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Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

Amygdala and insula hyper-reactivity to threat is implicated in social anxiety disorder (SAD) yet inconsistencies in activation have been reported. One source of variance are individual differences in 5-HTTLPR genotype where the short (S), relative to long (L) allele, corresponds with greater amygdala activation. However, the impact of genotype on insula to threat in SAD is not known. During functional MRI, 34 SAD patients and 28 healthy controls completed a perceptual assessment task comprising angry, fear, and happy faces. Results showed no diagnostic group differences in limbic/paralimbic regions but within SAD, greater insula, but not amygdala, activation to fearful faces was observed in patients with SS genotype compared with LaLa genotype. Findings indicate genotype influenced insula activation to threat in SAD.

A heightened sensitivity to unpredictable aversiveness is a key component of several anxiety disorders. Neuroimaging studies of unpredictable aversiveness have shown that the anterior region of the insula cortex (AIC) plays a central role in the anticipation of unpredictable aversiveness. The present study extended these findings by examining the role of the AIC in temporal unpredictability (i.e. not knowing when the stimulus will occur), a particularly critical aspect of unpredictability as it increases contextual anxiety and vigilance, given that the danger could happen 'at any time'. Nineteen healthy participants underwent functional MRI while anticipating either temporally unpredictable or predictable aversive (or neutral) images. Participants showed greater right AIC activation while anticipating unpredictable relative to predictable aversive images. In addition, activation in this region was correlated positively with self-reported individual differences in a key facet of intolerance of uncertainty (inhibitory behavior). Taken together, the present study suggests that the AIC plays an important role in the anticipation of temporally unpredictable aversiveness and may mediate key deficits in anxiety disorders.

Objective: To assess the effect of institution of noninvasive ventilation (NIV) on clinical outcome and quality of life (QOL) in a cohort of children with severe neuromuscular disorders., Methods: We reviewed records and obtained clinical data from the year prior to commencing NIV and annually thereafter. Data obtained included diagnosis, patient symptoms, mortality, NIV adverse effects, pulmonary function tests, polysomnographic data, length of hospitalizations, and health care costs. Patients and parents completed questionnaires assessing QOL with NIV and recalling QOL before NIV., Results: Fourteen of 17 (82%) suitable patients were enrolled. Follow-up ranged from 6 to 84 months (median 30). Symptoms of daytime sleepiness (p = 0.003) and headache (p = 0.046) improved after initiation of NIV. Sleep quality assessed by polysomnography also improved. Hospitalization rates (p = 0.002) and health care costs (p = 0.003) decreased. QOL remained stable after NIV, despite disease progression., Conclusion: Treatment of respiratory failure, in children with neuromuscular disease, with noninvasive ventilation results in a reduction in symptoms, hospitalizations, and health care costs without adverse effects on quality of life.

Recent studies suggest exaggerated responses in the limbic system of patients with generalized social anxiety disorder in response to threat/anxiety-related social situations and aversive conditioning, processes mediated by the glutamatergic system. This single-voxel, high-field 1H-magnetic resonance spectroscopy study examined concentrations of glutamate, and other metabolites, in the anterior cingulate cortex and occipital cortex (control region) of 10 medication-naive patients with generalized social anxiety and 10 matched healthy comparison subjects. Glutamate (relative to creatine) levels were significantly higher in patients than controls in the anterior cingulate, but not occipital, cortex. Anterior cingulate glutamate/creatine levels were also correlated with intensity of social anxiety symptoms. These findings provide new evidence of glutamate's involvement in the neural mechanism underlying social phobia.

The ability to detect dynamic changes in brain activity during affective processing within individual subjects in real-time can advance our understanding of the neural mechanisms of emotion, psychiatric illness, and therapeutic intervention. We investigated whether activity in limbic and paralimbic regions elicited by blocks of aversive (AV) and neutral (NEU) pictures can be detected by real-time fMRI. Real-time analysis of signal change during each block revealed that activations in insula and medial frontal cortex were more frequent during AV than NEU epochs. Single subject and group analysis off-line with conventional statistical parametric mapping methods matched the results obtained in real-time. Detecting cortico-limbic brain activation during perception and experience of emotionally salient visual stimuli with real-time fMRI technology is feasible., (Copyright 2004 Lippincott Williams & Wilkins)