Risk and Risk Preferences for Surgery and Medical Therapy in Ulcerative Colitis

描述(由申请人提供)： 溃疡性结肠炎(UC)具有显著的发病率和死亡率。虽然切除结肠是可以治愈的，但大多数人认为手术是最后的治疗手段，UC的治疗模式已经转变，强调在疾病发作期间在手术前逐步加强有效的免疫抑制治疗。这些药物带来了一些重大的潜在风险，包括严重感染、淋巴瘤、药物失效和死亡。越来越多患有中重度疾病的UC患者终生接触这些药物；在那些药物治疗失败的患者中，这些患者在手术前就有这种药物暴露。这种暴露有增加死亡率和手术后发病率的风险。治疗决策的另一个关键因素是患者本身的喜好。如果面对不同治疗选择和风险的适当表述，UC患者可能会有非常不同的意愿接受某些风险，以换取潜在的治疗益处。评估与免疫抑制治疗相关的发病率和死亡率问题的研究缺乏普适性，缺乏对混杂因素的控制，以及由于样本量小而缺乏力量。这项研究建议利用Medicaid-Medicare数据库，它确保了概括性、样本量，并允许评估一些潜在的混杂因素，包括药物使用。调整后的COX比例风险模型将用于确定接受内科和外科治疗的UC患者的相对存活率。为了在通灵的基础上进一步控制混杂，将采用倾向分数匹配。多变量Logistic回归将确定术前医疗暴露与术后发病率之间的关系。其他分析将评估自上次接受药物治疗以来的时间对发病率的影响。最后，通过联合分析，这项研究将对UC患者对内科和外科治疗UC的风险偏好进行系统的检查。 公共卫生相关性：确定与优先使用内科治疗而不是手术治疗相关的死亡率和发病率风险是至关重要的。如果延迟或避免手术使UC患者面临更高的死亡率或术后发病率，这些信息在知情的决策中至关重要。反过来，了解UC患者如何感知和评估内科和外科治疗的风险将对管理和治疗产生深远影响，并将为未来的治疗选择设定新的门槛。

DESCRIPTION (provided by applicant): Ulcerative colitis (UC) is associated with significant morbidity and mortality. While removal of the colon is curative, most feel surgery to be a treatment of last resort and treatment paradigms for UC have shifted to emphasize an escalation of potent immunosuppressant therapy during disease flares before going to surgery. These medications come [sic] some significant potential risks including serious infections, lymphoma, medication failure, and death. An Increasing number of UC patients with moderate to severe disease have life-long exposure to these medications; and in those in whom medical therapy fails, these patients have this medication exposure prior to surgery. This carries the risk of increased mortality and post-operative surgical morbidity as a result of this exposure. An additional key component of treatment decisions is the preferences of the patients themselves. If faced with an appropriate representation of different treatment options and risks, UC patients may have very different willingness to accept certain risks in exchange for potential therapeutic benefit. Studies evaluating morbidity and mortality issues related to immunosuppressant therapy have suffered from lack of generalizability, lack of control for confounders, and lack of power due to small sample sizes. This study proposes utilizing the Medicaid-Medicare database, which assure generalizability, sample size, and allows evaluation of a number of potential confounders including medication use. Cox proportional hazards models with adjustment will be used to determine relative survival of UC patients treated with medical and surgical therapy. To further control for confounding on the basis of channeling, matching on propensity scores will be employed. Multivariate logistic regression will determine the relationship between medical exposure prior to surgery and post-operative morbidity. Additional analysis will evaluate the impact on the odds of morbidity of time from last exposure of medical therapy. Finally, by using conjoint analysis, the study will perform a systematic examination of UC patients' risk preferences for medical versus surgical therapy for UC. PUBLIC HEALTH RELEVANCE: It is crtical [sic] to determine the mortality and morbidity risk associated with the use of medical therapy in preference of surgery. If delaying or avoiding surgery exposes UC patients to an increased mortality or post-operative morbidity, such information is critical in informed decision-making. In turn, understanding how UC patients perceive and value the risks of medical versus surgical therapy will have far-reaching effects on management and treatment and will set new thresholds for future therapeutic options.