A systematic review of computational models for the design of spinal cord stimulation therapies: from neural circuits to patient-specific simulations.

Seventy years ago, Hodgkin and Huxley published the first mathematical model to describe action potential generation, laying the foundation for modern computational neuroscience. Since then, the field has evolved enormously, with studies spanning from basic neuroscience to clinical applications for neuromodulation. Computer models of neuromodulation have evolved in complexity and personalization, advancing clinical practice and novel neurostimulation therapies, such as spinal cord stimulation. Spinal cord stimulation is a therapy widely used to treat chronic pain, with rapidly expanding indications, such as restoring motor function. In general, simulations contributed dramatically to improve lead designs, stimulation configurations, waveform parameters and programming procedures and provided insight into potential mechanisms of action of electrical stimulation. Although the implementation of neural models are relentlessly increasing in number and complexity, it is reasonable to ask whether this observed increase in complexity is necessary for improved accuracy and, ultimately, for clinical efficacy. With this aim, we performed a systematic literature review and a qualitative meta-synthesis of the evolution of computational models, with a focus on complexity, personalization and the use of medical imaging to capture realistic anatomy. Our review showed that increased model complexity and personalization improved both mechanistic and translational studies. More specifically, the use of medical imaging enabled the development of patient-specific models that can help to transform clinical practice in spinal cord stimulation. Finally, we combined our results to provide clear guidelines for standardization and expansion of computational models for spinal cord stimulation.

Outcomes after ileal pouch anal anastomosis in patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: Outcomes after ileal pouch anal anastomosis (IPAA) are not well established in patients with primary sclerosing cholangitis (PSC). We conducted a comprehensive outcomes assessment in these patients. METHODS: A retrospective case note review of complications in all PSC-IPAA (n=21) and matched ulcerative colitis patients with IPAA (UC-IPAA; n=79) after surgery in Oxford (1983-2012) was conducted, and functional outcomes (Öresland score) were evaluated (2012). Quality of life [Cleveland Global Quality of Life Questionnaire, Short Form-36 (SF-36)], and sexual function were also assessed (2012) including patients with PSC-associated UC without IPAA (PSC-UC; n=19). Sub-group analysis of patients with large duct (ld) PSC-IPAA (n=17) was also performed. RESULTS: The 1-, 5-, 10- and 20-year risk of acute pouchitis for PSC-IPAA was 10%, 19%, 31% and 65% respectively, compared to 3%, 10%, 14% and 28% in UC-IPAA (p=0.03). More PSC-IPAA (36%) had poor nocturnal pouch function (vs 2% in UC-IPAA; p=0.0016). There were no differences in surgical complications, quality of life or sexual function between the 3 main groups. LdPSC-IPAA had poorer pouch function (Öresland score: 7.7 vs 5.4 in UC-IPAA; p=0.02), and worse quality of life [SF-36 Physical: 42 vs 50.5 in UC-IPAA; 47.7 in PSC-UC; p=0.03 and Mental Health summary scores: 41.6 vs 51.2 in UC-IPAA; 42.3 in PSC-UC; p=0.04]. CONCLUSIONS: PSC-IPAA suffer more acute pouchitis and have worse functional outcomes than UC-IPAA. LdPSC-IPAA also have poorer quality of life.