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.     

Long-term neurological outcome of childhood brain tumors treated by surgery only.

PURPOSE: To evaluate the pattern of neurological late effects in patients who have received surgery only for a brain tumor in childhood and to identify possible risk factors for neurological sequelae. PATIENTS AND METHODS: The medical, histologic, and operative records were reviewed for 65 consecutive patients operated for a benign brain tumor from 1970 to 1997, and all patients were re-examined after a median length of follow-up of 10.7 years. Thirty-four patients had posterior fossa tumors, 22 patients had cerebral hemisphere tumors, and nine patients had midline tumors. RESULTS: At the time of follow-up, 20 patients (31%) had no neurological deficits, 22 patients (34%) had minor deficits that did not interfere with their daily life activities, and 23 patients (35%) had moderate or severe deficits such as severe ataxia, spastic paresis, seriously reduced vision, or epilepsy with more than two seizures per year. Fourteen of the 31 patients (45%) registered with ataxia preoperatively had recovered fully. Six of seven patients had persistence of a pre- or postoperatively developed hemiparesis. Thirteen of 23 patients had persistence of cranial nerve deficits that developed second to surgery. Fifty-five percent of the 18 patients with seizures at diagnosis were seizure-free at follow-up. At follow-up both ataxia and hemiparesis were significantly more frequent among females (P =.02 and P =.03, respectively). CONCLUSION: In patients who received operation as the only treatment for their brain tumor, there was a good chance of total or partial recovery of preoperative and postoperative neurological deficits, although only one third of the patients will have no long-term neurological deficits.     

Severe pyomyositis caused by Panton–Valentine leucocidin-positive methicillin-sensitive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> complicating a pilonidal cyst

Background To our best knowledge, Panton–Valentine leucocidin (PVL)-positive methicillin-sensitive Staphylococcus aureus (MSSA) has not been described yet as cause for severe pyomyositis. Case report We present a 23-year-old apparently healthy male patient without any typical predisposing findings who developed severe pyomyositis secondary to an operated pilonidal cyst. In the follow-up, the patient showed signs of immunocompromisation. The causative agent for purulent infection of multiple muscles was a MSSA strain harbouring PVL toxin. Results In the reported case, aggressive antibiotic and surgical treatment with additional application of immunoglobulins has lead to recovery from the disease without relapse. Conclusions PVL-positive S. aureus are associated with skin diseases, multiple abscesses and often complicated by severe sepsis and necrotising pneumonia. Under such circumstances, the mortality rate can reach up to 75%. In addition, the PVL toxin can cause immunocompromisation and might be therefore involved in the aetiology of pyomyositis. Aggressive antibiotic and surgical treatment with additional application of immunoglobulins is recommended for treatment.     

Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients.

BACKGROUND AND OBJECTIVES: An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. METHODS: Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. RESULTS AND CONCLUSIONS: The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, and patient education and support.     

Susceptibility of Nd:YAG laser-irradiated root surfaces in replanted teeth to external inflammatory resorption

Abstract— NdYAG laser-induced modification of the root surface may inhibit development of external inflammatory resorption in replanted teeth. This study tested this hypothesis in vivo. The pulp chambers of six mandibular premolars in each of two dogs were accessed, inoculated with plaque, and sealed (Groups 1, 2). Two additional premolars in each dog were endodontically treated without inoculation (Groups 3, 4). After 2 weeks, teeth were hemisected and extracted. Each root had a 2times3 mm surface area denuded of cementum on the buccal and lingual surface. In Groups 1 (n= 12 roots) and 3 (n=4), the denuded surfaces were wiped with 15% EDTA, coated with black ink, and irradiated with Nd:YAG laser (0.75 W, 15 ppc, 300 pm tip, 20 s). In Groups 2 (n= 12) and 4 (n= 4), the surfaces were wiped with 15% EDTA, and rinsed with sterile saline for 20 s. Roots were replanted within 5 min. The dogs were perfwion-euthanised 10 weeks after replantation. Block specimens were removed, decalcified, embedded and horizontally sectioned (6 pm) at 180-pm intervals, resulting in 10 to 14 cross-sections of each root. From these, the middle five consecutive sections were stained with hematoxylin and eosin, and observed by light microscopy for occurrence of surface, inflammatory and replacement resorption on the denuded surfaces. No obvious differences were noted between the laser-irradiated and non-irradiated surfaces. Inflammatory resorption was frequent in Groups 1 and 2, and absent in Groups 3 and 4. Replacement resorption was minimal in Groups 1 and 2, and frequent in Groups 3 and 4. Differences between Groups 1 and 2, and between Groups 3 and 4 were not significant, whereas the differences between the two pairs of groups were statistically significant (chi-square and two-way ANOVA, P>0.006). These results did not support the hypothesis, and questioned the clinical validity of the surface modification in NdYAG laser-irradiated den-tin. Therefore, the clinical application of NdYAG laser to the root surfaces of replanted teeth is not warranted.     

Deprivation of parenting disrupts development of homeostatic and reward systems in marmoset monkey offspring.

BACKGROUND: Early environment is a major determinant of long-term mental health, evidenced by the relationship between early-life neglect or abuse and chronically increased vulnerability to developmental psychopathology, including major depressive disorder (MDD). Animal studies can increase understanding of environmentally mediated causal risk processes. We describe how daily deprivation of biological parenting in primate infants disrupts development of homeostatic and reward systems central to MDD. METHODS: Nine breeding pairs of marmoset monkeys provided control twins (CON) and early-deprived twins (ED); the latter were socially isolated for 30-120 min/day on days 2-28. During the first year of life, basal urinary norepinephrine (NE) titers and cardiophysiologic activity were measured. At the end of year 1 (adolescence), automated neuropsychologic tests were conducted to measure responsiveness to changes in stimulus-reward association (simple/reversed visual discrimination learning) and to reward per se (progressive ratio [PR] reinforcement schedule). RESULTS: The ED monkeys exhibited increased basal urinary NE titers and increased systolic blood pressure relative to CON siblings. The ED monkeys required more sessions to reinstate stimulus-oriented behavior following reversal, suggesting increased vulnerability to perceived loss of environmental control; ED monkeys also performed less PR operant responses, indicating that reward was less of an incentive and that they were mildly anhedonic relative to CON. CONCLUSIONS: In marmoset monkeys, neglect-like manipulation of ED leads to chronic changes in homeostatic systems, similar to those in children and adolescents exposed to early-life adversity and in MDD, and to responses to environmental stimuli similar to those that characterize MDD.     

Regulation of the human alternative complement pathway: formation of a ternary complex between factor H, surface-bound C3b and chemical groups on nonactivating surfaces

Sephadex [alpha(1----6) cross-linked dextran] activates the human alternative pathway of complement. Substitution of hydroxyl groups of Sephadex with carboxymethyl groups (CM) results in a dose-dependent decrease of the activating capacity of the polymer in normal human serum. Sephadex bearing one CM group/glycosyl unit (CM-Seph 0.95) exhibited no activating capacity. CM groups did not interfere with the ability of the polymer to covalently bind C3b in the presence of purified alternative pathway proteins nor with the capacity of bound-C3b to form a C3 convertase in the absence of regulatory proteins. C3b that was bound to CM-Seph 0.95 was more susceptible to inactivation by factors H and I in serum than C3b bound to Sephadex. Binding studies using 125I-labeled H demonstrated that H bound with a similar affinity to the activating particle Sephadex, to Sephadex bearing C3b and to the nonactivating particle CM-Seph 0.95. However, factor H bound with a 5- to 7-fold higher affinity to CM-Seph 0.95 bearing C3b. These results demonstrate a requirement for both CM groups and C3b molecules in order for H to bind with high affinity to C3b on the non-activating surface, and indicate that H formed a ternary complex with surface-bound C3b and CM groups on CM-Seph 0.95. Using a chemically defined model system, the present study provides a molecular basis for the enhanced interaction between surface-bound C3b and factor H on nonactivators of the human alternative pathway.