Even minor alteration of plasma creatinine after open abdominal surgery is associated with 30-day mortality: A single-centre cohort study.

PURPOSE: Postoperative acute kidney injury is common and associated with increased length of hospital stay, costs and mortality. The impact from postoperative subclinical changes in plasma concentration of creatinine (p-creatinine) on postoperative mortality has received less attention. In this study, the association between the postoperative change of p-creatinine and all-cause mortality was investigated. METHODS: A single-centre register-based, retrospective study was conducted including patients ≥60 years undergoing open abdominal surgery from 2000 to 2013. Postoperative p-creatinine change was analysed for association with 30-day mortality following adjustment for age, gender, surgical setting and surgical procedure. Main findings A total of 3,460 patients were included in the study of whom 67.6% underwent emergency surgery. The 30-day mortality rate was 18.3%, and a given 10µmol/L daily postoperative increase in p-creatinine was associated with an increased mortality risk with an odds ratio (OR) of 2.67 (95% CI; 2.28-3.14, P<0.001). In patients undergoing emergency surgery, a daily 10µmol/L increase in p-creatinine increased the risk for a fatal outcome a 2.39 OR (CI 95%; 2.05-2.78), P<0.001). In patients undergoing elective surgery, a similar increase in p-creatinine increased risk of postoperative death with a 28.85 OR (CI 95%; 10.25-81.19). CONCLUSION: Even a minor postoperative p-creatinine increase following open abdominal surgery below the criteria for acute kidney injury was associated with increased 30-day mortality in patients aged 60 years or above.

Preoperative Hypoalbuminemia Predicts Early Mortality Following Open Abdominal Surgery in Patients Above 60 Years of Age.

BACKGROUND: Major abdominal surgery in older and frail patients is associated with considerable morbidity and mortality. Plasma albumin is routinely measured in the clinic and has been proposed as an indicator of frailty. This study aimed to investigate if plasma albumin is a predictor of mortality in older patients undergoing open abdominal surgery. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study of patients, aged ⩾60 years who underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1st, 2000 to May 31st, 2013 were consecutively identified in the Danish National Patient Registry. Plasma albumin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. RESULTS: 3,639 patients were included of whom 68.2% underwent emergency surgery. The rate of severe hypoalbuminemia (plasma albumin < 28 g/L) was 43.4%. Preoperative plasma albumin was lower in patients with a fatal 30-day outcome (mean 20.6 g/L vs 30.1 g/L in survivors, p < 0.0001). Other independent predictive parameters of 30-day mortality were age, male sex, and emergency surgery. We present an algorithm including these four variables for the prediction of 30-day mortality for patients aged ⩾60 years undergoing open abdominal surgery. CONCLUSION: Preoperative plasma albumin is a predictor of 30-day mortality in patients above 60 years of age following open abdominal surgery. Assessment of plasma albumin in conjunction with other risk factors such as age, sex, and surgical priority may improve preoperative decision-making.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

History of cardiovascular disease and cardiovascular biomarkers are associated with 30-day mortality in patients with hip fracture.

Hip fractures are associated with increased mortality and it is important to identify risk factors. This study demonstrates that preexisting cardiovascular disease as well as cardiovascular biomarkers that are associated with increased 30-day mortality. These findings can be used to identify high-risk patients who might benefit from specialized care. INTRODUCTION: This study investigates the association between cardiovascular disease (CVD), cardiovascular biomarkers, and 30-day mortality following a hip fracture. METHODS: The Danish National Patient Registry was used to investigate the association between CVD and mortality following hip fracture in a nationwide population-based cohort study. In a subset of the included patients (n = 355), blood samples were available from a local biobank. These samples were used for analyzing the association between specific biochemical markers and mortality. The primary outcome was 30-day mortality. RESULTS: A total of 113,211 patients were included in the population-based cohort study. Among these, heart failure was present in 9.4%, ischemic heart disease in 15.9%, and ischemic stroke in 12.0%. Within 30 days after the hip fracture, 11,488 patients died, resulting in an overall 30-day mortality of 10.1%. The 30-day mortality was significantly increased in individuals with preexisting CVD with multivariably adjusted odds ratios of 1.69 (95% confidence interval, 1.60-1.78) for heart failure, 1.23 (1.17-1.29) for ischemic heart disease, and 1.06 (1.00-1.12) for ischemic stroke. In the local database including 355 patients, 41 (11.5%) died within 30 days. The multivariably adjusted odds ratio for 30-day mortality increased with increasing NT-proBNP (2.36 [1.53-3.64] per quartile) and decreased with increasing HDL cholesterol (0.58 [0.41-0.82] per quartile). On this basis, we established a model for predicting the probability of death based on the biochemical markers. CONCLUSION: Preexisting CVD was associated with increased 30-day mortality after a hip fracture. Furthermore, high levels of NT-proBNP and low levels of HDL cholesterol were associated with increased 30-day mortality.

Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock.

The endocrine body rhythms including the hypothalamic-pituitary-thyroid axis seem to be regulated by the circadian timing system, and daily rhythmicity of circulating thyroid-stimulating hormone (TSH) is well established. The circadian rhythms are generated by endogenous clocks in the central brain oscillator located in the hypothalamic suprachiasmatic nucleus (SCN) as well as multiple peripheral clocks, but information on the existence and function of a thyroid clock is limited. The molecular machinery in all clock cells is composed of a number of clock genes and their gene products are connected by autoregulatory feedback loops. Here, we provide evidence for a thyroid clock in the rat by demonstrating 24-h antiphase oscillations for the mRNA of the canonical clock genes Per1 and Bmal1, which was unaffected by hypophysectomy. By immunostaining, we supported the existence of a core oscillator in the individual thyroid cells by demonstrating a daily cytoplasmatic-nuclear shuttling of PER1 protein. In normal rats, we found a significant daily rhythmicity in the circulating thyroid hormones preceded by a peak in TSH. In hypophysectomised rats, although the thyroid clock was not affected, the oscillations in circulating thyroid hormones were abolished and the levels were markedly lowered. No daily oscillations in the expression of TSH receptor mRNA were observed in neither control rats nor hypophysectomised rats. Our findings indicate that the daily rhythm of thyroid hormone secretion is governed by SCN signalling via the rhythmic TSH secretion rather than by the local thyroid clock, which was still ticking after hypophysectomy.

Hyponatremia and hypernatremia are associated with increased 30-day mortality in hip fracture patients.

UNLABELLED: Using data from the Danish national registries on 7317 patients, this study shows that abnormal plasma sodium levels, in the form of hyponatremia and hypernatremia, are prevalent and associated with increased 30-day mortality in hip fracture patients. INTRODUCTION: The aim of this study was to examine the prevalence of hyponatremia and hypernatremia in patients admitted with a fractured hip as well as the association with 30-day in mortality in these patients. METHODS: A total of 7317 hip fracture patients (aged 60 years or above) with admission plasma sodium measurements were included. Data on comorbidity, medication, and death was retrieved from Danish national registries. The association between plasma sodium and mortality was examined using Cox proportional hazard models. RESULTS: The prevalence of hyponatremia and hypernatremia on admission was 19.0 and 1.7 %, respectively. Thirty-day mortality was increased for patients with hyponatremia (12.2 %, p = 0.005) and hypernatremia (15.5 %, p = 0.03) compared to normonatremic patients (9.6 %). After adjustment for possible confounding factors, hyponatremia (1.38 [1.16-1.64], p = 0.0003) and hypernatremia (1.71 [1.08-2.70], p = 0.02) were still associated with increased risk of death by 30 days. Looking at the association between changes in plasma sodium during admission and mortality, there was no difference between patients with normalized and persistent hyponatremia (10.4 vs 11.3 %, p = 0.6) while a lower mortality was found for normalized hypernatremia compared to persistent hypernatremia (12.4 vs 33.3 %, p = 0.03). CONCLUSIONS: This study shows that abnormal plasma sodium levels are prevalent in patients admitted with a fractured hip and that both hyponatremia and hypernatremia are associated with increased risk of death within 30 days of admission.

Age and weight at final discharge from an early discharge programme for stable but tube-fed preterm infants.

AIM: Preterm birth is often associated with prolonged hospitalisation, complicating the parent-child relationship and breastfeeding rates. As a result, an early discharge programme was implemented in the department of neonatology at Rigshospitalet. The infants were stable, but required tube feeding, and during the programme, they received home visits by neonatal nurses. We evaluated the programme, focusing on the infants' well-being, using weight gain, breastfeeding rates and total duration of hospitalisation as outcomes. METHODS: Over an 11-year period, 500 infants participated in the programme and they constituted the early discharge group. They were compared with 400 infants discharged from the Naestved and Nykoebing Falster hospitals. RESULTS: The early discharge group's length of hospitalisation was only three days shorter than the comparison group, but they were eight days younger when they joined the programme (p < 0.0001). Total admission was 21 days longer (p < 0.0001). There was no difference in weight-for-age at discharge (p = 0.15), but infants in the early discharge group were more frequently fully or partly breastfed (88% versus 80%, p < 0.005). CONCLUSION: While recognising the limited comparability of the two groups, weight-for-age at discharge was similar, but the programme appeared to allow better breastfeeding success at the expense of a later final discharge.

Trauma treatment in a role 1 medical facility in Afghanistan.

BACKGROUND: Most of the emergency care delivered in Afghanistan is currently provided by the military sector and non-governmental organisations. Main Operating Base (MOB) Price in Helmand Province has a small medical centre and due to its location provides critical care to civilians and military casualties and this article describes the patterns in trauma patient care at the MOB Price medical centre regarding the types of patients and injuries. MATERIALS AND METHODS: The study population consists of 64 consecutive critically injured patients treated in MOB Price during a 4-month period from September to December 2010. The outcomes were battle-related injuries, treatment received before arriving to MOB Price, types of injury and treatment. RESULTS: There were 35 civilians (12 children and 23 adults), 28 Afghan National Security Forces and one International Security Assistance Force soldier; they were divided into three groups (civilian adults, civilian children and military). 22% of the patients suffered fragmentation injuries and civilians were more likely to incur fragment injury than military personnel (OR (95% CI) 7.04 (1.4 to 34.8)). Regarding intubation, there was a trend towards more civilians needing it than military personnel and significantly more children than adults underwent intubation (OR (95% Cl) 51 (5.2 to 498.5)). Gunshot wounds (GSW) occurred in 30% of the patients. Civilians patients had a lower OR for GSWs than military patients (OR (95% CI) 0.35 (0.1 to 1.1)). Other trends in injury types and treatment were apparent but did not reach significance due to the small number of patients. CONCLUSIONS: Both civilians and military personnel benefitted from the in-theatre Role 1 medical facility treatment. The most frequent injuries were fragmentation damage and GSW.

A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study.

CONTEXT: Optimal levels of vitamin D have been a topic of heavy debate, and the correlation between 25-hydroxyvitamin D [25(OH)D] levels and mortality still remains to be established. OBJECTIVE: The aim of the study was to determine the association between all-cause mortality and serum levels of 25(OH)D, calcium, and PTH. DESIGN AND SETTING: We conducted a retrospective, observational cohort study, the CopD Study, in a single laboratory center in Copenhagen, Denmark. PARTICIPANTS: Serum 25(OH)D was analyzed from 247,574 subjects from the Copenhagen general practice sector. In addition, serum levels of calcium, albumin-adjusted calcium, PTH, and creatinine were measured in 111,536; 20,512; 34,996; and 189,496 of the subjects, respectively. MAIN OUTCOME MEASURES: Multivariate Cox regression analysis was used to compute hazard ratios for all-cause mortality. RESULTS: During follow-up (median, 3.07 yr), 15,198 (6.1%) subjects died. A reverse J-shaped association between serum level of 25(OH)D and mortality was observed. A serum 25(OH)D level of 50-60 nmol/liter was associated with the lowest mortality risk. Compared to 50 nmol/liter, the hazard ratios (95% confidence intervals) of all-cause mortality at very low (10 nmol/liter) and high (140 nmol/liter) serum levels of 25(OH)D were 2.13 (2.02-2.24) and 1.42 (1.31-1.53), respectively. Similarly, both high and low levels of albumin-adjusted serum calcium and serum PTH were associated with an increased mortality, and secondary hyperparathyroidism was associated with higher mortality (P < 0.0001). CONCLUSION: In this study from the general practice sector, a reverse J-shaped relation between the serum level of 25(OH)D and all-cause mortality was observed, indicating not only a lower limit but also an upper limit. The lowest mortality risk was at 50-60 nmol/liter. The study did not allow inference of causality, and further studies are needed to elucidate a possible causal relationship between 25(OH)D levels, especially higher levels, and mortality.

Pain and knee function in relation to degree of bone bruise after acute anterior cruciate ligament rupture.

It is unknown whether the bone bruise that occurs in connection with acute anterior cruciate ligament (ACL) rupture is causing pain and dysfunction. We followed prospectively 17 patients [10 men, seven women, mean age 28 years (range 23-34)] with acute ACL rupture for 2 months. A magnetic resonance imaging (MRI) scan was performed shortly after the injury, and at 2 weeks, 1 month and 2 months. The patients reported the level of pain every day and filled in a Knee injury and Osteoarthritis Outcome Score sheet in connection with MRI. For every MRI of the knee, volume of bone bruise was calculated, and intensity was visually graded. Our study showed a reduction of the pain to 50% approximately 2 weeks after the injury, at which time the bone bruise was at maximum. There was a significant relationship between pain and the volume and intensity of the bone bruise in the medial tibia condyle, as well as pain and the bone bruise volume of the lateral femoral condyle. Patients with bone bruise of the medial tibia and patients with meniscal lesions had more pain. It is suggested that pain and decreased function after acute ACL injury most likely is related to soft tissue and cartilage injury and not to bone bruise.

Acute and long-term estradiol kinetics in smoking postmenopausal women.

AIM: We aimed to study 2-h estrogen kinetics in smoking versus non-smoking postmenopausal women receiving estrogen therapy. Moreover, we wished to study estrogen concentrations over 2 years in smokers using ten or fewer cigarettes daily versus non-smokers in postmenopausal women on estrogen treatment. METHOD: We used post-hoc analyses from two randomized trials. In study I, we included 150 women from three groups receiving therapies containing 1 or 2 mg 17ß-estradiol, where trough and 2-h blood samples was collected in cycles 1, 7 and 13. In study II, we included 94 completing women who had received either placebo or a regimen containing 1 mg 17ß-estradiol. RESULTS: In study I, 35% were smokers. At 2 h post tablet intake, serum estrone and estradiol concentrations were significantly lower in smokers as compared to non-smokers, i.e. mean serum estrone was 212 pg/ml (95% confidence interval (CI) 177-247 pg/ml) in smokers as opposed to 318 pg/ml (95% CI 278-359 pg/ml) in non-smokers on 1 mg estradiol (p = 0.0002). In study II, 19% were smokers. In the estrogen group, smoking lead to significantly lower levels of both serum estrone and serum estradiol at all post-randomization time points. No differences between smokers and non-smokers were seen on placebo. CONCLUSION: We conclude that smoking reduces serum estrogens at both trough and after 2 h in postmenopausal women on estrogen treatment. The effect of smoking on estrogen concentrations is fully expressed in women smoking ten or less cigarettes daily. These findings indicate that the influence of smoking upon the metabolism of estrogen therapy is constant and without dose-response for standard smoking intensities.

Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia.

The impact of HIV-1 co-infection on long-term mortality in patients with hepatitis C: a population-based cohort study.

OBJECTIVE: To investigate the impact of HIV co-infection on mortality in patients infected with hepatitis C virus (HCV). METHODS: From a nationwide Danish database of HCV-infected patients, we identified individuals diagnosed with HCV subsequent to an HIV diagnosis. For each co-infected patient, four control HCV patients without HIV were matched on age, gender and year of HCV diagnosis. Data on comorbidity, drug abuse, alcoholism and date of death were extracted from two healthcare databases. We constructed Kaplan-Meier curves and used Cox regression analyses to estimate mortality rate ratios (MRRs), controlling for comorbidity. RESULTS: We identified 483 HCV-HIV co-infected and 1932 HCV mono-infected patients, yielding 2192 and 9894 person-years of observation with 129 and 271 deaths, respectively. The 5-year probability of survival was 0.74 [95% confidence interval (CI) 0.69-0.80] for HCV-HIV co-infected patients and 0.87 (95% CI 0.85-0.89) for HCV mono-infected patients. Co-infection was associated with substantially increased mortality (MRR 2.1, 95% CI 1.7-2.6). However, prior to the first observed decrease in CD4 counts to below 300 cells/muL, HIV infection did not increase mortality in HCV-infected patients (MRR 0.9, 95% CI 0.5-1.50). CONCLUSIONS: HIV infection has a substantial impact on mortality among HCV-infected individuals, mainly because of HIV-induced immunodeficiency.

The influence of smoking on bone loss and response to nasal estradiol.

OBJECTIVE: To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. METHODS: Post-hoc exploratory analyses of data from 270 postmenopausal women randomized to 2 years' therapy with daily nasal administration of 17beta-estradiol or placebo sequentially combined with oral micronized progesterone in the active groups or placebo in the placebo group. RESULTS: During treatment with nasal estradiol, the bone mineral density (BMD) of the lumbar spine had increased less at 2 years in smokers as compared to non-smokers (2.6% vs. 3.9%, p = 0.03). Parallel changes were seen in the placebo group (-3.6% vs. -2.4%, p = 0.08). In the total hip BMD, there was no difference in the response to estradiol in smokers vs. non-smokers (1.4% vs. 1.4%, p = 0.89), whereas the change in the hip on the placebo was similar to that seen in the spine (-3.7% vs. -2.6%, p = 0.08). Supportive changes were seen in urinary CTX and in serum osteocalcin. CONCLUSIONS: These results indicate that cigarette smoking may reduce the efficacy of nasal estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women.

The influence of smoking on uterine bleeding during continuous and interrupted oral hormone therapy.

OBJECTIVE: To study the influence of smoking on uterine bleeding patterns during continuous and interrupted oral hormone therapy (HT). METHODS: Using a post-hoc strategy, we included five oral HT groups from three studies. The therapies consisted of continuous estrogen (estradiol, estradiol valerate or piperazine estrone sulfate) in combination with continuous progestogen (cyproterone acetate, gestodene or norethisterone acetate) or in combination with interrupted progestogen (norethisterone) given on days 4-6, 10-12, 16-18, 22-24 and 28-30. A total of 145 healthy postmenopausal women (54 smokers and 91 non-smokers), who had been followed for 2 years, were included in the analyses. Uterine bleeding data were collected from bleeding calendars. RESULTS: In general, smoking women experienced significantly less days with uterine bleeding per cycle than non-smoking women during continuous and interrupted HT (0.53 +/- 0.1 vs. 1.6 +/- 0.1; p < 0.001). Smoking women were also more likely than non-smoking women to be amenorrheic during these therapies (48.2% vs. 29.7%; p < 0.05). Finally, more smoking than non-smoking women attained amenorrhea during HT (94.4% vs. 76.9%p < 0.01). CONCLUSIONS: In healthy postmenopausal women, smoking may reduce uterine bleeding during interrupted and continuous HT regimens containing a broad selection of estrogens and progestogens. Further study with appropriate stratification for smoking status is warranted.

The influence of smoking on uterine bleeding during sequential oral hormone therapy.

OBJECTIVE: To study the influence of smoking on uterine bleeding patterns during sequentially administered oral hormone therapy (HT). METHODS: Using a post-hoc strategy, we included four sequential oral HT groups from two studies. The therapies consisted of estradiol from days 1 to 28 (estradiol or estradiol valerate) and progestogen (levonorgestrel or gestodene) on days 17-28. A total of 111 healthy, early postmenopausal women (38 smokers and 73 non-smokers) followed for 2 years were included in the analyses. Uterine bleeding data were collected from bleeding calendars. RESULTS: On the regimen containing levonorgestrel, smoking women had a cyclical bleeding significantly earlier than non-smoking women (about 2 days' difference). Moreover, smoking women had significantly longer bleeding than non-smoking women (about 1 day in difference). This was in contrast to the three regimens containing gestodene, where smoking seemed to have far less influence on uterine bleeding. CONCLUSIONS: On a regimen containing levonorgestrel, smokers exhibit an earlier and longer uterine bleeding than do non-smokers. This is in contrast to regimens containing gestodene, where smoking women are less likely to differ from non-smoking women with regard to bleeding. This indicates that smoking influences progestogen metabolism, and that this influence may vary with different progestogens. Further studies are needed.

Factors affecting postoperative mortality of patients with displaced femoral neck fracture.

Displaced femoral neck fractures are known to be associated with high rates of mortality. The purpose of the present study is to investigate pre- and postoperative factors which influence this mortality in a series of 1186 consecutive Danish patients presenting to one hospital's orthopaedic department with Garden type 3-4 fractures. Subsequent mortality data was obtained from the state population register (224 were still alive). The stepwise Cox proportional hazards model was used for multivariate analysis in order to obtain the predictors of postoperative mortality. The median survival of male subjects fell from 5.2 years in an age-matched control population to 1.6 years in the patients. In women survival time fell from 6.6 to 2.8 years. Almost all excess mortality occurred during the first 3 months following hemiarthroplasty. In order of significance, key factors negatively influencing mortality at 3 months were: cardiac complications, dementia, male sex, age, waiting time before operation, stroke and dislocation of the prosthesis and perioperative fracture. Of these, waiting time for surgery and dislocation of the prosthesis could be modified. A number of other studies have confirmed the importance of optimising these factors.

Association between polymorphisms of apolipoprotein E, bone mineral density of the lower forearm, quantitative ultrasound of the calcaneus and osteoporotic fractures in postmenopausal women with hip or lower forearm fracture.

A genetic contribution to the development of osteoporosis is well documented. Although the association between the common allelic variation of apolipoprotein E (APOE), fracture risk, bone loss and bone mineral density (BMD) has been examined in several studies, the results of these investigations are contradictory. The aim of this study was to examine the association between polymorphisms of APOE, BMD of the lower forearm, quantitative ultrasound of the calcaneus and osteoporotic fractures in a population of postmenopausal women with hip or lower forearm fractures admitted to a department of orthopaedic surgery and age-matched controls from the population register. The APOE genotypes of 327 women were studied: 73 with lower forearm fractures, 43 with hip fractures and 211 age-matched controls. The participants were not receiving antiosteoporotic treatment. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to detect the APOE genotypes. Quantitative ultrasound was measured at the calcaneus. Bone mineral density (BMD) of the lower forearm was measured with dual-energy X-ray absorptiometry. The distributions of genotype frequencies in this study were: E2/E2: 0.3%; E2/E3: 16.5%; E2/E4: 2.5%; E3/E3: 54.7%; E3/E4: 24.2%; E4/E4: 1.8%. All subpopulations were in Hardy-Weinburg equilibrium. There was no association between bone mass parameters and the APOE allele groups. Logistic regression analysis did not show any association between fractures and APOE allele groups. In conclusion, this study showed no association between bone mass parameters (BMD, speed of sound (SOS), broadband ultrasound attenuation (BUA)), hip or lower forearm fracture and APOE genotypes in a population of postmenopausal women and age-matched controls.

Association of a common allelic polymorphism (C677T) in the methylene tetrahydrofolate reductase gene with a reduced risk of osteoporotic fractures. A case control study in Danish postmenopausal women.

Twin studies indicate a substantial genetic component in the development of osteoporosis. One of the latest studied candidate genes is the one coding for methylene tetrahydrofolate reductase (MTHFR) (C677T) in which a point mutation gives rise to a thermolabile variant of MTHFR. The aim of this study was to investigate the influence of this mutation on peripheral measures of bone density and on the odds ratios (OR) for hip and lower forearm fracture in a case control study of Danish postmenopausal women. A total of 74 women with lower forearm fracture, 41 women with hip fracture, and 207 age-matched controls were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by dual X-ray absorptiometry at the distal forearm. The MTHFR (C677T) genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Only 2 of 21 individuals with the TT genotype had sustained a fracture as opposed to 46 of 142 with the CT genotype and 67 of 159 with the CC genotype (P = 0.007). Using logistic regression, the following odds ratios were found when comparing the individuals homozygotic for the C-allele with those homozygotic for the T-allele: lower forearm fracture OR = 3.93 (1.25; 12.40, P = 0.02), hip fracture OR = 6.99 (l.35; 36.92, P = 0.02) and the fractures combined OR = 4.33 (1.73; 10.81, P = 0.002). In this study, the MTHFR (C677T) genotypes were not significantly associated with BMD at the lower forearm or with ultrasound parameters measured at the calcaneus. However, a significant increase in the odds ratio of fracture was found for the wild-type C-allele.

Odds ratios for hip- and lower forearm fracture using peripheral bone densitometry; a case-control study of postmenopausal women.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) measured at the lumbar spine and particularly at the hip remain the gold-standard for diagnosing osteoporosis. However, devices for assessing the peripheral skeleton present several advantages in terms of lower price and portability. A major concern when using peripheral densitometry is the poor correlation with the central measurements. The main aim of this study is, therefore, to assess the possibility of expressing ultrasound measurements at the heel and bone mineral density (BMD) measured at the distal forearm as fracture odds ratios rather than an absolute measure of bone mass. METHODS: A total of 76 women with lower forearm fracture, 47 women with hip fracture and 231 age-matched women (controls) were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel using the DTU-one ultrasound scanner as well as BMD measured by dual X-ray absorptiometry on the DTX-200 at the distal forearm. RESULTS: BUA, SOS and BMD at the distal forearm were all significantly lower in fracture patients compared with their respective control groups. The odds ratio for lower forearm fracture was 3.1 (95% CI: 1.8; 5.2) for heel-BUA (T-score cutoff: -2.3), 4.1 (2.3; 7.4) for heel-SOS (-2.1) and 2.2 (1.3; 3.7) for lower forearm BMD (-2.7). The odds ratio for hip fracture was 3.4 (1.5-7.7) for heel-BUA (-2.7), 3.6 (1.6; 8.1) for heel-SOS (-2.6) and 3.2 (1.4; 7.4) for lower forearm BMD (-2.9). CONCLUSION: Peripheral densitometry can discriminate between hip- and lower forearm fracture patients and age-matched controls. Significantly elevated odds ratios for incurring these fractures can be calculated using device- and site specific t-score cutoff values. The results from this case-control study need to be confirmed by prospective cohort studies.