The bulk of causal inference studies rules out the presence of interference between units. However, in many real-world settings units are interconnected by social, physical or virtual ties and the effect of a treatment can spill from one unit to other connected individuals in the network. In these settings, interference should be taken into account to avoid biased estimates of the treatment effect, but it can also be leveraged to save resources and provide the intervention to a lower percentage of the population where the treatment is more effective and where the effect can spill over to other susceptible individuals. In fact, different people might respond differently not only to the treatment received but also to the treatment received by their network contacts. Understanding the heterogeneity of treatment and spillover effects can help policy-makers in the scale-up phase of the intervention, it can guide the design of targeting strategies with the ultimate goal of making the interventions more cost-effective, and it might even allow generalizing the level of treatment spillover effects in other populations. In this paper, we develop a machine learning method that makes use of tree-based algorithms and an Horvitz-Thompson estimator to assess the heterogeneity of treatment and spillover effects with respect to individual, neighborhood and network characteristics in the context of clustered network interference. We illustrate how the proposed binary tree methodology performs in a Monte Carlo simulation study. Additionally, we provide an application on a randomized experiment aimed at assessing the heterogeneous effects of information sessions on the uptake of a new weather insurance policy in rural China.
Through its national health system, Italy provides legal and free abortion through the third month for any reason and through the sixth month for maternal or fetal health problems, but one of the public health goals specified in Italian legislation is to minimize its use. One barrier to achieving this goal is inconsistent access to prescription contraception. Six out of 20 Italian regions offer free contraception programs paid for by the national health system. Tuscany was the most recent region to introduce such a program, in November 2018. The authors studied the impact of this program using regional administrative health data to compare the 3-year period before and the 2-year period after its introduction. They computed rates of abortion, contraception uptake, access to counseling centers, conception, and use of outpatient services for sexually transmitted diseases. Their analysis revealed positive effects on teenage conception and on overall utilization of outpatient services for sexually transmitted diseases and strongly suggests that this program has been effective in reducing abortions by promoting access to counseling and contraception services among young women.In Italy, abortion is a free service guaranteed to all women for any reason during the first trimester and for maternal or fetal health issues during the second trimester, although individual NEJM Catalyst is produced by NEJM Group, a division of the Massachusetts Medical Society.
ImportanceHemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged.ObjectiveTo evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock.Design, Setting, and ParticipantsThis retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of >10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022.ExposureContinuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines.Main Outcomes and MeasuresThe primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE.ResultsA total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from –4.6 (95% CI, –11.9 to 2.7) to 2.1 (95% CI, –2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from –1.3 (95% CI, –9.5 to 6.9) to 5.3 (95% CI, –2.1 to 12.8).Conclusions and RelevanceThe findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock.
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