Great Trees Require Strong Roots: Evaluating Data and Delegation Doctrine Underlying Proposed Reforms to FDA's Accelerated Approval Program.

In "Missing the Forest for the Trees: Aduhelm, Accelerated Approvals & the Agency," Dr. Matthew Herder argues that agency capture and politicized discretion drive delays in confirmatory trials of accelerated approval drugs amongst other concerns at US Food and Drug Administration (FDA). In highlighting this important problem and offering nuanced insight into agency workings based in part on interviews with twenty-three unnamed FDA officials and a three-drug case study, Dr.

Androgen deficiency in males.

The terms androgen deficiency, testosterone-deficiency syndrome and male hypogonadism have been used interchangeably. It is a clinical condition affecting a significant number of men in the US and worldwide, and is under-recognized and under-treated. The prevalence of low testosterone levels is higher in certain disease states, as specified by the American Association of Clinical Endocrinologists (AACE), the Endocrine Society, International Society of Andrology (ISA), International Society for the Study of the Aging Male (ISSAM), European Association of Urology (EAU), European Academy of Andrology (EAA) and American Society of Andrology (ASA).

Low testosterone and the association with type 2 diabetes.

Purpose: The purpose of this article is to describe androgen deficiency in men, the consequences of this clinically underdiagnosed endocrine disorder, and its relationship to the metabolic syndrome and the association with type 2 diabetes. An overview of prevalence, screening, diagnosis, treatment, and monitoring of male hypogonadism is presented. Method Established guidelines were used to provide definition, diagnosis, treatment, and monitoring information for male hypogonadism.

Regional striatal volume abnormalities in schizophrenia: effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type.

Striatal structures form critical nodes of multiple circuits that are implicated in the pathophysiology of schizophrenia and alcoholism. Here, we examined the separate and combined effects of schizophrenia and alcoholism and effects of medication type and drinking recency on striatal volumes. Accordingly, we measured caudate nucleus, putamen, and nucleus accumbens in 27 schizophrenic, 25 alcohol-dependent, 19 comorbid (schizophrenia and alcohol dependence or abuse), and 51 age-matched control men.

Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism.

Background: Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholism's effect on volumes of these structures has seldom been considered with in vivo measurement.

Methods: We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men.

Alcoholic men endorse more DSM-IV withdrawal symptoms than alcoholic women matched in drinking history.

Objective: Given gender differences in alcohol metabolism, drinking patterns and alcohol-related problems, we asked whether men and women recruited for research protocols from treatment programs would meet different subsets of alcohol dependence or withdrawal criteria or differ in current level of functioning.

Method: The subjects were 66 men and 62 women meeting DSM-III-R or DSM-IV criteria for alcohol dependence. Gender differences were tested infrequency counts of criteria endorsed and Global Assessment of Functioning (GAF) scores.

Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia.

Objective: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure.

Method: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects.

Clinical signs of cerebellar dysfunction in schizophrenia, alcoholism, and their comorbidity.

Abnormalities of cerebellar structure and function, long recognized as a hallmark of chronic alcohol abuse, have also occasionally been noted in patients with schizophrenia. We used a four-point rating scale to assess clinical signs of cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34) and alcohol dependence (N=15) as well as normal control subjects (N=28). Compared to controls, alcoholics had impaired ratings of gait ataxia and instability of stance with eyes closed, and schizophrenics had impaired ratings of stance with eyes closed.

Alcohol and the Cerebellum: Effects on Balance, Motor Coordination, and Cognition.

Alcoholics often suffer from motor incoordination resulting from alcohol-related cerebellar damage. However, the effect of cerebellar structural damage on cognitive functioning has not been clearly demonstrated. It is not known if the relationships observed between cerebellar damage and functional impairments persist with abstinence from alcohol.