Separable effects for adherence

Comparing different medications is complicated when adherence to these medications differs. We can overcome the adherence issue by assessing effectiveness under sustained use, as in the usual causal `per-protocol' estimand. However, when sustained use is challenging to satisfy in practice, the usefulness of this estimand can be limited. Here we propose a different class of estimands: separable effects for adherence. These estimands compare modified medications, holding fixed a component responsible for non-adherence. Under assumptions about treatment components' mechanisms of effect, the separable effects estimand can eliminate differences in adherence. These assumptions are amenable to interrogation by subject-matter experts and can be evaluated using causal graphs. We describe an algorithm for constructing causal graphs for separable effects, illustrate how these graphs can be used to reason about assumptions required for identification, and provide semi-parametric weighted estimators

A Graphical Description of Partial Exchangeability

Partial exchangeability is sufficient for the identification of some causal effects of interest. Here we review the use of common graphical tools and the sufficient component cause model in the context of partial exchangeability. We illustrate the utility of single world intervention graphs (SWIGs) in depicting partial exchangeability and provide an illustrative example of when partial exchangeability might hold in the absence of complete exchangeability

Colonoscopy Needs for Implementation of a Colorectal Cancer Screening Program in Ukraine

Background In Ukraine, there is no established colorectal cancer screening program. We aimed to project the number of screening colonoscopies needed for implementation of various CRC screening strategies in Ukraine. Methods We modified a previously developed Markov microsimulation model to reflect the natural history of adenoma and CRC progression among average-risk 50-74-year-olds. We simulated colonoscopies needed for the following screening strategies: no screening, fecal occult blood test yearly, FOBT yearly with flexible sigmoidoscopy every 5 years, FS every 5 years, fecal immunohistochemistry test (FIT) yearly, or colonoscopy every 10 years. Assuming 80% screening adherence, we estimated colonoscopies required at 1 and 5 years depending on the implementation rate. In one-way sensitivity analyses, we varied implementation rate, screening adherence, sensitivity, and specificity. Results Assuming an 80% screening adherence and complete implementation (100%), besides a no screening strategy, the fewest screening colonoscopies are needed with an FOBT program, requiring on average 6,600 and 26,800 colonoscopies per 100,000 persons at 1 and 5 years post-implementation, respectively. The most screening colonoscopies are required with a colonoscopy program, requiring on average 76,600 and 101,000 colonoscopies per 100,000 persons at 1 and 5 years post-implementation, respectively. In sensitivity analyses, the biggest driver of number of colonoscopies needed was screening adherence. Conclusions The number of colonoscopies needed and therefore the potential strain on the healthcare system vary substantially by screening test. These findings can provide valuable information for stakeholders on equipment needs when implementing a national screening program in Ukraine

Patient survival after simultaneous ALPPS and colorectal resection

BACKGROUND: Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data. METHODS: Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2. RESULTS: Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 (p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality (p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively. CONCLUSIONS: In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2

Opioid prescription patterns for children following laparoscopic appendectomy

Objective: To describe variability in and consequences of opioid prescriptions following pediatric laparoscopic appendectomy.Summary background data: Postoperative opioid prescribing patterns may contribute to persistent opioid use in both adults and children.Methods: We included children (2006-2014). For the primary outcome of days of opioids prescribed, we evaluated associations with discharging service, standardized to the distribution of baseline covariates. Secondary outcomes included refill, Emergency Department (ED) visit for constipation, and ED visit for pain.Results: Among 6732 children, 68% were prescribed opioids (range = 1-65 d, median = 4 d, IQR = 3-5 d). Patients discharged by general surgery services were prescribed 1.23 (95% CI = 1.06-1.42) excess days of opioids, compared with those discharged by pediatric surgery services. Risk of ED visit for constipation (n = 61, 1%) was increased with opioid prescription [1-3 d, risk ratio (RR) = 2.46, 95% CI = 1.31-5.78; 4-6 d, RR = 1.89, 95% CI = 0.83-4.67; 7-14 d, RR = 3.75, 95% CI = 1.38-9.44; \u3e14 d, RR = 6.27, 95% CI = 1.23-19.68], compared with no opioid prescription. There was similar or increased risk of ED visit for pain (n = 319, 5%) with opioid prescription [1-3 d, RR = 1.00, 95% confidence interval (CI) = 0.74-1.32; 4-6 d, RR = 1.31, 95% CI = 0.99-1.73; 7-14 d, RR = 1.52, 95% CI = 1.00-2.18], compared with no opioid prescription. Likewise, need for refill (n = 157, 3%) was not associated with initial days of opioid prescribed (reference 1-3 d; 4-6 d, RR = 0.96, 95% CI = 0.68-1.35; 7-14 d, RR = 0.91, 95% CI = 0.49-1.46; and \u3e14 d, RR = 1.22, 95% CI = 0.59-2.07).Conclusions: There was substantial variation in opioid prescribing patterns. Opioid prescription duration increased risk of ED visits for constipation, but not for pain or refill