Xiaoqin Wang, Li Yin.

Source: The Annals of Statistics, Volume 48, Number 1, 138--160.

Abstract:
In sequential causal inference, two types of causal effects are of practical interest, namely, the causal effect of the treatment regime (called the sequential causal effect) and the blip effect of treatment on the potential outcome after the last treatment. The well-known $G$-formula expresses these causal effects in terms of the standard parameters. In this article, we obtain a new $G$-formula that expresses these causal effects in terms of the point observable effects of treatments similar to treatment in the framework of single-point causal inference. Based on the new $G$-formula, we estimate these causal effects by maximum likelihood via point observable effects with methods extended from single-point causal inference. We are able to increase precision of the estimation without introducing biases by an unsaturated model imposing constraints on the point observable effects. We are also able to reduce the number of point observable effects in the estimation by treatment assignment conditions.

Aaditya K. Ramdas, Rina F. Barber, Martin J. Wainwright, Michael I. Jordan.

Source: The Annals of Statistics, Volume 47, Number 5, 2790--2821.

Abstract:
There is a significant literature on methods for incorporating knowledge into multiple testing procedures so as to improve their power and precision. Some common forms of prior knowledge include (a) beliefs about which hypotheses are null, modeled by nonuniform prior weights; (b) differing importances of hypotheses, modeled by differing penalties for false discoveries; (c) multiple arbitrary partitions of the hypotheses into (possibly overlapping) groups and (d) knowledge of independence, positive or arbitrary dependence between hypotheses or groups, suggesting the use of more aggressive or conservative procedures. We present a unified algorithmic framework called p-filter for global null testing and false discovery rate (FDR) control that allows the scientist to incorporate all four types of prior knowledge (a)–(d) simultaneously, recovering a variety of known algorithms as special cases.

Chengchun Shi, Rui Song, Wenbin Lu.

Source: The Annals of Statistics, Volume 47, Number 4, 2348--2377.

Abstract:
Precision medicine is an emerging medical paradigm that focuses on finding the most effective treatment strategy tailored for individual patients. In the literature, most of the existing works focused on estimating the optimal treatment regime. However, there has been less attention devoted to hypothesis testing regarding the optimal treatment regime. In this paper, we first introduce the notion of conditional qualitative treatment effects (CQTE) of a set of variables given another set of variables and provide a class of equivalent representations for the null hypothesis of no CQTE. The proposed definition of CQTE does not assume any parametric form for the optimal treatment rule and plays an important role for assessing the incremental value of a set of new variables in optimal treatment decision making conditional on an existing set of prescriptive variables. We then propose novel testing procedures for no CQTE based on kernel estimation of the conditional contrast functions. We show that our test statistics have asymptotically correct size and nonnegligible power against some nonstandard local alternatives. The empirical performance of the proposed tests are evaluated by simulations and an application to an AIDS data set.

Trang Quynh Nguyen, Elizabeth A. Stuart.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 518--520.

Fan Li, Fan Li.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2389--2415.

Abstract:
Causal or unconfounded descriptive comparisons between multiple groups are common in observational studies. Motivated from a racial disparity study in health services research, we propose a unified propensity score weighting framework, the balancing weights, for estimating causal effects with multiple treatments. These weights incorporate the generalized propensity scores to balance the weighted covariate distribution of each treatment group, all weighted toward a common prespecified target population. The class of balancing weights include several existing approaches such as the inverse probability weights and trimming weights as special cases. Within this framework, we propose a set of target estimands based on linear contrasts. We further develop the generalized overlap weights, constructed as the product of the inverse probability weights and the harmonic mean of the generalized propensity scores. The generalized overlap weighting scheme corresponds to the target population with the most overlap in covariates across the multiple treatments. These weights are bounded and thus bypass the problem of extreme propensities. We show that the generalized overlap weights minimize the total asymptotic variance of the moment weighting estimators for the pairwise contrasts within the class of balancing weights. We consider two balance check criteria and propose a new sandwich variance estimator for estimating the causal effects with generalized overlap weights. We apply these methods to study the racial disparities in medical expenditure between several racial groups using the 2009 Medical Expenditure Panel Survey (MEPS) data. Simulations were carried out to compare with existing methods.

Bret Zeldow, Vincent Lo Re III, Jason Roy.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1989--2010.

Abstract:
Bayesian Additive Regression Trees (BART) is a flexible machine learning algorithm capable of capturing nonlinearities between an outcome and covariates and interactions among covariates. We extend BART to a semiparametric regression framework in which the conditional expectation of an outcome is a function of treatment, its effect modifiers, and confounders. The confounders are allowed to have unspecified functional form, while treatment and effect modifiers that are directly related to the research question are given a linear form. The result is a Bayesian semiparametric linear regression model where the posterior distribution of the parameters of the linear part can be interpreted as in parametric Bayesian regression. This is useful in situations where a subset of the variables are of substantive interest and the others are nuisance variables that we would like to control for. An example of this occurs in causal modeling with the structural mean model (SMM). Under certain causal assumptions, our method can be used as a Bayesian SMM. Our methods are demonstrated with simulation studies and an application to dataset involving adults with HIV/Hepatitis C coinfection who newly initiate antiretroviral therapy. The methods are available in an R package called semibart.

Luis Gutiérrez, Andrés F. Barrientos, Jorge González, Daniel Taylor-Rodríguez.

Source: Bayesian Analysis, Volume 14, Number 2, 649--675.

Abstract:
We propose a Bayesian nonparametric strategy to test for differences between a control group and several treatment regimes. Most of the existing tests for this type of comparison are based on the differences between location parameters. In contrast, our approach identifies differences across the entire distribution, avoids strong modeling assumptions over the distributions for each treatment, and accounts for multiple testing through the prior distribution on the space of hypotheses. The proposal is compared to other commonly used hypothesis testing procedures under simulated scenarios. Two real applications are also analyzed with the proposed methodology.

Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function.

SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function.

Press release: Basel Committee invites comments on the design of a prudential treatment for crypto-assets, 12 December 2019.

BACKGROUND AND OBJECTIVES:

Use of specific services may help to optimize health for children with autism spectrum disorder (ASD); however, little is known about their service use patterns. We aimed to (1) define service use groups and (2) determine associations of sociodemographic, developmental, behavioral, and health characteristics with service use groups among school-aged children with ASD.

BACKGROUND AND OBJECTIVES:

Families of children with autism spectrum disorder (ASD) often experience challenges navigating multiple systems to access services. Family navigation (FN) is a model to provide information and support to access appropriate services. Few studies have been used to examine FN’s effectiveness for families of children with ASD. This study used mixed methods to (1) characterize FN services received by a sample of families in the Autism Treatment Network; (2) examine change in parent-reported activation, family functioning, and caregiver strain; and (3) explore families’ experiences with FN services.

Family involvement in the Autism Intervention Research Network on Physical Health, the Autism Treatment Network, and the Autism Learning Health Network, jointly the Autism Networks, has evolved and grown into a meaningful and robust collaboration between families, providers, and researchers. Family involvement at the center of the networks includes both local and national network-wide coproduction and contribution. Family involvement includes actively co-authoring research proposals for large grants, equal membership of network committees and workgroups, and formulating quality improvement pathways for local recruitment efforts and other network initiatives. Although families are involved in every aspect of network activity, families have been the driving force of specifically challenging the networks to concentrate research, education, and dissemination efforts around 3 pillar initiatives of addressing comorbidities of anxiety, attention-deficit/hyperactivity disorder, and irritability in autism during the networks’ upcoming funding cycle. The expansion of the networks’ Extension for Community Healthcare Outcomes program is an exciting network initiative that brings best practices in autism care to community providers. As equal hub members of each Extension for Community Healthcare Outcomes team, families ensure that participants are intimately cognizant of family perspectives and goals. Self-advocacy involvement in the networks is emerging, with plans for each site to have self-advocacy representation by the spring of 2020 and ultimately forming their own coproduction committee. The Autism Treatment Network, the Autism Intervention Research Network on Physical Health, and the Autism Learning Health Network continue to be trailblazing organizations in how families are involved in the growth of their networks, production of meaningful research, and dissemination of information to providers and families regarding emerging work in autism spectrum disorders.

The Autism Treatment Network and Autism Intervention Research Network on Physical Health were established in 2008 with goals of improving understanding of the medical aspects of autism spectrum disorders. Over the past decade, the combined network has conducted >2 dozen clinical studies, established clinical pathways for best practice, developed tool kits for professionals and families to support better care, and disseminated these works through numerous presentations at scientific meetings and publications in medical journals. As the joint network enters its second decade continuing this work, it is undergoing a transformation to increase these activities and accelerate their incorporation into clinical care at the primary care and specialty care levels. In this article, we describe the past accomplishments and present activities. We also outline planned undertakings such as the establishment of the Autism Learning Health Network, the increasing role of family members as co-producers of the work of the network, the growth of clinical trials activities with funding from foundations and industry, and expansion of work with primary care practices and autism specialty centers. We also discuss the challenges of supporting network activities and potential solutions to sustain the network.

Acne vulgaris is an extraordinarily common skin condition in adolescents. The mainstays of acne treatment have remained largely unchanged over recent years. In the context of increasing antibiotic resistance worldwide, there is a global movement away from antibiotic monotherapy toward their more restrictive use. Classically reserved for nodulocystic acne, isotretinoin has become the drug of choice by dermatologists for moderate to severe acne. Given the virtually ubiquitous nature of acne in teenagers, there remains an appreciable need for novel therapies. In this article, we will cover the currently used acne treatments, evaluate the issues and data supporting their use, explore the issues of compliance and the mental health implications of acne care, and recommend directions for the field of acne management in adolescents in the years ahead.

Give your skin a tasty treat and cook up your own beauty recipes, says Sandra Dick

NICOLA Sturgeon hopes to reopen IVF clinics “as quickly as possible” to stop the closure having a “devastating” impact on families’ lives during the pandemic.

A BIOTECH veteran has hailed a Glasgow firm that claims to have discovered two separate potential treatments for Covid-19 patients for use before they are put on ventilators.

Although gastroenteritis guidelines describe the need to perform oral rehydration, it remains underused, resulting in excessive use of intravenous rehydration. Other interventions, such as antiemetic administration, vary according to location, often resulting in differences in cost and outcomes.

In this nationwide cohort, intravenous rehydration use varied dramatically. Use was associated with the institution providing care and an increase in the need for future health care provider visits. Use of ondansetron also varied significantly across Canada. (Read the full article)

For treatment of obesity in preadolescent children, approaches that focus on parents taking sole responsibility for implementing weight-management strategies may be most effective. However, the optimal content, intensity, and duration of programs for obese children remain unclear.

Targeting parents only, a 10% relative weight loss is achievable in moderately obese preadolescent children and can be maintained 2 years from baseline, which justifies an investment in treatment as a secondary obesity-prevention strategy. (Read the full article)

The effectiveness of intravenous immunoglobulin treatment of patients with Kawasaki disease within 9 days of illness has been established. However, the effectiveness of such treatment ≥10 days after illness onset has not yet been clarified.

Intravenous immunoglobulin treatment ≥10 days after illness onset was observed to be effective for achieving inflammation resolution. Patients who are strongly suspected to have Kawasaki disease and demonstrate ongoing inflammation should therefore be treated as soon as possible. (Read the full article)

Over the past decade, drug oversight committees and professional organizations have debated the evidence regarding cardiac screening to identify undiagnosed disorders associated with sudden cardiac death in youth with attention-deficit/hyperactivity disorder before beginning treatment with stimulants.

How practicing pediatricians have responded to this controversy is not known. We present results from a national sample of pediatricians regarding current attitudes, barriers, and practices for cardiac screening in youth with attention-deficit/hyperactivity disorder before prescribing stimulants. (Read the full article)

Although China has the largest birth population in the world and a number of multicenter studies of neonatal respiratory failure are reported, there is a paucity of data regarding outcome measurement of very premature neonates requiring respiratory care and surfactant therapy.

This study is the largest survey, to date, in a Chinese network of 55 NICUs that presents the incidence, morbidity, and mortality rates, with risk factors of neonatal respiratory failure, with special emphasis on surfactant-treated very immature infants. (Read the full article)

Complementary and alternative medicine (CAM) use for pediatric asthma is increasing. It is well known that effective asthma management depends on patient adherence to treatment. The authors of previous cross-sectional studies have linked CAM use with decreased adherence to conventional asthma treatment regimens.

This longitudinal data set was unique, allowing us to focus on patients who initiated CAM and to follow subsequent asthma medication adherence. We found that CAM use was not associated with adherence, suggesting that patients may practice CAM alongside conventional therapies. (Read the full article)

Although several randomized trials have examined the efficacy of serotonin receptor inhibitors in the treatment of repetitive behaviors, there still remains clinical uncertainty as to whether these agents are effective in treating such behaviors in children and adults with autism spectrum disorders.

The goal of this meta-analysis was to examine randomized trials of serotonin receptor inhibitors for treating repetitive behaviors in autism spectrum disorders. Although a small but significant effect of these agents was observed, this effect is likely due to the selective publication of trial results. (Read the full article)

We lack prospective studies documenting "dosage effects" of chronic child maltreatment for both subsequent adolescent and adult outcomes. It is unknown whether effects are linear, shelving, or exponential, and we lack data across domains of outcomes.

Chronic child maltreatment reports are a robust indicator of future negative health and behavioral outcomes. There is a dose-response relationship between chronicity and outcomes in adolescence, but this is attenuated in adulthood once adverse child outcomes are controlled. (Read the full article)

Pediatric obesity is a prevalent public health issue that is associated with medical and physical consequences. Clinic-based interventions for pediatric obesity are effective, but they have limited reach and are costly.

This is the first examination of an empirically informed, scalable treatment of pediatric overweight and obesity delivered in YMCAs. The results indicate that a scalable, community-based pediatric obesity intervention can produce clinically meaningful changes in weight and quality of life. (Read the full article)

Studies have linked bullying with BMI, with overweight and obese youth vulnerable to bullying and its negative psychological and health consequences. However, there has been little comprehensive assessment of weight-based victimization, especially in weight loss treatment–seeking samples of youth.

WBV is prevalent in treatment-seeking youth, who report victimization from peers (92%), friends (70%), parents (37%), and teachers (27%). Providers should discuss WBV in their assessment and treatment of pediatric patients who are overweight or obese. (Read the full article)

Universal hepatitis B virus (HBV) vaccination is a cost-effective strategy to control HBV infection. Giving hepatitis B immunoglobulin to neonates of HBV carrier mothers additionally reduces transmission but is not widely used because of its expense and infrastructure requirements.

Maternal screening for hepatitis B surface antigen and hepatitis B immunoglobulin treatment of neonates of hepatitis B virus carrier mothers could be a cost-effective addition to universal vaccination in settings in which health infrastructure can support such an intervention. (Read the full article)

Clinic-based weight control programs for pediatric obesity are time and personnel intensive and not accessible to a large proportion of the population.

This is the first study to reveal the efficacy of a low-intensity, 5-month, guided self-help treatment of childhood obesity with effects on the target child’s weight immediately posttreatment and 6 months later. (Read the full article)

Antibiotics-induced rash in Epstein-Barr virus acute infectious mononucleosis, especially the aminopenicillins-induced type, was first described during the 1960s, with a reported incidence of 80% to 100%. This phenomenon was not further investigated but is well-established in pediatric textbooks.

The main observation of this study is that rash induced by amoxicillin in confirmed Epstein-Barr virus acute infectious mononucleosis was found at a rate of ~30%, which is much lower than previously reported. (Read the full article)

Child maltreatment is a serious and prevalent public health problem in the United States. Responsible for substantial morbidity and mortality, maltreatment affects children's physical and mental health.

Although many health impacts of child maltreatment have been documented, no claims-based study has quantified the impact of maltreatment on health service utilization and costs. This study presents systematic claims-based estimates of maltreatment impacts on utilization and costs for the Medicaid population. (Read the full article)

Shared decision-making involves the assessment of preferences and goals and has been prioritized in new attention-deficit/hyperactivity disorder treatment guidelines, yet no studies have examined the impact of both preferences and goals on treatment initiation.

Supporting the clinical utility of preference and goal assessment, we found that parental treatment preferences are associated with treatment initiation, and those with distinct goals select different treatments. (Read the full article)

Several studies have suggested that probiotics may prevent necrotizing enterocolitis and death in preterm infants. However, there are no data on the preventive effect of probiotics in infants with cyanotic congenital heart disease.

Although duration of hospitalization was not significantly decreased, Bifidobacterium lactis plus inulin appears to decrease the rate of nosocomial infection, necrotizing enterocolitis, and death in infants with cyanotic congenital heart disease. (Read the full article)

Income inequality is positively associated with several adverse child health and well-being outcomes. There is no existing research investigating the relationship between income inequality and child maltreatment rates.

This study is the first to demonstrate that increases in income inequality are associated with increases in child maltreatment rates at the county level. (Read the full article)

Phototherapy effectively treats unconjugated hyperbilirubinemia. However, in resource-poor settings, functional phototherapy devices are often unavailable due to financial constraints or erratic electrical power availability.

Filtered-sunlight phototherapy could be a cost-effective option in resource-poor settings with abundant sunlight. (Read the full article)

Pediatricians need to treat overweight in early childhood. Family-based interventions in specialized clinics are efficacious in children age 8 years and older. Data regarding treatment of younger children are limited in specialty clinics and primary care.

This study shows that a 12-month family-based behavioral intervention in primary care is more efficacious compared with Control condition with a child-only focus. Weight outcome differences between Intervention and Control persist in children and parents after a 12-month follow-up. (Read the full article)

Neonatal narcotic abstinence syndrome (NAS) has become more prevalent in the United States. There is no strong evidence base for NAS treatment and thus no consensus regarding NAS management, including the best treatment drug or best taper strategy.

This study demonstrates that regardless of the initial treatment opioid chosen, use of a standard treatment protocol with stringent weaning guidelines reduces duration of opioid exposure and length of hospital stay for infants with NAS. (Read the full article)

Stimulant medications are indicated for treatment of childhood attention-deficit/hyperactivity disorder (ADHD), but there is concern that stimulants may negatively affect growth. However, no longitudinal, population-based studies have examined height into adulthood for childhood ADHD cases.

This longitudinal, population-based study shows that neither childhood ADHD itself nor treatment with stimulants is associated with significant deficits in height into adulthood. (Read the full article)

Partner violence victimization is associated with mental and behavioral health effects linked to weight gain. Childhood maltreatment is directly linked to obesity and associated with neuroanatomic and psychosocial changes, which heighten vulnerability to subsequent stressors.

This study finds that dating violence victimization is associated with greater increases in BMI from adolescence to young adulthood among women. Women with previous exposure to childhood sexual abuse are especially vulnerable to dating violence–related increases in BMI. (Read the full article)

There are discrepancies regarding which treatment is best in clinical practice for children with parapneumonic empyema, with some authors favoring video-assisted thoracoscopy and others favoring intrapleural fibrinolytic agents.

This study is one of the few randomized clinical trials on this subject in children and the first multicenter trial. It exclusively included patients with septated empyema. Thoracoscopy and fibrinolysis with urokinase were equally effective for this condition. (Read the full article)

Migraine headaches are a common presenting complaint in emergency departments. Abortive treatment in this setting is not well studied, leading to considerable variation in treatment. The relationship between acute medications and emergency department revisits has not been studied.

Eighty-five percent of children with migraine are successfully discharged from the emergency department; only 1 in 18 children require a return visit. Prochlorperazine is associated with less revisits than metoclopramide, and diphenhydramine use is associated with increased risk of return visits. (Read the full article)

Obstructive sleep apnea syndrome (OSAS) is associated with significant comorbidity: behavioral problems, sleepiness, and impaired quality of life. However, the utility of OSAS symptoms versus polysomnography in the prediction of comorbidities or response to treatment is not well known.

Among children with OSAS, the Pediatric Sleep Questionnaire, a well-validated, simple 1-page symptom inventory, predicts key adenotonsillectomy-responsive OSAS comorbidities and their improvement after adenotonsillectomy. In contrast, polysomnographic results do not offer similar predictive value. (Read the full article)

Noninvasive ventilation (NIV) reduced the need of intubation in preterm infants with RDS. However, randomized studies comparing nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure are still lacking.

The present study shows no differences in short-term outcomes between 2 different NIV strategies, nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure, in preterm infants for the initial treatment of RDS. (Read the full article)

Mortality rates and health care expenditures are high among infants requiring surgery for necrotizing enterocolitis. The impact of different surgical managements on mortality remains equivocal. Adjusted economic differences for various surgical treatments may exist but have not been elucidated.

After performing a relatively large-scale, adjusted analysis of cost and mortality for surgical managements currently used for treating necrotizing enterocolitis, a cost-benefit for a particular surgical approach was demonstrated while accounting for comorbidities and group assignment bias. (Read the full article)