluated according to the Framework for Design and Evaluation of Complex Interventions to Improve Health. Three authors assessed the risk of bias and two authors extracted the effect data independently. Disagreement regarding bias assessment, extraction, and interpretation of results were resolved by consensus discussions. RESULTS: Of 642 records identified, we included 32 articles representing 29 studies. No articles fulfilled all quality requirements. All interventions were feasible to implement in a real-life setting, and theoretical evidence was provided for almost all studies. However, preclinical testing was reported in only a third of the articles. We judged three-quarters of the articles to have low risk for random sequence allocation and approximately half of the articles to have low risk for the following biases: allocation concealment, incomplete outcome data, and selective reporting. Slightly more than one fifth of the articles were judged as low risk for blinding of outcome assessment. Only 1 article had low risk of bias for blinding of participants and personnel. We excluded 12 articles showing high risk or unclear risk for both selective reporting and blinding of outcome assessment from the effect assessment. The authors' hypothesis was confirmed for 13 (65%) of the 20 remaining articles. Articles on self-management support were of higher quality, allowing us to assess effects in a larger proportion of studies. All except one self-management interventions were equally effective to or better than the control option. The self-management articles document substantial benefits for patients, and partly also for health professionals and the health care system. CONCLUSION: Electronic symptom reporting between patients and providers is an exciting area of development for health services. However, the research generally is of low quality. The field would benefit from increased focus on methods for conducting and reporting RCTs. It appears particularly important to improve blinding of outcome assessment and to precisely define primary outcomes to avoid selective reporting. Supporting self-management seems to be especially promising, but consultation support also shows encouraging results.

Bone mineral density at the hip in Norwegian women and men--prevalence of osteoporosis depends on chosen references: the Tromsø Study.

This study describes bone mineral density (BMD) and the prevalence of osteoporosis in women and men between 30-89 years in an unselected population. BMD was measured in g/cm(2) at total hip and femoral neck by dual-energy-X-ray absorptiometry in 3,094 women and 2,132 men in the 2001 Tromsø Study. BMD levels were significantly explained by age and declined progressively in both sexes from middle into old age, with highest decline in women. With osteoporosis defined as a T-score of two and a half standard deviation below the young adult mean BMD, the prevalence at the total hip in subjects above 70 years was 6.9% in men and 15.3% in women, respectively, using the Lunar reference material for T-score calculations. The prevalence increased significantly to 7.3% in men and 19.5% in women, when T-scores were calculated on basis of the young adult mean BMD (age group 30-39 years) in the study population. At the femoral neck, prevalence of osteoporosis increased from 13.5 to 18.5% in men, and from 20.4 to 35.2% in women above 70 years, respectively, depending on how T-scores were calculated. The study highlights the challenges with fixed diagnostic levels when measuring normally distributed physiologic parameters. Although BMD only partly explains fracture risk, future studies should evaluate which calculations give optimal fracture prediction.

Differences in precision in bone mineral density measured by SXA and DXA: the NOREPOS study.

The aims were to compare the precision (reliability) in single X-ray (SXA) and dual X-ray (DXA) absorptiometry, and to compare smallest detectable difference (SDD). An additional aim was to examine determinants for precision in bone mineral density (BMD). BMD was measured by SXA (DTX-100, Osteometer) in the forearm and by DXA (Lunar Expert) in the forearm and in the hip. Two measurements were performed at each site/method, and 195 of 207 participants had complete datasets. Participants were aged 47-49 and 71-74 years. The precision was estimated by Root Mean Square Standard Deviation (RMS SD) with 95% Confidence Interval (95%CI) and the corresponding coefficients of variation (CV%). Determinants (age, gender, BMD) were analysed by multiple linear regression with log (SD) and log (CV) as dependent variables. RMS SD tended to be largest in older women and in those with low BMD. RMS SD for SXA and DXA forearm was 4.6 (4.2-5.1) and 6.8 (6.1-7.4) and the corresponding CVs 1.0% and 1.4%. RMS SD for DXA hip was 11.0 (9.9-12.0) with CV 1.2%. To detect a 3% change in BMD one would need two repeated measurements by DXA in the distal forearm at each of two consultations, but only one measurement by SXA in the distal forearm and also only one measurement by DXA in the hip. Precision differed by type of densitometer affecting the number of repeated measurements needed to detect a given BMD difference.

In vivo and in vitro comparison of densitometers in the NOREPOS study.

The purpose of this study was to assess the agreement of in vivo hip scans on 3 densitometers (1 GE Lunar DPX-IQ and 2 GE Lunar Prodigy scanners) and to evaluate whether the European Spine Phantom (ESP) was able to reproduce the in vivo variability. Sixteen subjects had 3 repeated scans (with repositioning) on each densitometer, and the ESP was measured on each densitometer at least 40 times. Mean differences between hip scans on the Prodigy scanners were small and insignificant, and the in vivo results were not significantly different from the in vitro results. Bland and Altman plots showed no systematic differences between the Prodigy scanners over the range of bone mineral density (BMD). On the other hand, differences between Prodigy and DPX-IQ changed systematically over the range of BMD. The ESP did not fully reproduce the in vivo difference between Prodigy and DPX-IQ. In conclusion, the ESP is a valid substitute when assessing agreement between Prodigy scanners. However, when assessing agreement between different types of scanners, substitution of in vivo with in vitro measurements should be made with caution.

A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromso Study.

OBJECTIVES: As bone fragility is partly the result of sex hormone deficiency, we sought to determine whether circulating sex steroids or sex hormone-binding globulin (SHBG) predicts non-vertebral fractures. METHODS: Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels, and SHBG were measured in 1386 postmenopausal women and 1364 men aged 50-84 years at baseline in the Tromsø Study (1994-1995). Non-vertebral fractures were documented between 1994 and 2005. RESULTS: During 8.4 years (range 0.01-10.4) of follow-up, 281 women and 105 men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD and higher SHBG, but sex steroids were not lower. Each standard deviation (s.d.) increase in SHBG increased non-vertebral fracture risk in women (hazards ratio (HR) 1.17; 95% confidence interval (CI) 1.03-1.33) and men (HR 1.26; 95% CI 1.03-1.54). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95% CI 0.95-1.24) or men (HR 1.22; 95% CI 0.99-1.49). Each s.d. decrease in BMD increased fracture risk in women (HR 1.36; 95% CI 1.19-1.56) and men (HR 1.41; 95% CI 1.15-1.73). Fracture rates were highest in participants with SHBG in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1000 person-years in women and men respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone. Sex steroids were not associated with fracture risk. CONCLUSIONS: Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.

Circulating sex steroids, sex hormone-binding globulin, and longitudinal changes in forearm bone mineral density in postmenopausal women and men: the Tromsø study.

Bone loss during advancing age in women and men is partly the result of sex steroid deficiency. As the contribution of circulating sex steroids and sex hormone-binding globulin (SHBG) to bone loss remains uncertain, we sought to determine whether levels of sex steroids or SHBG predict change in bone mineral density (BMD) in women and men. A population-based study in the city of Tromsø of 6.5 years' duration (range 5.4-7.4) included 927 postmenopausal women aged 37-80 years and 894 men aged 25-80 years. Total estradiol and testosterone, calculated free levels, and SHBG were measured at baseline, and BMD change at the distal forearm was determined using BMD measurements in 1994-1995 and 2001. Bone loss was detected in postmenopausal women and men. Free estradiol and SHBG predicted age-adjusted bone loss in postmenopausal women, but only free estradiol was associated after further adjustment for body mass index and smoking in mixed models (P < 0.05). After same adjustment, only SHBG persisted as a significant independent predictor of bone loss in men (P < 0.001). However, only 1% of the variance in bone loss was accounted for by these measurements. We therefore conclude that the relations between sex steroids and bone loss are weak and measurements of sex steroids are unlikely to assist in clinical decision making.

Validation of the Cummings' risk score; how well does it identify women with high risk of hip fracture: the Tromsø Study.

OBJECTIVE: We examined a two-step case-finding strategy where the Cummings' risk score (NEJM 1995) was applied in a population-based setting together with bone mineral density (BMD) measurements in order to validate its ability to identify women with high risk of hip fracture. METHODS: All Tromsø women aged between 65 and 74 were invited to the Tromsø Osteoporosis Study (TROST) together with a 5% random sample of women aged 75-84 years (n = 1410). All had forearm BMD measurements in 1994/95 and were followed for 5 years with respect to first hip fracture. A risk score was constructed matching the Cummings score as closely as possible. RESULTS: In all 759, 578 and 73 women had 0-2, 3-4 and 5+ risk factors, respectively. Women with 5+ risk factors had a 5-year hip fracture risk of 11% (95% confidence interval (CI) 3.7-18.2%). BMD screening applied to these women identified 74% of them as osteoporotic and 19% as osteopenic with, respectively, 5-year hip fracture risk of 13% and 7.1%. CONCLUSION: In a population different from the one the score was generated in, this simple risk score identifies a group of women with high risk of hip fractures. With no additional BMD measurements, those high-risk women could benefit from early intervention measures.

Seasonal variation of estradiol, follicle stimulating hormone, and dehydroepiandrosterone sulfate in women and men.

CONTEXT: Seasonal variation in daylight regulates reproduction in animals living at higher latitude, but the influence of season on the sex hormones in humans remains unclear. OBJECTIVE, DESIGN, AND PARTICIPANTS: A cross-sectional population-based study in Tromsø, Norway (70 degrees N) included 1651 women and 1540 men aged 25-84 yr. Circulating total estradiol (and calculated free levels), FSH, and dehydroepiandrosterone sulfate (DHEAS) were measured between September 1994 and September 1995 and provided a unique opportunity to study effects of extreme seasonal variations in the daylight on hormone levels in an arctic population. MAIN OUTCOME MEASURE: Circulating total and free estradiol, FSH, and DHEAS were measured. RESULTS: Total and free estradiol showed differences between monthly means, with peak in June in postmenopausal women (P < 0.001), and in May in men (P = 0.002 and P < 0.001) by analysis of covariance. By cosinor analysis, a seasonal variation in total and free estradiol was evident in women (P = 0.02 and P = 0.03) and men (P = 0.004 and P = 0.001), but only 0.2-0.9% of the variation in total and free estradiol was explained by season. FSH and DHEAS showed no obvious seasonal variation in either sex. CONCLUSIONS: Seasonal variations should be considered while designing studies and interpreting results of estradiol measurements to avoid bias in comparative studies.

Diabetes mellitus and the risk of non-vertebral fractures: the Tromsø study.

We wanted to determine the risk of non-vertebral fracture associated with type and duration of diabetes mellitus, adjusting for other known risk factors. This is a population-based 6-year follow-up of 27,159 subjects from the municipality of Tromsø, followed from 1994 until 2001. The age range was 25-98 years. Self-reported diabetes cases were validated by review of the medical records. All non-vertebral fractures were registered by computerized search in radiographic archives. A total of 1,249 non-vertebral fractures was registered, and 455 validated cases of diabetes were identified. Men with type I diabetes had an increased risk of all non-vertebral [relative risk (RR) 3.1 (95% CI 1.3-7.4)] and hip fractures [RR 17.8 (95% CI 5.6-56.8)]. Diabetic women, regardless of type of diabetes, had significantly increased hip fracture risk [RR 8.9 (95% CI 1.2-64.4) and RR 2.0 (95% CI 1.2-3.6)] for type I and type II diabetes, respectively. Diabetic men and women using insulin had increased hip fracture risk. Duration of disease did not alter hip fracture risk. An increased risk of all non-vertebral fractures and, especially, hip fractures was associated with diabetes mellitus, especially type I. Type II diabetes was associated with increased hip fracture risk in women only.

Self-reported diseases and the risk of non-vertebral fractures: the Tromsø study.

We wanted to estimate the independent fracture risk associated with chronic diseases for men and women separately, adjusting for other known risk factors. This is a population-based study of all those who attended the fourth survey (1994-1995) in the Tromsø Study (n=27,159) who were followed until 31 December 2000 with respect to non-vertebral fractures. At baseline the age range was 25-98 years. Chronic disease cases were defined by self-report in questionnaires. All non-vertebral fractures were registered by computerized search in radiographic archives in the sole provider of radiographic service in the area. A total of 446 and 803 non-vertebral fractures were registered among men and women, respectively. Self-reported diabetes mellitus, stroke, asthma, hypo- and hyperthyroidism and psychiatric disorders were associated with increased fracture risk. Multivariate analyses showed an independent risk of fractures associated with self-reported diabetes mellitus, hypothyroidism and psychiatric disorders among men. Among women the independent risk was associated with self-reported asthma, hypo- and hyperthyroidism and psychiatric disorders. Self-reported heart disease had a protective effect on wrist fracture, especially in women. Increased burden of chronic diseases increase the risk of all non-vertebral (P<0.0001), wrist (P=0.005), proximal humerus (P=0.0004) and hip fracture (P=0.0002) in men, and for the proximal humerus (P=0.003) and hip fracture (P=0.04) in women. There was an independent fracture risk associated with self-reported diabetes mellitus, asthma, hypo- and hyperthyroidism and psychiatric disorders in men and women. Increasing burden of disease increased fracture risk in both men and women.

Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy.

OBJECTIVE: The purpose of this study was to construct new reference ranges for serial measurements of commonly used umbilical artery Doppler indices (pulsatility index, resistance index, and systolic:diastolic ratio). STUDY DESIGN: This was a prospective longitudinal study of the umbilical artery Doppler indices that were obtained serially at the free-loop of umbilical cord at 4-week intervals at 19 to 42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges with the use of multilevel modeling. RESULTS: Longitudinally established percentiles of Doppler indices from the present study show a continuous reduction throughout the second half of pregnancy without any plateau or increase near term, as reported previously. There was a significant negative association between Doppler indices and placental weight and neonatal birth weight, but not with gender. The intraobserver coefficients of variation for the umbilical artery pulsatility index, resistance index, and systolic:diastolic ratio were 10.5%, 6.8 %, and 13.0 %, respectively. CONCLUSION: New reference ranges for umbilical artery Doppler indices that are based on longitudinal observations appear to be slightly different from cross-sectional studies and are more appropriate for serial evaluation of fetal hemodynamics.

Reference ranges for umbilical vein blood flow in the second half of pregnancy based on longitudinal data.

OBJECTIVES: To construct new reference ranges for serial measurements of umbilical vein (UV) blood flow. METHODS: Prospective longitudinal study of blood flow velocities and diameter of the UV measured at four-weekly intervals during 19 to 42 weeks' gestation in 130 low-risk singleton pregnancies. Regression models and multilevel modeling were used to construct the reference ranges. RESULTS: On the basis of 511 sets of longitudinal observations, we established new reference percentiles of UV diameter, blood flow velocities, volume flow, and blood flow normalized for fetal weight and abdominal circumference. They reflected some of the developmental patterns of previous cross-sectional studies, but with important differences, particularly near term. The UV blood flow showed a continuous increase until term, whereas the flow normalized per unit fetal weight, a corresponding reduction. Calculating the blood flow on the basis of intensity-weighted mean velocity or 0.5 of the maximum velocity gave almost interchangeable results for most fetuses. CONCLUSION: New reference ranges for UV blood flow based on longitudinal observations appear slightly different from cross-sectional studies, and should be more appropriate for serial evaluation of fetal circulation.

Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromsø Study.

The role played by endogenous hormones in many diseases makes it important to understand factors influencing their levels. This study examined the distribution of total and free estradiol, FSH, and dehydroepiandrosterone sulfate (DHEAS) by age and sex and associations of these hormones with body mass index (BMI), lifestyle factors, and chronic diseases. Plasma samples taken from 1555 men and 1952 women 25-84 yr of age in 1994-1995 Tromsø Study were analyzed in 2001. Total estradiol increased with age among men (P < 0.001), with or without adjustment for BMI and lifestyle factors. FSH increased with age both in men (P < 0.001) as well as pre- (P < 0.001) and postmenopausal women (P = 0.01) after similar adjustment, and DHEAS decreased with age in both sexes (P < 0.001). With increasing BMI, free estradiol increased in men (P = 0.004), total and free estradiol increased in postmenopausal women (P < 0.001), and FSH decreased in men (P = 0.03) and postmenopausal women (P < 0.001). Men with chronic diseases had lower levels of DHEAS, compared with healthy men (P < 0.001). Smokers had higher DHEAS levels than nonsmokers. Further studies are needed to confirm these hormonal changes with age and disease.