Précising definitions as a way to combat overdiagnosis

Roughly, overdiagnosis (ODx) occurs when people are harmed by receiving diagnoses (often accompanied by interventions) that do not benefit them, usually because the diagnosed conditions do not pose a threat to their health. ODx is a theoretical as well as a practical problem as it relates to definitions of disease. Elsewhere, it has been argued that disease is a vague concept and that this vagueness may contribute to ODx. In response, we develop a stipulative or précising definition of disease, for the specific purpose of decreasing or preventing ODx. We call this disease_ODx, aimed at distinguishing cases where it would be beneficial to identify (and treat the condition) from those where diagnosis is more likely to harm than benefit. A preliminary definition of disease_ODx is that X is a disease_ODx iff there is dysfunction that has a significant risk of causing severe harm. This paper examines the 3 concepts in this definition, using a naturalistic account of function, a Feinbergian account of comparative harm, and a probabilistic understanding of risk. We then test the utility of this approach using examples of clinical conditions that are currently overdiagnosed.     

The effect of captopril treatment on potassium-induced stimulation of aldosterone production in vitro

Potassium and angiotensin (AII) show interdependence as stimuli of aldosterone production. However, potassium stimulates in vitro in the absence of AII. In the present study we examined for a contribution by AII to the in vitro stimulatory potential of potassium, an AII effect mediated on the adrenal before killing of the animal. Captopril, an angiotensin converting-enzyme inhibitor, was administered orally and by sc injection for 3 days so as to decrease levels of AII. Aldosterone secretory responses by adrenal capsules to graded increments in potassium were measured subsequently using a perifusion system. It was found that captopril pretreatment significantly reduced the magnitude of aldosterone secretory response to increments in potassium of 0.5 to 6.0 mM, from a baseline potassium concentration of 3.5 mM. Responses to the lowest increment in potassium, 0.5 and 1.0 mM, were virtually abolished by captopril treatment. The results suggest that AII sensitizes the adrenal glomerulosa such that very small changes in potassium concentration can affect aldosterone production.     

The beneficial effect of alcohol consumption on the prevalence and extent of centrilobular emphysema. A retrospective autopsy analysis

A collection of 204 inflation-fixed autopsy lungs was divided into three groups: normal, 93; centrilobular emphysema (CLE), 88; and "other," 23; the last includes lungs with other chronic processes. Clinical hospital records were reviewed to ascertain smoking history (no smoking, 31; smoking, 173) and alcohol use (none, 73; slight-to-moderate (Sli-Mod) drinkers, 66; heavy drinkers, 65). Lungs were subjected to morphometric determination of the extent of CLE, mucous gland hyperplasia in large airways, and goblet cell metaplasia in bronchioles. Prevalence of CLE diminished progressively as alcohol use increased. A logistic analysis showed that alcohol use was significantly associated (p less than 0.008) with reduced extent of CLE even after allowing for age and smoking effects. This apparent prophylactic effect of alcohol against CLE probably results from inhibition of inflammatory cells. It suggests that a drug with similar effects but without the deleterious side effects of alcohol might provide a meaningful degree of protection against emphysema in smokers.     

Neurite outgrowth on muscle cell surfaces involves extracellular matrix receptors as well as Ca2+-dependent and -independent cell adhesion molecules.

To identify the molecules on the neuronal surface that mediate axonal growth on myotubes, we have examined neurite formation by ciliary neurons grown on myotubes in the absence or presence of specific antibodies. Dramatic inhibition of neurite outgrowth was seen only when antibodies blocked simultaneously the functions of two cell adhesion molecules--neural cell adhesion molecule (N-CAM) and neural Ca2+-dependent CAM (N-Cal-CAM)--and the neuronal receptors for several extracellular matrix (ECM) proteins. Although the antibody used to block ECM receptors (JG22) has been shown to eliminate almost all neurite growth on ECMs, it had only small effects on neurite growth on myotubes, reducing somewhat the length of neurites. Similarly, antibodies to the two CAMs, when used alone, had no detectable effects on neurite length and, when used together, had only small inhibitory effects on neurite growth. Combination of anti-ECM receptor (JG22) with antibodies to either CAM, however, greatly shortened the length of neurites. These results imply that ECM receptors and the CAMs N-CAM and N-Cal-CAM are major macromolecules used by neuronal growth cones for interactions with myotubes. Each provides a distinct mechanism for regulating growth cone motility.     

Electrophysiology of Ethmozine (moricizine HCl) for ventricular tachycardia

Moricizine HCl, an antiarrhythmic phenothiazine drug, was investigated for its efficacy against ventricular tachycardia (VT) in a group of 60 patients from 8 institutions using electrophysiologic testing before and after oral administration. Moricizine HCl significantly prolonged PR, QRS, AH and HV intervals and cycle length for atrioventricular nodal block, but had minimal or no effect on repolarization or cardiac refractory periods. Induction of sustained VT (in 33 patients) and nonsustained VT (in 14 patients) occurred at baseline. During moricizine HCl therapy, sustained VT was induced in 31 patients and nonsustained VT in 7 patients. In individual patients, suppression of VT induction was obtained in 18% of patients with sustained VT and in 27% of patients with nonsustained VT. Cycle length of induced VT was significantly prolonged by moricizine HCl therapy. During prospective follow-up of 37 patients, electrophysiologic study predicted recurrence of nonrecurrence of VT with a sensitivity value of 82% and specificity of 65%.     

Alcohol and the Woman of Childbearing Age – A Public Health Problem

Recent work has established on a rational basis what has been understood instinctively throughout recorded history – that excessive maternal consumption of alcohol is harmful to the baby developing in utero. From conception onwards, the risk of anomalies of development (mostly minor) and retardation of intrauterine growth increases more or less in proportion to the level of alcohol consumption. Since much of the damage occurs early in pregnancy before most women realise that they are pregnant, the problem of prevention becomes one for the public health field. All professional workers concerned with women of child-bearing age should be aware, therefore, of what the facts are and how to help the woman who may become pregnant to reduce her alcohol intake. They have a dual role to play – detection of those at risk and effective counselling of the patients after their identification.     

Loneliness and its Association with Health Behaviors in People with a Lived Experience of a Serious Mental Illness

To explore the association between loneliness and efficacy to engage in health behaviors that are known to reduce the risk of early mortality in people with serious mental illness (SMI). This secondary data analysis was based on a cross-sectional study of 113 participants with SMI residing in New Hampshire. Ordinary Least Squares regressions were used to examine bivariate relationships between variables of interest. Participants had a primary mental health diagnosis of major depressive disorder (37.2%), schizophrenia spectrum disorder (28.3%), bipolar disorder (29.2%), or posttraumatic stress disorder (5.3%). High levels of loneliness were associated with low levels of self-efficacy to manage chronic diseases (p =?0.0001), as well as low levels of self-efficacy to manage psychological well-being (R² =?.31; F =?9.49, p =?0.0001; RMSE =?1.66). Loneliness may serve as a barrier to healthy behaviors, and thus, contribute to early mortality among people with SMI. The growing body of literature that demonstrates the importance of addressing loneliness in people with SMI should stimulate policymakers and researchers to target loneliness as a mechanism to address early mortality in people with SMI.