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.     

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.     

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.     

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.     

Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate.

This study evaluated factors influencing fracture (n = 197) and osteotomy (n = 200) healing in children with moderate to severe OI. Pamidronate treatment was associated with delayed healing after osteotomy, but not after fracture. The data suggest that both pamidronate and mechanical factors influence bone healing in this cohort. INTRODUCTION: Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). However, the effect of this treatment on bone healing is not well characterized. We therefore retrospectively analyzed the healing of lower limb fractures and osteotomies in children with moderate to severe OI, both before and after the start of pamidronate treatment. MATERIALS AND METHODS: Bone healing was evaluated on standard radiographs after 197 lower limb fractures (132 femur and 65 tibia) in 82 patients (age at fracture, 0.0-19.9 years) and 200 intramedullary rodding procedures in 79 patients (age at surgery, 1.2-19.8 years). Delayed healing was diagnosed when a fracture or osteotomy line was at least partially visible 12 months after the event. RESULTS: Delayed fracture healing was observed more frequently during than before pamidronate treatment. However, the effect of pamidronate was no longer significant when age differences were taken into account (odds ratio [OR], 1.76; 95% CI, 0.61-5.10). Better mobility status was a strong independent predictor of delayed healing after fractures that occurred during pamidronate treatment. After osteotomies, delayed healing was more frequent when pamidronate had been started before surgery (OR, 7.29; 95% CI, 2.62-20.3), and this effect persisted after adjustment for multiple confounders. During pamidronate treatment, older age (OR per year of age, 1.25; 95% CI, 1.06-1.47) and osteotomy of the tibia (OR, 3.51; 95% CI, 1.57-7.82) were independent predictors of delayed healing. CONCLUSIONS: This study suggests that pamidronate therapy is associated with delayed healing of osteotomy sites after intramedullary rodding procedures. Better mobility status, but not pamidronate treatment, seems to be predictive of delayed healing after fractures.     

Sudden infant death, Williams-Beuren-Syndrom oder beides?

SummaryThe Williams-Beuren syndrome is a genetic disorder caused by a deletion of the elastin gene mapped on chromosome 7 (7q11.23). This results in multi-organ malformation, mental retardation and generalised elastin arteriopathy, which can lead to cardiac and vascular complications and to sudden death. We present two cases in which a postmortem examination was initially carried out with the presumptive diagnosis of sudden infant death, but cardiac malformations and facial dysmorphisms were recognised that could confirm the diagnosis of Williams-Beuren syndrome. In both cases nearly the same pathological findings were seen in the heart and lungs by histological examination. We will discuss if these findings could have caused death and if they can confirm our presumptive diagnosis of a William-Beuren syndrome which could not be verified by a genetic investigation.     

Enzyme immunoassay of histamine in foods

A competitive enzyme immunoassay of histamine in foodstuffs has been developed using a monoclonal antibody against a histamine‐benzoquinone adduct. In this assay, histamine present in food samples was treated with 1,4‐benzoquinone to form histamine‐benzoquinone by a simple and quick reaction and a histamine‐benzoquinone‐horse‐radish peroxidase conjugate was used as the labelled hapten. The apparent association constant (K_a) of the antibody used was 3.6 ×10⁶ l/mol and Gibbs’ energy of the immune complex formation has been estimated to find the optimal incubation time of the assay. The method enabled determination of histamine in fish, cheese, wine and beer at a concentration as low as 7 ng/ml with an accuracy of ± 15%. The recovery of the immunoassay was 88.9–114%. Cross‐reactivities of histidine, tyramine, tryptamine and its derivatives were lower than 0.001% and did not affect the assay.     

Monospecific but not polyreactive human hybridoma rheumatoid factors exhibit preferential binding specificities for IgG3 and IgG4

Summary Among 38 human hybridoma-derived monoclonal rheumatoid factors (RFs) generated from patients with either rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), two groups of RFs can be identified. Monospecific RFs were derived primarily from patients with RA and are characterized by a binding specificity for IgG3 and/or IgG4. Polyreactive RFs were derived largely from patients with SLE and show a broader pattern of reactivity to all four isotypes of IgG. Neither population of RFs was exclusive to either disease. The binding specificities identified appear to be different from the RFs isolated from patients with mixed cryoglobulinemia and may reflect a different antigen selection mechanism.     

Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.     

Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood–spinal cord barrier

Angiogenesis precedes recovery following spinal cord injury and its extent correlates with neural regeneration, suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to the formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two-component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant + ECs or implant + NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a fourfold increase in functional vessels compared with the lesion control, implant alone or implant + NPCs groups and a twofold increase in functional vessels over the implant + ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for the formation of the blood–spinal cord barrier. No other groups have shown positive staining for the blood–spinal cord barrier in the injury epicenter. This work provides a novel method to induce angiogenesis following spinal cord injury and a foundation for studying its role in repair.