ABSTRACT
Seminal plasma induces immune tolerance towards paternal allogenic antigens within the female reproductive tract and during foetal development. Recent evidence suggests a role for extracellular vesicles in seminal plasma (spEVs). We isolated spEVs from seminal plasma that was donated by vasectomized men, thereby excluding any contributions from the testis or epididymis. Previous analysis demonstrated that such isolated spEVs originate mainly from the prostate. Here we observed that when isolated fluorescently labelled spEVs were mixed with peripheral blood mononuclear cells, they were endocytosed predominantly by monocytes, and to a lesser extent also by T-cells. In a mixed lymphocyte reaction, T-cell proliferation was inhibited by spEVs. A direct effect of spEVs on T-cells was demonstrated when isolated T cells were activated by anti-CD3/CD28 coated beads. Again, spEVs interfered with T cell proliferation, as well as with the expression of CD25 and the release of IFN-γ, TNF, and IL-2. Moreover, spEVs stimulated the expression of Foxp3 and IL-10 by CD4+CD25+CD127- T cells, indicating differentiation into regulatory T-cells (Tregs). Prior treatment of spEVs with proteinase K revoked their effects on T-cells, indicating a requirement for surface-exposed spEV proteins. The adenosine A2A receptor-specific antagonist CPI-444 also reduced effects of spEVs on T-cells, consistent with the notion that the development of Tregs and their immune suppressive functions are under the influence of adenosine-A2A receptor signalling. We found that adenosine is highly enriched in spEVs and propose that spEVs are targeted to and endocytosed by T-cells, after which they may release their adenosine content into the lumen of endosomes, thus allowing endosome-localized A2A receptor signalling in spEVs targeted T-cells. Collectively, these data support the idea that spEVs can prime T cells directly for differentiation into Tregs.
Subject(s)
Cell Differentiation , Extracellular Vesicles , Semen , T-Lymphocytes, Regulatory , Humans , Extracellular Vesicles/metabolism , Extracellular Vesicles/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Semen/metabolism , Semen/immunology , Male , Cell Proliferation , Lymphocyte Activation/immunologyABSTRACT
OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2â¯pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0⯵IU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5â¯pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.
Subject(s)
Thyrotropin , Thyroxine , Humans , Thyroxine/blood , Thyroxine/analysis , Thyrotropin/blood , Thyrotropin/analysis , Thyrotropin/standards , Reference Values , Thyroid Function Tests/standards , Thyroid Function Tests/methods , Adult , Female , Male , Middle Aged , Product Labeling/standardsABSTRACT
OBJECTIVES: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. METHODS: We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results <38â¯g/L for the diagnosis of protein energy wasting. RESULTS: Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2â¯%, respectively vs. 66.7â¯% for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3â¯%) as opposed to BCP (0.7-1.5â¯%). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8â¯% vs. 0.7-1.5â¯% vs. 0.4-1.6â¯%). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. CONCLUSIONS: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.
Subject(s)
Bromcresol Green , Renal Insufficiency, Chronic , Humans , Serum Albumin/analysis , Bromcresol Purple , Renal Dialysis , Renal Insufficiency, Chronic/diagnosisABSTRACT
BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).
Subject(s)
Anemia, Iron-Deficiency , Anemia , Malaria , Infant, Newborn , Female , Humans , Pregnancy , Iron/therapeutic use , Pregnant Women , Pregnancy Trimester, Second , Birth Weight , Anemia, Iron-Deficiency/drug therapy , Malaria/drug therapy , Malaria/prevention & control , Anemia/drug therapy , Malawi/epidemiologyABSTRACT
OBJECTIVES: Testosterone testing is relevant for evaluating castration adequacy and diagnosis of castration-resistant prostate cancer (PCa). However, the recommended testosterone cut-off of 1.7 nmol/L (50 ng/dL) to define adequate castration is based on consensus and not validated for the automated immunoassays (AIA) used in today's medical laboratories. Furthermore, appropriate population intervals have not been determined by a state-of-the-art assay. We investigated the analytical suitability of this cut-off and the accuracy of the present-day AIAs for testosterone analysis in castrated PCa patients. METHODS: Leftover serum from 120 PCa patients castrated with luteinizing hormone-releasing hormone agonists was analysed for testosterone by five methods: Architect i2000 (Abbott), Access (Beckman), Cobas 6000 (Roche), Atellica (Siemens), LC-MS/MS. For all assays, the castration 95th, 97.5th and 99th percentile upper limits were determined. Furthermore, Passing-Bablok regression, mean bias and Spearman's correlation coefficients were compared to the LC-MS/MS method and total error based on biological variation. RESULTS: All castration upper limits, ranging from 0.472 nmol/L (LC-MS/MS) to 1.25 nmol/L (Access) (95% percentile), were significantly lower than the current castration cut-off (1.7 nmol/L). Slopes of Passing-Bablok regressions comparing the AIA with the LC-MS/MS method ranged from 1.4 (Cobas and Atellica) to 3.8 (Access). The Architect showed the highest correlation with LC-MS/MS (ρ=0.58). All AIA failed to meet the desirable total error criterion. CONCLUSIONS: These results suggest that a lower general testosterone castration cut-off may be more appropriate in evaluating the adequacy of castration in PCa and that present-day AIA lack analytical accuracy to quantify testosterone levels in castrated PCa.
Subject(s)
Prostatic Neoplasms , Testosterone , Castration , Chromatography, Liquid , Humans , Immunoassay , Male , Tandem Mass SpectrometryABSTRACT
A postmenopausal woman in her 60s was referred due to an elevated haemoglobin value found during her annual check-up. On physical examination, characteristic features of hyperandrogenism were observed which were not earlier mentioned. Laboratory investigations revealed polycythaemia accompanied by a normal erythropoietin and a negative analysis for JAK2-V617F mutation. A disproportionally and markedly elevated testosterone in combination with normal levels of adrenal androgens raised the suspicion of an ovarian source. CT scan showed nodular hyperdense lesions in both ovaries. A bilateral oophorectomy was performed and histological evaluation unfolded a Leydig cell ovarian tumour. Testosterone levels and haematological parameters normalised after surgery. Polycythaemia secondary to hyperandrogenism in postmenopausal women is an extremely rare condition and patients should be carefully analysed for the presence of androgen-secreting neoplasms. Diagnosis of the underlying pathology requires careful history, physical examination and comprehensive investigation. Treatment for this condition is surgery and resolves polycythaemia.
Subject(s)
Hyperandrogenism , Leydig Cell Tumor , Ovarian Neoplasms , Polycythemia , Androgens , Female , Humans , Hyperandrogenism/diagnosis , Leydig Cell Tumor/complications , Leydig Cell Tumor/diagnosis , Leydig Cell Tumor/surgery , Male , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Polycythemia/complications , TestosteroneABSTRACT
BACKGROUND: In 2017 the Atellica® UAS 800 urine sediment analyzer was introduced by Siemens Healthineers. We investigated its applicability in the standardization and automation of the laboratory urinalysis workflow, including the prediction of urine culture outcome and glomerular pathology. METHODS: We evaluated the performance characteristics of the Atellica® UAS 800 and its correlation with the iQ200 (Beckman Coulter). In addition, we studied the agreement between Atellica® UAS 800 and CLINITEK Novus® and determined the predictive value of bacteria and leukocyte counts for urine culture outcome. Furthermore, we investigated the ability of Atellica® UAS 800 to identify pathological casts and dysmorphic erythrocytes in comparison to manual microscopy. RESULTS: Erythrocyte and leukocyte analyses indicated high intra- and inter-run precisions and good correlations with the iQ200. We found that the Atellica® UAS 800 detects bacteria with higher sensitivity than the iQ200. The Atellica® UAS 800 and CLINITEK Novus® showed a high degree of conformity. We determined seven combinations of clinical cut-off values of bacteria and leukocytes for predicting urine culture outcome with sensitivity, specificity, and negative predictive values of 95%, 52%, and 93%, respectively. Using the Atellica® UAS 800, hyaline casts, erythrocyte casts, leukocyte casts, and dysmorphic erythrocytes were correctly recognized in 76%, 22%, 2%, and 39% of the samples, respectively. CONCLUSIONS: The Atellica® UAS 800 is a robust, fast, and user-friendly analyzer, which accurately quantifies erythrocytes, leukocytes, bacteria and squamous epithelial cells, and may be utilized for predicting positive urine cultures. The detection of clinically important pathological casts and dysmorphic erythrocytes proved insufficient.
Subject(s)
Urinalysis/instrumentation , Automation , Bacteria/metabolism , Erythrocytes/cytology , Humans , Leukocytes/cytology , Logistic Models , ROC Curve , Sensitivity and SpecificityABSTRACT
A 53-year-old woman was referred for medical evaluation of therapy-resistant dyslipidaemia accompanied by elevated creatine kinase levels. Because cessation or alteration of her medication did not improve laboratory abnormalities, hypothyroidism was considered, despite the fact that thyroid stimulating hormone levels were within the reference interval. On further evaluation, she was found to have panhypopituitarism and empty sella turcica as shown by MRI. These findings were unexpected since there was no clinical suspicion during detailed evaluation. When supplementary questions were asked, she brought up a history of severe postpartum haemorrhage 30 years ago, for which she underwent a hysterectomy. Based on these findings, the patient was diagnosed with Sheehan's syndrome. This syndrome is a rare but potentially life-threatening complication of postpartum haemorrhage, characterised by varying degrees of hypopituitarism that are most commonly presented many years after delivery. The patient recovered after adequate hormone replacement therapy.
Subject(s)
Empty Sella Syndrome , Hypopituitarism , Creatine Kinase , Female , Humans , Hypopituitarism/diagnosis , Magnetic Resonance Imaging , Middle Aged , ThyrotropinABSTRACT
BACKGROUND: Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring. OBJECTIVES: We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation. METHODS: We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23). RESULTS: Analysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L). CONCLUSIONS: Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.
Subject(s)
Bone and Bones/metabolism , Dietary Supplements , Ferrous Compounds/administration & dosage , Ferrous Compounds/pharmacology , Fibroblast Growth Factors/metabolism , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/genetics , Gene Expression Regulation/drug effects , Humans , Infant , Kenya , Postpartum PeriodABSTRACT
OBJECTIVES: Carbohydrate-deficient transferrin (CDT) measurements are commonly used for the identification and follow-up of individuals suspected of chronic alcohol abuse. This study describes the analytical characteristics of the CDT assay on the Helena Biosciences V8 electrophoresis analyzer and compares its diagnostic performance to the International Federation of Clinical Chemistry and Laboratory Medicine approved high performance liquid chromatography (HPLC) method and the N-Latex CDT immunonephelometric assay. METHODS: The analytical performance of the V8 assay, including the linearity and the imprecision, was studied at two separate locations. Method comparison analysis was performed by studying the correlation, bias and agreement between the V8, HPLC and the N-Latex assays in 231 patient samples. RESULTS: The total imprecision ranged between 5.1 and 24.3% and was ≤13.1% for samples with concentrations above the clinical cut-off value (≥1.62%). The method comparisons revealed excellent correlations with r2≥0.97 for all comparisons. Measurements on the V8 showed a bias of -0.83 (-22.24%) and -0.40 (-12.26%) with the HPLC and N-Latex assays, respectively. The assays showed excellent agreements (Kappa scores ≥ 0.8) in classifying subjects with elevated CDT values. Receiver operating characteristic (ROC)-curve analysis, using the HPLC classification as reference, revealed areas under the ROC-curves of 0.981 (95% CI, 0.97-0.99) and 0.996 (0.99-1.00) for the N-Latex and V8 assays, respectively. CONCLUSIONS: CDT measurements on the V8 assay are highly correlated with both the HPLC and the N-Latex assay and show excellent agreement in classifying subjects with elevated CDT values. Overall, the V8 CDT analysis is a robust, reliable and effective method to measure CDT concentrations in serum samples.
Subject(s)
Electrophoresis, Capillary , Alcoholism , Biomarkers , Chromatography, High Pressure Liquid , Humans , Immunoturbidimetry , Latex , Transferrin/analogs & derivativesABSTRACT
Background The morphological assessment of urinary erythrocytes (uRBC) is a convenient screening tool for the differentiation of nephrological (dysmorphic) and urological (isomorphic) causes of hematuria. Considering the morphological heterogeneity, this analysis is often perceived as difficult. There is no clear (inter)national consensus and there is a lack of external quality assessment programs. To gain insight into the heterogeneity within and between laboratories, we scrutinized the current state of this analysis in Dutch medical laboratories. Methods The laboratories, affiliated with the Dutch Foundation for Quality Assessment in Medical Laboratories, were invited to participate in a web-based survey, consisting of two questionnaires. The first one provided information about the institution and laboratory organization, and the second explored the variability in the morphological analysis of uRBC on the basis of categorization of 160 uRBC images. Statistical analysis was premised on binomial significance testing and principal component analysis. Results Nearly one third of the Dutch medical laboratories (65/191) with 167 staff members participated in the survey. Most of these laboratories (83%) were an integral part of secondary care. The statistical analysis of the evaluations of the participants in comparison to the consensus (three experts from two different medical laboratories) suggested a great degree of heterogeneity in the agreement. Nearly half of the participants consciously disagreed with the consensus, whereas one fifth demonstrated a random relationship with it. Conclusions In Dutch medical laboratories, results from morphological analysis of uRBC are heterogeneous, which point out the necessity for standardization and harmonization.
Subject(s)
Erythrocytes/cytology , Hematuria/diagnosis , Urine/cytology , Adult , Aged , Diagnostic Tests, Routine/statistics & numerical data , Female , Hematuria/etiology , Hematuria/urine , Humans , Internet , Laboratories/statistics & numerical data , Male , Middle Aged , Netherlands , Surveys and Questionnaires , Young AdultABSTRACT
Serum ferritin concentration is the preferred biomarker to assess population iron status in the absence of inflammation. Interpretation of this biomarker is complicated in populations with a high burden of infection, however, because inflammation increases serum ferritin concentration independently of iron status. We aimed to compare estimates of iron status of Kenyan pregnant women, with circulating ferritin concentrations adjusted for inflammation using newly proposed methods by the BRINDA project, or using previously proposed adjustment methods. We re-analyzed data from pregnant Kenyan women living in a rural area where malaria is highly endemic (n = 470) or in an urban area (n = 402). As proposed by the BRINDA group, we adjusted individual ferritin concentration by internal regression for circulating concentrations of C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Other adjustment methods comprised: (a) arithmetic correction factors based on CRP or AGP; (b) exclusion of subjects with inflammation (CRP >5 mg/L or AGP >1 g/L); and (c) higher ferritin cut-off value (<30 µg/L). We additionally adjusted for Plasmodium infection as appropriate. Lastly, we assessed iron status without adjustment for inflammation. All correction methods increased prevalence of iron deficiency compared to the unadjusted estimates. This increase was more pronounced with the internal regression correction method. The iron deficiency prevalence estimate increased from 53% to 87% in rural Kisumu study and from 30% to 41% in the urban Nairobi study after adjusting for inflammation (CRP and AGP) using the BRINDA internal regression method. When we corrected for both inflammation and Plasmodium infection using the regression correction, it resulted in lower prevalence estimates compared to uninfected women. Application of linear regression methods to adjust circulating ferritin concentration for inflammation leads to markedly decreased point estimates for ferritin concentration and increased estimates for the prevalence of iron deficiency in pregnancy.
Subject(s)
Anemia, Iron-Deficiency/epidemiology , Ferritins/blood , Inflammation/blood , Iron Deficiencies , Pregnancy Complications/epidemiology , Adult , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/etiology , Biomarkers/blood , C-Reactive Protein/analysis , Female , Humans , Kenya/epidemiology , Malaria/blood , Malaria/complications , Malaria/epidemiology , Nutritional Status , Orosomucoid/analysis , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/etiology , Prevalence , Regression Analysis , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data , Young AdultABSTRACT
Despite the fact that a small percentage of peri en postmenopausal women have mild elevations in human chorionic gonadotrophin (hCG) concentrations (<14 IU/L) besides high levels of gonadotrophins, a considerable number of clinicians are not aware of this phenomenon. We report a case of a 53-year-old woman with an unusually high hCG concentration (>40 IU/L) given her menopausal state. Although a pregnancy or a malignancy was unlikely on the basis of stable hCG levels, elevated gonadotrophins and a negative transvaginal ultrasound, her physicians were uncertain and chose an expectant approach by repeated testing. Ultimately, after consulting the laboratory, analytical interference was ruled out and pituitary origin of unusual high hCG level could be confirmed after conduction of a suppression test by oestrogen-progesterone hormone replacement therapy. Until that time, the patient had undergone a vast amount of laboratory tests and gynaecology consultations, resulting in an enormous amount of confusion, anxiety and overdiagnosis.
Subject(s)
Chorionic Gonadotropin/blood , Menopause/blood , Neoplasms/blood , Perimenopause/blood , Pregnancy/blood , Diagnosis, Differential , Female , Gonadotropins/blood , Hormone Replacement Therapy/methods , Humans , Medical Overuse , Menopause/physiology , Menopause/psychology , Middle Aged , Neoplasms/diagnosis , Neoplasms/drug therapy , Perimenopause/physiology , Pituitary Gland/drug effects , Pituitary Gland/physiopathology , Pregnancy/physiology , Ultrasonography/methodsSubject(s)
Anti-Bacterial Agents , C-Reactive Protein , Habits , Humans , Netherlands , Point-of-Care Systems , Primary Health CareSubject(s)
Adrenal Gland Neoplasms/urine , Metanephrine/urine , Urine Specimen Collection , Female , Humans , MaleABSTRACT
OBJECTIVE: Introduction of biofortified cassava as school lunch can increase vitamin A intake, but may increase risk of other deficiencies due to poor nutrient profile of cassava. We assessed the potential effect of introducing a yellow cassava-based school lunch combined with additional food-based recommendations (FBR) on vitamin A and overall nutrient adequacy using Optifood (linear programming tool). DESIGN: Cross-sectional study to assess dietary intakes (24 h recall) and derive model parameters (list of foods consumed, median serving sizes, food and food (sub)group frequency distributions, food cost). Three scenarios were modelled, namely daily diet including: (i) no school lunch; (ii) standard 5d school lunch with maize/beans; and (iii) 5d school lunch with yellow cassava. Each scenario and scenario 3 with additional FBR were assessed on overall nutrient adequacy using recommended nutrient intakes (RNI). SETTING: Eastern Kenya. SUBJECTS: Primary-school children (n 150) aged 7-9 years. RESULTS: Best food pattern of yellow cassava-based lunch scenario achieved 100 % RNI for six nutrients compared with no lunch (three nutrients) or standard lunch (five nutrients) scenario. FBR with yellow cassava and including small dried fish improved nutrient adequacy, but could not ensure adequate intake of fat (52 % of average requirement), riboflavin (50 % RNI), folate (59 % RNI) and vitamin A (49 % RNI). CONCLUSIONS: Introduction of yellow cassava-based school lunch complemented with FBR potentially improved vitamin A adequacy, but alternative interventions are needed to ensure dietary adequacy. Optifood is useful to assess potential contribution of a biofortified crop to nutrient adequacy and to develop additional FBR to address remaining nutrient gaps.
Subject(s)
Diet , Manihot/chemistry , Programming, Linear , Recommended Dietary Allowances , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Dietary Fats/administration & dosage , Female , Folic Acid/administration & dosage , Food Services , Humans , Kenya , Lunch , Male , Mental Recall , Micronutrients/administration & dosage , Micronutrients/blood , Nutrition Assessment , Nutritive Value , Riboflavin/administration & dosage , Schools , Serving Size , Vitamin A/administration & dosage , Vitamin A/bloodABSTRACT
Background: Bacterial resistance to antibiotics represents a serious global challenge that is associated with high morbidity and mortality. One of the most important causes of this threat is antibiotic overuse. The Dutch College of General Practitioners (DCGP) recommends the use of point-of-care (POC) testing for C-reactive protein (CRP) in two guidelines ('Acute Cough' and 'Diverticulitis') to achieve a more sensible prescription pattern of antibiotics. Objective: To evaluate the use of POC-CRP testing in light of the DCGP guidelines and the effect of CRP measurements on antibiotic prescription policy in primary care. Methods: In a prospective observational study, which included 1756 patients, general practitioners (GPs) were asked to complete a questionnaire after every POC-CRP testing, stating the indication for performing the test, the CRP result and their decision whether or not to prescribe antibiotics. Indications were verified against the DCGP guidelines and categorized. Antibiotic prescription was evaluated in relation to CRP concentrations. Results and Conclusion: Indications to perform POC-CRP test and the prescription pattern of antibiotics based on CRP value varied considerably between GPs. Differences in antibiotic prescription rate were most obvious in patients who presented with CRP values between 20 and 100 mg/l, and could in part be explained by the indication for performing POC-CRP test and patient age. Most GPs followed the DCGP guidelines and used low CRP values to underpin their decision to refrain from antibiotic prescription. Peer-based reflection on differences in POC-CRP usage and antibiotic prescription rate amongst GPs may further nourish a more critical approach to prescription of antibiotics.
Subject(s)
Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/analysis , Point-of-Care Testing/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Primary Health Care/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Female , Guideline Adherence , Humans , Male , Middle Aged , Netherlands , Practice Guidelines as Topic , Prospective Studies , Young AdultABSTRACT
BACKGROUND: Zinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12-36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency. METHODS: We used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α1-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration < 12 µg/L. We also developed models to assess the diagnostic utility of ZPP and haemoglobin concentration when used to screen for iron deficiency. RESULTS: Whole blood ZPP and erythrocyte ZPP were independently associated with haemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, and C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to prevalence of 97.5% and 95.1% when assessed by whole blood ZPP and erythrocyte ZPP with conventional cut-off points (70 µmol/mol and 40 µmol/mol haem, respectively). Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p = 0.003, and 84.2%, p = 0.001, respectively, versus 62.7%). A diagnostic rule (0.038689 [haemoglobin concentration, g/L] + 0.00694 [whole blood ZPP, µmol/mol haem] >5.93120) correctly ruled out iron deficiency in 37.4%-53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%. CONCLUSIONS: In young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened. TRIAL REGISTRATION: ClinicalTrials.gov NCT02073149 (25 February 2014).