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.     

Surgical therapy of achalasia after prior pneumatic dilatation]

Of 15 patients operated on for achalasia in the Department of General and Abdominal Surgery at the University of Mainz between September 1985 and April 1990, 14 were followed-up. All the patients had received an extramucous myotomy combined with Dor's semifundoplication; in twelve, one or more preoperative balloon dilatations had been performed. The results are reported in this study. The average age of the patients was 55.3 years (18 to 76 years), and the average follow-up period 21 months (six to 53 months). No postoperative complications were seen in any of the case. All patients reported appreciable improvements in their symptoms, six being completely symptom-free. Occasional dysphagia was reported in six cases, one patient had occasional, another frequent, nocturnal heartburn, which however had already presented preoperatively. In all seven cases submitted to postoperative radiological examination, the diameter of the esophagogastric junction was increased, and the diameter of the middle-third of the esophagus decreased. No gastroesophageal reflux or signs of inflammation were seen in any of the cases. The low complication rate and the high success rate despite prior balloon dilatation or bougienage support the use of Heller's operation combined with Dor's semifundoplication for the surgical treatment of achalasia after failed balloon dilatation.     

ISA--Information System Anesthesia. Decision support by a computer-based information system

"ISA"-Information System Anesthesia-will support the anesthesiologist by presenting information concerning the anesthesia approach. In addition to computing patient data (monitoring), there are three special fields where computers are used in anesthesia: (1) simulation systems for anesthesia training (preventing critical incidents); (2) critiquing systems to comment on the planned anesthesia decisions; and (3) reference systems for rapid information gathering. Simulation and critiquing systems are mainly useful for personal training. Reference systems present information concerning the anesthesia problems to aid in decision-making. ISA is a reference system designed to support the decision process for neurosurgical operations; a new method of presenting information by personal computer in the surgical working area. For each neurosurgical operation there is a graduation of condensed and detailed information with the option of also obtaining general anesthesia knowledge.     

Erythropoiesis, serum erythropoietin, and serum IGF-I in rats during accelerated growth

In this study we have examined the correlation between activity of erythropoiesis and serum concentrations of erythropoietin and insulin-like growth factor I in male and female rats during accelerated growth (day 30-90). We found that fractional incorporation of iron into newly formed red blood cells was linearily correlated with body weight gain. Total iron incorporation into newly formed red blood cells reflecting total daily red cell formation increased almost linearily between day 25 and 80 after birth in both sexes. While serum erythropoietin concentrations decreased in the time interval investigated (25-120 days), serum IGF-I levels increased in both sexes between day 25 and 55. In this period, individual values of total iron incorporation into red blood cells and serum IGF-I concentrations were linearily correlated. Our observations support the concept that IGF-I rather than erythropoietin modulates erythropoiesis during accelerated growth and thus manages a proportional increase in body mass and oxygen transport capacity.     

Patient-centered outcomes after laparoscopic cholecystectomy

Background

Laparoscopic cholecystectomy (LC) is the second most common general surgical operation performed in the United States, yet little has been reported on patient-centered outcomes.

Methods

We prospectively followed 100 patients for 2 years as part of an institutional review board–approved study. The Surgical Outcomes Measurement System (SOMS) was used to quantify quality-of-life (QoL) values at various time points postoperatively.

Results

Maximum pain was reported at 24 h (5.5 ± 2.2), and decreased to preoperative levels at 7 days (1.2 ± 2.3 vs. 2.0 ± 1.6, P = 0.096). Bowel function improved from before the operation to 3 weeks after surgery (10.7 ± 3.8 vs. 12.0 ± 3.2, P < 0.05), but then regressed to preoperative levels. Physical function worsened from before surgery (31.7 ± 6.2) to 1 week (27.5 ± 5.9, P < 0.0001), but surpassed preoperative levels at 3 weeks (33.5 ± 3.4, P < 0.01). Return to the activities of daily living occurred at 6.3 ± 4.7 days and work at 11.1 ± 9.0 days. Fatigue increased from before surgery (15.8 ± 6.2) to week 1 (20.7 ± 6.6, P < 0.0001) before improving at week 3 (14.0 ± 5.8, P < 0.01). Forty-four patients contacted the health care team 61 times before their 3 weeks appointment, most commonly for wound issues (26.2 %), pain (24.6 %), and gastrointestinal issues (24.6 %). Seventy-two percent reported that the procedure had no negative effect on cosmesis at 6 months. Satisfaction with the procedure was high, averaging 9.52 out of 11.

Conclusions

QoL is significantly affected in the 24 h after LC but returns to baseline at week 3. Cosmesis and overall satisfaction are high, and QoL improvements are maintained in the long term except for bowel function, which regresses to preoperative levels of impairment. Analysis of patient-initiated contacts after LC may provide feedback on discharge counseling to increase patient satisfaction.     

Predictors of complications in therapeutic plasma exchange

Plasma exchange (PE) is used for blood purification to modulate proteins involved in pathological processes. As the number of patients receiving PE treatment and the heterogeneity of the underlying diseases is steadily increasing, we evaluated the most frequent complications and analyzed causes leading to adverse reactions. 883 PE procedures in 113 patients between the years 2000 to 2006 were retrospectively analyzed with respect to complications. Additionally, underlying diseases and settings of PE procedure were analyzed to identify high‐risk patients and respective PE settings. A total of 226 adverse reactions were recorded (25.6% of all PE procedures). Most complications were mild (n = 121, 13.7%) or moderate (n = 98, 11.0%). In seven cases (n = 7, 0.7%), severe, life‐threatening adverse events were induced by PE either due to severe allergic reactions (n = 4, 0.5%) or to sepsis (n = 3, 0.3%). Patients with neurologic diseases had a significantly higher risk to develop complications compared to those with internal diseases (P = 0.013). This was due to a higher rate of PE associated adverse events (in particular hypotension) and complications associated with vascular access. Among patients from internal medicine those with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) had the highest risk to develop complications. Patients with neurological diseases compared to those with medical conditions and patients with HUS/TTP compared to those with other diseases had a higher risk to develop complications. However, severe adverse events are rare. Thus, PE seems to be a safe and recommendable procedure. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Cheyne-Stokes Respiration and Prognosis in Modern-Treated Congestive Heart Failure

In patients with congestive heart failure (CHF), a high prevalence of sleep-disordered breathing has been described. Cheyne-Stokes respiration (CSR) is present in up to 40% of patients with CHF. During the last decade, the medical treatment has been substantially improved. This study was designed to analyze the prognosis of CSR in modern-treated patients with CHF. For this purposes, in 57 patients with CHF who received modern treatment, a 5-year follow-up after initial full night polysomnography was performed. The mean follow-up period was 38 ± 18 months. Mean age was 62 ± 13 years and the mean ejection fraction was 25 ± 7 percent. Respiratory polygraphy revealed CSR with a respiratory disturbance index >5 per hour of sleep in 39 of 57 patients. Twelve patients died. CSR was only characterized by a tendency of worsening (log-rank test, p = 0.25). However, there was a significant difference toward positive outcome for patients who received cardiac resynchronization therapy (log-rank test, p = 0.036). Using Multivariate Cox’s proportional hazard regression with the factors resynchronization and CSR, the effect of resynchronization was almost significant (p = 0.08). In conclusion, no significant change of Cheyne-Stokes prevalence can be found in our small group of modern-treated patients with CHF. Cardiac resynchronization therapy was associated with improved patient outcome.     

Thromboxane synthase inhibitors induce apoptosis in migration-arrested glioma cells

OBJECTIVE: Because of the wide dissemination of malignant glioma cells by the time that malignant glioma is diagnosed, anti-invasive strategies that are designed to limit their further spread may be of little value unless mechanisms of the invasive cascade can be used to render invasive cells susceptible to cytoreductive treatments. We recently determined that elevated thromboxane synthase gene expression and enzymatic activity are associated with a highly migratory phenotype of glioma cells in vitro and that specific inhibitors of this enzyme block cell migration. Interference with this inherent phenotype of malignant gliomas also affects glioma cell proliferation and apoptosis. METHODS: To study the effect of thromboxane synthase inhibitors on motility, metabolic activity, and cell death, we used five human glioma cell lines, four glioblastoma-derived, low-passage cell cultures, normal human astrocytes, and fibroblasts. Motility was measured in a monolayer migration assay. Caspase activation as an early event in apoptotic cell death was assessed using a caspase 3 cleavage assay. Intracellular deoxyribonucleic acid (DNA) fragmentation was detected by enzyme-linked immunosorbent assay quantification of histone-complexed DNA. Subsequent cell death was scored by trypan blue exclusion. RESULTS: In this study, we demonstrate that the treatment of human glioma cells with the specific thromboxane synthase inhibitor furegrelate leads first to caspase activation (detectable 6 h after treatment), then to DNA fragmentation (24-48 h after treatment) and subsequent cell death. Caspase inhibitors abrogate this effect. Furthermore, the inhibition of thromboxane synthase by furegrelate increases cells' susceptibility to the induction of DNA fragmentation by camptothecin, etoposide, N,N'-bis(2-chloroethyl)-N-nitrosourea, and anti-CD95 antibodies. No induction of apoptosis was observed in normal astrocytes and fibroblasts. CONCLUSION: These data indicate that thromboxane synthase may represent a vortex of divergent signaling cascades that regulate motility and apoptosis in glioma cells. This paradigm may offer a novel perspective in the treatment of patients with malignant gliomas.     

Expanded newborn screening in Bavaria: tracking to achieve requested repeat testing

OBJECTIVES: Expansion of newborn screening programs may increase the risk of missing cases through procedural failures. A coordinated process quality assurance procedure to track recalls was, therefore, introduced in parallel to expansion (including MS-MS and 17alpha-OHP) in Bavaria. METHODS: Using comprehensive computerized registration and automated monitoring a state-funded center coordinated all individual measures to achieve complete testing of all repeat requests-case-specific contacts to physicians, midwives, and parents. Mailing and phoning from the center were supplemented by local public health activities including home visits if needed. RESULTS: Among 243,422 children tested in 1999 and 2000 overall recall was 3.62% (8,809 children): 0.30% (726) were due to sample inadequacy, 1.35% (3,282) to early sampling (<48 h), and 1.97% (4,801) to abnormal results. Of all recalls, 80.9% were received following the initial request, 1,679 (19.1%) required special efforts. Of these, 873 were achieved following a single and 601 following repeated central activities, and 102 were achieved following local support. Sixty-three cases of parental refusal and 47 untraceable children remained. Altogether, 98.8% recalls were achieved, corresponding to 99.96% of all tested children for which definite screening results could be obtained. CONCLUSIONS: Expansion of newborn screening programs does not necessarily mean unsolvable problems in tracking of recalls if adequate logistics is established in parallel.