Person-centred, integrated and pro-active care for multi-morbid elderly with advanced care needs: a propensity score-matched controlled trial.

BACKGROUND: Person-centred care (PCC) focusing on personalised goals and care plans derived from "What matters to you?" has an impact on single disease outcomes, but studies on multi-morbid elderly are lacking. Furthermore, the combination of PCC, Integrated Care (IC) and Pro-active care are widely recognised as desirable for multi-morbid elderly, yet previous studies focus on single components only, leaving synergies unexplored. The effect of a synergistic intervention, which implements 1) Person-centred goal-oriented care driven by "What matters to you?" with 2) IC and 3) pro-active care is unknown. METHODS: Inspired by theoretical foundations, complexity science, previous health service research and a patient-driven evaluation of care quality, we designed the Patient-Centred Team (PACT) intervention across primary and secondary care. The PACT team collaborate with the patient to make and deliver a person-centred, integrated and proactive multi-morbidity care-plan. The control group receives conventional care. The study design is a pragmatic six months prospective, controlled clinical trial based on hospital electronic health record data of 439 multi-morbid frail elderly at risk for emergency (re) admissions referred to PACT and 779 propensity score matched controls in Norway, 2014-2016. Outcomes are emergency admissions, the sum of emergency inpatient bed days, 30-day readmissions, planned and emergency outpatient visits and mortality at three and six months follow-up. RESULTS: The Rate Ratios (RR) for emergency admissions was 0,9 (95%CI: 0,82-0,99), for sum of emergency bed days 0,68 (95%CI:0,52-0,79) and for 30-days emergency readmissions 0,72 (95%CI: 0,41-1,24). RRs were 2,3 (95%CI: 2,02-2,55) and 0,9 (95%CI: 0,68-1,20) for planned and emergency outpatient visits respectively. The RR for death at 3 months was 0,39 (95% CI: 0,22-0,70) and 0,57 (95% CI: 0,34-0,94) at 6 months. CONCLUSION: Compared with propensity score matched controls, the care process of frail multi-morbid elderly who received the PACT intervention had a reduced risk of high-level emergency care, increased use of low-level planned care, and substantially reduced mortality risk. Further study of process differences between groups is warranted to understand the genesis of these results better. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT02541474 ), registered Sept 2015.

Bone loss and the risk of non-vertebral fractures in women and men: the Tromsø study.

SUMMARY: We assessed the association between the rate of forearm bone loss and non-vertebral fracture. Bone loss at the distal forearm predicted fractures, independently of baseline BMD, but not independently of follow-up BMD in women. The BMD level where an individual ends up is the significant predictor of fracture risk. INTRODUCTION: Bone loss may predict fracture risk independently of baseline BMD. The influence of follow-up BMD on this prediction is unknown. The aim of this study was to assess the association between bone loss and fracture risk in both sexes in a prospective population-based study. METHODS: We included 1,208 postmenopausal women (50 to 74 years), and 1,336 men (55 to 74 years) from the Tromsø Study, who had repeated distal and ultra-distal forearm BMD measurements. Non-vertebral fractures were registered from 2001 to 2005. RESULTS: A total of 100 women and 46 men sustained fractures during the follow-up time. Independent of baseline BMD, the RR associated with distal site bone loss of 1 SD %/year was 1.23 (1.01-1.50) for low-trauma fractures (excluding hand, foot, skull & high-trauma) and 1.32 (1.07-1.62) for osteoporotic fractures (hip, wrist and shoulder). However, bone loss did not predict fracture after adjusting for follow-up BMD. The BMD level where an individual ends up became the significant predictor of fracture risk and not the rate of bone loss. Follow-up BMD at ultra-distal site was associated with low-trauma fractures in both sexes. While ultra-distal site BMD changes were not associated with fracture risk in both sexes. CONCLUSION: Bone loss at the distal forearm predicted non-vertebral fractures, independently of baseline BMD, but not independently of follow-up BMD, in women. The BMD level where an individual ends up is the significant predictor of fracture risk and not the rate of bone loss.

Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial.

UNLABELLED: Vitamin K2 may preserve bone strength and reduce fracture risk. In this randomised double-blind placebo-controlled trial among healthy postmenopausal Norwegian women, 1 year supplementation of vitamin K2 in the form of Natto capsules had no effect on bone loss rates. INTRODUCTION: Japanese studies indicate that vitamin K2 (menaquinone-7 (MK-7)) intake may preserve bone strength, but this has not been documented in Europeans. The aim of this study was to assess the effect of MK-7 on bone mineral density (BMD) changes in postmenopausal Norwegian women. METHODS: Three hundred thirty-four healthy women between 50 and 60 years, 1-5 years after menopause, were recruited to a randomised double-blind placebo-controlled trial. The participants were randomly assigned into two groups, one receiving 360 microg MK-7 in the form of Natto capsules and the other the same amount of identical-looking placebo capsules containing olive oil. BMD was measured at total hip, femoral neck, lumbar spine and total body at baseline and 12 months together with serum levels of bone-specific alkaline phosphatase, Crosslaps, total osteocalcin (N-mid OC), carboxylated (cOC) and under-carboxylated osteocalcin (ucOC). RESULTS: After 12 months, there were no statistical differences in bone loss rates between the groups at the total hip or any other measurement site. Serum levels of cOC increased and ucOC decreased in the treatment versus the placebo group (p < 0.001). CONCLUSION: MK-7 taken as Natto over 1 year reduced serum levels of ucOC but did not influence bone loss rates in early menopausal women.

How do we deal with multiple goals for care within an individual patient trajectory? A document content analysis of health service research papers on goals for care.

OBJECTIVES: Patients with complex long-term needs experience multiple parallel care processes, which may have conflicting or competing goals, within their individual patient trajectory (iPT). The alignment of multiple goals is often implicit or non-existent, and has received little attention in the literature. RESEARCH QUESTIONS: (1) What goals for care relevant for the iPT can be identified from the literature? (2) What goal typology can be proposed based on goal characteristics? (3) How can professionals negotiate a consistent set of goals for the iPT? DESIGN: Document content analysis of health service research papers, on the topic of 'goals for care'. SETTING: With the increasing prevalence of multimorbidity, guidance regarding the identification and alignment of goals for care across organisations and disciplines is urgently needed. PARTICIPANTS: 70 papers that describe 'goals for care', 'health' or 'the good healthcare process' relevant to a general iPT, identified in a step-wise structured search of MEDLINE, Web of Science and Google Scholar. RESULTS: We developed a goal typology with four categories. Three categories are professionally defined: (1) Functional, (2) Biological/Disease and (3) Adaptive goals. The fourth category is the patient's personally defined goals. Professional and personal goals may conflict, in which case goal prioritisation by creation of a goal hierarchy can be useful. We argue that the patient has the moral and legal right to determine the goals at the top of such a goal hierarchy. Professionals can then translate personal goals into realistic professional goals such as standardised health outcomes linked to evidence-based guidelines. Thereby, when goals are aligned with one another, the iPT will be truly patient centred, while care follows professional guidelines. CONCLUSIONS: Personal goals direct professional goals and define the success criteria of the iPT. However, making personal goals count requires brave and wide-sweeping attitudinal, organisational and regulatory transformation of care delivery.

The Tromsø study: determinants of precision in bone densitometry.

Studies of precision determinants in bone densitometry are scarce. A total of 111 subjects recruited from the population-based multipurpose Tromsø Study (Norway), 27-75 years of age, had repeated forearm bone single X-ray absorptiometry (SXA) measurements. Measurement conditions were systematically varied in series up to eight scans. Median coefficients of variation (CV) for two scans performed 1 week apart, by two different operators were 0.79% and 0.98% at distal and ultradistal sites, respectively. The CV distribution was skewed: 5% of the subjects had individual CVs above 2.2% (distal) and 3.4% (ultradistal). Age (P = 0.0097) and repositioning were important determinants of precision. The SXA bone mineral density (BMD)-measurement method is sufficiently precise to establish BMD level. The minimal individual percentage BMD change that can be detected with 95% certainty was 2% and 3% at distal and ultradistal sites, respectively. Detection of BMD changes less than this should rely on multiple repeat measurements at each point in time.

Hormone replacement therapy: knowledge, attitudes, self-reported use - and sales figures in Nordic women.

OBJECTIVES: To evaluate knowledge about, attitudes towards and use of hormone replacement therapy (HRT) in Norwegian women - and to compare self-reported use with sales statistics of HRT in the Nordic countries during recent years. MATERIAL AND METHODS: Random samples of Norwegian women age 16-79 were interviewed by the Central Bureau of Statistics in 1994 (n=737), in 1996 (n=665) and in 1998 (n=680). Statistics on the sale of estrogen were provided by the Norwegian Medical Depot and Nordic Council on Medicines. RESULTS: One in three women had received information about HRT during the last 2 years (1994), mainly through weekly magazines and physicians. The proportion answering in accordance with the prevailing view of HRT's effects ('correct knowledge') varied from 36.4 to 47.2%. Those informed by a physician possessed correct knowledge, had positive attitudes towards HRT and were willing to use HRT more often than women informed through other channels. Women with a high level of education had received information and had correct knowledge more often than others, but they were still less willing to use HRT and did not use HRT more often than the less educated. In the age group 45-69 years the use of HRT was 16.3% in 1994, 19.1% in 1996 and 19. 1% in 1998 (P=0.421, trend). In addition to received information, attitudes towards and knowledge about estrogen were the most important factors predicting use of HRT after adjusting for other variables. According to sales figures, the use of systemic estrogen in Norway has increased more than 360% since 1990. Although no other Nordic country has experienced a corresponding increase, Iceland had the highest sales figures in 1997. CONCLUSIONS: Based on the limited proportion of women receiving information on HRT and the ambivalence found in groups of educated women, we suggest that more and better information should be given middle-aged women to make them better able to make informed choices regarding use of HRT.

Kinetics of IL-2 receptor expression on lymphocyte subsets from goats infected with Mycobacterium avium subsp. paratuberculosis after specific in vitro stimulation.

Quantification of surface IL-2R expression on activated lymphocytes by flow cytometry have recently been reported to be useful in measuring cellular immunity against Mycobacterium avium subsp. paratuberculosis in goats (Whist et al., 2000, Vet. Immunol. Immunopathol. 73, 207-218). To characterise the phenotype of the peripheral lymphocytes expressing IL-2R after in vitro stimulation with purified protein derivative (PPD) from M. a. paratuberculosis, cells were processed for dual or triple colour analysis by flow cytometry (CD4 and IL-2R or CD8, gammadelta-TcR and IL-2R). To distinguish the response of antigen-specific T cells from non-specific stimulation, we performed a time-course study of proliferating cells in a group of M. a. paratuberculosis-infected animals and a control group. Following in vitro stimulation with PPD of whole blood for three different periods of time, IL-2R expression was detected mainly not only in gammadelta-T cells, but also in CD4+ and CD8+ T cells. We found a specific response of gammadelta-T cells from infected animals after 24h of stimulation. Following 120h of stimulation, however, gammadelta-T cells from control animals up-regulated IL-2R to the same level as those from infected animals, indicating either a non-specific stimulation or activation due to a first line of defence against Mycobacterium antigens. The CD4+ cells showed a specific response to PPD stimulation at all three time points. A minor population of antigen reactive gammadelta+ cells also expressed CD8. The proliferative responses differed between alphabeta and gammadelta-T cells; the IL-2R+ alphabeta T cell population mainly comprised proliferating cells, while the gammadelta+ population showed less expansion.

In vitro responses to purified protein derivate of caprine T lymphocytes following vaccination with live strains of Mycobacterium avium subsp paratuberculosis.

Live attenuated vaccines provide protection against intestinal lesions in goats infected with Mycobacterium avium subsp. paratuberculosis. To examine the role of different T lymphocyte subsets in the development of this protective immunity, CD4(+), CD8(+) and gamma delta T cell receptor (TCR)(+) cells from peripheral blood of goat kids vaccinated with live attenuated strains of M. a. paratuberculosis were studied. After in vitro stimulation with purified protein derivate, the expression of gamma-interferon (IFN-gamma) and the activation marker interleukin-2 receptor (IL-2R) was analysed by flow cytometry. A depletion experiment was performed, where the phenotypes and IL-2R expression was studied after stimulation of cultures depleted of a T lymphocyte subpopulation. Close to all of the IFN-gamma producing cells were of the CD4(+) subset, while only a small number were CD8(+) cells. The gamma delta TCR(+) cells were highly activated, but did not produce IFN-gamma after in vitro stimulation. Depletion of CD4(+) cells lead to a decrease in the percentage of total gamma delta TCR(+) cells and gamma delta TCR(+)IL2-R(+) cells. Removing the gamma delta TCR(+) cells increased the relative numbers of CD4(+), but not the CD4(+)IL-2R(+) cells. Insight into the in vitro recall responses of T cell subsets from animals vaccinated with live paratuberculosis vaccines is essential in the development of more efficient vaccines.

Subclinical paratuberculosis in goats following experimental infection. An immunological and microbiological study.

An experimental oral infection of goats with a caprine isolate of Mycobacterium a. subsp. paratuberculosis was used to investigate immunological and bacteriological events during the subclinical phase of infection. Seven goats at 5-8 weeks of age were given a bacterial suspension in milk-replacement three times weekly for 9 weeks. Six animals were kept as controls. Cellular recall responses against M. a. paratuberculosis were analysed by means of a lymphocyte proliferation test, an IFN-gamma assay and an IL-2 receptor assay. All inoculated animals had detectable CMI responses from 9 weeks post-inoculation and through the 2 years of study, although the responses were highest during the first year. Antibodies against M. a. paratuberculosis could be detected from weeks 15-20 in four of the seven animals, and one additional animal became antibody positive at week 35, while two inoculated animals did not produce significant antibody titres during the experiment. At about 1-year post-inoculation, two animals became faecal shedders, while two others started to excrete bacteria into faeces about 2 years post-inoculation. The appearance of M. a. paratuberculosis in faeces was not associated with a decline in cellular responses as far as could be assessed using the current methods for measuring CMI. Pathological lesions due to M. a. paratuberculosis infection and presence of bacteria were recorded in the intestine and/or mesenteric lymph nodes of five animals while lymph node changes suggestive of paratuberculosis were observed in one animal. Only the two animals with no signs of an active infection at necropsy showed a considerable decline in the cellular parameters during the last year of the study, particularly in the IFN-gamma assay. The two animals with the highest levels of M. a. paratuberculosis responsive CD8+ lymphocytes in the circulation about 1-year post-inoculation had no detectable lesions in the distal ileum and colon at necropsy, while high numbers of gammadelta T-cells responsive to M. a. paratuberculosis in the circulation were associated with disseminated lesions in the distal ileum and colon.

Standards for reporting randomized controlled trials in medical informatics: a systematic review of CONSORT adherence in RCTs on clinical decision support.

INTRODUCTION: The Consolidated Standards for Reporting Trials (CONSORT) were published to standardize reporting and improve the quality of clinical trials. The objective of this study is to assess CONSORT adherence in randomized clinical trials (RCT) of disease specific clinical decision support (CDS). METHODS: A systematic search was conducted of the Medline, EMBASE, and Cochrane databases. RCTs on CDS were assessed against CONSORT guidelines and the Jadad score. RESULT: 32 of 3784 papers identified in the primary search were included in the final review. 181 702 patients and 7315 physicians participated in the selected trials. Most trials were performed in primary care (22), including 897 general practitioner offices. RCTs assessing CDS for asthma (4), diabetes (4), and hyperlipidemia (3) were the most common. Thirteen CDS systems (40%) were implemented in electronic medical records, and 14 (43%) provided automatic alerts. CONSORT and Jadad scores were generally low; the mean CONSORT score was 30.75 (95% CI 27.0 to 34.5), median score 32, range 21-38. Fourteen trials (43%) did not clearly define the study objective, and 11 studies (34%) did not include a sample size calculation. Outcome measures were adequately identified and defined in 23 (71%) trials; adverse events or side effects were not reported in 20 trials (62%). Thirteen trials (40%) were of superior quality according to the Jadad score (≥3 points). Six trials (18%) reported on long-term implementation of CDS. CONCLUSION: The overall quality of reporting RCTs was low. There is a need to develop standards for reporting RCTs in medical informatics.

An exploratory study of patient attitudes towards symptom reporting in a primary care setting. Benefits for medical consultation and syndromic surveillance?

OBJECTIVES: The aim of this study was to investigate people's attitude towards providing symptom information electronically before a consultation. Specific areas investigated include a) attitudes and experiences with regards to acquisition of information related to symptoms, b) attitudes towards computer based communication of symptoms to the general practitioner and how they preferred to carry out such reporting, and c) attitudes towards storage, use and presentation of symptom-data in general, and particularly in a symptom based surveillance setting. METHODS: Data was collected from 83 respondents by use of convenience sampling. RESULTS: The respondents were familiar with using the Internet for health purposes, such as acquisition of information related to their symptoms prior to a consultation. The majority of respondents had a positive attitude towards providing information about their symptoms to the general practitioner's office as soon as possible after falling ill. Over half of the respondents preferred to use e-mail or a web-interface to perform this task. Eighty four percent were willing to have their symptom data stored in their EPR and 76 percent agreed that the general practitioner might access the symptoms together with the prevalence of matching diseases in order to assist the diagnostic process during the next consultation. CONCLUSIONS: The results of this study support the applicability of electronically mediated pre-consultation systems both for improving primary care consultation and for use in symptom based surveillance, including real-time surveillance.

Longitudinal changes in forearm bone mineral density in women and men aged 45-84 years: the Tromso Study, a population-based study.

The aim of this study was to describe changes in bone mineral density in Norwegian women and men aged 45-84 years in a population-based, longitudinal study. Bone mineral density (g/cm2) was measured at distal and ultradistal forearm sites with single x-ray absorptiometric devices in 3,169 women and 2,197 men at baseline in 1994-1995 and at follow-up in 2001 (standard deviation, 0.4 years). The mean annual bone loss was -0.5% and -0.4% in men and -0.9% and -0.8% in women not using hormone replacement therapy at the distal and ultradistal sites, respectively. In men, age was a negative predictor of bone mineral density change at both sites. Women not using hormone replacement therapy had the highest bone loss at the ultradistal site 1-5 years after menopause. The correlation between the two measurements was high: r = 0.93 and r = 0.90 in women and r = 0.96 and r = 0.93 in men for the distal and ultradistal sites, respectively. More than 70% kept their quartile positions, indicating a high degree of tracking of bone mineral density measurements. Although the study population live above the polar circle, the rate of bone loss was not higher at the distal and ultradistal forearm sites compared with that of other cohorts.

Umbilical vein constriction at the umbilical ring: a longitudinal study.

OBJECTIVE: It has been suggested that constriction of the umbilical vein (UV) at the umbilical ring has hemodynamic effects. We aimed to determine the occurrence and extent of such constriction in serial observations. METHODS: This was a prospective longitudinal study of UV velocities at the umbilicus measured at approximately 4-week intervals between 19 and 42 weeks' gestation in 129 low-risk singleton pregnancies. Each participant was examined three to five times. Multilevel modeling was used to construct the reference ranges and to test associations between variables. RESULTS: Gestational age-specific reference percentiles of UV velocities at the umbilicus were established based on 469 observations. Fetuses were able to alter the UV velocities considerably during the second half of pregnancy, signifying a varying degree of UV constriction. Of a total of 129 fetuses, 56 (43.4%) never had high UV blood velocity (i.e. > 46 cm/s, the highest quartile), 42 (32.6%) fetuses had high UV blood velocity on one occasion and 31 (24.0%) fetuses on two or more occasions. In 36 (27.9%) fetuses the UV velocity at the umbilical ring was > 300% of the mean gestational age-specific reference value at the intra-abdominal section on at least one occasion. Constriction of the UV at the umbilical ring did not affect the pulsatility of the umbilical artery, and was not associated with adverse perinatal outcome in this study. CONCLUSIONS: Low-risk fetuses may well constrict the UV at the abdominal wall with velocities extending over wide ranges on one or more occasions during the second half of pregnancy. Rather than being a risk for complications, the constriction seems to be part of physiological development and possibly a regulatory mechanism.

Features of the metabolic syndrome and the risk of non-vertebral fractures: the Tromsø study.

INTRODUCTION: We wanted to examine whether the features of the metabolic syndrome carried an increased risk of non-vertebral fracture. METHODS: This is a population-based, 6-year follow-up of 27,159 subjects from the municipality of Tromsø, followed from 1994 until 2001. Age range was 25-98 years. Non-fasting serum levels of high-density lipoprotein (HDL), triglycerides and glucose, blood pressure (BP), weight and height were measured at baseline. All non-vertebral fractures were registered by computerised search in radiographic archives. RESULTS: A total of 1,249 non-vertebral fractures were registered. Increasing number of metabolic syndrome features was associated with significantly reduced fracture risk in both men and women, p= 0.004 and p<0.0001, respectively. High BP was protective against fracture in men [relative risk (RR) 0.89; 95% confidence interval (CI) 0.8-0.99)] while increased body mass index (BMI) was protective in women (RR 0.91; 95% CI 0.84-0.98). Increasing non-fasting serum levels of HDL increased fracture risk in women (RR 1.12; 95% CI 1.05-1.21). BMI modified the effect of HDL in men. Accordingly, high HDL increased fracture risk in men with high BMI (RR 1.51; 95% CI 1.2-1.9). CONCLUSIONS: Increasing burden of metabolic syndrome features protects against non-vertebral fractures. Reduced non-vertebral fracture risk was associated with high BP in men and increased body mass in women. Lower non-fasting serum levels of HDL protect against fractures in women and obese men.

Carotid plaque echogenicity and risk of nonvertebral fractures in women: a longitudinal population-based study.

Atherosclerosis and osteoporosis appear to be related, but prospective studies on the relationship are sparse. In order to examine whether carotid artery plaques with different morphology predict nonvertebral fractures, we followed 2,733 women, aged 55-74 years (75% of the eligible population in Tromsø, Norway), for 6 years. At baseline, plaque morphology in terms of ultrasound echogenicity was categorized into three groups, ranging from low echogenicity (echolucent plaques with a high content of soft tissue) to strong echogenicity (echogenic plaques with a high content of dense fibrous tissue and calcified material). We found that the age-adjusted relative risk (RR) of fracture was significantly higher among women with echogenic plaques than among women without plaques: 1.7 (95% confidence interval [CI] 1.0-2.7). After adjustment for bone mineral density at baseline in addition to age, the RR was 1.6 (95% CI 1.0-2.6), and further adjustments for body mass index, body height, high-density lipoprotein cholesterol, smoking status, and muscle strength did not influence the association. Subjects with other plaque types were not at an increased risk compared to subjects without plaques: RR < or = 1.1, after multiple adjustments. We conclude that in the general population elderly women with echogenic carotid plaques are at higher risk of nonvertebral fractures than women without plaques.

Bone mineral density measures in longitudinal studies: the choice of phantom is crucial for quality assessment. The Tromsø study, a population-based study.

Determination of change in bone mineral density (BMD) requires high-precision densitometry techniques. The purpose of the study is to investigate to what degree different densitometer phantoms reflect observed changes in human BMD and to investigate to what degree fluctuations in densitometers' measurement level influence bone loss estimates. Densitometer influence was assessed using the aluminum forearm phantom (AFP) provided by the manufacturer, the European forearm phantom (EFP) of semi-anthropomorphic calcium-hydroxyapatite, and repeated population measurements on different densitometer combinations. The mean follow-up time was 6.4 years (SD 0.6). Measured population bone loss varied from 4.6%/year to 3.2%/year, depending on densitometer combinations. These variations could not be explained by differences in sex, age, height, weight and baseline BMD. They were predicted by EFP measurements, but not AFP measurements. The EFP measurements indicate that X-ray tube replacement changed the densitometers' measurement level in one of three instances, whereas "wear and tear" did not. We used the EFP data for adjustment of the densitometers' measurement levels. After adjustment, the overall crude bone loss was reduced from 4.14% to 3.92%. Mean annual loss was reduced from 0.64% or 0.61%. We conclude that densitometer performance might influence the accuracy of bone loss estimates. Changes in performance are not detected by aluminum phantoms. Quality control of BMD measurements in longitudinal studies should be performed with anthropomorphic calcium-hydroxyapatite phantoms in order to detect possible differences between the participating densitometers' measurement levels.

Reference ranges for serial measurements of blood velocity and pulsatility index at the intra-abdominal portion, and fetal and placental ends of the umbilical artery.

OBJECTIVE: To construct reference ranges for serial measurements of umbilical artery (UA) blood flow velocity and pulsatility index (PI) at standardized insonation sites during the second half of pregnancy. METHODS: This was a prospective longitudinal study of the umbilical circulation. UA blood flow velocities were measured at the intra-abdominal portion, fetal end and placental end at 4-weekly intervals at 19-42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges using regression statistics and multilevel modeling. RESULTS: UA blood velocities and PI were higher at the intra-abdominal portion and fetal end than at the placental end. The gestational age-related increase of end-diastolic velocity was greater than the corresponding increase of the peak systolic velocity at all locations. The mean differences (delta values) of UA blood velocities between the fetal and placental ends increased and that of PI decreased with advancing gestational age. CONCLUSION: UA Doppler parameters vary significantly at different locations. We have established new reference ranges for the UA velocities and PI at standardized locations based on longitudinal observations, which should be useful for the surveillance of fetuses with repeated observations.

Doppler-derived umbilical artery absolute velocities and their relationship to fetoplacental volume blood flow: a longitudinal study.

OBJECTIVES: To construct reference ranges for serial measurements of the umbilical artery (UA) absolute blood flow velocities in the second half of pregnancy and to test the hypothesis that significant associations exist between UA velocities and placental volume blood flow assessed from umbilical vein blood flow velocities and diameter. METHODS: This was a prospective longitudinal study of the umbilical circulation. UA absolute velocities and umbilical vein blood flow were measured at 4-weekly intervals between 19 and 42 weeks' gestation in 130 low-risk singleton pregnancies. A total of 511 observations were used to construct the reference ranges and assess the association between UA absolute velocities and placental volume flow using multilevel modeling. RESULTS: Both UA absolute velocities and placental volume blood flow showed a steady increase throughout the second half of pregnancy. However, the gestational age-related increase in the UA end-diastolic velocity (EDV) was greater than the corresponding increase in the peak systolic velocity (PSV). The time-averaged intensity-weighted mean velocity (TAWMV)/time-averaged maximum velocity (TAMXV) was 0.6 indicating probably not a completely parabolic velocity profile. There was a significant positive association (P < 0.00001) between UA absolute velocities and placental volume blood flow, but this association was modified by the gestational age. The intraobserver coefficients of variation for the UA PSV, EDV, TAMXV and TAWMV and placental volume blood flow were 10.17%, 16.29%, 11.46%, 18.18% and 8.61%, respectively. CONCLUSION: We have established new reference ranges for the UA absolute velocities based on longitudinal data. They show a significant association with fetoplacental volume blood flow and may have a clinical value in the assessment of the umbilical circulation.

Longitudinal changes in forearm bone mineral density in women and men aged 25-44 years: the Tromsø study: a population-based study.

The aim of this study was to describe and compare bone mineral density (BMD) development in Norwegian women and men aged 25-44 years in a population-based, longitudinal study. BMD was measured twice at distal and ultradistal forearm sites by single x-ray absorptiometry in 258 women and 147 men (mean follow-up time, 6.4 (standard deviation, 0.6) years). At the distal site, a small annual gain of approximately 0.1% became a small loss beginning at age 34 years in men and age 36 years in women. At the ultradistal site, BMD change was predicted by age in women only, and bone loss started at age 38 years. A high degree of tracking of BMD measurements was observed for both sexes and both sites, r > 0.93. Depending on total BMD change, participants were grouped into "losers", "nonlosers", and "gainers", and more than 6% lost more than the smallest detectable amount of BMD: > or =3.46% at the distal site and > or =5.14% at the ultradistal site. In both sexes, bone mineral content (grams) decreased, whereas area (centimeters squared) increased significantly in "losers" compared with "gainers". This finding might represent physiologic compensation preserving bone strength. No cohort effects were observed when 1994 and 2001 measures from similar age groups were compared.

Long-term mental distress, bone mineral density and non-vertebral fractures. The Tromsø Study.

The purpose of this study was to examine, prospectively, the risk of non-vertebral fractures and low bone mineral density in a population-based cohort with respect to indicators of subjective mental distress. In 1979-1980 all males born 1925-1959 and all females born 1930-1959 living in Tromsø were invited (21,441; response rate, 78%). The same individuals were invited to the subsequent studies in 1986-1987 and 1994-1995 (74% attended the first two, and 71% attended all three surveys). Non-vertebral fractures were registered by linkage to the hospital X-ray register for the period 1988-1995, and forearm bone mineral density (BMD) was available in a subsample of 4,690 who had attended three times. Questions about mental distress (depression, insomnia and coping problems) were repeated three times and analyzed as cumulated exposure. Women who reported being depressed at two time points had an adjusted odds ratio (OR) =2.5 (95% confidence interval [CI] 1.3-4.9) for sustaining a non-vertebral fracture and OR=3.1 (95% CI 1.3-7.2) for sustaining an osteoporotic fracture, compared with those without depression on any occasion. The corresponding odds ratios for those with coping problems at two time points were slightly higher, whereas sleeping problems seem only to be weakly associated with non-vertebral fractures. The pattern of associations and the magnitude of OR estimates were mainly the same in women younger than 50 years and those 50 years and older. Women using nerve medicine and reporting depression twice had an odds ratio of 4.4 (95% CI 1.1-17.7) for sustaining a non-vertebral fracture, and those using nerve medicine and reporting coping problems twice had a corresponding OR 4.7 (95% CI 1.2-18.4). Among men no significant associations were found for either fracture type. No association was found between mean BMD and number of times reporting depression, insomnia or coping problems, in women or men. Long-term mental distress is associated with risk of all non-vertebral fractures and osteoporotic fractures in middle-aged women, but not in men. Mental distress itself seems to be more important than the use of nerve medicine.