A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: Monitoring of testosterone replacement therapy with testosterone buciclate

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I- study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2x4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunsassay of r = 0.89. The sample volume required by this method is only 180 mu l for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean+/-SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean+/-SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception

Outpatient costs in pharmaceutically treated diabetes patients with and without a diagnosis of depression in a Dutch primary care setting

<p>Abstract</p> <p>Background</p> <p>To assess differences in outpatient costs among pharmaceutically treated diabetes patients with and without a diagnosis of depression in a Dutch primary care setting.</p> <p>Methods</p> <p>A retrospective case control study over 3 years (2002-2004). Data on 7128 depressed patients and 23772 non-depressed matched controls were available from the electronic medical record system of 20 general practices organized in one large primary care organization in the Netherlands. A total of 393 depressed patients with diabetes and 494 non-depressed patients with diabetes were identified in these records. The data that were extracted from the medical record system concerned only outpatient costs, which included GP care, referrals, and medication.</p> <p>Results</p> <p>Mean total outpatient costs per year in depressed diabetes patients were €1039 (SD 743) in the period 2002-2004, which was more than two times as high as in non-depressed diabetes patients (€492, SD 434). After correction for age, sex, type of insurance, diabetes treatment, and comorbidity, the difference in total annual costs between depressed and non-depressed diabetes patients changed from €408 (uncorrected) to €463 (corrected) in multilevel analyses. Correction for comorbidity had the largest impact on the difference in costs between both groups.</p> <p>Conclusions</p> <p>Outpatient costs in depressed patients with diabetes are substantially higher than in non-depressed patients with diabetes even after adjusting for confounders. Future research should investigate whether effective treatment of depression among diabetes patients can reduce health care costs in the long term.</p

Current use and barriers and facilitators for implementation of standardised measures in physical therapy in the Netherlands

In many countries, the need for physical therapists to use standardised measures has been recognised and is recommended in clinical practice guidelines. Research has shown a lack of clinimetric knowledge and clinical application of measurement instruments in daily practice may hamper implementation of these guidelines. The aims of this study are 1) to investigate the current use of measurement instruments by Dutch physical therapists; 2) to investigate the facilitators and barriers in using measurement instruments

Are Pain Intensity and Pain Related Fear Related to Functional Capacity Evaluation Performances of Patients with Chronic Low Back Pain?

Introduction: Pain related fear and pain intensity have been identified as factors negatively influencing Functional Capacity Evaluation (FCE) performances in patients with CLBP. Conflicting results have been reported in the literature. The objective of this study was to analyze the relationships between pain intensity and pain-related fear on the one hand, and performances during an FCE on the other hand in two samples of patients with chronic low back pain (CLBP). Methods: Two cross sectional observation studies were performed with two samples of patients with CLBP (study 1: n = 79; study 2: n = 58). Pain related fears were operationally defined as the score on the Tampa Scale of Kinesiophobia in study 1, and the Fear Avoidance Beliefs Questionnaire (FABQ) in study 2. Pain intensity was measured with a Numeric Rating Scale in both studies. Avoidance behavior observed during FCE was in both studies operationally defined as the unwillingness to engage in high intensity performance levels of three different functional activities: high intensity lifting, prolonged standing in a forward bend position, and fast repetitive bending at the waist. Results: A total of 25 correlations between pain and pain related fear, and performance variables were calculated, out of which 7 were significant (p < 0.05). The strength of these significant correlations ranged from r = −0.23 to r = −0.50. Multivariate linear regression analyses revealed non-significant relationships in most instances. Pain and pain related fear contributed little if any to these models. Conclusions: The relation between pain and pain related fear and FCE performance is weak or non-existent in patients with CLBP

Inter-rater reliability and stability of diagnoses of autism spectrum disorder in children identified through screening at a very young age

To examine the inter-rater reliability and stability of autism spectrum disorder (ASD) diagnoses made at a very early age in children identified through a screening procedure around 14 months of age. In a prospective design, preschoolers were recruited from a screening study for ASD. The inter-rater reliability of the diagnosis of ASD was measured through an independent assessment of a randomly selected subsample of 38 patients by two other psychiatrists. The diagnoses at 23 months and 42 months of 131 patients, based on the clinical assessment and the diagnostic classifications of standardised instruments, were compared to evaluate stability of the diagnosis of ASD. Inter-rater reliability on a diagnosis of ASD versus non-ASD at 23 months was 87% with a weighted κ of 0.74 (SE 0.11). The stability of the different diagnoses in the autism spectrum was 63% for autistic disorder, 54% for pervasive developmental disorder, not otherwise specified (PDD-NOS), and 91% for the whole category of ASD. Most diagnostic changes at 42 months were within the autism spectrum from autistic disorder to PDD-NOS and were mainly due to diminished symptom severity. Children who moved outside the ASD category at 42 months made significantly larger gains in cognitive and language skills than children with a stable ASD diagnosis. In conclusion, the inter-rater reliability and stability of the diagnoses of ASD established at 23 months in this population-based sample of very young children are good

Protocol of the COSMIN study: COnsensus-based Standards for the selection of health Measurement INstruments

BACKGROUND: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. METHOD: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. DISCUSSION: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase

Neonatal mortality: an invisible and marginalised trauma

Neonatal mortality is a major health problem in low and middle income countries and the rate of improvement of newborn survival is slow. This article is a review of the PhD thesis by Mats Målqvist, titled ‘Who can save the unseen – Studies on neonatal mortality in Quang Ninh province, Vietnam,’ from Uppsala University. The thesis aims to investigate structural barriers to newborn health improvements and determinants of neonatal death. The findings reveal a severe under-reporting of neonatal deaths in the official health statistics in Quang Ninh province in northern Vietnam. The neonatal mortality rate (NMR) found was four times higher than what was reported to the Ministry of Health. This underestimation of the problem inhibits adequate interventions and efforts to improve the survival of newborns and highlights the invisibility of this vulnerable group

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background: Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method: In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results: We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion: We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values

A Pilot Study of Abnormal Growth in Autism Spectrum Disorders and Other Childhood Psychiatric Disorders

The aims of the current study were to examine whether early growth abnormalities are (a) comparable in autism spectrum disorders (ASD) and other childhood psychiatric disorders, and (b) specific to the brain or generalized to the whole body. Head circumference, height, and weight were measured during the first 19 months of life in 129 children with ASD and 59 children with non-ASD psychiatric disorders. Both groups showed comparable abnormal patterns of growth compared to population norms, especially regarding height and head circumference in relation to height. Thus abnormal growth appears to be related to psychiatric disorders in general and is mainly expressed as an accelerated growth of height not matched by an increase in weight or head circumference