What makes a biostatistician?

Biostatisticians play an important role in medical research. They are co-responsible for an appropriate and efficient study design, they are involved in monitoring the study conduct, they plan and perform the data analysis, and they are involved in interpreting and publishing the results. However, how are the biostatisticians prepared for their tasks and responsibilities? Graduate programs in biostatistics are being offered, but some practicing biostatisticians completed their studies in a mathematical or epidemiological program, or obtained their degree in subject-specific fields (such as medicine or biology). Therefore, the expertise and the competencies can vary widely between the individual biostatisticians, also depending on the application field. In this article, focusing on European and US practices, we discuss the required professional expertise for the main areas of applications in the medical field as well as the necessary soft skill competencies of a biostatistician.     

Cataract Surgery in HIV Seropositive Patients: Long-Term Follow-Up

Purpose: To study epidemiology and clinical findings of cataract in HIV+ patients.

Methods: A total of 32 HIV+ patients, 11 with uveitis/retinitis before surgery and 21 without, mean follow-up 44.9 ± 36.6 months, and 114 HIV- patients, 57 with uveitis/retinitis before surgery and 57 without, were retrospectively compared.

Results: Visual acuity improved in all HIV+ patients (p < 0.001), who were younger (p = 0.01) and more frequently males (p = 0.027). HIV+ patients with uveitis prior surgery improved less (p = 0.046) than HIV- (p < 0.001); their anterior chamber inflammation was similar to baseline. Male sex (p = 0.005), younger age (p < 0.001), dyslipidaemia (p = 0.058), HBV+ (p = 0.037), and unilateral cataract (p = 0.001) were more frequent in HIV+ patients with senile cataract, but they showed the same postoperative course as HIV- patients.

Conclusion: Cataract surgery in HIV+ patients is safe and effective. Uveitis prior to surgery did not significantly affect the postoperative course. Systemic comorbidities are more frequent in HIV+ patients with senile cataract than in HIV- subjects.     

Subdental synchondrosis and anatomy of the axis in aging: a histomorphometric study on 30 autopsy cases

During skeletal development the two ossification centers of the odontoid process are separated from the corpus of the axis by a subdental synchondrosis. This synchondrosis is thought to close and disappear spontaneously in adolescence although this has never been studied in detail. The basis of the dens is of clinical relevance as type II dens fractures are located here. To characterize the morphological architecture of the axis with particular attention to the subdental synchondrosis, the complete axis was harvested from thirty age-matched and gender-matched patients of the three different age groups at autopsy. The subdental synchondrosis and the bone structure of the dens, the basis of the dens and the body of C2 were analyzed by radiography, histology and quantitative histomorphometry. At the macroscopic level the persistency of the subdental synchondrosis in the adult cervical spine was detected in 87% (26 of 30) of the specimens. Histomorphometry revealed a residual disc blastema with an average size of 25.8% of the sagittal depth of the basis of the dens at this level. Bony integration of the synchondrosis was poor throughout all ages. Histologically a cartilaginous matrix composition of the subdental synchondrosis persisted throughout all groups. The trabecular microarchitecture demonstrated a significant reduction of bone volume and trabecular number as well as an increased trabecular separation within the basis of the dens as compared to the corpus or the dens of C2. This histomorphometric data regarding a poor integration of the synchondrosis into the trabecular network and the reduced bone mass within the basis of the dens might offer a previously underestimated explanation for the occurrence of type II dens fractures and their association with pseudoarthrosis, respectively.Matthias Gebauer and Christian Lohse contributed equally to this study and therefore share first authorship.     

Posttraumatic stress, depression, and health among older adults in primary care.

OBJECTIVE: The authors examined 1) rates of trauma and posttraumatic stress (PTS) in older adults in primary care; 2) factors related to more posttraumatic stress symptoms; and 3) the influence of posttraumatic stress and depression on health perceptions and negative health behaviors (i.e., suicidal ideation, smoking, and at-risk drinking). METHODS: As part of participation in a study at the Philadelphia VAMC and the University of Pennsylvania, a random subset (N = 2,718) of older adults (age > or = 65 years) with scheduled primary care visits were screened concerning demographics, the General Health Questionnaire-12, suicidal thoughts, alcohol consumption, cigarette smoking, perceived health status, PTS, and cognitive impairment. RESULTS: The rate of trauma in older adult primary care patients was high in both the VA (37%) and university-based clinics (24%). Many older adults reported interference from at least one of the three posttraumatic stress items assessed (VA, 18%; university-based primary care, 8%). In a model including demographic factors, higher PTS and depression were uniquely related to more negative health perceptions. In a model including demographic factors, both higher PTS and depression were uniquely related to higher likelihood of suicidal ideation. In contrast, PTS no longer contributed to a model of smoking once depression was included. Neither PTS nor depression significantly contributed to a model of at-risk drinking. CONCLUSIONS: Trauma and posttraumatic stress are frequent and significant problems for older adults in primary care. Both posttraumatic stress and depression are related to more negative health perceptions and higher likelihood of suicidal ideation.     

Evidence for frequent divergence impairment in French dyslexic children: deficit of convergence relaxation or of divergence per se?

Aim There is a controversy as to whether dyslexic children present visuo-motor disabilities such as vergence and accommodative problems assessed with orthoptic tests. The purpose of this study is to re-examine this issue in a large population of children. Methods Extensive orthoptic evaluation was made in 57 dyslexic and 46 non-dyslexic (“normal”) age-matched children. Convergence and divergence capacities were evaluated at two distances (30 cm and 400 cm). Results Binocular vision measured with stereo-acuity tests was normal in dyslexics. In contrast, the near point of convergence was significantly more remote in dyslexics; most importantly, divergence at both far and near distance was significantly more reduced in dyslexics (median value 4 pD and 10 pD, respectively, at far and near) than in “normals” (median value 6 pD and 12 pD, at far and near). Conclusion The existence of the divergence deficit at far distance indicates the presence of deficit of divergence per se, independently from convergence and accommodation relaxation. This result is novel and corroborated by physiological studies indicating distinct control of convergence and divergence, both at the cortical and subcortical premotor level. We conclude that vergence deficits are frequently present in dyslexics, and that dyslexics should be re-educated; training should address distinctively convergence and divergence subsystems.     

Reproducibility of food atopy patch tests over time in the general child population

Background  The atopy patch test (APT) is no longer an experimental method; it is increasingly being used as a standard diagnostic tool for the characterization of patients with aeroallergen- and food-triggered disorders. Some technical aspects of this test still remain to be answered. We aimed to study the reproducibility of this test over time in the general child population.
Methods  In a general population of 118 children, we investigated the reproducibility of duplicate APTs with four food allergens in their native form, which were repeated at set intervals from the first test: 7 days (group 1), 14 days (group 2), and 21 days (group 3).
Results  We observed very poor reproducibility on both sides of the back in all three studied subgroups. The reproducibility rates and Cohen's κ values did not improve when we did not consider the side of the back. There were no differences in the prevalence of atopy between the subjects with reproducible and nonreproducible APT results. All three groups studied showed no difference in the prevalence rates of atopy. There was no relationship between APT and skin prick test positivity for the same allergen. Questionnaire-derived data about previous food-related reactions did not help in the evaluation of the doubtful nonreproducible APT results with food allergens.
Conclusions  Our results show that the reproducibility of food APTs is poor and unsatisfactory over time, and there is an urgent need for the development of optimal, stable, and good-quality APT testing substances.     

Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane.

BACKGROUND: The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however. METHOD: Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-na?ve, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD. RESULTS: Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder. CONCLUSIONS: These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD.     

Analysis of the degree of precision of a computer-assisted dietary survey method

A computer-assisted method for the registration of food intakes in real time according to a concise and simple procedure was subjected to a series of controls in order to assess precision. The method employs the 'portion' of a composite dish as unit of measure. The constancy of the portion was tested. The results show that the recipes of the diet of a subject may be stored and utilized in deferred time without loss of precision: data to be recorded in real time are then very limited. The length of period of analysis was also studied. The time of investigation should not be shorter than two weeks to obtain precise information on the feeding habits of an individual subject, whereas for a group of subjects the diary of a single day provides information of sufficient precision.     

Glucuronidation of Entacapone, Nitecapone, Tolcapone, and Some Other Nitrocatechols by Rat Liver Microsomes

Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds. Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification. Results. Apparent K_m values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold V_max values compared with 4-nitrophenol (68.6 nmol min^–1 mg^–1), while all disubstituted catechols exhibited much lower glucuronidation rate. V_max/K_m values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: K_m nitecapone >> entacapone > tolcapone; V_max nitecapone > entacapone > tolcapone; V_max/K_m tolcapone > nitecapone > entacapone. Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro.     

Differential induction of cytochrome P-450 by the enantiomers of trans-stilbene oxide

Optically pure (+)- and (-)-trans-stilbene oxide (TSO) enantiomers were administered to immature male Sprague-Dawley rats. (+)-TSO was the more potent inducer of liver microsomal cytochrome P-450-dependent monooxygenases. The greater potency of (+)-TSO may be explained on the basis of stereoselective metabolism since a far greater concentration of TSO was found in liver microsomes of (+)-TSO-treated rats. Furthermore, of the enzymes known to metabolize TSO, cytosolic epoxide hydrolase turned over the (-)-TSO enantiomer at a faster rate, consistent with the greater persistence of the (+)-enantiomer. Although this report is of chiral effects in potency of enzyme induction, stereoselective metabolism (i.e. disposition) rather than inherent structural characteristics (recognition) may be responsible for these effects.