Comparing dynamic treatment regimes using repeated‐measures outcomes: modeling considerations in SMART studies

A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient's past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi‐stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated‐measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder, and adult alcoholism. In all three SMARTs, we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated‐measures outcome. Copyright © 2015 John Wiley & Sons, Ltd.     

Resolution of recalcitrant chronic papillary conjunctivitis associated with epiphora following punctoplasty and lacrimal stenting

Objective

To assess the use of lacrimal stenting for chronic papillary conjunctivitis associated with epiphora in young adults with little or no atopic background.

Anorectal malformations and perineal hemangiomas: The Arm-Net Consortium experience

AimPerineal hemangiomas rarely occur in patients with anorectal malformations (ARMs), but they can pose a significant challenge and warrant special attention. Surgical incision of posterior sagittal anorectoplasty (PSARP) may involve the hemangioma site resulting in hemorrhage, damage to blood supply, leading to complications and adversely affecting outcome. The aim of this study was to review the experience of the ARM-Net Consortium in the management of perineal hemangioma associated with ARM and evaluate treatment strategies.Materials and methodsData on all patients with ARM and a perineal hemangioma located in the planes of the PSARP dissection who were managed at participating ARM-Net centers were collected retrospectively by questionnaire, as follows: ARM type, hemangioma distribution and penetration, imaging findings, medical/surgical management, timing of definitive repair, complications and outcome.ResultsTen patients from eight centers were included. Three patients each had a rectobulbar or rectovestibular fistula, 2 had a rectoperineal fistula, and one had a rectoprostatic fistula; in one patient, the hemangioma was too disfiguring to determine malformation type. Mean follow-up time was 36.6 months (median 29 months). Colostomies were performed before definitive repair in 8 patients. Five patients received systemic beta-blockers before PSARP: 3 were operated uneventfully following partial/complete involution of the hemangioma, and 2 are awaiting surgery. The two patients with rectoperineal fistula were managed expectantly. The remaining 3 patients underwent surgery with no preoperative medical treatment, and all had complications: mislocated neoanus in three and complete perineal dehiscence in one.ConclusionAttempting PSARP in the presence of a perineal hemangioma may lead to complications and adversely affect outcome. This study confirms the benefits of beta blocker treatment before surgical reconstruction.Level of evidenceTreatment study, level III.     

Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages

The death of retinal ganglion cells (RGCs) is a hallmark of many retinal neuropathies. Neuroprotection, axonal regeneration, and cell renewal are vital for the integrity of the visual system after insult but are scarce in the adult mammalian retina. We hypothesized that monocyte-derived macrophages, known to promote healing in peripheral tissues, are required after an insult to the visual system, where their role has been largely overlooked. We found that after glutamate eye intoxication, monocyte-derived macrophages infiltrated the damaged retina of mice. Inhibition of this infiltration resulted in reduced survival of RGCs and diminished numbers of proliferating retinal progenitor cells (RPCs) in the ciliary body. Enhancement of the circulating monocyte pool led to increased RGC survival and RPC renewal. The infiltrating monocyte-derived macrophages skewed the milieu of the injured retina toward an antiinflammatory and neuroprotective one and down-regulated accumulation of other immune cells, thereby resolving local inflammation. The beneficial effect on RGC survival depended on expression of interleukin 10 and major histocompatibility complex class II molecules by monocyte-derived macrophages. Thus, we attribute to infiltrating monocyte-derived macrophages a novel role in neuroprotection and progenitor cell renewal in the injured retina, with far-reaching potential implications to retinal neuropathies and other neurodegenerative disorders.     

Posttraumatic Cognitions Inventory (PTCI): psychometric properties and gender differences in an Israeli sample

The Posttraumatic Cognitions Inventory (PTCI; Foa, Ehlers, Clark, Tolin, & Orsillo, 1999) was found to have three factors: negative view of self, negative view of world, and self-blame. We validated the PTCI among 326 Israeli adults exposed to various types of traumas. Results provided support for the original three-factors. Negative cognitions about self scale had the highest correlations with severity of PTSD and depression symptoms, whereas self-blame had only weak correlations with these measures. Among men, negative cognitions about self were associated most strongly with PTSD severity whereas among women, negative cognitions about self were associated primarily with depression. Gender may play an important role in posttraumatic cognitions and their relationship to PTSD and depression.