Grace periods in comparative effectiveness studies of sustained treatments.

Researchers are often interested in estimating the effect of sustained use of a treatment on a health outcome. However, adherence to strict treatment protocols can be challenging for individuals in practice and, when non-adherence is expected, estimates of the effect of sustained use may not be useful for decision making. As an alternative, more relaxed treatment protocols which allow for periods of time off treatment (i.

Estimating the Effect of Bariatric Surgery on Cardiovascular Events Using Observational Data?

Background: Observational studies have reported strongly protective effects of bariatric surgery on cardiovascular disease, but with oversimplified definitions of the intervention, eligibility criteria, and follow-up, which deviate from those in a randomized trial. We describe an attempt to estimate the effect of bariatric surgery on cardiovascular disease without introducing these sources of bias, which may not be entirely possible with existing observational data.

Methods: We propose two target trials among persons with diabetes: (1) bariatric operation (vs.

Assumption-lean falsification tests of rate double-robustness of double-machine-learning estimators.

The class of doubly robust (DR) functionals studied by Rotnitzky et al. (2021) is of central importance in economics and biostatistics. It strictly includes both (i) the class of mean-square continuous functionals that can be written as an expectation of an affine functional of a conditional expectation studied by Chernozhukov et al.

Comparison of the Test-negative Design and Cohort Design With Explicit Target Trial Emulation for Evaluating COVID-19 Vaccine Effectiveness.

Background: Observational studies are used for estimating vaccine effectiveness under real-world conditions. The practical performance of two common approaches-cohort and test-negative designs-need to be compared for COVID-19 vaccines.

Methods: We compared the cohort and test-negative designs to estimate the effectiveness of the BNT162b2 vaccine against COVID-19 outcomes using nationwide data from the United States Department of Veterans Affairs.

Marshall Joffe's Contributions to Causal Inference, Biostatistics, and Epidemiology.

We pay tribute to Marshall Joffe, PhD, and his substantial contributions to the field of causal inference with focus in biostatistics and epidemiology. By compiling narratives written by us, his colleagues, we not only present highlights of Marshall's research and their significance for causal inference but also offer a portrayal of Marshall's personal accomplishments and character. Our discussion of Marshall's research notably includes (but is not limited to) handling of posttreatment variables such as noncompliance, employing G-estimation for treatment effects on failure-time outcomes, estimating effects of time-varying exposures subject to time-dependent confounding, and developing a causal framework for case-control studies.

Video article: the subtemporal extradural approach to cavernous sinus tumour.

Objective: Here we demonstrate via operative video the subtemporal extradural approach to a tumour in the cavernous sinus.

Methods: The extradural approach is performed here in a paediatric patient (a 15-year-old child) via a right extended pterional osteoplastic craniotomy with removal of the zygomatic arch. The operative microscope is introduced, and the dura is divided at the superior orbital fissure into endosteal and meningeal layers using a diamond knife.

Sensitivity analysis using bias functions for studies extending inferences from a randomized trial to a target population.

Extending (i.e., generalizing or transporting) causal inferences from a randomized trial to a target population requires assumptions that randomized and nonrandomized individuals are exchangeable conditional on baseline covariates.

Rejoinder: A formal causal interpretation of the case-crossover design.

We thank the discussants for their insightful commentary and questions. In our rejoinder, we extend our analysis to additional settings, control strategies, and sources of bias relevant to how case-crossover is often used in practice, as suggested by multiple discussants. In particular, we consider: control exposures that follow occurrence of events, settings with shared exposure trajectories (which are common in case-crossover studies of effects of air pollution), bias due to non-transient treatment effects, removing bias due to time trends in treatment using control subjects, and extending our results to the continuous time setting.

MULTIPLY ROBUST ESTIMATORS OF CAUSAL EFFECTS FOR SURVIVAL OUTCOMES.

Multiply robust estimators of the longitudinal g-formula have recently been proposed to protect against model misspecification better than the standard augmented inverse probability weighted estimator (Rotnitzky et al., 2017; Luedtke et al., 2018).

A formal causal interpretation of the case-crossover design.

The case-crossover design of Maclure is widely used in epidemiology and other fields to study causal effects of transient treatments on acute outcomes. However, its validity and causal interpretation have only been justified under informal conditions. Here, we place the design in a formal counterfactual framework for the first time.

Coherent modeling of longitudinal causal effects on binary outcomes.

Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Toward this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies.

Quantitative and functional visual field outcomes after endoscopic trans-sphenoidal pituitary adenectomy.

Objective: Quantitative data on visual outcomes after trans-sphenoidal surgery is lacking in the literature. This study aims to address this by quantitatively assessing visual field outcomes after endoscopic trans-sphenoidal pituitary adenectomy using the capabilities of modern semi-automated kinetic perimetry.

Methods: Visual field area (deg) calculated on perimetry performed before and after surgery was statistically analysed.

A generalized theory of separable effects in competing event settings.

In competing event settings, a counterfactual contrast of cause-specific cumulative incidences quantifies the total causal effect of a treatment on the event of interest. However, effects of treatment on the competing event may indirectly contribute to this total effect, complicating its interpretation. We previously proposed the separable effects to define direct and indirect effects of the treatment on the event of interest.

On Causal Inferences for Personalized Medicine: How Hidden Causal Assumptions Led to Erroneous Causal Claims About the D-Value.

Personalized medicine asks if a new treatment will help a particular patient, rather than if it improves the average response in a population. Without a causal model to distinguish these questions, interpretational mistakes arise. These mistakes are seen in an article by Demidenko [2016] that recommends the "D-value," which is the probability that a randomly chosen person from the new-treatment group has a higher value for the outcome than a randomly chosen person from the control-treatment group.

IDENTIFICATION AND INFERENCE FOR MARGINAL AVERAGE TREATMENT EFFECT ON THE TREATED WITH AN INSTRUMENTAL VARIABLE.

In observational studies, treatments are typically not randomized and therefore estimated treatment effects may be subject to confounding bias. The instrumental variable (IV) design plays the role of a quasi-experimental handle since the IV is associated with the treatment and only affects the outcome through the treatment. In this paper, we present a novel framework for identification and inference using an IV for the marginal average treatment effect amongst the treated (ETT) in the presence of unmeasured confounding.

Direct Lateral Minimally Invasive Approach for Excision of a L1/L2 Neurofibroma-A Technical Note and Literature Review.

A case of resection of a large dumbbell-shaped nerve sheath tumor at L1/L2 via a direct lateral minimally invasive approach is described. The tumor was removed via a lateral, subdiaphragmatic, rib-sparing, retropleural, retroperitoneal approach. The thoracolumbar junction can be challenging via the lateral approach and to the best of our knowledge this is the first report of excision of a paravertebral tumor via this approach.

Rapid Growth of a Facet Joint Cyst Mimicking an Aggressive Tumor in the Lumbar Spine.

A 67-year-old patient with a history of fully treated bowel carcinoma presented with a short history of unilateral lumbosacral radiculopathy. No neurological deficit was found on examination. Magnetic resonance imaging (MRI) demonstrated initially L4/5 foraminal narrowing that was believed to be the cause for the patient's symptoms; however, a nerve root block led to no improvement in symptoms.

Potential Biases Arising From Epidemic Dynamics in Observational Seroprotection Studies.

The extent and duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods for alleviating biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated.

The Hudson Brace technique for emergency burr holes, an aide-memoire for the front-line military surgeon.

Traumatic brain injury is the leading cause of death in conflict and early surgical intervention achieves better outcomes. The British Army surgical kit includes a Hudson Brace and bit and Gigli saw for decompression of the cranial cavity. Here we demonstrate the Hudson Brace technique for non-neurosurgeons.

Parametric g-formula implementations for causal survival analyses.

The g-formula can be used to estimate the survival curve under a sustained treatment strategy. Two available estimators of the g-formula are noniterative conditional expectation and iterative conditional expectation. We propose a version of the iterative conditional expectation estimator and describe its procedures for deterministic and random treatment strategies.

Potential biases arising from epidemic dynamics in observational seroprotection studies.

The extent and duration of immunity following SARS-CoV-2 infection are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods to alleviate biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated.

Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke.

Background and Purpose- Long-term effect of lifestyle changes on stroke incidence has not been estimated in randomized trials. We used observational data to estimate the incidence of stroke under hypothetical lifestyle strategies in the NHS (Nurses' Health Study). Methods- We considered 3 nondietary strategies (smoking cessation, exercising ≥30 min/d, gradual body mass index reduction if overweight/obese) and several dietary strategies (eating ≥3 servings/wk of fish, ≤3 servings/wk of unprocessed red meat, no processed red meat, ≥1 servings/d of nuts, etc).

Fronto-orbital advancement and reconstruction using reverse frontal bone graft without the use of orbital bar: a technical note.

Introduction: We describe our technique of using reverse frontal bone graft for FOAR for patients with metopic or coronal synostosis and present our complications using the Leeds classification system for complications in craniosynostosis surgery.

Methods: Since April 2015, seventeen patients have been operated using this technique. We perform a frontal bone graft that is then reversed, and supraorbital margins are drilled out.