Exploring the phase stability in interpenetrated diamondoid covalent organic frameworks.

Soft porous crystals, which are responsive to external stimuli such as temperature, pressure, or gas adsorption, are being extensively investigated for various technological applications. However, while substantial research has been devoted to stimuli-responsive metal-organic frameworks, structural flexibility in 3D covalent organic frameworks (COFs) remains ill-understood, and is almost exclusively found in COFs exhibiting the diamondoid (dia) topology. Herein, we systemically investigate how the structural decoration of these 3D dia COFs-their specific building blocks and degree of interpenetration-as well as external triggers such as temperature and guest adsorption may promote or suppress their phase transformations, as captured by a collection of 2D free energy landscapes. Together, these provide a comprehensive understanding of the necessary conditions to design flexible diamondoid COFs. This study reveals how their flexibility originates from the balance between steric hindrance and dispersive interactions of the structural decoration, thereby providing insight into how new flexible 3D COFs can be designed.

Quantifying the Likelihood of Structural Models through a Dynamically Enhanced Powder X-Ray Diffraction Protocol.

Structurally characterizing new materials is tremendously challenging, especially when single crystal structures are hardly available which is often the case for covalent organic frameworks. Yet, knowledge of the atomic structure is key to establish structure-function relations and enable functional material design. Herein, a new protocol is proposed to unambiguously predict the structure of poorly crystalline materials through a likelihood ordering based on the X-ray diffraction (XRD) pattern. Key of the procedure is the broad set of structures generated from a limited number of building blocks and topologies, which is submitted to operando structural characterization. The dynamic averaging in the latter accounts for the operando conditions and inherent temporal character of experimental measurements, yielding unparalleled agreement with experimental powder XRD patterns. The proposed concept can hence unquestionably identify the structure of experimentally synthesized materials, a crucial step to design next generation functional materials.

The short IQCODE as a predictor for delirium in hospitalized geriatric patients.

BACKGROUND: Delirium is a serious complication, which occurs frequently in older patients with pre-existing cognitive impairment. There is a need for a simple tool to assess chronic cognitive impairment and the associated risk of delirium during hospitalization. AIMS: To assess the usefulness of the short IQCODE questionnaire in predicting delirium during hospitalization in older patients in a geriatric ward. METHODS: A prognostic study in the Geriatric Department at Aarhus University Hospital, Aarhus Denmark. Consecutive patients were enrolled during March to December, 2017. After consent of the patient, the staff interviewed the relatives by phone using the short IQCODE questionnaire. Delirium was assessed morning and evening until discharge by the Confusion Assessment Method. The ability of short IQCODE to predict delirium was examined. RESULTS: Three hundred and fifty-three patients were eligible, and 306 completed the IQCODE. Delirium occurred among 19% of the patients during hospitalization. The IQCODE score was associated with the risk of delirium with a receiver operating characteristic (ROC) area of 0.72. A cut-point of 3.3 could separate the patients in a larger group with a risk of approximately 26% to develop delirium and a smaller group having a risk of approximately 6%. CONCLUSION: The IQCODE is a useful tool to predict delirium among older inpatients, but it may not stand alone. It can be a useful supplement to other clinical information and observations in detecting patients needing dementia-friendly treatment and care.

Low risk of venous thromboembolism following early pregnancy loss in pregnancies conceived by IVF.

STUDY QUESTION: What is the risk of venous thromboembolism (VTE) in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF? SUMMARY ANSWER: The VTE risk is low in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF. WHAT IS KNOWN ALREADY: There is an excess VTE risk during first trimester in complete IVF pregnancies leading to delivery. It is unknown whether this excess VTE risk also is present in IVF pregnancies terminated by early pregnancy loss (implantation failure, missed abortion, or spontaneous or induced abortion before 10 completed gestational weeks). STUDY DESIGN, SIZE, DURATION: A nationwide registry-based cohort study including all Danish IVF pregnancies registered in the Danish IVF Register between 1995 and 2005. Women who underwent frozen embryo replacement or oocyte donation were not included. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all 24 931 IVF treatments leading to pregnancy among 19 260 women. We identified 16 701 complete IVF pregnancies, 7567 IVF pregnancies with early pregnancy loss, and 663 IVF pregnancies terminated by late abortion (≥gestational weeks 10). We followed women for 12 weeks after termination of pregnancy and calculated the absolute risk of VTE during follow-up with 95% CI. As a relative risk estimate, we calculated the risk ratio for VTE following IVF pregnancies with early loss compared to the VTE risk following complete IVF pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: During the 12 weeks of follow-up, only one case of VTE occurred in the group of early pregnancy loss, none in the late abortion group, and 13 VTE cases occurred in complete IVF pregnancies. The VTE risk per 10 000 pregnancies was 1.3 [0.03-7.4] for IVF pregnancies with early loss and 7.8 [4.1-13.3] for complete pregnancies; the corresponding risk ratio was 0.17 [0.02-1.3]. Thus, we found a low absolute VTE risk in the 12 weeks following early pregnancy loss in IVF pregnancies. The relative VTE risk was low in comparison to the VTE risk in early gestation reported for complete IVF pregnancies and for Danish background pregnancies. LIMITATIONS, REASONS FOR CAUTION: Despite the use of complete nationwide data, only a few VTE events were available for the statistical analyses thereby limiting the precision of our estimates. We included both inpatient and outpatient VTE hospital diagnoses, but we cannot rule out the occurrence of VTE cases not diagnosed at hospital and hence not registered in the National Patient Registry. No information was available on the use of prophylactic low molecular weight heparin: access to such might have helped to explain our findings, but would not have changed our conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The results of the present study do not indicate a need for prophylactic anticoagulant therapy in women suffering early IVF pregnancy loss without other risk factors. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare.

Increased venous thrombosis incidence in pregnancies after in vitro fertilization.

STUDY QUESTION: Is venous thrombosis risk increased in pregnancies after in vitro fertilization? SUMMARY ANSWER: The venous thrombosis incidence was significantly increased in pregnancies after in vitro fertilization; especially in the first trimester and in the first 6 weeks post-partum. WHAT IS KNOWN ALREADY: In vitro fertilization without pregnancy is not associated with increased venous thrombosis incidence. STUDY DESIGN, SIZE, DURATION: This national register-based cohort study covered the period from 1995 to 2005. PARTICIPANTS/MATERIALS, SETTING, METHODS: All Danish pregnancies conceived by in vitro fertilization (n = 18 787) were included. Venous thrombosis incidence rates in pregnancies after in vitro fertilization were compared with venous thrombosis incidence rates in reference pregnancies, by calculating incidence rate ratios. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 48 cases were identified. In pregnancies after in vitro fertilization, the overall venous thrombosis incidence rate was 28.6 per 10 000 pregnancy-years (95% confidence interval (CI) 20.6-39.6) in comparison to 10.7 per 10 000 woman-years in reference pregnancies. Post-partum, the venous thrombosis incidence rate was 27.9 per 10 000 woman-years (95% CI 15.8-49.1) after in vitro fertilization in comparison to 17.5 per 10 000 woman-years in reference pregnancies. The overall venous thrombosis incidence rate ratio during in vitro fertilization (IVF) pregnancies compared with reference pregnancies was 3.0 (95% CI 2.1-4.3). The venous thrombosis incidence rate ratios during pregnancy were 2.8 (95% CI 1.9-4.1) in singleton IVF pregnancies and 4.4 (95% CI 2.4-8.3) in multiple IVF pregnancies, compared with reference pregnancies. The venous thrombosis incidence rate ratio post-partum was 1.2 (95% CI 0.6-2.8) for singleton IVF pregnancies and 3.9 (95% CI 1.7-8.8) for multiple IVF pregnancies compared with reference pregnancies. The post-partum venous thrombosis risk was higher in multiple IVF pregnancies compared with singleton IVF pregnancies. Maternal age, smoking and parity did not significantly affect the venous thrombosis risk. Ovarian hyperstimulation syndrome and polycystic ovarian syndrome did increase the risk of venous thrombosis during pregnancy. Caesarean section also increased the post-partum venous thromboembolism risk, but the increase was not significant. LIMITATIONS, REASONS FOR CAUTION: Other known confounders in our reference population could have contributed to the results. Access to such data may have helped to explain the observations, but would not have changed the conclusion that IVF pregnancies have an increased risk of venous thrombosis compared with other pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: Our study adds new insights by demonstrating an excess venous thrombosis incidence post-partum after in vitro fertilization. The high venous thrombosis incidence in first trimester after in vitro fertilization supports previous studies. Our findings are generalizable to other Western Countries. STUDY FUNDING/COMPETING INTERESTS: Expenses for the acquirement of data were covered by a grant from The Secretary of Doctors further education, Central Denmark Region. None of the authors have any competing interests to declare. TRIAL REGISTRATIONS NUMBER: Not applicable.

Comparison of three weight maintenance programs on cardiovascular risk, bone and vitamins in sedentary older adults.

OBJECTIVE: Obese patients with knee osteoarthritis (OA) are encouraged to lose weight to obtain symptomatic relief. Risk of vascular events is higher in people with OA compared to people without arthritis. Our aim in this randomized trial was to compare changes in cardiovascular disease (CVD) risk-factors, nutritional health, and body composition after 1-year weight-loss maintenance achieved by [D]diet, [E]knee-exercise, or [C]control, following weight loss by low-energy-diet. DESIGN AND METHODS: Obese individuals (n = 192, >50 years) with knee OA, 63 years (SD 6), weight 103.2 kg (15.0), body-mass index 37.3 kg/m(2) (4.8), were enrolled into a 68-week weight-loss trial. RESULTS: Mean changes in weight, in D, E, and C were -11.0, -6.3, and -8.3 kg (P = 0.002). Reduction in waist circumference in D, E, and C were -8.4, -4.6, and -7.0 cm (P = 0.007). D reduced waist circumference significantly more than E: -3.8 cm (95%CI -6.2 to -1.4; P = 0.0024). There was no difference between the groups in changes in CVD risk factors; blood pressure, triglycerides, and cholesterol. Nutritional health was improved in all groups. For markers of bone, no statistical difference was found between the groups. CONCLUSIONS: Dietary support, or control, maintained improvements in cardiovascular risk factors to the same extent and none of the interventions had a detrimental effect on bone.

Outcomes of extremely low birth weight infants given early high-dose erythropoietin.

OBJECTIVE: To evaluate long-term outcomes of 60 extremely low birth weight (ELBW) infants treated with or without three injections of high-dose erythropoietin (Epo). STUDY DESIGN: A retrospective analysis of anthropometric and neurodevelopmental outcome data comparing 30 ELBW infants enrolled in a phase I/II study examining the pharmacokinetics of high-dose Epo (500, 1000 and 2500 U/kg × 3 doses) administered to 30 concurrent controls. RESULT: Birth characteristics and growth from 4 to 36 months were similar for untreated and Epo-treated patients. Multiple linear regression analysis of neurodevelopmental follow-up scores from 17/25 Epo-treated and 18/26 control infants identified that Epo correlated with improvement of cognitive (R=0.22, P=0.044) and motor (R=0.15, P=0.026) scores. No negative long-term effects of Epo treatment were evident. CONCLUSION: Retrospective analysis of the only available long-term follow-up data from ELBW infants given high-dose Epo treatment suggests that Epo treatment is safe and correlates with modest improvement of neurodevelopmental outcomes.

No evidence that assisted reproduction increases the risk of thrombosis: a Danish national cohort study.

BACKGROUND: Case reports have reported venous and arterial thromboses in women undergoing assisted reproduction. No large systematic studies on the risk of thrombosis have been published. The objective of our study was to investigate whether the risk of thrombosis is increased in women undergoing assisted reproduction. METHODS: A national register-based cohort study was conducted on all women undergoing IVF or ICSI treatment in Denmark from 1994 to 2005. Data were obtained from the National Patient Registry and the IVF Registry. Women with prior malignant or cardiovascular disease were excluded. Thrombosis occurring within the first 6 and 12 months after assisted reproduction was considered potentially related to the treatment. Thromboses during pregnancy as well as the pregnancy-related diagnoses were excluded from the statistical analysis. The incidence rates of venous and arterial thromboses were compared with previously published estimates of the risk of thrombosis among young Danish women. RESULTS: We analyzed 30 884 Danish women undergoing 75 141 treatments from 1994 to 2005. The mean age of the women at first treatment was 32.3 years. The delivery rate per cycle was 22%. The incidence rate ratio, with 95% confidence interval (CI), of venous thrombosis within 6 months was 0.95 (CI: 0.38-1.95). The incidence rate ratio of arterial thrombosis within 6 months was 0.36 (CI: 0.04-1.30). CONCLUSIONS: Our study showed no evidence that assisted reproduction increases the risk of thrombosis.

Doppler ultrasound compared with strain gauge for measurement of systolic ankle blood pressure.

This study assesses measurement variation in the measurement of ankle systolic blood pressure (ABP) when measured with Doppler ultrasound and with the strain gauge method. Ninety-seven patients were included. ABP was measured with Doppler ultrasound and with the strain gauge method. The methods were compared graphically by scatterplots and analyzed by paired t test, analysis of variance, and Pitman's paired variance ratio test. ABP was measured by strain gauge in all extremities, whereas no Doppler signal was obtainable in 7 limbs (4%). There was no systematic difference in measurements between the means of the two measurements. However, a substantial difference of more than 25 mm Hg was found in 15% of limbs and more than 20 mm Hg in 20%. In the majority of patients, measurements of ABP by Doppler ultrasound and the strain gauge method give similar results, but for a minority the discrepancy is substantial.

Can long-term antibiotic treatment prevent progression of peripheral arterial occlusive disease? A large, randomized, double-blinded, placebo-controlled trial.

PURPOSE: The purpose was to investigate in a large, randomized, double-blinded, placebo-controlled trial, whether antibiotic treatment can prevent progression of peripheral arterial disease (PAD). MATERIAL AND METHODS: Five hundred and seven patients were included; all patients had an established diagnosis of PAD. Their mean age was 66 years (36-85), and 59% were males. Patients were randomized to Roxithromycin 300 mg daily for 28 days. Baseline investigations were ankle blood pressure, ankle-brachial blood pressure index (ABPI), walking distance, C. pneumoniae serology, cholesterol and medical history. Follow-up was performed every 6 months. Primary events were defined as death, peripheral revascularization and major lower limb amputation. Secondary events were thrombosis, stroke, transient cerebral ischaemic attack and myocardial infarction. Change in ABPI was also investigated. Data were analyzed mainly by Cox regression and linear regression. RESULTS: Included patients with PAD were randomized. Two patients withdrew. Of the remaining, 248 received roxithromycin and 257 placebo. In the treatment group 55% were seropositive and 53% in the placebo group. Mean follow-up was 2.1 years (range 0.06-5.1 years). In the placebo group, 26 died and 80 primary events occurred in total. In the treatment group, 28 died and 74 primary events were observed. The hazard ratio of death was 1.13 (95% CI: 0.68; 1.90), and of primary events 0.92 (95% CI: 0.67; 1.26). Also on secondary events and ABPI changes, no significant differences were found. CONCLUSION: Long-term treatment with roxithromycin is ineffective in preventing death, amputation, peripheral revascularization, myocardial infarction, stroke, transient cerebral ischaemic attack, thrombosis and decline in ABPI in patients with an established diagnosis of PAD.

High-risk and low-risk screening for abdominal aortic aneurysm both reduce aneurysm-related mortality. A stratified analysis from a single-centre randomised screening trial.

BACKGROUND: Cardiovascular diseases and chronic obstructive pulmonary disease (COPD) are both associated with abdominal aortic aneurysms (AAA). The aim of this study was therefore to analyse whether screening for AAA could be restricted to men with such diseases (high risk group). METHODS: Before the date of randomisation of a population screening trial of 12,639 64-73-year-old males, all discharge diagnoses from the National Patient Registry concerning AAA-related diseases were merged with the screening results on attendance, AAA prevalence, and AAA-related mortality and overall mortality. Differences in proportions were compared by Chi square tests and differences in mortality by Cox regression analyses. RESULTS: The attendance rate was 78.8% and 6.7% had an AAA in the high risk group compared to 75.8% attendance (P<0.001) and 2.9% (P<0.001) in the remaining population. Cumulatively, screening of only high risk men with would have required 72.9% (95% C.I.: 72.3-74.5%) fewer screening invitations, would have discovered 46.1% (95% C.I.: 38.9-53.4%) of the AAA cases diagnosed and prevented 46.7% (95% C.I.: 28.3-65.7%) of the AAA-related deaths. However, screening decreased AAA-related mortality both among men with and without known COPD or cardiovascular diseases: mortality ratio: 0.22 (95% C.I.: 0.08-0.65), P=0.006, and 0.24 (95% C.I: 0.09-0.63, P=0.004, respectively. CONCLUSION: High-risk population screening would prevent less than half of AAA-related deaths. Therefore, restricting screening to such high-risk groups does not seem justified, but cost effectiveness analyses are needed to reach a firm conclusion.

Preliminary ten year results from a randomised single centre mass screening trial for abdominal aortic aneurysm.

BACKGROUND: At present, several regions and countries are considering screening for abdominal aortic aneurysm (AAA). However, The Chichester Aneurysms Screening Trial has reported poor long term benefit of screening for AAA. We therefore supplement previously published data with a preliminary analysis of the ten-year mortality from AAA, based upon population-based data until 2002 (7 years) and incomplete hospital-based information on deaths until 2005 (10 years). METHODS AND MATERIAL: In 1994 we started a randomised screening trial of 12,639 64-73 year-old males; 6,306 were controls, and 6,333 were invited to an abdominal ultrasound scan at their district hospital. Information on all deaths until 15.3.2005 was obtained from the Office of Civil Registration. Information on AAA related deaths was obtained from the national registry of Causes of Deaths from 1.4.1994 to 31.12.2001, and supplemented with AAA deaths known to the Danish National Patient Registry until 15.3.2005. Operations were obtained from the Danish National Vascular Registry from 1.4.1994 to 15.3.2005. Death certificates and medical records were reviewed by two independent assessors. The analyses were based on "intention to treat" from the date of randomisation. RESULTS: The attendance rate was 76.6% and 191 (4.0%) had an AAA. The median observation time was 9.58 years. In the invited group 13 subjects were acutely operated on compared to 40 in the control group (Risk ratio: 0.32 (95% C.I. 0.17-0.60, P<0.001)), and 14 died due to AAA compared to 51 in the control group (Hazard ratio: 0.27 (95% C.I.: 0.15-0.49, P<0.001). CONCLUSION: Over ten years, screening reduced mortality from AAA by 73%, and the frequency of emergency operations by 68%.

Hypopituitarism and mortality in pituitary adenoma.

BACKGROUND AND OBJECTIVE: Previous studies on hypopituitarism and mortality have concluded that insufficient pituitary function is associated with decreased survival. For several reasons the results are difficult to compare - particularly because definitions and treatment of hypopituitarism have varied and various underlying disorders have been included. The purpose was to assess the relationship between mortality and pituitary function. PATIENTS AND DESIGN: One hundred and sixty consecutive patients (99 men and 61 women) with functionless, suprasellar pituitary adenoma. All were operated on transsphenoidally during the period 1985-1996. Additional radiotherapy was given to 29 patients. Mortality was calculated 12.4 years (median, range 8.1-19.9) after operation. Postoperative hormonal deficits were treated in most, though GH substitution was given only to a minority of patients. RESULTS: Postoperatively 30% of the patients had normal pituitary function (normal adrenocortical, thyroid and gonadal function), 26% were panhypopituitary and 36% had partial pituitary insufficiency. Forty-one patients had died (34.7 expected) yielding a standard mortality ratio (SMR) of 1.18 (95% confidence limits (CI) 0.87-1.60). SMR was significantly increased in women (1.97, CI 1.20-3.21) but not in men (0.83, CI 0.55-1.26). SMR in patients with normal pituitary function, panhypopituitarism and partial insufficiency were not different from that in the general population. SMR in hypopituitary women was substantially higher than in men with pituitary insufficiency. Treatment with growth hormone in GH-deficient patients did not influence survival. CONCLUSION: Pituitary surgery for nonfunctioning adenoma and subsequent pituitary insufficiency had no effect on mortality in men, but was associated with significantly increased mortality in women. Suboptimal hormonal substitution in women may play a role.

Cost-effectiveness analysis of screening for abdominal aortic aneurysms based on five year results from a randomised hospital based mass screening trial.

BACKGROUND: The aim of this study was to estimate the cost effectiveness of screening for abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: All 12,639 men born in the years 1921-1933 (aged 64-73) living in Viborg County, Denmark, were randomly allocated either to receive an invitation to abdominal ultrasound scanning for AAA or to be controls. Costs for screening and surveillance were assessed prospectively. Diagnosis Related Group (DRG) costs from 1999 were used concerning admissions with uncomplicated and complicated operations. Admissions for AAA surgery were retrospectively classified according to complications in patient records. RESULTS: Mean follow-up time was 52 months. 76.6% of invited men attended screening, and 191 (4.0%) had an AAA. As previously reported, the cumulative 5-year AAA-specific mortality in the invited group was significantly reduced by 67% compared to the control group (P = 0.003). The costs were estimated to be Euro 11.23 per scan. The costs per life-year saved were Euro 9057 (Euro 5872-20,063) after 5 years, and were expected to decrease to Euro 2708 (Euro 1758-6031) after 10 years and to Euro 1825 (Euro 1185-4063) after 15 years. CONCLUSION: Screening of 64-73 years old males in Denmark seems cost effective.

Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma.

BACKGROUND AND OBJECTIVE: There is agreement in the literature that pituitary apoplexy is a rare disorder. As our experience differs from this view, we analysed the incidence in patients operated on for a nonfunctioning pituitary adenoma. PATIENTS AND DESIGN: One hundred ninety-two consecutive patients with a suprasellar, clinically inactive adenoma operated on during the period 1985-1996 were retrospectively reviewed. A diagnosis of pituitary apoplexy was made from relevant neurological symptoms together with pertinent findings at operation. RESULTS: Pituitary apoplexy occurred in 41 patients (21%), in 23 patients within 12 days prior to the operation. The male/female ratio was 1.9. Median follow-up time was 13.7 years (range 8.9-19.9). During this period, 12 patients had died, yielding a standard mortality ratio of 1.09 (95% CI 0.62-1.92), similar to that in the patients who had not sustained pituitary apoplexy. Postoperatively, 24% of the patients had normal pituitary function, 38% were panhypopituitary and partial pituitary insufficiency was present in 38%. Subnormal GH secretion was present in virtually all patients tested. Two patients died within 60 days of surgery and in two no or incomplete data were available, although they most likely were panhypopituitary. CONCLUSION: Most of our findings add little to what is known about pituitary apoplexy. On one point, however, they are contrary to previously presented data. We found a much higher incidence of pituitary apoplexy despite rather rigorous criteria for the diagnosis. The outcome as regards survival and endocrine function was not different from that in patients with a nonfunctioning adenoma who did not suffer pituitary apoplexy.

Female fecundity before and after operation for familial adenomatous polyposis.

BACKGROUND: Knowledge about the fertility of women suffering from familial adenomatous polyposis (FAP) is scarce and inconclusive. The purpose of this study was to investigate the fecundity of women with FAP before and after operation, and to compare the findings with those of a general population database and women with ulcerative colitis. METHODS: A questionnaire concerning reproductive experiences and waiting times to pregnancy was sent to all 230 women on the polyposis registers in Denmark, Finland, Sweden and Norway in whom primary surgery had consisted of ileorectal anastomosis or ileal pouch-anal anastomosis. Data on the general population and women with ulcerative colitis came from an existing database. Cox regression and Kaplan-Meier plots were used for analysis. RESULTS: The fecundity of women with FAP before operation and after colectomy with ileorectal anastomosis was similar to that of the general population. However, fecundity dropped to 54 per cent (P = 0.015) following proctocolectomy with ileal pouch-anal anastomosis, although it was greater than the postoperative fecundity of women with ulcerative colitis. CONCLUSION: The significant reduction in female fecundity after ileal pouch-anal anastomosis should be communicated to young women with FAP before it is decided which surgical option to follow.

Vitamin B-12 treatment has limited effect on health-related quality of life among individuals with elevated plasma methylmalonic acid: a randomized placebo-controlled study.

OBJECTIVE: To examine the hypothesis that treatment with vitamin B-12 improves health-related quality of life (HRQOL) in individuals with biochemical signs of vitamin B-12 deficiency. DESIGN: A randomized placebo-controlled study. SETTING: Municipality of Aarhus, Denmark. SUBJECTS: Nonhospitalized individuals (n = 140) with a modest increase in plasma methylmalonic acid (0.40-2.00 micromol L-1) not previously treated with vitamin B-12. INTERVENTION: The participants were randomized to vitamin B-12 injection treatment or placebo weekly for 4 weeks and re-examined 3 months later. The investigator and the participants were blinded to the intervention. MAIN OUTCOME MEASURE: Change in HRQOL assessed by the SF-36 questionnaire from baseline to follow-up examination 3 months later. RESULTS: The participants reported a significantly worser HRQOL than the age- and sex-matched Danish general population (P < 0.001). However, no change was observed after treatment with vitamin B-12 for seven of eight health dimensions. A significant improvement was found only in general health when compared with the placebo group (P = 0.03). CONCLUSIONS: Vitamin B-12 treatment influenced only one of eight dimensions of HRQOL amongst participants with biochemical signs of vitamin B-12 deficiency. We therefore question the benefit of vitamin B-12 treatment amongst elderly with a modestly increased plasma methylmalonic acid as the only sign of vitamin B-12 deficiency.

Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage.

UNLABELLED: A new field of clinical and scientific interest has recently developed based on the discovery that the hematopoietic cytokine erythropoietin (Epo) has important non-hematopoietic functions in the brain and other organs, particularly during development. The biological effects of Epo in the central nervous system (CNS) involve activation of its specific receptor and corresponding signal transduction pathways. Epo receptor expression is abundant in the developing mammalian brain, and decreases as term approaches. Epo has been identified as a neurotrophic and neuroprotective agent in a wide variety of experimental paradigms, from neuronal cell culture to in vivo models of brain injury. Several mechanisms by which Epo produces neuroprotection are recognized. Epo (i) decreases glutamate toxicity, (ii) induces the generation of neuronal anti-apoptotic factors, (iii) reduces inflammation, (iv) decreases nitric oxide-mediated injury, and (v) has direct antioxidant effects. CONCLUSION: Collectively, the evidence suggests that Epo may provide a new approach to the treatment of a variety of CNS disorders in adults and children, especially as a possible therapy for perinatal asphyxia. This review summarizes the current knowledge on the neurotrophic and neuroprotective functions of Epo in the developing and injured brain.