Thermal Profiles: Novel phenotypic measurements of animal growth and metabolic efficiency.

The costs of production for high density protein and the impacts food production have on the environment are becoming increasingly important issues in animal agriculture. The objective of the present study was to investigate the use of novel thermal profiles including a Thermal Efficiency Index (TEI) on the ability to identify efficient animals in a fraction of the time and at a significantly lower cost of conventional feed station and performance technology. Three hundred and fourty four high performance Duroc sires from a genetic nucleus herd were used in the study. The animals were monitored for feed consumption and growth performance using conventional feed station technology for a 72 day period. Animals were monitored in these stations between approximately 50 kg and 130 kg live body weight. An infrared thermal scan was performed on the animals at the end of the performance test by collecting automated dorsal thermal images and using these biometrics to measure both bio-surveillance values and a thermal phenotypic profile including the TEI (mean dorsal temperature /body weight 0.75). The thermal profile values were significantly correlated (r = 0.40, P < 0.0001) with a current industry best practice for performance in Residual Intake and Gain (RIG). The data from the current study suggest these rapid, real time, cost effective values for TEI constitute a useful precision farming tool for the animal industries to reduce the cost of production and green house gas (GHG) impact for high density protein production.

Identification and characterisation of de novo germline structural variants in two commercial pig lines using trio-based whole genome sequencing.

BACKGROUND: De novo mutations arising in the germline are a source of genetic variation and their discovery broadens our understanding of genetic disorders and evolutionary patterns. Although the number of de novo single nucleotide variants (dnSNVs) has been studied in a number of species, relatively little is known about the occurrence of de novo structural variants (dnSVs). In this study, we investigated 37 deeply sequenced pig trios from two commercial lines to identify dnSVs present in the offspring. The identified dnSVs were characterised by identifying their parent of origin, their functional annotations and characterizing sequence homology at the breakpoints. RESULTS: We identified four swine germline dnSVs, all located in intronic regions of protein-coding genes. Our conservative, first estimate of the swine germline dnSV rate is 0.108 (95% CI 0.038-0.255) per generation (one dnSV per nine offspring), detected using short-read sequencing. Two detected dnSVs are clusters of mutations. Mutation cluster 1 contains a de novo duplication, a dnSNV and a de novo deletion. Mutation cluster 2 contains a de novo deletion and three de novo duplications, of which one is inverted. Mutation cluster 2 is 25 kb in size, whereas mutation cluster 1 (197 bp) and the other two individual dnSVs (64 and 573 bp) are smaller. Only mutation cluster 2 could be phased and is located on the paternal haplotype. Mutation cluster 2 originates from both micro-homology as well as non-homology mutation mechanisms, where mutation cluster 1 and the other two dnSVs are caused by mutation mechanisms lacking sequence homology. The 64 bp deletion and mutation cluster 1 were validated through PCR. Lastly, the 64 bp deletion and the 573 bp duplication were validated in sequenced offspring of probands with three generations of sequence data. CONCLUSIONS: Our estimate of 0.108 dnSVs per generation in the swine germline is conservative, due to our small sample size and restricted possibilities of dnSV detection from short-read sequencing. The current study highlights the complexity of dnSVs and shows the potential of breeding programs for pigs and livestock species in general, to provide a suitable population structure for identification and characterisation of dnSVs.

Dalteparin and anti-Xa: a complex interplay of therapeutic drug monitoring.

BACKGROUND: Monitoring low-molecular-weight heparins is generally not required. However, guidelines advise to monitor anti-Xa levels in patients with renal insufficiency or a BMI above 50, and in pregnancy. Measuring anti-Xa levels is a complex challenge since sampling should be performed three to five hours after subcutaneous injection and after steady state concentrations have been reached. Strict compliance is pivotal for justified dose adjustments. OBJECTIVES: We questioned compliance to our protocol and performed this study to explore that. METHODS: This retrospective cohort study included patients ≥ 18 years receiving therapeutic dalteparin in a Dutch academic medical centre. Patients with a first anti-Xa level measured between February 23rd and December 30th, 2017 were selected. According to our local guideline, monitoring anti-Xa activity is indicated in patients on therapeutic doses of dalteparin who are pregnant, morbidly obese (BMI > 50), or have renal insufficiency (clearance < 60 ml/min). Accurate sampling was defined as measuring levels after at least three injections (after which a patient may reach steady state) and then four hours after the injection with dalteparin. The frequency of compliance to our protocol was assessed. RESULTS: We included 158 patients with 396 anti-Xa levels, of which 41% (65/158) of all first anti-Xa levels were drawn without appropriate indication. Almost half, 48% (211/396), were sampled incorrectly and 25% of these (53/211) were followed by a dose adjustment. In total, 74% (293/396) of the samples were not indicated or were taken at the wrong time. CONCLUSIONS: Monitoring anti-Xa levels is a complex clinical challenge. This study showed that non-compliance with recommendations for anti-Xa monitoring was high, often resulting in unjustified dose adjustments.

Treating repetitive suicidal intrusions using eye movements: study protocol for a multicenter randomized clinical trial.

BACKGROUND: Suicide is a major public health problem, and it remains unclear which processes link suicidal ideation and plans to the act of suicide. Growing evidence shows that the majority of suicidal patients diagnosed with major depression or bipolar disorder report repetitive suicide-related images and thoughts (suicidal intrusions). Various studies showed that vividness of negative as well as positive intrusive images may be reduced by dual task (e.g. eye movements) interventions taxing the working memory. We propose that a dual task intervention may also reduce frequency and intensity of suicidal imagery and may be crucial in preventing the transition from suicidal ideation and planning to actual suicidal behaviour. This study aims a) to evaluate the effectiveness of an Eye Movement Dual Task (EMDT) add-on intervention targeting suicidal imagery in depressed patients, b) to explore the role of potential moderators and mediators in explaining the effect of EMDT, and c) to evaluate the cost-effectiveness of EMDT. METHODS: We will conduct a multi-center randomized clinical trial (RCT) evaluating the effects of EMDT in combination with usual care (n = 45) compared to usual care alone (n = 45). Participants will fill in multiple online batteries of self-report questionnaires as well as complete a semi-structured interview (Intrusion Interview), and online computer tasks. The primary outcome is the frequency and intrusiveness of suicidal imagery. Furthermore, the vividness, emotionality, and content of the suicidal intrusions are evaluated; secondary outcomes include: suicidal behaviour and suicidal ideation, severity of depression, psychological symptoms, rumination, and hopelessness. Finally, potential moderators and mediators are assessed. DISCUSSION: If proven effective, EMDT can be added to regular treatment to reduce the frequency and vividness of suicidal imagery. TRIAL REGISTRATION: The study has been registered on October 17th, 2018 at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR7563 ).

Validation of flow cytometric analysis of platelet function in patients with a suspected platelet function defect.

Essentials The diagnosis of mild platelet function disorders (PFDs) is challenging. Validation of flow cytometric testing in patients with suspected PFDs is required. Flow cytometry has added value to light transmission aggregometry (LTA) in diagnosis of PFDs. There is fair agreement in diagnosing PFDs between LTA and flow cytometry. SUMMARY: Background Light transmission aggregometry (LTA) is the most commonly used test for the diagnosis of platelet function disorders (PFDs), but has moderate sensitivity for mild PFDs. Flow cytometry has been recommended for additional diagnostics of PFDs but is not yet standardized as a diagnostic test. We developed a standardized protocol for flow cytometric analysis of platelet function that measures fibrinogen binding and P-selectin expression as platelet activation markers in response to agonist stimulation. Objectives To determine the additional value of flow cytometric platelet function testing to standard LTA screening in a cross-sectional cohort of patients with a suspected PFD. Methods Platelet function was assessed with flow cytometry and LTA in 107 patients suspected of a PFD in whom von Willebrand disease and coagulation factor deficiencies were excluded. Both tests were compared in terms of agreement and discriminative ability for diagnosing patients with PFDs. Results Out of 107 patients, 51 patients had an elevated bleeding score; 62.7% of the patients had abnormal platelet function measured with flow cytometry and 54.2% of the patients were abnormal based on LTA. There was fair agreement between LTA and flow cytometry (κ = 0.32). The discriminative ability of flow cytometric analysis in patients with an elevated bleeding score was good (AUC 0.82, 0.74-0.90), but moderate for LTA (AUC 0.70, 0.60-0.80). Both tests combined had a better discriminative ability (AUC 0.87, 0.80-0.94). Conclusion Flow cytometric analysis of platelet function has added value in diagnostics of PFDs in patients with unexplained bleeding tendency.

Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists.

Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: Background It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated. Results Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203-430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP < 400. Conclusion In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients.

Neutrophil CD64 expression as a longitudinal biomarker for severe disease and acute infection in critically ill patients.

INTRODUCTION: Neutrophilic granulocytes express cluster of differentiation 64 (CD64) antigen upon activation. CD64 can be used as a marker of bacterial infection and sepsis. The goal of this study was to determine whether CD64 is a useful biomarker for critically ill patients and analyze longitudinal measurements with regard to outcome and sepsis severity. METHODS: In this prospective observational study, CD64 analysis was performed daily until discharge from ICU or death. Demographics, clinical, laboratory data, and outcome defined as 28-day survival were recorded. Patients were included when admitted to the ICU with sepsis, severe sepsis, or septic shock and within 24 h from start of antibiotic treatment. RESULTS: Hundred and fifty-five consecutive patients were enrolled. At baseline, a difference in CD64 of 2.26 (1.33-4.47) vs. 1.49 (0.89-2.24) (P = 0.004) was seen between patients with a positive culture and negative culture. CD64 at day 1 was higher with patients with septic shock when compared with sepsis (P = 0.012). No difference of CD64 between survivors and nonsurvivors was seen. CONCLUSION: This study demonstrated that CD64 discriminates between critically ill patients with culture positive and negative sepsis and correlates with severity of disease. However, CD64 index is not a good predictor for 28-day mortality in the critically ill patient.

Verification and quality control of routine hematology analyzers.

Verification of hematology analyzers (automated blood cell counters) is mandatory before new hematology analyzers may be used in routine clinical care. The verification process consists of several items which comprise among others: precision, accuracy, comparability, carryover, background and linearity throughout the expected range of results. Yet, which standard should be met or which verification limit be used is at the discretion of the laboratory specialist. This paper offers practical guidance on verification and quality control of automated hematology analyzers and provides an expert opinion on the performance standard that should be met by the contemporary generation of hematology analyzers. Therefore (i) the state-of-the-art performance of hematology analyzers for complete blood count parameters is summarized, (ii) considerations, challenges, and pitfalls concerning the development of a verification plan are discussed, (iii) guidance is given regarding the establishment of reference intervals, and (iv) different methods on quality control of hematology analyzers are reviewed.

Elevated mean neutrophil volume represents altered neutrophil composition and reflects damage after myocardial infarction.

Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU, p < 0.0001) and correlated with simultaneously measured CK levels (R = 0.357, p < 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU), p < 0.0001). MNV correlated with infarct size (R = 0.705, p = 0.007) and inversely correlated with left ventricular ejection fraction (R = -0.718, p = 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU, p = 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU, p = 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia-reperfusion.

Long Term Results of Kissing Stents in the Aortic Bifurcation.

BACKGROUND: To evaluate the long-term outcome after aortoiliac kissing stent placement and to analyze variables, which potentially influence the outcome of endovascular reconstruction of the aortic bifurcation. METHODS: All patients treated with aortoiliac kissing stents at our institution between April 1995 and August 2011 were retrospectively identified from a prospective single-center database. Data regarding patient characteristics (age, gender, smoking, cardio- and cerebrovascular risk factors, hyperlipidaemia, diabetes mellitus and use of antihypertensive medication), symptoms, pre-interventional examination and imaging, procedural details and follow-up were retrieved. Patency rates were calculated with Kaplan-Meier analysis. Factors affecting the patency were determined with Cox uni- and multivariate analysis. RESULTS: A total of 215 patients (63% men, mean age 61 ±â€ˆ10 years) were included. The median follow-up period was 31 (IQR 47.1) months. Primary, primary assisted, and secondary patency rates were 97%, 97%, and 99%, respectively, at one month; 92%, 95% and 94% at four months; 75%, 86%, and 91% at two years; 70%, 81%, and 91% at 5 years; and 67%, 81%, and 91% at ten years. Younger age and previous aortoiliac treatment were predictors for reduced primary and primary assisted patency. Smoking, previous aortoiliac intervention, TASC C and D lesions were predictors for reduced secondary patency. CONCLUSIONS: Reconstruction of the aortoiliac bifurcation with kissing stents is feasible, safe and effective in all types of lesions with satisfying long term patencies. TASC C and D lesions are associated with a higher occlusion rate. Younger age and previous aortoiliac interventions are predictors for reduced primary and primary assisted patency.

Polymorphisms in the glucocorticoid receptor gene and in the glucocorticoid-induced transcript 1 gene are associated with disease activity and response to glucocorticoid bridging therapy in rheumatoid arthritis.

Glucocorticoids (GC) are widely used in rheumatoid arthritis (RA). Ongoing active disease due to GC resistance may unfavorably influence long-term disease outcome in RA. We studied the association between the presence of glucocorticoid receptor (GR) and glucocorticoid-induced transcript 1 (GLCCI1) gene polymorphisms, which modulate GC sensitivity, and baseline disease activity score (DAS) and efficacy of GC bridging therapy in RA. We prospectively studied in vivo GC sensitivity in 138 patients with recent-onset or longstanding RA. In vivo GC sensitivity was expressed as the relative decrease in DAS following 2 weeks of standardized GC therapy. All patients were genotyped for the GR polymorphisms BclI (rs41423247), N363S (rs6195), 9ß (rs6198), ER22/23EK (rs6189 + rs6190), and the GLCCI1 variant rs37972 and subsequently divided in groups carrying a polymorphism associated with increased GC sensitivity (BclI-G allele, N363S-G allele, GLCCI1-C allele) or decreased GC sensitivity (9ß-G allele, ER22/23EK-A/A allele, GLCCI1-T allele). Differences in baseline DAS and relative decrease in DAS in the different genotype groups were analyzed using analysis of covariance and linear regression. Baseline DAS was higher in patients who carried polymorphisms of the GR and GLCCI1 genes associated with decreased GC sensitivity. GLCCI1 genotype, but not GR genotypes, was associated with improvement in DAS in male patients with RA. The GLCCI1 gene minor allele (rs37972) may be associated with less efficient GC bridging therapy in male RA patients. Carriers of the BclI-G, N363S-G, or GLCCI1-C alleles had lower levels of baseline disease activity, suggesting a role for the GLCCI1 and GR gene in regulation of GC sensitivity to endogenously produced cortisol.

Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis.

OBJECTIVE: To investigate if erythrocyte-methotrexate-polyglutamate (MTX-PG) concentrations in patients with rheumatoid arthritis (RA) are associated with disease activity or adverse events. METHODS: We used a longitudinal study design with two cohorts. The derivation cohort included 102 and the validation cohort included 285 patients with RA on MTX. We measured erythrocyte-MTX-PG with 1-5 glutamate residues at 3 months, 6 months and 9 months after MTX start with a liquid chromatography (LC)-mass spectrometry (MS)/MS assay. Outcomes were disease activity score in 28 joints (DAS28) and adverse events. Longitudinal associations of MTX-PG concentrations after 3 months, 6 months and 9 months with DAS28 were tested with a linear mixed model adjusted for age, gender, baseline DAS28, MTX dose and comedication. RESULTS: In the derivation cohort, mean DAS28 decreased from 4.26 (SE=0.14) at baseline to 2.72 (SE=0.13) after 9 months. Thirty per cent of patients in the derivation cohort experienced more than three adverse events after 3 months, which decreased to 18% after 9 months. In the validation cohort, DAS28 and adverse events were comparable with the derivation cohort. In the derivation cohort, MTX-PG1 (ß=-0.005), MTX-PG2 (ß=-0.022), MTX-PG3 (ß=-0.007) and total MTX-PG (ß=-0.004) were associated (p<0.05) with lower DAS28 over 9 months. In the validation cohort, MTX-PG2 (ß=-0.015), MTX-PG3 (ß=-0.010), MTX-PG4 (ß=-0.008) and total MTX-PG (ß=-0.003) were associated with lower DAS28 over 9 months. None of the MTX-PGs was associated with adverse events. CONCLUSIONS: In this first longitudinal study, we showed that an increase in erythrocyte-MTX-PG concentration was associated with a decreased DAS28 over 9 months in two cohorts, and is therefore a potential tool for therapeutic drug monitoring of MTX in RA.

[A woman with pain, stiffness and skin abnormalities]. / Een vrouw met pijn, stijfheid en huidafwijkingen.

A young woman was diagnosed with SAPHO syndrome. She presented with retrosternal pain and lumbar stiffness in combination with hidradenitis. DXA scan indicated secondary osteoporosis of the lumbar spine caused by chronic inflammation. Bone scintigraphy showed increased sternal uptake. Treatment with immunosuppressive agents was started after which the stiffness improved.

Genetic and phenotypic parameters for carcass and meat quality traits in commercial crossbred pigs.

Pork quality and carcass characteristics are now being integrated into swine breeding objectives because of their economic value. Understanding the genetic basis for these traits is necessary for this to be accomplished. The objective of this study was to estimate phenotypic and genetic parameters for carcass and meat quality traits in 2 Canadian swine populations. Data from a genomic selection study aimed at improving meat quality with a mating system involving hybrid Landrace × Large White and Duroc pigs were used to estimate heritabilities and phenotypic and genetic correlations among them. Data on 2,100 commercial crossbred pigs for meat quality and carcass traits were recorded with pedigrees compromising 9,439 animals over 15 generations. Significant fixed effects (company, sex, and slaughter batch), covariates (cold carcass weight and slaughter age), and random additive and common litter effects were fitted in the models. A series of pairwise bivariate analyses were implemented in ASReml to estimate phenotypic and genetic parameters. Heritability estimates (±SE) for carcass traits were moderate to high and ranged from 0.22 ± 0.08 for longissimus dorsi muscle area to 0.63 ± 0.04 for trimmed ham weight, except for firmness, which was low. Heritability estimates (±SE) for meat quality traits varied from 0.10 ± 0.04 to 0.39 ± 0.06 for the Minolta b* of ham quadriceps femoris muscle and shear force, respectively. Generally, most of the genetic correlations were significant (P < 0.05) and ranged from low (0.18 ± 0.07) to high (-0.97 ± 0.35). There were high negative genetic correlations between drip loss with pH and shear force and a positive correlation with cooking loss. Genetic correlations between carcass weight (both hot and cold) with carcass marbling were highly positive. It was concluded that selection for increasing primal and subprimal cut weights with better pork quality may be possible. Furthermore, the use of pH is confirmed as an indicator for pork water-holding capacity and cooking loss. The heritabilities of carcass and pork quality traits indicated that they can be improved using traditional breeding methods and genomic selection, respectively. The estimated genetic parameters for carcass and meat quality traits can be incorporated into the breeding programs that emphasize product quality in these Canadian swine populations.

A two-nucleotide deletion renders the mannose-binding lectin 2 (MBL2) gene nonfunctional in Danish Landrace and Duroc pigs.

The mannose-binding lectins (MBLs) are central components of innate immunity, facilitating phagocytosis and inducing the lectin activation pathway of the complement system. Previously, it has been found that certain single-nucleotide polymorphisms (SNPs) in porcine MBL1 and MBL2 (pMBL1, pMBL2) affect mRNA expression, serum concentration, and susceptibility to disease, but the combinatory effect of pMBL1 and pMBL2 genotypes needs further elucidation. In the present study, pMBL1 and pMBL2 alleles, combined pMBL haplotypes, and MBL-A concentration in serum were analyzed in purebred Landrace (N = 30) and Duroc (N = 10) pigs. Furthermore, the combined pMBL haplotypes of 89 Piètrain × (Large White × Landrace) crossbred pigs were studied, and the genotypes of 67 crossbreds challenged with Escherichia coli were compared to their individual disease records. In the purebred animals, three non-synonymous SNPs and a two-nucleotide deletion were detected in the coding sequence of pMBL2. The two-nucleotide deletion was present at a frequency of 0.88 in the Landrace pigs and 0.90 in the Duroc pigs, respectively. In the crossbreds, the T allele of the SNP G949T in pMBL1-previously shown to have profound effect on MBL-A concentration even in the heterozygote condition-was detected in 47 % of the animals. Finally, an association was found between low-producing MBL genotypes and low body weight on the day of weaning in the same animals.

Optimizing fracture prevention: the fracture liaison service, an observational study.

UNLABELLED: The response rate to the invitation to the fracture liaison service and reasons for non-response were evaluated in 2,207 fragility fracture patients. Fifty-one percent responded; non-responders were most often not interested (38 %) or were hip fracture patients. After 1 year of treatment, 88 % was still persistent and 2 % had a new fracture. INTRODUCTION: To increase the percentage of elderly fracture patients undergoing a dual energy x-ray absorptiometry (DXA) measurement, and to investigate why some patients did not respond to invitation to our fracture liaison service (FLS). METHODS: In four Dutch hospitals, fracture patients ≥ 50 years were invited through a written or personal invitation at the surgical outpatient department, for a DXA measurement and visit to our FLS. Patients who did not respond were contacted by telephone. In patients diagnosed with osteoporosis, treatment was started. Patients were contacted every 3 months during 1 year to assess drug persistence and the occurrence of subsequent fractures. RESULTS: Of the 2,207 patients who were invited, 50.6 % responded. Most frequent reasons for not responding included: not interested (38 %), already screened/under treatment for osteoporosis (15.7 %), physically unable to attend the clinic (11.5 %), and death (5.2 %). Hip fracture patients responded less frequently (29 %) while patients with a wrist (60 %) or ankle fracture (65.2 %) were more likely to visit the clinic. In 337 responding patients, osteoporosis was diagnosed and treatment was initiated. After 12 months of follow-up, 88 % of the patients were still persistent with anti-osteoporosis therapy and only 2 % suffered a subsequent clinical fracture. CONCLUSION: In elderly fracture patients, the use of a FLS leads to an increased response rate, a high persistence to drug treatment, and a low rate of subsequent clinical fractures. Additional programs for hip fracture patients are required, as these patients have a low response rate.

Quantitative ultrasound of the heel as triage test to measure bone mineral density compared with dual energy X-ray absorptiometry in men with prostate cancer commencing with androgen deprivation therapy.

OBJECTIVE: Androgen deprivation therapy (ADT) puts patients at an increased risk of developing osteoporosis. Assessment of bone mineral density (BMD) is most commonly performed by dual energy X-ray absorptiometry (DXA). Alternative ways of estimating BMD, such as quantitative ultrasound (QUS) measurement of the heel, are explored as DXA is expensive, non-portable and uses ionising radiation. We therefore investigated the diagnostic value of QUS as compared with DXA in patients commencing ADT. METHODS: In this cross-sectional study of 60 patients with prostate cancer who were about to start ADT, BMD was measured with DXA and QUS. The fracture risk score, as implemented by the Dutch National Osteoporosis Guideline, was also measured. RESULTS: No significant correlations were found between the separate DXA T scores and worst DXA T score, and the QUS T scores. Correlations between DXA T scores/QUS scores and fracture risk score were also non-significant. If QUS had been used as a screening tool, with a threshold of T ≤ -0.5 to perform DXA, then relevant osteopenia/osteoporosis (worst DXA T score ≤ -2.0) would have been missed in 1/18 (5.6%) patients. The negative predictive value is 0.95. Using QUS as a screening test prior to DXA and a QUS threshold T score ≤ -0.5 would avoid 21 (35%) DXA scans at the cost of missing one (5.6%) case. CONCLUSION: QUS testing cannot replace DXA scans fully as a diagnostic test. However, QUS can be incorporated as triage test prior to DXA to reduce the need for unnecessary DXA scans and the associated costs.

Components in soy allergy diagnostics: Gly m 2S albumin has the best diagnostic value in adults.

BACKGROUND: Thus far, four soy allergens have been characterized. Their diagnostic value was assessed only using a case-control design with controls not suspected of soy allergy or in a soy-allergic population without controls. Our objective was to analyze the diagnostic value of specific immunoglobulin E (sIgE) to Gly m 2S albumin, Gly m 4, 5, and 6, and their possible relation with severity or culprit soy product. METHODS: Adult patients suspected of soy allergy were included (n = 46). Allergy was confirmed by challenge (n = 19) or history (n = 16) and excluded by challenge in 11 patients. Soy components were analyzed by ImmunoCAP. Diagnostic value was assessed in the challenged patient group by an area under receiver operating characteristic (ROC) curve (AUC). RESULTS: Specific immunoglobulin E to Gly m 2S albumin had the highest AUC (0.79), comparable to skin prick test (SPT) and sIgE to soy extract (0.76 and 0.77, respectively). All patients were sensitized to either soy extract or Gly m 4 (sIgE ≥ 0.35 kU/l). sIgE to soy extract, Gly m 5, and Gly m 6 was significantly higher in patients with mild symptoms (P = 0.04, 0.02 and 0.02, respectively). Patients only reacting to soy milk had higher sIgE levels to Gly m 4 (median 9.8 vs 1.1 kU/l, P = 0.01). CONCLUSION: Specific immunoglobulin E to Gly m 2S albumin had the best accuracy in diagnosing soy allergy. Gly m 5 and 6 were related to mild symptoms. Higher levels of Gly m 4 were related to allergy to soy milk.