Outcomes in pregnancies complicated by methamphetamine use.

OBJECTIVE: Methamphetamine use is widespread. Our goal was to examine the effects of methamphetamine use on various maternal and neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study looking at all pregnancies between 2005 and 2008 in the state of California that were associated with a diagnosis of methamphetamine use. Outcomes examined included gestational hypertension, preeclampsia, preterm birth, small for gestational age, birthweight, abruption, intrauterine fetal death, neonatal death, infant death, jaundice, and gestational diabetes mellitus. Statistical analysis included chi-squared tests and multivariable logistic regression analyses. RESULTS: After adjustment for multiple confounding variables on multivariable regression analysis, results indicated that compared with control subjects, methamphetamine users had greater odds of gestational hypertension (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6-2.0), preeclampsia (OR, 2.7; 95% CI, 2.4-3.0), intrauterine fetal death (OR, 5.1; 95% CI, 3.7-7.2), and abruption (OR, 5.5; 95% CI, 4.9-6.3). Additionally, these patients had higher odds of preterm birth (OR, 2.9; 95% CI, 2.7-3.1), neonatal death (OR, 3.1; 95% CI, 2.3-4.2), and infant death (OR, 2.5; 95% CI, 1.7-3.7). CONCLUSION: Methamphetamine use in pregnancy was found to be associated with specific patterns of increased maternal and fetal morbidity and death. With these results in mind, further work can be done to improve the care of pregnancies that are complicated by methamphetamine use in hopes of reducing these complications.

Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer.

Twenty-six patients with extensive gynecologic, colorectal or genitourinary cancer who suffered uncontrolled, incapacitating pelvic pain were enrolled in this study during a 1-year period. All the patients receiving oral opioids who developed poor pain response due to the progression of disease or untoward side effects necessitating other modes of therapy were eligible to participate. Bilateral percutaneous neurolytic superior hypogastric plexus blocks with 10% phenol were performed in every patient, 1 day after receiving successful diagnostic blocks using 0.25% bupivacaine (BUP). All patients reported a visual analog pain score (VAPS) of 10 of 10 before the block. Eighteen patients (69%) had satisfactory pain relief (VAPS < 4 of 10): 15 (57%) after 1 block and 3 (12%) after a second block. The remaining 8 patients (31%) had moderate pain control (VAPS 4-7 of 10) after 2 blocks and received epidural bupivacaine-morphine (BUP-MS) therapy with good results. Both groups experienced significant reductions in oral opioid therapy after the neurolytic blocks. No additional blocks were required by patients who had a good response during a follow-up period of 6 months. No complications related to the block were experienced by any patient. In conclusion, neurolytic superior hypogastric plexus block was both effective in relieving pain in 69% of the patients studied (95% confidence interval of 48-85%). Additional neurolytic blocks using higher volumes of the neurolytic agent may be needed in patients with extensive retroperitoneal disease, a group in whom moderate or poor results should be expected.

What can we learn from global sensitivity analysis of biochemical systems?

Most biological models of intermediate size, and probably all large models, need to cope with the fact that many of their parameter values are unknown. In addition, it may not be possible to identify these values unambiguously on the basis of experimental data. This poses the question how reliable predictions made using such models are. Sensitivity analysis is commonly used to measure the impact of each model parameter on its variables. However, the results of such analyses can be dependent on an exact set of parameter values due to nonlinearity. To mitigate this problem, global sensitivity analysis techniques are used to calculate parameter sensitivities in a wider parameter space. We applied global sensitivity analysis to a selection of five signalling and metabolic models, several of which incorporate experimentally well-determined parameters. Assuming these models represent physiological reality, we explored how the results could change under increasing amounts of parameter uncertainty. Our results show that parameter sensitivities calculated with the physiological parameter values are not necessarily the most frequently observed under random sampling, even in a small interval around the physiological values. Often multimodal distributions were observed. Unsurprisingly, the range of possible sensitivity coefficient values increased with the level of parameter uncertainty, though the amount of parameter uncertainty at which the pattern of control was able to change differed among the models analysed. We suggest that this level of uncertainty can be used as a global measure of model robustness. Finally a comparison of different global sensitivity analysis techniques shows that, if high-throughput computing resources are available, then random sampling may actually be the most suitable technique.

Condor-COPASI: high-throughput computing for biochemical networks.

BACKGROUND: Mathematical modelling has become a standard technique to improve our understanding of complex biological systems. As models become larger and more complex, simulations and analyses require increasing amounts of computational power. Clusters of computers in a high-throughput computing environment can help to provide the resources required for computationally expensive model analysis. However, exploiting such a system can be difficult for users without the necessary expertise. RESULTS: We present Condor-COPASI, a server-based software tool that integrates COPASI, a biological pathway simulation tool, with Condor, a high-throughput computing environment. Condor-COPASI provides a web-based interface, which makes it extremely easy for a user to run a number of model simulation and analysis tasks in parallel. Tasks are transparently split into smaller parts, and submitted for execution on a Condor pool. Result output is presented to the user in a number of formats, including tables and interactive graphical displays. CONCLUSIONS: Condor-COPASI can effectively use a Condor high-throughput computing environment to provide significant gains in performance for a number of model simulation and analysis tasks. Condor-COPASI is free, open source software, released under the Artistic License 2.0, and is suitable for use by any institution with access to a Condor pool. Source code is freely available for download at http://code.google.com/p/condor-copasi/, along with full instructions on deployment and usage.

Weather/temperature-sensitive vasomotor rhinitis may be refractory to intranasal corticosteroid treatment.

Vasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions. A recently introduced INS with established efficacy in allergic rhinitis and enhanced affinity, fluticasone furoate, may possess the potency and safety profile required to treat chronic VMR(w/t). Two replicate studies (FFR30006 and FFR30007) were conducted in six countries to evaluate the efficacy and safety of fluticasone furoate nasal spray in subjects with VMR(w/t). After a 7- to 14-day screening period, subjects (n = 699) with symptomatic VMR(w/t) received fluticasone furoate, 110 mug q.d. or placebo for 4 weeks in these two randomized, double-blind, parallel-group studies. Subjects rated their nasal symptoms (congestion, rhinorrhea, and postnasal drip) twice daily on a 4-point categorical scale and evaluated their overall response to treatment at study end. Fluticasone furoate did not significantly improve daily reflective total nasal symptom scores, the primary end point, versus placebo (p = 0.259) and there was no improvement in any other measure of efficacy. The active treatment was well tolerated. Fluticasone furoate was not effective in treating subjects with a newly defined condition, weather-sensitive VMR. These unexpected results suggest that VMR(w/t) is a distinct subgroup of VMR that is refractory to treatment with INSs. Additional study of other treatments for VMR(w/t) (including INSs) is warranted.