Feeds:
Posts
Comments

Archive for the ‘Substance Abuse’ Category


What drug interfered with the performance of Sharapova?

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Meldonium — The Drug That Brought Down Sharapova

Gayle Nicholas Scott, PharmD

When tennis player Maria Sharapova recently revealed that she had tested positive for the banned drug meldonium, the reaction of most healthcare providers was, “What is it?”

Meldonium is manufactured and sold as Mildronate by the pharmaceutical company Grindeks in the Baltic nation of Latvia. Meldonium is not available in the United States or elsewhere in the European Union (it was grandfathered in Latvia) other than via purchase on the Internet.

The World Anti-Doping Agency classifies meldonium as a “metabolic modulator” and moved the drug from its watch list to its list of banned substances in January 2016.

Other “metabolic modulators” are insulin and trimetazidine, an anti-ischemic metabolic agent that increases myocardial glucose utilization through inhibition of fatty acid metabolism.[1,2] Trimetazidine is approved in the European Union for the treatment of angina, but it is not approved in the United States.

The chemical name for meldonium is trimethylhydrazinium propionate. Meldonium works by decreasing the availability of levocarnitine (L-carnitine). L-carnitine is found naturally in milk and meats, and also can be synthesized by the body from lysine and methionine with the help of gamma-butyrobetaine hydroxylase. L-carnitine helps move long-chain fatty acids into the mitochondria for oxidation and energy production in the muscles.

Ironically, L-carnitine, which meldonium inhibits, is taken as a dietary supplement alone and as an ingredient in energy drinks to increase athletic performance. (L-carnitine is available in the United States as the prescription drug Carnitor®, which is indicated for carnitine deficiency owing to inborn errors of metabolism and for end-stage renal disease requiring dialysis.) After two decades of research, no consistent evidence has emerged indicating that carnitine supplements can improve exercise or physical performance. Carnitine supplements do not appear to increase the body’s use of oxygen or improve metabolic status when exercising, and may not increase the amount of carnitine in muscle.[3,4]Carnitine is not on the list of banned substances.[1]

As a modulator of L-carnitine metabolism, meldonium inhibits gamma-butyrobetaine hydroxylase and L-carnitine transmembrane transport of long-chain fatty acids, thus decreasing L-carnitine levels in tissue and plasma. Reducing the amount of bioavailable L-carnitine shifts the source of metabolic energy production from fatty acid oxidation to glucose metabolism. Aerobic glucose oxidation consumes less oxygen than fatty acid oxidation and increases the effectiveness of adenosine triphosphate (ATP) generation. Additionally, meldonium appears to increase glucose uptake. In ischemic conditions (hypoxia), meldonium appears to restore the balance between cellular oxygen supply and demand, and prevents ATP transport impairment.[3,5]

All published clinical efficacy studies on meldonium, except one,[6] are in Russian. Abstracts of randomized controlled trials have reported the efficacy of meldonium in reducing angina, arrhythmias, and anxiety and other early sequelae of myocardial infarction[7-10]; as an “adaptogen” in patients with cardiovascular disease[11,12]; and in treating angina and reducing myocardial ischemia after percutaneous coronary intervention,[6,13,14] heart failure,[15] and diabetic peripheral neuropathy.[16] Doses, when included in the abstracts, ranged from 750 to 1000 mg per day. Only one abstract mentioned adverse effects, stating that none occurred.[7]

A pharmacokinetic study of meldonium showed that the drug has a dose-dependent half-life and volume of distribution with accumulation on multiple-dose administration. In eight healthy volunteers who received meldonium for 13 days, almost all reported insomnia, half reported burping, and one quarter reported “dreaminess.” No serious adverse effects were reported.[17]

A study in healthy, nonvegetarian volunteers receiving 1000 mg meldonium per day for 4 weeks showed that plasma concentrations of L-carnitine decreased by 18%. Urine samples showed an increase in L-carnitine excretion. Adverse effects were not mentioned.[18] Meldonium is excreted in the urine largely unchanged, making urine testing a valid monitor presence of meldonium.[19]

No long-term studies on the safety and efficacy of meldonium have been published. No studies on the effect of meldonium on athletic performance in humans have been published. One study on the reliability of urine testing in professional sports[19]mentions an article and an abstract, but neither of those appears in PubMed. The abstract purports to be a review of “recent studies on mildronate especially in fields associated with physical work capabilities and sport” but cites only the study mentioned in the urine testing review.[20] Most articles about meldonium cited on PubMed are by Latvian authors.

Animal research suggests the potential usefulness of meldonium in Alzheimer disease,[21-23] Parkinson disease,[24,25] and diabetes.[26-29] Meldonium increased sexual activity in boars[30] but not in male rats.[31] Research in rodents found that meldonium can cause carnitine deficiency in offspring, so the drug should not be taken in pregnancy.[32]

Because meldonium is excreted renally, serum levels may be higher in patients with reduced kidney function, and the drug may accumulate with repeated dosing.[19] L-carnitine appears to antagonize the effects of meldonium[33]; otherwise, drug interactions are not known.

To recap, meldonium is an interesting drug developed by Latvian researchers. Published research suggests that it may be an effective treatment for cardiovascular diseases, such as angina. Little information about its adverse effects has been published, however, and the long-term safety of meldonium is not known. And although reliable research on meldonium’s use for athletic performance is not available, the World Anti-Doping Agency has declared it a banned substance.

Read Full Post »


Yesterday and today are not the same

Larry H. Bernstein

LPBI

 

The New Generation Gap

https://www.project-syndicate.org/commentary/new-generation-gap-social-injustice-by-joseph-e–stiglitz-2016-03

Joseph E. Stiglitz

Joseph E. Stiglitz, recipient of the Nobel Memorial Prize in Economic Sciences in 2001 and the John Bates Clark Medal in 1979, is University Professor at Columbia University, Co-Chair of the High-Level Expert Group on the Measurement of Economic Performance and Social Progress at the OECD, and Chief Economist of the Roosevelt Institute. A former senior vice president and chief economist of the World Bank and chair of the US president’s Council of Economic Advisers under Bill Clinton, in 2000 he founded the Initiative for Policy Dialogue, a think tank on international development based at Columbia University. His most recent book is Rewriting the Rules of the American Economy.

NEW YORK – Something interesting has emerged in voting patterns on both sides of the Atlantic: Young people are voting in ways that are markedly different from their elders. A great divide appears to have opened up, based not so much on income, education, or gender as on the voters’ generation.

There are good reasons for this divide. The lives of both old and young, as they are now lived, are different. Their pasts are different, and so are their prospects.

The Cold War, for example, was over even before some were born and while others were still children. Words like socialism do not convey the meaning they once did. If socialism means creating a society where shared concerns are not given short shrift – where people care about other people and the environment in which they live – so be it. Yes, there may have been failed experiments under that rubric a quarter- or half-century ago; but today’s experiments bear no resemblance to those of the past. So the failure of those past experiments says nothing about the new ones.

Older upper-middle-class Americans and Europeans have had a good life. When they entered the labor force, well-compensated jobs were waiting for them. The question they asked was what they wanted to do, not how long they would have to live with their parents before they got a job that enabled them to move out.

That generation expected to have job security, to marry young, to buy a house – perhaps a summer house, too – and finally retire with reasonable security. Overall, they expected to be better off than their parents.

While today’s older generation encountered bumps along the way, for the most part, their expectations were met. They may have made more on capital gains on their homes than from working. They almost surely found that strange, but they willingly accepted the gift of our speculative markets, and often gave themselves credit for buying in the right place at the right time.

Today, the expectations of young people, wherever they are in the income distribution, are the opposite. They face job insecurity throughout their lives. On average, many college graduates will search for months before they find a job – often only after having taken one or two unpaid internships. And they count themselves lucky, because they know that their poorer counterparts, some of whom did better in school, cannot afford to spend a year or two without income, and do not have the connections to get an internship in the first place.

Today’s young university graduates are burdened with debt – the poorer they are, the more they owe. So they do not ask what job they would like; they simply ask what job will enable them to pay their college loans, which often will burden them for 20 years or more. Likewise, buying a home is a distant dream.

These struggles mean that young people are not thinking much about retirement. If they did, they would only be frightened by how much they will need to accumulate to live a decent life (beyond bare social security), given the likely persistence of rock-bottom interest rates.

In short, today’s young people view the world through the lens of intergenerational fairness. The children of the upper middle class may do well in the end, because they will inherit wealth from their parents. While they may not like this kind of dependence, they dislike even more the alternative: a “fresh start” in which the cards are stacked against their attainment of anything approaching what was once viewed as a basic middle-class lifestyle.

These inequities cannot easily be explained away. It isn’t as if these young people didn’t work hard: these hardships affect those who spent long hours studying, excelled in school, and did everything “right.” The sense of social injustice – that the economic game is rigged – is enhanced as they see the bankers who brought on the financial crisis, the cause of the economy’s continuing malaise, walk away with mega-bonuses, with almost no one being held accountable for their wrongdoing. Massive fraud was committed, but somehow, no one actually perpetrated it. Political elites promised that “reforms” would bring unprecedented prosperity. And they did, but only for the top 1%. Everyone else, including the young, got unprecedented insecurity.

These three realities – social injustice on an unprecedented scale, massive inequities, and a loss of trust in elites – define our political moment, and rightly so.

More of the same is not an answer. That is why the center-left and center-right parties in Europe are losing. America is in a strange position: while the Republican presidential candidates compete on demagoguery, with ill-thought-through proposals that would make matters worse, both of the Democratic candidates are proposing changes which – if they could only get them through Congress – would make a real difference.

Were the reforms put forward by Hillary Clinton or Bernie Sanders adopted, the financial system’s ability to prey on those already leading a precarious life would be curbed. And both have proposals for deep reforms that would change how America finances higher education.

But more needs to be done to make home ownership possible not just for those with parents who can give them a down payment, and to make retirement security possible, given the vagaries of the stock market and the near-zero-interest world we have entered. Most important, the young will not find a smooth path into the job market unless the economy is performing much better. The “official” unemployment rate in the United States, at 4.9%, masks much higher levels of disguised unemployment, which, at the very least, are holding down wages.

But we won’t be able to fix the problem if we don’t recognize it. Our young do. They perceive the absence of intergenerational justice, and they are right to be angry.

Read more at https://www.project-syndicate.org/commentary/new-generation-gap-social-injustice-by-joseph-e–stiglitz-2016-03#vxQE74VR3kfAWbf1.99

 

 

Read Full Post »


Anorexia Nervosa and Related Eating Disorders

Writer and Curator: Larry H. Bernstein, MD, FCAP 

 

Introduction

Anorexia nervosa is a stress related disorder that occurs mainly in women, closely related to bulimia, and is related to self-esteem, or to a preoccupation with how the individual would like to see themselves. It is not necessarily driven by conscious motive, but lies in midbrain activities that govern hormonal activity and social behavior

 

Eating disorders

Christopher G Fairburn, Paul J Harrison
Lancet 2003; 361: 407–16

Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behavior therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.

Eating disorders are of great interest to the public, of perplexity to researchers, and a challenge to clinicians. They feature prominently in the media, often attracting sensational coverage. Their cause is elusive, with social, psychological, and biological processes all seeming to play a major part, and they are difficult to treat, with some patients actively resisting attempts to help them.

Anorexia nervosa and bulimia nervosa are united by a distinctive core psychopathology, which is essentially the same in female and male individuals; patients overevaluate their shape and weight. Whereas most of us assess ourselves on the basis of our perceived performance in various domains—eg, relationships, work, parenting, sporting prowess—patients with anorexia nervosa or bulimia nervosa judge
their self-worth largely, or even exclusively, in terms of their shape  and weight and their ability to control them. Most of the other features
of these disorders seem to be secondary to this psychopathology and to its consequences—for example, self-starvation. Thus, in anorexia nervosa there is a sustained and determined pursuit of weight loss and, to the extent that this pursuit is successful, this behavior is not seen as a problem. Indeed, these patients tend to view their low weight as an accomplishment rather than an affliction. In bulimia nervosa, equivalent attempts to control shape and weight are undermined by frequent episodes of uncontrolled overeating (binge eating) with the result that patients  often describe themselves as failed anorexics.  The core psychopathology has other manifestations; for example,  many patients mislabel certain adverse physical and emotional states as feeling fat, and some repeatedly scrutinize aspects of their shape,
which could contribute to them overestimating their size.

Panel 1: Classification and diagnosis of eating disorders

Definition of an eating disorder

  • There is a definite disturbance of eating habits or weight- control behavior
  • Either this disturbance, or associated core eating disorder features, results in a clinically significant impairment of physical health or psychosocial functioning (core eating disorder features comprise the disturbance of eating and any associated over-evaluation of shape or weight)
  • The behavioral disturbance should not be secondary to any general medical disorder or to any other psychiatric condition

Classification of eating disorders

  • Anorexia nervosa
  • Bulimia nervosa
  • Atypical eating disorders (or eating disorder not otherwise specified)

Principal diagnostic criteria

  • Anorexia nervosa
  1. Over-evaluation of shape and weight—ie, judging self-worth largely, or exclusively, in terms of shape and weight
  2. Active maintenance of an unduly low bodyweight—eg, body-mass index 17·5 kg/m2
  3. Amenorrhea in post-menarche females who are not taking an oral contraceptive. The value of the amenorrhea criterion can be questioned since most female patients who meet the other two diagnostic criteria are amenorrheic, and those who menstruate
    seem to resemble closely those who do not
  • Bulimia nervosa
  1. Over-evaluation of shape and weight—ie, judging self-worth largely,
    or exclusively, in terms of shape and weight
  2. Recurrent binge eating—i.e., recurrent episodes of uncontrolled overeating
  3. Extreme weight-control behavior—e.g., strict dietary restriction, frequent self-induced vomiting or laxative misuse

Diagnostic criteria for anorexia nervosa are not met

  • Atypical eating disorders

Eating disorders of clinical severity that do not conform to the diagnostic criteria for anorexia nervosa or bulimia nervosa

Research into the pathogenesis of the eating disorders has focused almost exclusively on anorexia nervosa and bulimia nervosa. There is undoubtedly a genetic predisposition and a range of environmental risk factors, and there is some information with respect to the identity and relative importance of these contributions. However, virtually nothing is known about the individual causal processes involved, or about how they interact and vary across the development and maintenance of the disorders.

 

Panel 3: Main risk factors for anorexia nervosa and bulimia nervosa

  • General factors
  1. Female
  2. Adolescence and early adulthood
  3. Living in a Western society
  • Individual-specific factors

Family history

  • Eating disorder of any type
  • Depression
  • Substance misuse, especially alcoholism (bulimia nervosa)
  • Obesity (bulimia nervosa)

Premorbid experiences

  • Adverse parenting (especially low contact, high expectations, parental discord)
  • Sexual abuse
  • Family dieting
  • Critical comments about eating, shape, or weight from family and others
  • Occupational and recreational pressure to be slim Premorbid characteristics

Low self-esteem

  • Perfectionism (anorexia nervosa and to a lesser extent bulimia nervosa)
  • Anxiety and anxiety disorders
  • Obesity (bulimia nervosa)
  • Early menarche (bulimia nervosa)

There has been extensive research into the neurobiology of eating disorders. This work has focused on neuropeptide and monoamine (especially 5-HT) systems thought to be central to the physiology of eating and weight regulation. Of the various central and peripheral abnormalities reported, many are likely to be secondary to the aberrant eating and associated weight loss. However, some aspects of 5-HT function remain abnormal after recovery, leading to speculation that there is a trait monoamine abnormality that might predispose to the development of eating disorders or to associated characteristics such as perfectionism. Furthermore, normal dieting in healthy women alters central 5-HT function, providing a potential mechanism by which eating disorders might be precipitated in women vulnerable for other reasons.

Specific psychological theories have been proposed to account for the development and maintenance of eating disorders. Most influential in terms of treatment have been cognitive behavioral theories. In brief, these theories propose that the restriction of food intake that characterizes the onset of many eating disorders has two main origins, both of which may operate. The first is a need to feel in control of life, which gets displaced onto controlling eating. The second is over-evaluation of shape and weight in those who have been sensitized to their appearance. In both instances, the resulting dietary restriction is highly reinforcing. Subsequently, other processes begin to
operate and serve to maintain the eating disorder.

 

Depression, coping, hassles, and body dissatisfaction: Factors associated with disordered eating

Rose Marie Ward, M. Cameron Hay
Eating Behaviors 17 (2015) 14–18
http://dx.doi.org/10.1016/j.eatbeh.2014.12.002

The objective was to explore what predicts first-year college women’s disordered eating tendencies when they arrive on campus. The 215 first-year college women completed the surveys within the first 2 weeks of classes. A structural model examined how much the Helplessness, Hopelessness, Haplessness Scale, the Brief COPE, the Brief College Student Hassle Scale, and the Body Shape Questionnaire predicted eating disordered tendencies (as measured by the Eating Attitudes Test). The Body Shape Questionnaire, the Helplessness, Hopelessness, Haplessness Scale (inversely), and the Denial subscale of the Brief COPE significantly predicted eating disorder tendencies in first-year college women. In addition, the Planning and Self-Blame subscales of the Brief COPE and the Helplessness, Hopelessness, Haplessness Scale predicted the Body Shape Questionnaire. In general, higher levels on the Helplessness, Hopelessness, Haplessness Scale and higher levels on the Brief College Student Hassle Scale related to higher levels on the Brief COPE. Coping seems to remove the direct path from stress and depression to disordered eating and body dissatisfaction.

Eating disorders and disordered eating on college campuses are a pervasive problem. Research estimates that approximately 8–13.5% of college women meet the criteria for clinically diagnosed eating disorders such as anorexia nervosa, bulima nervosa, or eating disorders not otherwise specified. In addition, negative moods and stress seem to relate eating disorders. Diagnosable eating disorders emerge in the broader context of disordered eating, that is — engaging in practices such as restricting calories, eating less fat, skipping meals, using nonprescription diet pills, using laxatives, or inducing vomiting. Whereas disordered eating is broadly associated with the dynamics of human development in adolescence in the United States and the socio-cultural pressure to be thin, college environments may particularly predispose young women to disordered eating. In a national survey, 57% of female college students reported trying to lose weight, while only 38% of female college students categorized themselves as overweight.

The mean for the overall EAT scale was 8.89 (SD=9.26, mode=2, median = 6, range 0 to 60). Over 13% (n = 22) of the sample met the criteria for potential eating disorders with overall scores of 20 or greater. One primary model was tested using the quantitative measurement data. The model fit the data, χ2 (n = 191, 72) = 89.33, p = .08, CFI N .99, TLI = .99, and RMSEA = .035.

Note: Only significant paths shown; *p < .05; **p < .01; ***p < .001; HHH = Helplessness, Hopelessness, Haplessness Scale; Hassles = Brief College Student Hassle Scale; EAT = Eating Attitudes Test-26; BSQ = Body Satisfaction Questionnaire; CFI = Comparative Fit Index; TLI = Tucker-Lewis Index; RMSEA = Root Mean Squared Error of Approximation.

Structural modeling predicting eating disorder tendencies

Structural modeling predicting eating disorder tendencies

Structural modeling predicting eating disorder tendencies. Note: Only significant paths shown; *p < .05; **p < .01; **p < .001; HHH = Helplessness, Hopelessness, Haplessness Scale; Hassles = Brief College Student Hassle Scale; EAT = Eating Attitudes Test-26; BSQ = Body Satisfaction Questionnaire; CFI = Comparative Fit Index; TLI= Tucker–Lewis Index; RMSEA = Root Mean Squared Error of Approximation.

By identifying the risk factors through research, interventions can be developed that empower people to take control of their own eating behavior. This kind of intervention is supported by the finding that those students with more agentive, active coping styles, or who did not report frequent experiences of helplessness, haplessness, and hopelessness were less likely to have disordered eating behaviors. Whereas active coping has been associated with lower disordered eating in some studies (e.g., Ball & Lee, 2000), others suggest a more complicated relationship between denial or avoidant coping and disordered eating.

 

The cognitive behavioral model for eating disorders: A direct evaluation in children and adolescents with obesity

Veerle Decaluwe, Caroline Braet
Eating Behaviors 6 (2005) 211–220
http://dx.doi.org:/10.1016/j.eatbeh.2005.01.006

Objective: The cognitive behavioural model of bulimia nervosa. The clinical features and maintenance of bulimia nervosa. In K.D. Brownell, and J.P. Foreyt (Eds.), Handbook of eating disorders: physiology, psychology and treatment of obesity, anorexia and bulimia (pp. 389–404). New York: Basic Books.] provides the theoretical framework for cognitive behavior therapy of Bulimia Nervosa. For a long time it was assumed that the model can also be used to understand the mechanism of binge eating among obese individuals. The present study aimed to test whether the specific hypotheses derived from the cognitive behavioral theory of bulimia nervosa are also valid for children and adolescents with obesity. Method: The prediction of the model was tested using structural equation modeling. Data were collected from 196 children and adolescents.  Results: In line with the model, the results suggest that a lower self-esteem predicts concerns about eating, weight and shape, which in turn predict dietary restraint, which then further is predictive of binge eating.
Discussion: The findings suggest that the mechanisms specified in the model of bulimia nervosa is also operational among obese youngsters. The cognitive behavioral model of Bulimia Nervosa (BN), outlined by Fairburn, Cooper, and Cooper (1986), provides the theoretical framework for cognitive behavior therapy of BN (Fairburn, Marcus, & Wilson, 1993; Wilson, Fairburn, & Agras, 1997). According to this model, over-evaluation of eating, weight and shape plays a central role in the maintenance of BN. It is assumed that over-concern in combination with a low self-esteem can lead to dietary restraint (e.g. strict dieting and other weight control behavior). However, the rigid and unrealistic dietary rules are difficult to follow and the eating behavior is seen as a failure. Moreover, minor dietary slips are considered as evidence of lack of control and can lead to an all-or-nothing reaction in which all efforts to control eating are abandoned. This condition makes people vulnerable to binge eating. In order to minimize weight gain as a result of overeating, some patients practice compensatory purging (compensatory vomiting or laxative misuse).

The present study aimed to directly evaluate the model among a population of children and adolescents suffering from obesity. It is justified to study this model in a group at-risk. Binge eating is [V. Decaluwe´, C. Braet / Eating Behaviors 6 (2005) 211–220] not restricted to adulthood and is recognized among children with obesity as well (Decaluwe´ & Braet, 2003). Even in childhood, associated eating and shape concerns and comorbid psychopathology are manifest. Until now, little is known about how the risk factors for BED operate. A case-control study by Fairburn et al. (1998) reported a number of adverse factors in childhood, carrying a higher risk of developing BED, including negative self-evaluation, parental depression, adverse experiences (sexual or physical abuse and parental problems), overweight and repeated exposure to negative comments about shape, weight and eating. Moreover, it seems that childhood obesity is not only a risk factor for developing BED, but also one of the risk factors for the development of BN (Fairburn, Welch, Doll, Davies, & O’Connor, 1997). If Fairburn’s model is able to predict binge eating in an obese population, we can discover how the risk factors are related to one another and how they are operating to predict disordered eating among obese youngsters.

To conclude, in the present study, we were interested whether the cognitive behavioral theory would predict disordered eating in a young obese population. Because the study focuses on subjects at risk for developing binge-eating problems, BED or BN, we considered the cognitive behavioral theory as a risk factor model for eating disorders rather than a model for the maintenance of eating disorders.

  1. Method

2.1. Design

The prediction of the models was evaluated using structural equation modeling (LISREL 8.50; Jo¨reskog & So¨rbom, 2001). The dependent variables were binge eating, over-evaluation of eating, shape and weight, and dietary restraint. The independent variable was self-esteem. Purging behavior was not included in the structural equation modeling since binge eating among children occurs in the absence of compensatory behavior. Next, it is worth noting that the concept of self-esteem is implicit in the original cognitive model of BN. In order to compare the present research with the study of Byrne and McLean (2002), self-esteem was included in the evaluation of the model.

A sample of 196 children and adolescents with obesity (78 boys and 118 girls) between the ages of 10 and 16 participated in the study (M=12.73 years, SD=1.75). All subjects were seeking help for obesity. The sample consisted of children seeking inpatient or outpatient treatment. All children seeking inpatient or outpatient treatment between July 1999 and December 2001 were invited to participate. The response rate was 72%. Children younger than 10 or older than 16 and mentally retarded children were excluded from the study. All participating children obtained a diagnosis of primary obesity. The group had a mean overweight of 172.69% (SD=27.09) with a range of 120–253%. The study was approved by the local research ethics committee. The subjects were visited at their homes before they entered into treatment. Informed consent was obtained from both the children and their parents. Two subjects (1%), both female, met the full diagnostic criteria for BED and 18 subjects (9.2%) experienced at least one binge-eating episode over the previous three months (overeating with loss of control), but did not endorse all of the other DSM-IV criteria that are required for a diagnosis of BED.

To conclude, in the present study, we were interested whether the cognitive behavioral theory would predict disordered eating in a young obese population. Because the study focuses on subjects at risk for developing binge-eating problems, BED or BN, we considered the cognitive behavioral theory as a risk factor model for eating disorders rather than a model for the maintenance of eating disorders.

A two-step procedure was followed to construct the measurement model. We first conducted a confirmatory factor analysis on the variance–covariance matrix of the items of the exogenous construct (independent latent variable) b self-esteem Q. The construct b self-esteem Q is composed of 5 items of the Global self-worth subscale of the SPPA. Goodness-of-fit statistics were generated by the analysis. Items with poor loading (absolute t-value = 1.96) were removed. This resulted in a satisfactory model, χ2 (2)=6.23, p=0.04, GFI=0.97, AGFI=0.87 after omitting 1 item. The parameter estimates between the observed items and the latent variable ranged from 0.49 to 0.88.

Self-esteem was highly negatively correlated with over-evaluation of eating, weight and shape (standardized ϒ=-0.59, t=-5.05), indicating that higher levels of concerns about eating, weight and shape were associated with a lower self-esteem. Over-evaluation of eating, weight and shape, in turn, was shown to be significantly related with dietary restraint (standardized β=0.70, t=2.71), indicating that more concerns about eating, weight or shape were associated with higher levels of dietary restraint. Finally, dietary restraint was significantly associated with binge eating (standardized β=0.45, t=2.14), indicating that higher levels of dietary restraint were associated with a higher level of binge eating. The feedback from binge eating to over-evaluation of eating, weight and shape was not significant. Overall, the results appeared to suggest that a lower self-esteem predicts concerns over eating, weight and shape, which in turn predict dietary restraint. This would then be predictive of binge eating.

To our knowledge, this was the first study that directly evaluated the CBT model of BN among children. Overall, the model was found to be a good fit of the data. The main predictions of the model were confirmed. We can conclude that the CBT model provides a relatively valid explanation of the prediction of binge-eating problems in a young obese sample. Three findings supported the model and one finding did not confirm the model.

First, in line with the model, the construct self-esteem was a predictor of the over-evaluation of eating, weight and shape. This finding is also consistent with findings of Byrne and McLean (2002) and previous research in children and adolescents, which also found an association between over-concern with weight and shape and a lower self-esteem.

Second, the over-evaluation of eating, weight and shape, in turn, was a direct predictor of dietary restraint. Our findings were in line with prospective studies that found that thin-ideal internalization and body dissatisfaction (components of the over-evaluation of shape and weight) had a significant effect on dieting. Our findings also support the cross sectional study of Womble et al. (2001), who found a direct association between body dissatisfaction and dietary restraint among obese women. As in adults, children seem to respond in the same manner by dieting to lose weight. To our knowledge, the relationship between over-evaluation and dietary restraint has never been explored before among children with obesity.

Third, in accordance with the CBT model of BN, the key pathway between dietary restraint and binge eating was confirmed: higher levels of dietary restraint were associated with higher rates of binge eating. It seems that the subjects of this study were not able to maintain their dietary restraint.

 

Transdiagnostic Theory and Application of Family-Based Treatment for Youth With Eating Disorders

Katharine L. Loeb, James Lock, Rebecca Greif, Daniel le Grange
Cognitive and Behavioral Practice 19 (2012) 17-30

This paper describes the transdiagnostic theory and application of family-based treatment (FBT) for children and adolescents with eating disorders. We review the fundamentals of FBT, a transdiagnostic theoretical model of FBT and the literature supporting its clinical application, adaptations across developmental stages and the diagnostic spectrum of eating disorders, and the strengths and challenges of this approach, including its suitability for youth. Finally, we report a case study of an adolescent female with eating disorder not otherwise specified (EDNOS) for whom FBT was effective. We conclude that FBT is a promising outpatient treatment for anorexia nervosa, bulimia nervosa, and their EDNOS variants. The transdiagnostic model of FBT posits that while the etiology of an eating disorder is unknown, the pathology affects the family and home environment in ways that inadvertently allow for symptom maintenance and progression. FBT directly targets and resolves family level variables,  including secrecy, blame, internalization of illness, and extreme active or passive parental responses to the eating disorder. Future research will test these mechanisms, which are currently theoretical.

 

The Evolution of “Enhanced” Cognitive Behavior Therapy for Eating Disorders: Learning From Treatment Nonresponse

Zafra Cooper and Christopher G. Fairburn
Cognitive and Behavioral Practice 18 (2011) 394–402

In recent years there has been widespread acceptance that cognitive behavior therapy (CBT) is the treatment of choice for bulimia nervosa. The cognitive behavioral treatment of bulimia nervosa (CBT-BN) was first described in 1981. Over the past decades the theory and treatment have evolved in response to a variety of challenges. The treatment has been adapted to make it suitable for all forms of eating disorder—thereby making it “transdiagnostic” in its scope— and treatment procedures have been refined to improve outcome. The new version of the treatment, termed enhanced CBT (CBT-E) also addresses psychopathological processes “external” to the eating disorder, which, in certain subgroups of patients, interact with the disorder itself. In this paper we discuss how the development of this broader theory and treatment arose from focusing on those patients who did not respond well to earlier versions of the treatment.

In recent years there has been widespread acceptance that cognitive behavior therapy (CBT) is the treatment of choice for bulimia nervosa (National Institute for Health and Clinical Excellence, 2004; Wilson, Grilo, & Vitousek, 2007; Shapiro et al., 2007). The cognitive behavioral treatment of bulimia nervosa (CBT-BN) was first described in 1981 (Fairburn). Several years later, Fairburn (1985) described further procedural details along with a more complete exposition of the theory upon which the treatment was based (1986). This theory has since been extensively studied and the treatment derived from it, CBT-BN (Fairburn et al., 1993), has been tested in a series of treatment trials (e.g., Agras, Crow, et al., 2000; Agras, Walsh, et al., 2000; Fairburn, Jones, et al., 1993). A detailed treatment manual was published in 1993 (Fairburn, Jones, et al.). In 1997 a supplement to the manual was published (Wilson, Fairburn, & Agras) and the theory was elaborated in the same year (Fairburn).

According to the cognitive behavioral theory of bulimia nervosa, central to the maintenance of the disorder is the patient’s over-evaluation of shape and weight, the so-called “core psychopathology” [Fig. 1 – not shown – schematic form the core eating disorder maintaining mechanisms (modified from Fairburn, Cooper, & Shafran, 2003 )]. Most other features can be understood as stemming directly from this psychopathology, including the dietary restraint and restriction, the other forms of weight-control behavior, the various forms of body checking and avoidance, and the preoccupation with thoughts about shape, weight, and eating (Fairburn, 2008).

The only feature of bulimia nervosa that is not obviously a direct expression of the core psychopathology is binge eating. The cognitive behavioral theory proposes that binge eating is largely a product of a form of dietary restraint (attempts to restrict eating), which may or may not be accompanied by dietary restriction (actual undereating). Rather than adopting general guidelines about how they should eat, patients try to adhere to multiple demanding, and highly specific, dietary rules and tend to react in an extreme and negative fashion to the (almost inevitable) breaking of these rules.

A substantial body of evidence supports CBT-BN, and the findings indicate that CBTBN is the leading treatment. However, at best, half the patients who start treatment make a full and lasting response. Between 30% and 50% of patients cease binge eating and purging, and a further proportion show some improvement while others drop out of treatment or fail to respond. These findings led us to ask the question, “Why aren’t more people getting better?”

In the light of our experience with patients, we proposed that in certain patients one or more of four additional maintaining processes interact with the core eating disorder maintaining mechanisms and that when this occurs they constitute further obstacles to change. The first of these maintaining mechanisms concerns the influence of extreme perfectionism (“clinical perfectionism”). The second concerns difficulty coping with intense mood states (“mood intolerance”). Two other mechanisms concern the impact of unconditional and pervasive low self-esteem (“core low self-esteem”), and marked interpersonal problems (“interpersonal difficulties”).  This new theory represents an extension of the original theory illustrated in Fig. 1. Fig. 2 shows in schematic form both the core maintaining mechanisms and the four hypothesized additional mechanisms.

This program of work illustrates the value of focusing attention on those patients who benefit least from treatment. Doing so resulted in the enhanced form of CBT, which appears to be markedly more effective and more useful (in terms of the full range of patients treated) than its forerunner, CBT-BN.

 

A novel measure of compulsive food restriction in anorexia nervosa: Validation of the Self-Starvation Scale (SS)

Lauren R. Godier, Rebecca J. Park
Eating Behaviors 17 (2015) 10–13
http://dx.doi.org/10.1016/j.eatbeh.2014.12.004

The characteristic relentless self-starvation behavior seen in Anorexia Nervosa (AN) has been described as evidence of compulsivity,with increasing suggestion of transdiagnostic parallels with addictive behavior. There is a paucity of standardized self-report measures of compulsive behavior in eating disorders (EDs). Measures that index the concept of compulsive self-starvation in AN are needed to explore the suggested parallels with addictions. With this aima novel measure of self-starvation was developed (the Self-Starvation Scale, SS). 126 healthy participants, and 78 individuals with experience of AN, completed the new measure along with existing measures of eating disorder symptoms, anxiety and depression. Initial validation in the healthy sample indicated good reliability and construct validity, and incremental validity in predicting eating disorder symptoms. The psychometric properties of the SS scale were replicated in the AN sample. The ability of this scale to predict ED symptoms was particularly strong in individuals currently suffering from AN. These results suggest the SS may be a useful index of compulsive food restriction in AN. The concept of ‘starvation dependence’ in those with eating disorders, as a parallel with addiction, may be of clinical and theoretical importance.

The compulsive nature of Anorexia Nervosa (AN) has increasingly been compared to the maladaptive cycle of compulsive drug-seeking behavior (Barbarich-Marsteller, Foltin, & Walsh, 2011). Individuals with AN engage in persistent weight loss behavior, such as extreme self-starvation and excessive exercise, to modulate anxiety associated with ingestion of food, in a similar way to the use of mood altering drugs in substance dependence. Substance dependence is described as a persistent state in which there is a lack of control over compulsive drug-seeking, and lack of regard for the risk of serious negative consequences, which may parallel the relentlessness with which individuals with AN pursue weight loss despite profoundly negative physiological and psychological consequences.

Considering the parallels suggested between AN and substance dependence, it may be useful to use the concept of ‘dependence’ on starvation when measuring compulsive behaviors in eating disorders (EDs) such as AN. For that reason, a novel measure of self-starvation, the Self-Starvation Scale (SS) was derived, in part by adapting the Yale Food Addiction Scale (YFAS) (Gearhardt, Corbin, & Brownell, 2009) for this construct.

The set of online questionnaires was created using Bristol Online Surveys (BOS; Institute of Learning and Research Technology, University of Bristol, UK). In addition to the new measure described below, ED symptoms were measured using the Eating Disorder Examination-Questionnaire (EDE-Q) (Fairburn & Beglin, 2008), and the Clinical Impairment Assessment (CIA) (Bohn & Fairburn, 2008). Depression symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) (Kroenke, Spitzer, & Williams, 2001). Anxiety symptoms were measured using the Generalized Anxiety Disorder Assessment-7 (GAD-7) (Spitzer, Kroenke, Williams, & Lowe, 2006). The mirror image concept of ‘food addiction’ was measured using the YFAS (Gearhardt et al., 2009). Excessive exercise was measured using the Compulsive Exercise Test (CET) (Taranis, Touyz, & Meyer, 2011). Impulsivity was measured using the Barratt Impulsivity Scale-11 (BIS-11) (Patton, Stanford, & Barratt, 1995). Substance abuse symptoms were measured using the Leeds Dependence Questionnaire (LDQ) (Raistrick et al., 1994).

The results of this study suggest that using the criteria of dependence in capturing compulsive self-starvation behavior in AN may have some validity. The utility of this criteria in capturing compulsive behavior across disorders, including AN, suggests that compulsivity as a construct of behavior may have transdiagnostic application (Godier & Park, 2014; Robbins, Gillan, Smith, de Wit, & Ersche, 2012), on which disorder-specific themes are superimposed.

Read Full Post »


Clinical Effects and Cardiac Complications of Recreational Drug Use: Blood pressure changes, Myocardial ischemia and infarction, Aortic dissection, Valvular damage, and Endocarditis, Cardiomyopathy, Pulmonary edema and Pulmonary hypertension, Arrhythmias, Pneumothorax and Pneumopericardium

Reporter: Aviva Lev-Ari, PhD, RN

The cardiac complications of recreational drug use

INTRODUCTION

The use of recreational drugs has reached epidemic proportions in many countries and threatens to overwhelm economic, social, and health care systems. It is estimated that almost 1 in 4 people in developed countries have used recreational drugs at some time during their life. It is therefore inevitable that many doctors will have to manage and treat the ill effects associated with the abuse of these drugs.

In addition to their effects on the central nervous system, many of these agents induce profound changes in the heart and circulation that are responsible for a significant proportion of drug-related morbidity. This article reviews the cardiovascular complications associated with some of the commonly used recreational drugs.

Summary points

  • The abuse of recreational drugs is common and it is inevitable that doctors will have to manage and treat their associated ill effects
  • Recreational drugs are complex and can induce profound changes in cardiovascular function, both acute and chronic
  • Recreational drugs are often taken together, which can result in complex synergistic interactions with potentially detrimental effects
  • A high index of suspicion with early intervention and management is often the key to successful treatment

METHODS

Data were obtained by electronically searching MEDLINE, Embase, Poisindex (Micromedex Healthcare Series 2000), and standard textbooks of pharmacology and toxicology. Specific drugs or their chemical names were used as the main search term.

DRUGS AND SUBSTANCES

Cocaine, amphetamine, and ecstasy

Pharmacology

Cocaine, amphetamine, and ecstasy all share similar adverse effects on the cardiovascular system, related predominantly to sympathetic nervous system activation. Cocaine and its free-base form crack act by inhibiting the re-uptake of norepinephrine and dopamine at sympathetic nerve terminals. Circulating catecholamine concentrations can be elevated as much as 5-fold in cocaine users.1 At high doses, cocaine can impair myocyte electrical conduction and contractility.1

Amphetamine and its derivative ecstasy produce indirect sympathetic activation by releasing norepinephrine, dopamine, and serotonin from central and autonomic nervous system terminals. ​terminals.

Table 1

Suggested mechanisms by which cocaine, amphetamine, and ecstasy can cause hypotension
  • Paradoxical suppression of the central sympathetic nervous system
  • Relative catecholamine depletion
  • Acute myocardial depression due to ischemia, direct toxic effect of the drug
  • Mechanical complications, such as acute aortic rupture, tension pneumothorax, pneumopericardium

Clinical effects

Sympathetic activation can lead to varying degrees of tachycardia, vasoconstriction, unpredictable blood pressure effects, and arrhythmias, depending on the dose taken and the presence or absence of coexisting cardiovascular disease.

Blood pressure changes

The high levels of circulating catecholamines and sympathetic activation commonly cause hypertension. However, hypotension can also occur (see box).2

Myocardial ischemia and infarction

Cocaine and amphetamine can cause myocardial ischemia and infarction in patients with or without coronary artery disease. The mechanism is uncertain, but may be related to the elevated catecholamine concentration, which increases myocardial oxygen demand, coronary artery spasm, platelet aggregation, and thrombus formation.2,3,4 Cocaine can produce a procoagulant effect by decreasing concentrations of protein C and antithrombin 3 and potentiating thromboxane production.2

Long-term use of cocaine and amphetamine can cause repetitive episodes of coronary spasm and paroxysms of hypertension, which may result in endothelial damage, coronary artery dissection, and acceleration of atherosclerosis.

Aortic dissection, valvular damage, and endocarditis

Paroxysmal increases in blood pressure can lead to aortic dissection or valvular damage that increases the risk of endocarditis affecting mainly left-sided cardiac structures.1 Endocarditis is often associated with unusual organisms such as Candida, Pseudomonas, or Klebsiella and frequently has an aggressive clinical course with marked valvular destruction, abscess formation, and a need for surgical intervention.

Cardiomyopathy

Prolonged administration of cocaine or amphetamines can also lead to a dilated cardiomyopathy.2 Etiologic mechanisms include repeated episodes of subendocardial ischemia and fibrosis and myocyte necrosis produced by exposure to excessive catecholamine concentrations, infectious agents, and heavy metal contaminants (manganese is present in some cocaine preparations).

Pulmonary edema and pulmonary hypertension

Noncardiogenic pulmonary edema and pulmonary hypertension can also occur with cocaine and amphetamine misuse, although the precise underlying mechanism remains unknown.

Arrhythmias

The adverse cardiovascular changes and sympathetic stimulation associated with cocaine and amphetamine ingestion predispose to myocardial electrical instability, precipitating a wide and unpredictable range of supraventricular and ventricular tachyarrhythmias. The presence of fibrotic scars, myocardial ischemia, and left ventricular hypertrophy can act as a substrate for arrhythmogenesis. Cocaine possesses class 1 antiarrhythmic properties (blocks sodium channels) and can impair cardiac conduction causing prolongation of the PR interval, QRS complex, and QT interval. Cocaine can also cause a wide range of bradyarrhythmias, including sinus arrest and atrioventricular block.

Pneumothorax and pneumopericardium

Cocaine inhalation in association with a forced Valsalva maneuver (the positive ventilatory pressure increases drug absorption and therefore enhances the drug effect) can rarely give rise to a pneumothorax or pneumopericardium.

Lysergic acid diethylamide (LSD) and psilocybin (“magic mushrooms”)

Pharmacology

Lysergic acid diethylamide (LSD) and psilocybin are commonly used hallucinogenic agents that are structurally related and have similar physiologic, pharmacologic, and clinical effects. LSD is about 100 times more potent than psilocybin. Their mechanisms of action are complex with various agonist, partial agonist, and antagonist effects at serotonergic, dopaminergic, and adrenergic receptors.2

Clinical effects

The adrenergic effects of these drugs are usually mild and can give rise to general sympathetic arousal leading to dilated pupils, tachycardia, hypertension, and hyperreflexia. Although cardiovascular complications are rarely serious, supraventricular tachyarrhythmias and myocardial infarction have been reported.5 Changes in serotonin-induced platelet aggregation and sympathetically induced arterial vasospasm may have been contributory factors leading to the onset of myocardial infarction.5

Narcotic analgesics

Pharmacology

Morphine and its semisynthetic analogue heroin are the most commonly used recreational narcotic drugs. Narcotic agents act centrally on the vasomotor center to increase parasympathetic and reduce sympathetic activity.

Clinical effects

These autonomic changes, combined with histamine release from mast cell degranulation, can result in bradycardia and hypotension. Cardiac arrhythmias—including premature atrial and ventricular ectopic activity, atrial fibrillation, idioventricular rhythm, and ventricular tachyarrhythmias—have all been reported.2 Bacterial endocarditis, affecting mainly right-sided cardiac structures, is a well-known complication of intravenous narcotic drug abuse, and it is sometimes associated with pulmonary abscesses. Heroin overdose can cause noncardiogenic pulmonary edema, the onset of which can be delayed for up to 24 hours after admission.6 A disruption in alveolar-capillary membrane integrity has been suggested as a mechanism.

Volatile substance abuse

The abuse of volatile substances is an increasing problem among young male adolescents. The products used are legal, cheap, and easily available. Following inhalation, feelings of euphoria, excitement, and invulnerability can occur rapidly, but are short-lived.

Clinical effects

Cardiac arrhythmias are presumed to be the main cause of death from volatile substance abuse. Volatile substances may induce supraventricular or ventricular tachyarrhythmias by sympathetic activation or by myocardial sensitization to circulating catecholamines.7 Some abusers spray the substances directly into the mouth, which can result in intense vagal stimulation and a reflex bradycardia. Profound bradycardia can evolve into asystole or secondary ventricular tachyarrhythmias. Some volatile compounds can reduce sinoatrial node automaticity, prolong the PR interval, and induce atrioventricular block.2 Myocardial ischemia and infarction have been reported and are believed to be caused by a combination of coronary vasospasm, hypoxia caused by the formation of carboxyhemoglobin or methemoglobinemia, or excessive sympathetic stimulation.2Long-term misuse can induce a poorly characterized cardiomyopathy.8

Cannabis

Pharmacology

Cannabis has a biphasic effect on the autonomic nervous system, depending on the dose absorbed.3 Low or moderate doses can increase sympathetic and reduce parasympathetic activity, producing a tachycardia and an increase in cardiac output. In contrast, higher doses inhibit sympathetic and increase parasympathetic activity, resulting in bradycardia and hypotension. Reversible ECG abnormalities affecting the P and T waves and the ST segment have been reported.9It is not clear whether these changes occurred as a direct result of cannabis, independent of its effect on the heart rate.

Clinical effects

Although supraventricular and ventricular ectopic activity can occur, life-threatening tachy- or bradyarrhythmias have not been reported. In patients with ischemic heart disease, cannabis increases the frequency of anginal symptoms at low levels of exercise. This occurs as a result of a drug-induced increase in heart rate and myocardial contractility that increases myocardial oxygen demand.2

CONCLUSION

The abuse of illegal drugs is endemic in society and has the potential to cause major acute changes in cardiovascular function and irreversible damage to the heart. These drugs are frequently taken together as “cocktails,” often in conjunction with alcohol. These combinations can have complex synergistic interactions, with potentially detrimental effects.

Many patients who present with complications will be unable or unwilling to provide a history of illegal drug use. Recreational drug use should always be suspected and looked for in patients presenting with unexplained or unusual cardiovascular disturbances associated with mood disturbances or central nervous system dysfunction. As drug misuse continues to permeate every level of society, it is inevitable that physicians will have to manage the devastating complications of these compounds. An awareness of the life-threatening cardiovascular effects, along with early diagnosis and intervention, is often the key to successful treatment.

Figure 1

Recreational drug use has become more widespread
Figure 2

Young people in nightclubs often take a cocktail of drugs and alcohol

Notes

Competing interests: None declared

References

1. Mouhaffet A, Madu E, Satmary W, Fraker T. Cardiovascular complications of cocaine. Chest1995;107: 1426-1434. [PubMed]
2. Ghuran A, Nolan J. Recreational drug misuse: issues for the cardiologist. Heart 2000;83: 627-633.[PMC free article] [PubMed]
3. Bashour T. Acute myocardial infarction resulting from amphetamine abuse: spasm thrombus interplay. Am Heart J 1994;128: 1237-1238. [PubMed]
4. Heesch CM, Wilhelm CR, Ristich J, Adnane J, Bontempo FA, Wagner WR. Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans.Heart 2000;83: 688-695. [PMC free article] [PubMed]
5. Borowiak KS, Ciechanowski K, Waloszczyk P. Psilocybin mushroom (Psilocybe semlanceata) intoxication with myocardial infarction. Clin Toxicol 1998;36: 47-49. [PubMed]
6. Osterwalder JJ. Patients intoxicated with heroin or heroin mixtures: how long should they be monitored? Eur J Emerg Med 1995;2: 97-101. [PubMed]
7. Flanagan RJ, Ives RJ. Volatile substance abuse. Bull Narc 1994;46: 49-78. [PubMed]
8. Wiseman MN, Banim S. “Glue sniffer’s” heart? BMJ 1987;294: 739. [PMC free article] [PubMed]
9. Kochaar M, Hosko MJ. Electrocardiographic effects of marijuana. JAMA 1973;225: 25-27.[PubMed]
SOURCE

Read Full Post »