Comparison of image quality in chest, hip and pelvis examinations between mobile equipment in nursing homes and static indirect radiography equipment in the hospital.

INTRODUCTION: A hospital environment can be a significant burden and a health risk especially for dementia patients. Mobile x-ray equipment (ME) is used to enable imaging of these patients at home. The aim was to compare image quality (IQ) of chest, hip and pelvis images from ME to the stationary equipment (SE) used in a hospital department. METHODS: We analysed examinations of the chest (n = 20), hip (n = 64) and pelvis (n = 32). Images were equally obtained from each setting of ME and SE. All images were graded using Visual Grading Analysis (VGA) by three radiographers (hip and pelvis) and three radiologists (chest). Technical IQ assessment was done by 80 additional images of a Contrast-Detail Radiography phantom (CDRAD). RESULTS: All chest images were approved for diagnostic use, as well as the hip AP and pelvis images from SE. 'Approved proportion of ME images was for HIP antero-posterior (AP) and pelvis, 78% [95% CI: 52-94%] and 81% [95% CI: 54-96%] respectively. Hip axial had an overall low, but not significant different approval rate. Ordered logistic regression indicated higher IQ of HIP AP and pelvic images from SE. This contrasts that the CDRAD substudy indicated better IQ, expressed as IQFinv, from ME. CONCLUSION: The VGA showed higher IQ for the SE system, while the CDRAD showed higher IQ for the ME system. IMPLICATIONS FOR PRACTICE: Dementia patients can be examined at their home if the acquisition is optimised according to image quality in conjunct to radiation dose. Performing imaging out of the hospital and coordinating the patients' further treatment are new work areas for radiographers and requires excellent communication skills.

Fertility after uterine artery embolization of fibroids: a systematic review.

PURPOSE: The impact of uterine artery embolization (UAE) for the purpose of diminishing the effect of uterine fibroids on fertility is unclear. We have investigated the reported rates of pregnancy and miscarriage after treatment of uterine fibroids with UAE. MATERIALS AND METHODS: We searched for relevant information in PubMed and Embase for randomized controlled trials (RCT), controlled clinical trials, comparative before-after trials, cohort studies, case-control studies and case series where UAE treatment of premenopausal women was performed for uterine fibroids with and where a control intervention was included. The PRISMA guideline was used to do a systematic review using the main outcomes pregnancy rate and miscarriage rate. Risk of bias was assessed by the Cochrane risk of bias tool or by ROBINS-I. The quality of evidence was assessed by the GRADE approach. RESULTS: We included 17 studies (989 patients): 1 RCT, 2 cohort studies, and 14 case series. Pregnancy rates after UAE were 50% in the RCT and 51 and 69% in the cohort studies. Among the case series median pregnancy rate was 29%. Miscarriage rates were 64% in the RCT. Miscarriage rates at 56 and 34% were found in the cohort studies after UAE. The median miscarriage rate was 25% in the case series. CONCLUSION: Pregnancy rate was found to be lower and miscarriage rate higher after UAE than after myomectomy. However, we found very low quality of evidence regarding the assessed outcomes and the reported proportions are uncertain. There is a need for improved prospective randomized studies to improve the evidence base. Systematic review registration number: CRD42016036661.

Method for a homogeneous distribution of pollens in an environmental exposure chamber.

BACKGROUND: A variety of different environmental exposure chambers (EECs) have been used to evaluate treatments for allergic rhinitis. OBJECTIVE: To describe and test a system for a homogenous distribution of grass pollen, Phleum Pratense, in an EEC to be used for controlled pollen exposure studies in allergic participants. METHODS: A chamber made of stainless steel with completely rounded corners, seating four individuals at a time, was used. Room pressure, temperature, humidity and the air change rate were kept constant throughout the study period. A rotating pipette dispensed a uniform supply of pollen into a turntable's v-shaped grooves. A stainless steel capillary tube sucked the pollens into a venturi throat at which time the pollens were mixed with a high-pressure airstream of compressed high-efficiency particulate arrestance filtered air and then transported to a spreading plate inside the EEC. To achieve uniform concentrations in the EEC, the turntable's rotating speed was continuously adjusted using information from video-coupled feedback and feed forward mechanisms. Pollen levels were detected using standard volumetric air samplers and laser particle counters. The target pollen exposure level was 1000 pollens/m(3) . Twenty-one participants were exposed to pollens in the EEC twice for 210 min. Participants evaluated their symptoms every 30 min using a total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching and sneezing. RESULTS: Across fifteen study days, the average pollen level was 982 pollens/m(3) (SD, 102 pollens/m(3) ). On average, participants experienced a 10% difference in overall pollen levels between their two visits to the EEC. The mean TNSSs rose throughout the exposure period, with a low at baseline of 0.43 (SD, 0.68) to a high of 4.71 (SD, 2.43) just before exiting the EEC. CONCLUSION AND CLINICAL RELEVANCE: This EEC provides a reproducible, precise and homogenous distribution of pollens making it suitable for single-centre allergy clinical trials.

Selective, non-covalent conjugation of synthetic peptides with recombinant proteins mediated by host-guest chemistry.

The combination of potent chemical moieties with biologically active proteins is key to some of today's most innovative therapeutic drugs. In order to obviate any chemical modification of the proteins, we present a novel and powerful strategy for the selective conjugation of recombinant protein domains with synthetically derived peptides via a cucurbit[8]uril host-guest chemistry approach.

New paradigms in PCOS: impaired glucose tolerance and cardiovascular risk. Clinical approach.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic risk factors, in addition to chronic anovulation and factors related to androgen excess. Women with PCOS have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, resulting in a higher risk of type 2 diabetes mellitus, subclinical atherosclerosis, vascular dysfunction, and apparently cardiovascular disease and mortality. The aim of the present article was to summarize current knowledge with focus on a suggestion to the clinical approach and handling of these metabolic risk factors.

Overweight in polycystic ovary syndrome. An update on evidence based advice on diet, exercise and metformin use for weight loss.

AIM: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women affecting 5-10%. Nearly 50% are overweight or obese, which result in a more severe phenotype of PCOS. Weight loss is therefore considered the first line treatment in overweight women with PCOS. The aim of this study was to appoint evidence based and clinically applicable advises on weight loss in overweight women with PCOS. METHODS: A review of the existing literature on weight loss through lifestyle modification and/or metformin treatment in overweight women with PCOS. The primary outcome was weight loss. The clinical manifestations of hyperandrogenism and menstrual cyclicity were secondary outcomes. Metabolic parameters were not included in the present review. RESULTS: Weight loss is most effectively achieved through a 12-1500 kcal/day diet, which results in a clinically relevant weight loss. The type of diet has no implications for degree of weight loss. Physical activity has no significant additive effect on weight loss. Metformin combined with a low calorie diet has subtle additive effect on weight loss and level of androgens when compared to diet alone. CONCLUSION: Weight loss through life style changes, preferably a low calorie diet, should be the first line treatment in overweight/obese women with PCOS. Metformin can be considered as an additional treatment but has subtle additive effect.

Age associated differences in prevalence of individual rotterdam criteria and metabolic risk factors during reproductive age in 446 caucasian women with polycystic ovary syndrome.

Clinical manifestations and metabolic risk factors may differ according to age in patients with polycystic ovary syndrome (PCOS). Therefore, a retrospective trans-sectional study in academic tertiary-care medical center was designed. A cohort of 446 premenopausal, Caucasian women (age range 15-49 years) with PCOS were divided into 4 subgroups according to age: group 1 (15-19 years, n=42), group 2 (20-29 years, n=180), group 3 (30-39 years, n=187), group 4 (40-49 years, n=37) and underwent clinical evaluation (Ferriman-Gallwey score, BMI, waist, blood pressure), hormone analyses (sex hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, oral glucose tolerance tests (OGTT) (n=234), and ACTH tests (n=201). BMI, waist, Ferriman-Gallwey score, blood pressure, and lipid profile were higher in older vs. younger age groups whereas androgen levels were lower. Measures of insulin resistance were unchanged between age groups, but glucose levels were significantly higher in older age groups. Rotterdam criteria: The prevalence of PCO and biochemical hyperandrogenism decreased in the oldest age group whereas clinical hyperandrogenism increased. Young patients are characterized by PCO and biochemical hyperandrogenism, whereas older patients are more obese with more severe hirsutism and more cardiovascular and metabolic risk factors.

Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis.

Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.

The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement.

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement.

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

Modifying antibody specificity by chain shuffling of V / V between antibodies with related specificities.

Histo-blood group antigens are important markers of developmental stages and as such also often of tumours. Generation of antibodies towards these carbohydrate structures is still a challenging task as they may lack specificity, affinity or are only of the IgM class. We have examined four own antibodies to Lewis Y/H type 2 for their fine specificities using a large panel of mono- and oligosaccharides. Sequence alignment to other antibodies with similar specificity revealed an overall limited variation, and that our antibodies constitute a novel set. Based on produced and analysed chimeric mouse-human antibodies, extensive chain shuffling experiments were performed in order to analyse influences of the respective H and L chains on the specificity of the antibodies, and to generate modified antibodies with improved properties. One chIgG1 out of the shuffled antibodies revealed improved specificity and markedly enhanced functional affinity to Lewis Y compared to the parental chIgG1 antibodies. Therefore, the combinatorial approach of chain shuffling provides a platform to improve specificity and/or affinity of anti-carbohydrate antibodies.

Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis.

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-gamma inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test. IP-10 and MCP-2 were determined in supernatants from whole blood stimulated with Mycobacterium tuberculosis-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis. TB patients produced significantly higher levels (median) of IP-10 (2158 pg x mL(-1)) and MCP-2 (379 pg x mL(-1)) compared with interferon (IFN)-gamma (215 pg x mL(-1)). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (>89%). By combining IP-10 and IFN-gamma tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students. In conclusion, interferon-gamma inducible protein-10 and monocyte chemotactic protein-2 responses to Mycobacterium tuberculosis-specific antigens could be used to diagnose infection. Combining interferon-gamma inducible protein-10 and interferon-gamma may be a simple approach to increase the detection rate of the Mycobacterium tuberculosis-specific in vitro tests.

Re-activation of bovine tuberculosis in a patient treated with infliximab.

Treatment with tumour necrosis factor-alpha inhibitors increases the risk of tuberculosis (TB). Screening for latent TB infection (LTBI) and prophylactic treatment has become mandatory. A 79-yr-old female with a history of severe erosive sero-positive rheumatoid arthritis was screened for LTBI before initiation of treatment with infliximab. The tuberculin skin test (TST) was negative, chest radiography was normal and she had no known risk factors for TB. After 4 months of treatment with infliximab, the patient developed ascites caused by Mycobacterium bovis. The TST was repeatedly negative. QuantiFERON-TB (QFT) testing performed during screening and immunosuppressive treatment was indeterminate, whereas the QFT test performed at the time of ascites puncture was positive. The patient history revealed previous work at a dairy, with probable exposure to unpasteurised milk from M. bovis-infected cattle. Re-activation of bovine tuberculosis is a risk in people with recent or previous exposure to unpasteurised dairy products. The QuantiFERON-TB test has the potential to detect Mycobacterium bovis infection. Indeterminate test results reflect either anergy, due to poor immunity, or technical problems and should be cautiously interpreted and as a minimum be repeated. Studies are ongoing to determine the role of QuantiFERON-TB testing in the screening for latent tuberculosis infection.

A monoclonal antibody to Lewis Y/Lewis b revealing mimicry of the histone H1 to carbohydrate structures.

Antibodies to either peptide or carbohydrate tumour antigens are established tools for diagnostics and therapy. We here describe an antibody (A70-A/A9) recognizing a carbohydrate epitope common to the tumour-associated Lewis Y and Lewis b antigens (Fucalpha1-2Galbeta1-4/3[Fucalpha1-3/4]GlcNAcbeta-). Its specificity was established without doubt with a panel of 86 synthetic mono- and oligosaccharidic structures. This antibody was found to cross-react with the nuclear protein histone H1. Binding to H1 was specific, periodate-insensitive (non-carbohydrate) and saturable. Histone H1 was able to inhibit Lewis Y binding very effectively in a concentration-dependent manner. We conclude that it represents an example of natural peptide mimicry of a carbohydrate epitope. It may explain the observed occurrence of 'anti-histone autoantibodies' in cancer patients.

Elevated levels of soluble urokinase receptor in serum from mycobacteria infected patients: still looking for a marker of treatment efficacy.

In search for a serological marker, which may be used to monitor treatment efficacy in patients with extra-pulmonary mycobacterial infections, serum samples were collected prospectively from patients during a 6-months treatment period. The levels of soluble urokinase-type plasminogen activator receptor (suPAR) and soluble tumour necrosis factor receptor II (sTNFrII) were measured and compared with erythrocyte sedimentation rate (SR) and C-reactive protein levels (CRP). sTNFrII levels were elevated at the time of diagnosis and declined in parallel with traditional inflammation markers (SR and CRP). suPAR levels were elevated to more than double (median 7.7 ng/ml, range 5.6-25.8) compared to levels previously reported for patients with pulmonary tuberculosis. The serum suPAR levels however remained high during the entire treatment period. This may reflect that significant inflammatory activity is continuing for more than 6 months in patients with extrapulmonary mycobacterial infections, despite adequate anti-tuberculosis treatment.

Angiogenesis inhibition with bevacizumab and the surgical management of colorectal cancer.

BACKGROUND: Bevacizumab is an angiogenesis inhibitor and a new therapy for the treatment of colorectal cancer. It is a humanized monoclonal antibody that targets vascular endothelial growth factor. METHODS: This review is based on a literature search of Medline, Pubmed, ISI web of knowledge and other published work for original articles, reviews and abstracts relevant to the surgical management of colorectal cancer with bevacizumab. RESULTS AND CONCLUSION: Combined with current chemotherapy regimens, bevacizumab offers a significant survival advantage, making it likely to see widespread use. Despite being generally well tolerated, serious toxicities, including wound complications and gastrointestinal perforation, have been reported that affect surgical management. Consideration should be given to the timing of surgical and adjuvant intervention when using this drug.

Levonorgestrel and 17beta-estradiol given transdermally for the prevention of postmenopausal osteoporosis.

AIM: To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis. METHODS: 212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between -1.0 and -2.5 S.D. of the premenopausal mean value) postmenopausal women aged 45-65 years participated in a 2-year prospective study. Treatments were 45 microg 17beta-estradiol combined with 30 (n = 69) or 40 microg (n = 72) levonorgestrel daily or placebo (n = 71) given as a 7-day patch. All received a daily supplement of 500 mg calcium. BMD at lumbar spine (L2-L4), hip and total body, as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin (sOC), serum bone-specific alkaline phosphatase (sBSAP), urinary calcium (uCa) and urinary CrossLaps (uCTX)) were measured regularly. RESULTS: BMD at the lumbar spine, hip and total body increased by 8, 6 and 3% (P < 0.001), respectively, in the hormone groups versus placebo. The bone markers all decreased accordingly (sOC: 37%, sBSAP: 34% and uCTX: 65% from baseline (all P < 0.001)), except for uCa that did not change significantly. No significant dose-related effect of levonorgestrel was found. Vaginal bleeding/spotting decreased from 48 to 25% of the HRT-treated women during the study period. Skin tolerance was good in 84% of the women with no difference between the study groups. No incidences of endometrial hyperplasia, uterine or mammary cancer occurred. CONCLUSION: The transdermal combination of 17beta-estradiol and levonorgestrel has a positive effect on BMD in an osteopenic postmenopausal population. Furthermore, a high safety profile was observed.

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.

Influence of lipoteichoic acid D-alanylation on protein secretion in Lactococcus lactis as revealed by random mutagenesis.

Lactococcus lactis, a food-grade nonpathogenic lactic acid bacterium, is a good candidate for the production of heterologous proteins of therapeutic interest. We examined host factors that affect secretion of heterologous proteins in L. lactis. Random insertional mutagenesis was performed with L. lactis strain MG1363 carrying a staphylococcal nuclease (Nuc) reporter cassette in its chromosome. This cassette encodes a fusion protein between the signal peptide of the Usp45 lactococcal protein and the mature moiety of a truncated form of Nuc (NucT). The Nuc secretion efficiency (secreted NucT versus total NucT) from this construct is low in L. lactis (approximately 40%). Twenty mutants affected in NucT production and/or in secretion capacity were selected and identified. In these mutants, several independent insertions mapped in the dltA gene (involved in D-alanine transfer in lipoteichoic acids) and resulted in a NucT secretion defect. Characterization of the dltA mutant phenotype with respect to NucT secretion revealed that it is involved in a late secretion stage by causing mature NucT entrapment at the cell surface.