Single-bed rooms in a geriatric ward prevent delirium in older patients.

BACKGROUND: Few studies have investigated treatment environment risk factors for delirium in geriatric patients. In March 2017, a geriatric department was moved from old hospital buildings with multiple-bed rooms (old wards) to a new hospital with single-bed rooms (new wards), with no changes regarding uptake area, staff and admission criteria. AIMS: The aim of this study was to investigate the risk of delirium among patients in single-bed rooms compared with multiple-bed rooms. METHODS: An observational prospective study included patients aged ≥ 75 years admitted between 15 September 2016 and 19 March 2017 to the old wards and between 20 March and 19 December 2017 to the new wards. Exclusion criteria were terminal illness, somnolence at admission and inability to communicate in Danish. Delirium was assessed by trained nurses, nurse assistants, occupational therapists and physiotherapists every morning and evening using the Confusion Assessment Method (CAM). RESULTS: We included 1014 patients. Patients' characteristics were similar between patients admitted to the old wards and to the new wards. Delirium was present at admission in 105 patients, with no significant difference between the old and new wards. Patients in the new wards had a significantly reduced incidence of delirium during hospital stay compared with patients in the old wards; hazard ratio 0.66 (95% CI 0.48-0.93, p < 0.02). No difference between the old and the new wards was observed in the duration of the first delirium episode. CONCLUSION: We found evidence that the risk of delirium is reduced in single-bed rooms compared with multiple-bed rooms in geriatric wards.

Analgesic and psychoactive medications and the risk of falls in relation to delirium in single-bed rooms compared to multiple-bed rooms in geriatric inpatients.

BACKGROUND: Previously, we demonstrated a substantial reduction of delirium incidence among geriatric patients after relocating from old hospital buildings with multiple-bed rooms to a new hospital with single-bed rooms. AIMS: To investigate whether (1) the reduced incidence of delirium in single-bed rooms was associated with a simultaneous change in medication use, (2) the relocation had affected the incidence of falls, (3) the use of analgesics and psychoactive medications was associated with the risk of delirium and falls. METHODS: We included 461 admissions to the old wards and 553 admissions to the new wards. Delirium was assessed by the Confusion Assessment Method. Data on drug use and falls during hospitalization were extracted from medical records. RESULTS: There was no difference in drug use between the wards. In the new wards, patients who had experienced delirium had a much higher risk of falls than patients without delirium, while in the old wards this contrast was small. The risk of delirium was increased among patients who received antipsychotic drugs and anti-dementia drugs, Patients who received these drugs had an insignificantly increased risk of falls. CONCLUSION: Medication of analgesics and psychoactive drugs was similar in the old and new wards. In single-bed rooms, but not in multiple-bed rooms there was a much higher risk of falls among inpatients that developed delirium than among other patients. Patients who had used antipsychotics and anti-dementia drugs during hospitalization had increased risk of developing delirium and an insignificantly higher risk of falls.

Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality: a nationwide combined clinical and register-based cohort study (The EPICOM study).

AIMS/HYPOTHESIS: The aims of this study were to examine long-term mortality and morbidity rates in mothers with type 1 diabetes, both overall and according to the level of albuminuria prior to pregnancy, the presence of hypertension, pre-eclampsia and periconceptional HbA1c. METHODS: This study was a part of the EPICOM (Environmental Versus Genetic and Epigenetic Influences on Growth, Metabolism and Cognitive Function in Offspring of Mothers with Type 1 Diabetes) study, which is a prospective follow-up study focusing on pregnancies complicated by maternal type 1 diabetes. We carried out a nationwide combined clinical and register-based cohort study of mortality rates and hospital admissions in mothers with diabetes (n = 986) who gave birth between 1992 and 2000. Control mothers (n = 91,441) were women from the background population, matched according to age and year of childbirth. Age at follow-up was 32-66 years. RESULTS: Mortality rate was increased threefold in mothers with diabetes compared with control mothers (HR 3.41 [95% CI 2.42, 4.81]; p < 0.0001), and was also increased with pre-gestational kidney dysfunction (normoalbuminuria, HR 2.17 [95% CI 1.28, 3.68]; microalbuminuria, HR 3.36 [95% CI 0.82, 13.8]; macroalbuminuria, HR 12.9 [95% CI 5.45, 30.7]). Moreover, the presence of hypertension prior to or at any time during pregnancy and of pre-eclampsia also increased mortality rate (hypertension, HR 4.34 [95% CI 2.13, 8.84]; pre-eclampsia, HR 5.55 [95% CI 2.71, 11.4]). Mortality rate also increased with higher levels of HbA1c in early pregnancy (HbA1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA1c <64 mmol/mol (<8%) in the first trimester and normal pre-gestational urinary albumin excretion rate (n = 517), mortality rate was comparable with that of control mothers. Among mothers with diabetes, mortality rate was associated with HbA1c level: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.52 (95% CI 1.19, 1.94; p = 0.001). In mothers with diabetes, the overall incidence of hospital admissions was more than double (incidence rate ratio [IRR] 2.69 [95% CI 2.59, 2.80]; p < 0.0001) that of control mothers, as were admissions with various diagnoses from 14 out of 19 ICD-10 chapters. Among mothers with diabetes, the IRR for hospital admissions increased with the level of HbA1c: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.07 (95% CI 1.04, 1.10; p < 0.0001). CONCLUSIONS/INTERPRETATION: Overall, mothers with type 1 diabetes have a two- to threefold increase in mortality and morbidity rates. HbA1c levels, level of albuminuria around the time of conception, and the presence of hypertension and pre-eclampsia are important risk factors for mortality/morbidity in this cohort. However, it is reassuring that mothers with type 1 diabetes without kidney complications and with HbA1c <64 mmol/mol (<8%) in early pregnancy have a similar survival potential during the period where they are raising their children to that of control mothers from the background population.

Labour outcomes in caseload midwifery and standard care: a register-based cohort study.

BACKGROUND: Research on caseload midwifery in a Danish setting is missing. This cohort study aimed to compare labour outcomes in caseload midwifery and standard midwifery care. METHODS: A historical register-based cohort study was carried out using routinely collected data about all singleton births 2013-2016 in two maternity units in the North Denmark Region. In this region, women are geographically allocated to caseload midwifery or standard care, as caseload midwifery is only available in some towns in the peripheral part of the uptake areas of the maternity units, and it is the only model of care offered here. Labour outcomes of 2679 all-risk women in caseload midwifery were compared with those of 10,436 all-risk women in standard midwifery care using multivariate linear and logistic regression analyses. RESULTS: Compared to women in standard care, augmentation was more frequent in caseload women (adjusted odds ratio (aOR) 1.20; 95% CI 1.06-1.35) as was labour duration of less than 10 h (aOR 1.26; 95% CI 1.13-1.42). More emergency caesarean sections were observed in caseload women (aOR 1.17; 95% CI 1.03-1.34), but this might partly be explained by longer distance to the maternity unit in caseload women. When caseload women were compared to women in standard care with a similar long distance to the hospital, no difference in emergency caesarean sections was observed (aOR 1.04; 95% CI 0.84-1.28). Compared to standard care, infants of caseload women more often had Apgar ≤7 after 5 min. (aOR 1.57; 95% CI 1.11-2.23) and this difference remained when caseload women were compared to women with similar distance to the hospital. For elective caesarean sections, preterm birth, induction of labour, dilatation of cervix on admission, amniotomy, epidural analgesia, and instrumental deliveries, we did not obseve any differences between the two groups. After birth, caseload women more often experienced no laceration (aOR 1.17; 95% CI 1.06-1.29). CONCLUSIONS: For most labour outcomes, there were no differences across the two models of midwifery-led care but unexpectedly, we observed slightly more augmentation and adverse neonatal outcomes in caseload midwifery. These findings should be interpreted in the context of the overall low intervention and complication rates in this Danish setting and in the context of research that supports the benefits of caseload midwifery. Although the observational design of the study allows only cautious conclusions, this study highlights the importance of monitoring and evaluating new practices contextually.

Black or white coffee before anaesthesia?: A randomised crossover trial.

BACKGROUND: In current preoperative fasting guidelines, coffee with milk is still regarded by many as solid food. Evidence on the consequences for gastric volume of adding milk to coffee 2 h before anaesthesia is still weak. OBJECTIVES: The aim of this study was to compare the gastric volume by MRI in healthy volunteers after drinking coffee with and without added milk. DESIGN: A randomised crossover trial where all participants were exposed to three coffee and milk mixtures performed as a noninferiority study with a predefined noninferiority limit of 12 ml. SETTING: Department of Day Surgery and Department of Radiology, Aarhus University Hospital, Aarhus, Denmark. The study was conducted between August 2013 and February 2014. PARTICIPANTS: Total 32 healthy volunteers, aged 18 to 71 years. INTERVENTIONS: The participants fasted for 6 h for solid food, and 2 h before the MRI examination of gastric volume, each participant ingested one of three coffee mixtures: 175 ml coffee, including either 0 or 20 or 50% full fat milk. Each participant was studied by MRI three times separated by a minimum time interval of 2 days. The order of coffee mixture ingested was determined by random allocation. MAIN OUTCOME MEASURE: Gastric volume as measured by MRI. RESULTS: The mean gastric volume for black coffee was 27.8 ml, for coffee with 20% milk 17.9 ml and for coffee with 50% milk 20.6 ml. Compared to black coffee, the gastric volume for 20% milk was significantly decreased with a difference of -10.0 ml (95% confidence interval, -18.2, -1.8), and for 50% milk it was insignificantly decreased, -7.2 ml (95% confidence interval, -17.4, +2.9). The upper confidence interval for the difference in gastric volume between the 'no milk added' group and each 'milk added' group did not reach the noninferiority limit of 12 ml. CONCLUSION: The study provides evidence that adding up to 50% full fat milk to coffee leads to no or only a minimal increase of the gastric volume 2 h later. The results support a liberalisation of policy on the addition of milk to hot drinks before planned anaesthesia. TRIAL REGISTRATION: www.Clinicaltrials.gov identifier: NCT02361632.

Age-dependent thrombin generation predicts 30-day mortality and symptomatic thromboembolism after multiple trauma.

Trauma-induced coagulopathy (TIC) is a risk factor for death and is associated with deviations in thrombin generation. TIC prevalence and thrombin levels increase with age. We assayed in vivo and ex vivo thrombin generation in injured patients (n = 418) to specifically investigate how age impacts thrombin generation in trauma and to address the prognostic ability of thrombin generation. Biomarkers of thrombin generation were elevated in young (< 40 years) and older (≥ 40 years) trauma patients. In vivo thrombin generation was associated with Injury Severity Score (ISS) and this association was stronger in young than older patients. In vivo thrombin generation decreased faster after trauma in the young than the older patients. Across age groups, in vivo thrombin generation separated patients dying/surviving within 30 days at a level comparable to the ISS score (AUC 0.80 vs. 0.82, p > 0.76). In vivo and ex vivo thrombin generation also predicted development of thromboembolic events within the first 30 days after the trauma (AUC 0.70-0.84). In conclusion, younger trauma patients mount a stronger and more dynamic in vivo thrombin response than older patients. Across age groups, in vivo thrombin generation has a strong ability to predict death and/or thromboembolic events 30 days after injury.

Increased morbidity evaluated on hospital contacts and prescriptions among 100,834 Danish breast cancer survivors.

BACKGROUND: Cardiovascular disease competes with breast cancer (BC) as the leading cause of death for females diagnosed with breast cancer. Not much is known concerning morbidity and medicine use in the short and long term after a BC diagnosis. AIM: The aim of this study was to determine acute and long-term morbidity in Danish women treated for BC. METHOD: A nationwide registry-based cohort study of 100,834 BC patients identified in the clinical database of Danish Breast Cancer Cooperative Group (DBCG) and 1,100,320 (10 per patient) age-matched Danish women without BC, serving as controls. Morbidity was studied using complete data on hospital contacts and medicinal use. RESULTS: The risk of hospital contacts was significantly increased in BC survivors compared with controls evaluated both by means of Cox regression and negative binomial regression analysis both during and after cessation of breast cancer treatment. Young age at breast cancer diagnosis was associated with the most pronounced increase in risk of hospital contacts, both during and after cessation of BC treatment. Medicinal use was significantly increased among BC patients compared to controls, both during (HR 1.27 (1.26-1.28), p < 0.0001) and after BC treatment (HR 1.18 (1.17-1.19), p < 0.0001, and present for all subgroups of medicine. CONCLUSION: Overall, BC survivors have a pronounced increase in hospital contacts and medicinal use compared to women without BC. Premenopausal status at BC diagnosis was associated with an overall higher excess morbidity and a higher burden both during and after treatment.

Socio-economic factors affect mortality in 47,XYY syndrome-A comparison with the background population and Klinefelter syndrome.

Mortality among males with 47,XYY is increased due to a host of conditions and diseases. Clinical studies have suggested a poorer educational level and social adaptation among 47,XYY persons. We wanted to study the socio-economic profile in 47,XYY persons and the impact on mortality. We conducted a register study using several Danish nationwide registries. 206 47,XYY men and 20,078 controls from the background population and 1,049 controls with Klinefelter syndrome were included. Information concerning marital status, fatherhood, education, income, and retirement were obtained. Compared to the background population, 47,XYY men had fewer partnerships, were less likely to become fathers, had lower income and educational level, and retired at an earlier age. The mortality among 47,XYY men was significantly increased with a hazard ratio (HR) of 3.6 (95% confidence interval: 2.6-5.1). Adjusting for marital and educational status reduced this HR to 2.7. Compared to Klinefelter syndrome, 47,XYY had significantly fewer partnerships, were more likely to become fathers, but had lower income. Mortality among 47,XYY men was increased compared with Klinefelter syndrome with a HR of 1.36. The results show a severely inferior outcome in all investigated socio-economic parameters compared to the background population and an affected profile compared with Klinefelter syndrome, even though the population in Denmark has equal and free access to health care and education. We conclude that 47,XYY is often associated with a poorer socio-economic profile, which partly explains the increased mortality.

Disorders of the eye, ear, skin, and nervous system in women with Turner syndrome -a nationwide cohort study.

The literature about eye, ear, nose, skin, and nervous system disorders in women with Turner syndrome is equivocal. Impaired vision and hearing in women with Turner syndrome have been described, and case reports of Turner syndrome girls suffering from epilepsy have been published, but no large population-based-studies have explored the occurrence of any of these disorders. We aimed to investigate the risk of admission with disorders related to the eye, ear, nose, skin, and nervous system, compared with background females, and the impact of hormone replacement therapy on these conditions. 1,156 females with TS diagnosed during 1960-2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115,577 age-matched background females. Negative binomial regression was used to analyze hospital discharge diagnoses, reporting incidence rate ratios (IRR). Women with Turner syndrome have an increased risk of developing eye disorders (IRR 4.3 (95% CI 3.5-5.4), including cataract, glaucoma, ocular movement, and accommodation. The risk of ear disorders (IRR 35.0 (27.9-43.9)) and nose (IRR 2.2 (1.4-3.6)) was increased in women with Turner syndrome, due to otitis media, cholesteatoma, and hearing loss. Disorders of the nervous system such as epilepsy were increased IRR 6.2 (2.4-15.9), along with skin conditions IRR 2.2 (95%CI 1.7-2.7) like psoriasis, atopic dermatitis, and ingrown nails.

Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy.

OBJECTIVE: Although the overall risk of cancer is not increased in Turner syndrome, the pattern of cancer occurrence differs from the general population. We aim to describe the cancer morbidity pattern in Turner syndrome and evaluate the effect of long-term hormone replacement therapy (HRT). DESIGN: Nationwide epidemiological study. METHODS: 1156 females with Turner syndrome diagnosed during 1960-2014, were linked with data from the Danish National Patient Registry. Statistics Denmark randomly identified 115 578 female controls. Stratified Cox regression was used to analyze cancer morbidity, mortality and effect of HRT. RESULTS: Overall risk of cancer was not elevated (hazard ratio 1.04 (95% CI: 0.80-1.36)). The risk of skin cancer and benign skin neoplasms was two-fold increased, while the risk of breast cancer was decreased (hazard ratio 0.4 (0.2-0.9)). Turner syndrome (45,X) had a two- to five-fold increased risk of benign CNS tumors, colon and rectal cancers, benign skin neoplasms and skin cancer. Turner syndrome women with a 45,X/46,XX karyotype had an increased risk of tongue cancer. HRT had no impact on the risk of any cancer investigated in this study. CONCLUSIONS: The lack of one X chromosome might play a role in skin neoplasms, CNS tumors, colon and rectal cancers. The risk of breast cancer is lower than in the general population. Long-term HRT during the premenopausal age range seems not to exert a cancerous effect in Turner syndrome. Increased vigilance concerning specific types of cancer in Tuner syndrome harboring a 45,X karyotype is needed.

Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome - a nationwide cohort study.

BACKGROUND: Liver and gastrointestinal diseases are frequent in women with Turner syndrome. However, their association with bleeding disorders, anaemia and the impact of hormone replacement therapy is unknown. AIMS: To investigate the risk of liver and gastrointestinal diseases, haemorrhage and anaemia in women with Turner syndrome compared with the female background population, and the long-term impact of hormone replacement therapy on these conditions. METHODS: One thousand one hundred and fifty-six women with Turner syndrome diagnosed during 1960-2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115 577 age-matched female controls. Negative binomial regression was used to analyse hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression. RESULTS: Liver disease increased 13-fold (IRR 12.9 (95% CI 5.8-28.8)), due to toxic liver disease (IRR 8.0 (95% CI 1.8-35.4)), liver insufficiency (IRR 6.7 (95% CI 1.7-26.9)), fibrosis/cirrhosis (IRR 16.5 (95% CI 2.2-122.1)) and unspecified liver disease (IRR 10.6 (95% CI 4.4-25.3)). Furthermore, presence of abnormal liver enzymes increased 12-fold (IRR 12.4 (95% CI 4.2-36.6)). The risk of gastrointestinal haemorrhage (IRR 3.4 (95% CI 1.8-6.2)), anaemia (IRR 3.2 (95% CI 2.0-5.0)) and coagulation disorders (IRR 2.9 (95% CI 1.1-7.1)) was increased. However these diagnoses were not associated with inflammatory bowel disease. Gastrointestinal mortality was increased three-fold (HR 3.1 (95% CI 1.5-6.2)), partly due to death by liver disease (HR 3.0 (95% CI 1.1-8.2)), gastrointestinal haemorrhage (HR 29.6 (95% CI 3.1-285.1)) and capillary malformations (HR 18.6 (95% CI 4.1-85.0)). There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases. CONCLUSIONS: The risk of being diagnosed with liver disease was higher than previously reported. The occurrence of gastrointestinal haemorrhage and anaemia was increased in Turner syndrome. There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases was detected.

Human kidney graft survival correlates with structural parameters in baseline biopsies: a quantitative observational cohort study with more than 14 years' follow-up.

This prospective cohort study evaluates associations between structural and ultrastructural parameters in baseline biopsies from human kidney transplants and long-term graft survival after more than 14 years' follow-up. Baseline kidney graft biopsies were obtained prospectively from 54 consecutive patients receiving a kidney transplant at a single institution. Quantitative measurements were performed on the baseline biopsies by computer-assisted light microscopy and electron microscopy. Stereology-based techniques estimated the fraction of interstitial tissue, the volume of glomeruli, mesangial fraction, and basement membrane thickness of glomerular capillaries. The fraction of occluded glomeruli and scores according to the Banff classification were achieved. Kidney graft survival was analyzed by Kaplan-Meier estimates and Cox regression. Association to long-term kidney function was also analyzed. The long-term surviving kidney transplants were characterized at implantation by less arteriolar hyaline thickening (P < 0.001) and less interstitial fibrosis (P = 0.001), as well as a lower fraction of occluded glomeruli (P = 0.004) and lower glomerular volume (P = 0.03). At the latest follow-up, eGFR was decreased by 12 ml/min/1.73 m2 per unit increase in the score for arteriolar hyalinosis at implantation (P = 0.02), and eGFR was decreased by 19 ml/min/1.73 m2 per 106 µm3 increase in glomerular volume at baseline (P = 0.03). The unbiased Cavalieri estimate of glomerular volume and the ultrastructural parameters are the first to be evaluated in a cohort study with prospective follow-up for more than 14 years. The study shows that baseline biopsies from human kidney grafts contain extraordinary long-term prognostic information, and it highlights the importance of these intrinsic graft factors.

Mortality and incidence in women with 47,XXX and variants.

47,XXX syndrome is among the most common sex chromosomal disorders; however, apart from screening surveys, epidemiological data are limited. We report data on 136 women diagnosed with 47,XXX or a compatible karyotype in Denmark during 1963-2008. We identified an incidence of 10.7 per 100,000 liveborn girls, which was lower than expected and was stable during the study period. Age at diagnosis ranged from 0 to 73 years, with a diagnostic delay of 18.2 years or more in half the 47,XXX persons. We compared persons with 47,XXX with an age-matched cohort of the female background population (born same year and month), identified in Statistics Denmark (n = 13,400). Mortality was significantly increased in total with a hazard ratio of 2.5 (1.6-3.9), corresponding to a difference in median survival of 7.7 years. When we divided causes of death into 19 chapters according to the International Classification of Diseases, a generally increased mortality was identified in all informative chapters. Furthermore, we identified significantly increased mortality in cardiovascular diseases, in the chapter concerning chromosomal and congenital defects, and in the chapter of unspecified diseases. Better delineation of the clinical phenotype of 47,XXX is needed; available information does not readily explain the increased mortality.

Self-rated health and functioning in patients with chronic renal disease.

INTRODUCTION: Chronic renal disease is associated with high morbidity and mortality and with considerable economic costs, and it has an extensive influence on patients' everyday lives. The aim of this study was to investigate self-rated health and functioning in patients with chronic renal disease which may serve as a baseline for continuous monitoring of self-rated health and functioning. MATERIAL AND METHODS: A total of 227 patients aged 18 years or older with chronic renal disease in predialysis and haemodialysis treatment participated in a cross-sectional study. The study included a questionnaire and data from hospital records, a laboratory register and the Danish National Patient Registry. RESULTS: Self-rated health and functioning were lower among study participants than in the general Danish population. Among patients below the age of 65 years, 57% of those who were in predialysis and 16% of those receiving haemodialysis treatment were employed. Predictors of disability were haemodialysis, being diagnosed with diabetes, and increasing age. A total of 33% received community home help services, 25% primary nursing and 10% community rehabilitation services. CONCLUSION: In this study information about self-rated health and functioning was collected among patients with chronic renal disease; this information may supplement continuously collected clinical data on patients who are in active treatment for chronic renal failure. Data from this study can form the basis for planning and for quality control intervention aimed at maintaining or improving functioning in patients with chronic renal disease.

What are the effects of supporting early parenting by newborn behavioral observations (NBO)? A cluster randomised trial.

BACKGROUND: Professional support to enhance the early parent-infant relationship in the first months after birth is recommended, but little is known about the effect of universal interventions. The objective was to investigate the effect of health visitors' use of the Newborn Behavioral Observations system in new families. METHODS: A cluster-randomised study was conducted in four Danish municipalities. Health visitors' geographical districts constituted the units for randomisation (n = 17). In the intervention group, 1332 families received NBO from 3 weeks after birth; in the comparison group, 1234 received usual care. Self-administered questionnaires were collected at baseline one to two weeks after birth, and at follow-up three and nine months postpartum. The outcomes were change over time measured by The Karitane Parenting Confidence Scale (KPCS), The Major Depression Inventory (MDI), The Ages and Stages Questionnaire: social-emotional (ASQ:SE) and The Mother and Baby Interaction Scale (MABIC). Data were analysed with mixed-effects linear regression using the intention-to-treat approach. RESULTS: At baseline, no significant differences between the two groups were seen regarding maternal and infant factors. At follow-up three and nine months after birth, the change in maternal confidence and mood, infant's socio-emotional behaviour, and early parent-infant relationship moved in a slightly more positive direction in the intervention group than in the comparison group, though not statistically significant. The only significant effect was that the intervention mothers reported higher level of knowledge about infant's communication skills, response to cues, and how to sooth and establish a relation with the infant, compared to the comparison group. CONCLUSIONS: We found no effect of the NBO system delivered in a universal context to all families in a community setting. The only significant difference between groups was a higher maternal degree of knowledge regarding early parenting in the intervention group. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03070652 . Registrated February 22, 2017.

Sex Hormone Replacement Therapy in Turner Syndrome: Impact on Morbidity and Mortality.

CONTEXT: The long-term effects of female hormone replacement therapy (HRT) in Turner syndrome (TS) are unknown. OBJECTIVE: To examine morbidity, mortality and medicinal use in TS and the impact of HRT in 45,X women. DESIGN AND SETTING: National cohort study, following all TS individuals ever diagnosed in Denmark from 1977 to 2014. PATIENTS AND METHODS: In the Danish Cytogenetic Central Registry, we identified 1156 females diagnosed with TS from 1960 to 2014, and, subsequently, Statistics Denmark randomly identified 115 577 age-matched female controls. TS women and their matched controls were linked with person-level data from the National Patient Registry and the Medication Statistics Registry, and they were compared concerning mortality, hospitalizations, and medical prescriptions. Among 329 45,X women, 44 had never been HRT treated, and 285 had been treated at some point. HRT treated women were compared with untreated concerning mortality, hospitalizations, and medical prescriptions. RESULTS: Endocrine and cardiovascular mortality and morbidity were significantly increased in TS compared with the matched controls. Comparing HRT treated with nontreated 45,X women, we found a similar mortality (hazard ratio 0.83, 95% confidence interval 0.38-1.79). Among the HRT-treated 45,X women, we found a significantly lower use of antihypertensives, antidiabetics, and thyroid hormones and significantly reduced hospitalization rates for stroke and osteoporotic fractures. CONCLUSION: Women with TS have an increased overall mortality and morbidity. HRT seems to have a beneficial effect on endocrine conditions, hypertension, and stroke in women with 45,X karyotype, with no clear impact on mortality.

Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk.

OBJECTIVES: Klinefelter syndrome (KS), 47,XXY, can be viewed as a disease model for investigating the risk of thrombosis in male hypogonadism and the subsequent risk related to testosterone treatment. We describe rates of thrombotic risk factors, thrombosis and thrombosis mortality in KS and the association with testosterone treatment. METHODS: National registry-based matched cohort study with follow-up from 1995 to 2016 set in Denmark. For the study, 1155 men with KS were each matched by year and month of birth to 100 men from the background population. First thrombotic events and thrombosis mortality was evaluated by event rates and hazard ratios (HRs) and by applying testosterone treatment as a time-dependent covariate. RESULTS: The KS cohort had higher incidence of venous thromboembolism relative to the comparison cohort (HR, 3.95; 95% CI, 2.83-5.52). Total thrombotic deaths were increased in KS (HR, 1.76; 95% CI, 1.18-2.62), and all-cause mortality was increased in KS following arterial thrombosis (HR 1.73; 95% CI 1.22-2.47). Only 48.7% of men with KS redeemed prescriptions for testosterone. Untreated men with KS were on average born 12 years before those treated, and the majority of untreated men with KS with available biochemistry were hypogonadal. Testosterone treatment in KS was associated with a non-significant decrease in venous thromboembolism and thrombotic deaths. CONCLUSION: Thrombosis and thrombotic deaths are increased in KS. Only half of the men with KS ever received testosterone treatment, despite overt hypogonadism in the non-treated. Testosterone treatment in Klinefelter syndrome was insignificantly associated with lower incidence rates of venous thrombosis and thrombotic deaths.

Tinzaparin for the treatment of foetal growth retardation: An open-labelled randomized clinical trial.

OBJECTIVE: Foetal growth retardation (FGR) is a leading cause of perinatal death and long-term harms at survivors. Placental infarction plays a role in FGR, yet, no trials have evaluated whether low molecular weight heparins increase birth weight in ongoing FGR pregnancies. METHODS: An open-labelled randomized trial in Denmark during 2011-2016, including singleton pregnant women with FGR (estimated foetal weight < 2.3 percentile) diagnosed before gestational weeks 32. Participants were randomly assigned using sealed, blinded envelopes 1:1 to tinzaparin (4500 IU daily until 37 gestational weeks) or no tinzaparin. The primary outcomes were the observed birthweight relative to the expected for gestational age and gender, and foetal growth rates in the two trial groups evaluated by an intention to treat analysis. RESULTS: We enrolled 53 women. The mean gestational age was 261 days in the tinzaparin group and 246 days in the no treatment group. The mean birth weight was 2229 g in the tinzaparin group compared to 1968 g in the no treatment group. However, the birth weight relative to the expected from gestational age and gender was only 2.5 percentage points higher in the tinzaparin group [-5.1 to 10.0] (p = 0.51). The foetal growth rate during follow-up was 124 g/week in the tinzaparin group and 119 g/week in the no treatment group, a difference of 5 g/week [-19 to 29] (p = 0.67). Two perinatal deaths both occurred in the no treatment group. CONCLUSION: We found no evidence of a tinzaparin effect on the foetal growth rate or the birth weight after adjustment for gestational age.

Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses.

BACKGROUND: Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder in man; it affects approximately one in 660 men and is a common cause of hypogonadism and infertility. Our current knowledge of morbidity in KS is based on observational studies and case reports and therefore is limited. DESIGN: We used Danish registers to obtain dates of hospital admissions and discharge diagnoses in a cohort of all males diagnosed with KS in Denmark and a randomly selected, age-matched control group. Our cohort consisted of 832 KS subjects and 4033 control subjects, contributing with a total of approximately 100,000 person years. We used stratified Cox regression analysis on main groups of diagnoses. Where significant results were found, subsequent analyses were performed on subgroups of diagnoses. RESULTS: We found a significantly increased risk of being hospitalized among the KS subjects [hazard ratio (HR), 1.69; 95% confidence interval, 1.54-1.86]. The increased admission risk was present in all but one of the main diagnosis groups, with the highest HRs for congenital malformations (HR, 10.7), psychiatric disorders (HR, 3.7), and endocrine and metabolic disorders (HR, 3.2). We compared hospitalization rates before and after the diagnosis of KS and found that the increased rate was present even before the diagnosis of KS. CONCLUSIONS: Males suffering from KS experienced an increased hospitalization rate from a variety of disorders. Some are likely to be caused by hypogonadism, and some may be linked to the syndrome per se, whereas others are not readily explained. However, other factors, e.g. socioeconomic, may be involved.

Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome.

AIM: Our aim was to study prevalence, incidence, age at diagnosis, and mortality in Turner syndrome (TS) in Denmark. METHODS: Using the Danish Cytogenetic Register, we identified all cases (n = 781) of TS alive in Denmark during 1970-2001. Sixty-nine deceased women with TS were identified in the Causes of Death Register. We divided the cohort into women having the karyotype 45,X, karyotypes including an isochromosome Xq, and all other karyotypes associated with TS. We describe the number of patients diagnosed in Denmark yearly, incidence rates, and the age at diagnosis. Standardized mortality ratios (SMR) were calculated. RESULTS: A total of 349 women had a 45,X karyotype, 86 had a karyotype including an isochromosome Xq (isoXq), and 346 had another TS karyotype. Mortality was increased in TS with an SMR of 2.86 (95% confidence interval, 2.18-3.55). SMR was increased for coronary diseases, congenital malformations, endocrine diseases, and other causes. The mortality was increased for all types of karyotypes in comparison with the general population but was highest among females with 45,X and isoXq. There was a steady increase in prevalence, but incidence was unchanged. Age at diagnosis was mainly distributed in three periods: less than 1 yr of age (14.9%), during adolescence (10-17 yr) (33.2%), and during adulthood (38.5%), with a median age at diagnosis of 15.1 yr, decreasing during the study period (P < 0.01). CONCLUSIONS: Patients with TS and especially the karyotypes 45,X and isoXq have a higher mortality compared with the background population. TS was diagnosed with a considerable diagnostic delay. Prevalence is increasing, but incidence of TS was stable.