Effect of young sibling visitation on respiratory syncytial virus activity in a NICU.

OBJECTIVE: To determine whether the restriction of young sibling (<13 years) visitation in the neonatal intensive care unit (NICU) during the respiratory syncytial virus (RSV) season was associated with a reduction in the rate of RSV infection among NICU patients. STUDY DESIGN: A retrospective chart review of all RSV positive infants from the 2001-2010 RSV seasons. The 2001-2006 RSV seasons (group 1) contained 639 admissions and the 2007-2010 (group 2, with sibling restriction) contained 461 admissions. Groups were compared by using the Fisher's Exact Test. RESULTS: There was a reduction of RSV positive infants from 6.7% in Group 1 to 1.7% in Group 2 (P<0.0001). There was a reduction of symptomatic infants from the number of infants with symptomatic RSV infection from 23/639 infants with young sibling visitation to 2/461 (P<0.001). CONCLUSION: Exclusion of young sibling visitors <13 years of age during RSV season was associated with a significant reduction in the number of RSV positive infants in the NICU.

Craving for alcohol and drugs in animals and humans: biology and behavior.

Research studies indicate that sites and pathways for appetitive drive states, that are located in the limbic system, appear to be responsible for normal and pathological craving for alcohol and other addicting drugs. Pathological craving for alcohol and drugs in humans has been substantiated by animal studies, which have identified neurosubstrates and neurotransmitters associated with behavioral models of addiction. Repetitive administration of alcohol and drugs appears to affect hedonic homeostasis of the appetitive drives leading to the hedonic alleostasis where negative reinforcement exceeds positive returns despite continued drug use. Neuroimaging studies have concentrated on areas in the brain related to reward or reinforcement of alcohol/drug use, but the technique can be employed to find support for a neurosubstrate to distinguish normal craving or "liking" from pathological craving or "wanting" a drug. Identifying the neurobasis of "wanting" a drug long after not "liking it" is central to understanding pathological craving and loss of control over drug use in addiction in humans. Neuroimaging is currently the only method to directly visualize sites for craving in the brain in humans. Neuroimaging techniques will provide methods, which are not possible in animals, for studying addictive disease in humans.

Genetic comparison of seizure control by norepinephrine and neuropeptide Y.

Epilepsy is a disease of neuronal hyperexcitability, and pharmacological and genetic studies have identified norepinephrine (NE) and neuropeptide Y (NPY) as important endogenous regulators of neuronal excitability. Both transmitters signal through G-protein-coupled receptors, are expressed either together or separately, and are abundant in brain regions implicated in seizure generation. NPY knock-out (NPY KO) and dopamine beta-hydroxylase knock-out (DBH KO) mice that lack NE are susceptible to seizures, and agonists of NE and NPY receptors protect against seizures. To examine the relative contributions of NE and NPY to neuronal excitability, we tested Dbh;Npy double knock-out (DKO) mice for seizure sensitivity. In general, DBH KO mice were much more seizure-sensitive than NPY KO mice and had normal NPY expression, demonstrating that an NPY deficiency did not contribute to the DBH KO seizure phenotype. DKO mice were only slightly more sensitive than DBH KO mice to seizures induced by kainic acid, pentylenetetrazole, or flurothyl, although DKO mice were uniquely prone to handling-induced seizures. NPY contributed to the seizure phenotype of DKO mice at high doses of convulsant agents and advanced stages of seizures. These data suggest that NE is a more potent endogenous anticonvulsant than NPY, and that NPY has the greatest contribution under conditions of extreme neuronal excitability.

Alpha(1) and beta(2) adrenoreceptor agonists inhibit pentylenetetrazole-induced seizures in mice lacking norepinephrine.

It has been known for many years that norepinephrine (NE) is a potent endogenous anticonvulsant, yet there is confusion as to which receptor(s) mediate this effect. This is probably due to multiple factors, including the importance of distinct signaling pathways for different seizure paradigms, a lack of comprehensive pharmacological studies, and difficulty in interpreting existing pharmacological results due to the presence of endogenous NE. We sought to circumvent these problems by testing the anticonvulsant activity of selective agonists for most known adrenoreceptors (ARs) in dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack endogenous NE. Dbh -/- mice are hypersensitive to pentylenetetrazole (PTZ)-induced seizures, demonstrating that endogenous NE inhibits PTZ-induced seizures in the wild type. Pretreatment of Dbh -/- mice with an alpha(1)AR or beta(2)AR, but not an alpha(2)AR or beta(1)AR agonist significantly protected against PTZ-induced seizures. In contrast, only the beta(2)AR agonist showed anticonvulsant activity in heterozygous controls. Furthermore, an alpha(1)AR antagonist exacerbated PTZ-induced seizures in control mice, whereas a beta(2)AR antagonist had no effect. We conclude that activation of the alpha(1)AR is primarily responsible for the anticonvulsant activity of endogenous NE in the murine PTZ model of epilepsy. Endogenous NE probably does not activate the beta(2)AR under these conditions, but exogenous activation of the beta(2)AR produces an anticonvulsant effect.

Why physicians are unprepared to treat patients who have alcohol- and drug-related disorders.

Most primary care physicians do not feel competent to treat alcohol- and drug-related disorders. Physicians generally do not like to work with patients with these disorders and do not find treating them rewarding. Despite large numbers of such patients, the diagnosis and treatment of alcohol- and drug-related disorders are generally considered peripheral to or outside medical matters and ultimately outside medical education. There is substantial evidence that physicians fail even to identify a large percentage of patients with these disorders. Essential role models are lacking for future physicians to develop the attitudes and training they need to adequately approach addiction as a treatable medical illness. Faculty development programs in addictive disorders are needed to overcome the stigma, poor attitudes, and deficient skills among physicians who provide education and leadership for medical students and residents. The lack of parity with other medical disorders gives reimbursement and education for addiction disorders low priority. Medical students and physicians can also be consumers and patients with addiction problems. Their attitudes and abilities to learn about alcohol- and drug-related disorders are impaired without interventions. Curricula lack sufficient instruction and experiences in addiction medicine throughout all years of medical education. Programs that have successfully changed students' attitudes and skills for treatment of addicted patients continue to be exceptional and limited in focus rather than the general practice in U.S. medical schools. The authors review the findings of the literature on these problems, discuss the barriers to educational reform, and propose recommendations for developing an effective medical school curriculum about alcohol- and drug-related disorders.

A case of cutaneous ulcerative alternariosis: rare association with diabetes mellitus and unusual failure of itraconazole treatment.

Alternaria species are ubiquitous dematiaceous fungi that are increasingly recognized as pathogens in immunocompromised patients or those with significant underlying disease, but they are also pathogens in otherwise healthy hosts. We describe a case of dermal cutaneous ulcerative alternariosis in a frail 83-year-old patient with diet-controlled diabetes mellitus. Histological analysis revealed hyphal morphology in tissue sections that was initially confused with that of a zygomycetous fungus, and multiple positive culture results were necessary to identify the organism. Treatment with oral itraconazole and surgical debridement were ineffective; clinical improvement was achieved by means of treatment with intravenous amphotericin B lipid complex. We review the literature regarding the role of diabetes mellitus in cutaneous alternariosis and regarding the efficacy of treatment with itraconazole, which has been used very successfully. To our knowledge, this is only the second case report noting diabetes mellitus uncomplicated by steroid administration as a possible predisposing factor for cutaneous infection.

Ethanol-associated behaviors of mice lacking norepinephrine.

Although norepinephrine (NE) has been implicated in animal models of ethanol consumption for many years, the exact nature of its influence is not clear. Lesioning and pharmacological studies examining the role of NE in ethanol consumption have yielded conflicting results. We took a genetic approach to determine the effect of NE depletion on ethanol-mediated behaviors by using dopamine beta-hydroxylase knockout (Dbh -/-) mice that specifically lack the ability to synthesize NE. Dbh -/- males have reduced ethanol preference in a two-bottle choice paradigm and show a delay in extinguishing an ethanol-conditioned taste aversion, suggesting that they drink less ethanol in part because they find its effects more aversive. Both male and female Dbh -/- mice are hypersensitive to the sedative and hypothermic effects of systemic ethanol administration, and the sedation phenotype can be rescued pharmacologically by acute replacement of central NE. Neither the decreased body temperature nor changes in ethanol metabolism can explain the differences in consumption and sedation. These results demonstrate a significant role for NE in modulating ethanol-related behaviors and physiological responses.

Effectiveness of coerced addiction treatment (alternative consequences): a review of the clinical research.

Of central importance is that our clinical experience and treatment outcome studies to date strongly suggest that coercion is fundamental to addiction treatment and favorable outcomes from therapeutic interventions. Often the alcoholic/drug abuser must be given an opportunity to feel, face, or experience the "consequences" of their alcohol and drug addiction before the denial of their illness can be penetrated and motivation for treatment to recover from addictive illness can be developed. Continued use of alcohol and drugs is an unhealthy and dangerous state for those who are addicted and for others who are affected by their addictive illnesses. Effective therapeutic interventions and long-term recovery are more likely to succeed if avoiding "alternative consequences" are contingent on continued compliance with addiction treatment by those who suffer from addictive illnesses.

Prediction of treatment outcomes: lifetime depression versus the continuum of care.

We sought to determine the impact of a lifetime diagnosis of major depression on addiction treatment outcome. Structured interviews were conducted upon admission, and consecutive structured interviews were conducted prospectively for treatment outcome at 6 and 12 month follow-up periods. A multisite evaluation study of patients undergoing addiction treatment for alcohol and drug dependence was conducted in private outpatient facilities. Two thousand twenty-nine subjects from 33 independent programs were enrolled in a national registry for addiction treatment outcomes. The patients received abstinence-based addiction treatment with referral to a 12-step recovery program, often Alcoholics Anonymous, and continuing care in the treatment programs. The outcome areas measured were treatment completion, posttreatment substance use, exposure to psychosocial relapse risk factors, involvement with continuing care (formal aftercare and peer support groups), and posttreatment vocational functioning, health care utilization, and legal involvement. The prevalence rate of depressive symptoms over at least a 2-week period (major depression) in our sample was 28%. Multivariate analysis with stepwise multiple regression indicated that the most powerful predictors (relatively) of posttreatment alcohol/drug use were peer support group attendance and program continuing care involvement. Lifetime depression by itself and in interaction with each of these factors accounted for less than 2% of the variance in outcome. Logistic regression yielded similar results in the prediction of abstinence versus relapse. Posttreatment more than pretreatment factors appear to be more decisive in predicting risk for relapse.

Structural and functional neuroimaging findings in substance-related disorders.

Intoxication with alcohol results in depressed global glucose metabolism that continues into the stages of withdrawal and abstinence. The decrease in metabolism, however, is not equal across the brain, with certain regions more affected than others. Such a pattern of disturbance suggests that the effect of alcohol on the brain cannot simply be a nonspecific depressant effect secondary to decreased blood flow or glucose transport into the cells but may be related to the dysfunction of the various neurotransmitter systems. Different authors have suggested the dysfunction to be related to the GABAergic, cholinergic, and dopaminergic systems. Long-term alcoholism is associated with atrophy of several brain regions. The frontal lobes and limbic structures seem to be most vulnerable. The data are encouraging with regard to the normalization in brain metabolism and in size of vulnerable brain regions with continued abstinence. In addition to findings of improvement in cognitive functioning and many health parameters, these findings arm clinicians with further data on the benefits of abstinence in the struggle to aid patients in maintaining their sobriety. Several areas remain to be addressed. In particular, clinicians are in need of data, neuroimaging and otherwise, that serve as prognostic indicators, thus allowing patients at higher risk for relapse to be identified and provided with more intensive treatment. A similar need exists for indicators of diagnostic heterogeneity that would guide the development of more highly tailored treatment regimens for identified subgroups of patients. Currently, we have rudimentary knowledge of the gender differences of the effects of alcohol and cocaine on the brain.

Mortality risks in alcoholism and effects of abstinence and addiction treatment.

The mortality rate from alcoholism and related comorbidities is high. Studies show multiple causes of premature death from alcoholism. Several studies showed that abstinence had a positive effective on the overall survival of alcoholics. Alcoholics who abstained from alcohol, particularly continuously, showed reduced mortality rates and increased years of longevity than alcoholics who relapsed to alcohol consumption. The sources of the findings tend to be derived from treatment populations, in which abstinence is expected to occur in higher rates than in the general population.

The role of the physician in addiction prevention and treatment.

With increasing pressure on general physicians by managed care organizations and the public to treat and advocate for drug and alcohol addicted patients, it is more necessary than ever that physicians have the knowledge and skills to appropriately address this segment of the population. Specifically, physicians need a better understanding of the prevalence of alcohol and drug dependence in a variety of populations, along with increased awareness of the economic impact of addictive illnesses on our society. Routine screening questions should be incorporated into patient encounters, and physicians should be able to identify environments that may pose a risk for the development of addiction. Physicians need training and practice in referring patients to treatment teams, monitoring patients in recovery, and providing interventions that will eliminate or reduce substance abuse before it becomes addiction. The treatment outcomes in abstinence-based programs, particularly those combined with referral to AA, have been encouraging, demonstrating that addiction is a treatable illness and not a character defect. In addition, several studies provide evidence that addiction treatment is cost-beneficial, resulting in reduced medical costs, lowered absenteeism, and increased productivity. Despite these encouraging results, there is still room for improvement. Treatment is not always effective, and it is not sufficiently available to everyone who needs it. Addicted individuals are both stigmatized and marginalized, and many are too ill to advocate for themselves. Widespread recognition in the medical community of addiction as a treatable illness will contribute to a greater understanding of addictive disorders and reduce the stigma attached to the diagnosis and treatment of addiction. For this to occur, better training for physicians in the recognition and management of addictive disorders, starting at the medical school level, is necessary. The approval of addiction medicine as a clinical specialty by the American Medical Association also has helped to advance the legitimacy of addiction as a treatable illness, and provides a focal point for the synthesis and integration of clinical, teaching, and research activities central to addiction medicine. The combination of knowledge, skills, and attitudes outlined in the article will go a long way toward increasing physicians' abilities to assist their patients with recovery from addiction.

Paecilomyces lilacinus fungemia in an adult bone marrow transplant recipient.

Paecilomyces lilacinus is a rare fungal pathogen in humans. We report a case of fungemia caused by P. lilacinus in a non-neutropenic adult, 120 days after bone marrow transplant. The patient's primary risk factor was the presence of an indwelling vascular catheter. Her initial clinical course was characterized by fever, chills, and rigors. Blood cultures from the central line and peripheral veins were positive, as was a peripheral specimen drawn after removal of the catheter. Two initial peripheral specimens were positive for P. lilacinus only by blind subculture and/or sustained incubation. She developed peripheral pulmonary nodules following the fungemia, thus raising the possibility of disseminated disease, but definitive diagnosis was confounded by Pseudomonas bacteremia. The nodules cleared and she recovered following removal of the central line and treatment with amphotericin B and 5-fluorocytosine, despite in vitro resistance to these antifungal drugs. This case underscores the increasing importance of P. lilacinus as a human pathogen capable of producing disease in immunocompetent, as well as in immunocompromised hosts. Also of note is that blood culture systems may require extended incubation or subcultures in order to detect fungi.

Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence.

The primary care physician is in a good position to diagnose, manage and intervene with patients who are undergoing the process of treatment and recovery from alcohol and drug disorders. Medications such as benzodiazepines are effective in the treatment of withdrawal syndromes, and naltrexone and disulfiram can be used to augment relapse prevention. Patients may also participate in psychosocial methods of addiction treatment that can reduce the risk of relapse and improve their psychosocial, health, legal and employment status.

Comorbid cigarette and alcohol addiction: epidemiology and treatment.

The close association of nicotine addiction and alcoholism is well established. As many as 80% of alcoholics smoke, and 30% of smokers are alcoholics. The mortality from cigarette smoking and alcoholism individually is very high, as an estimated 400,000 deaths from tobacco and 100,000 deaths from alcoholism are reported annually. Cigarettes and alcohol interact to cause certain cancers, e.g., head and neck. Only recently has attention been focused on the role of tobacco in abstinent alcoholics. An important study found high rates of mortality from tobacco in abstinent alcoholics in recovery. However, the mortality rates from alcoholism were high and predominant. Of great importance is that studies show that abstinence from alcohol essentially eliminates the premature deaths or increased mortality rates from active alcoholism. Similar studies showing a reduction in mortality from abstinence in nicotine addiction have not been forthcoming. The importance of treating nicotine addiction, however, is clear to reduce the high mortality rates from tobacco smoking in active or abstinent alcoholics.

Lifetime diagnosis of major depression as a multivariate predictor of treatment outcome for inpatients with substance use disorders from abstinence-based programs.

A multisite, longitudinal study of patients undergoing inpatient alcohol and drug dependence treatment was conducted in private inpatient facilities, consisting of 4339 subjects from 38 independent programs enrolled in a national addiction treatment outcomes registry. Structured interviews were conducted upon admission, including documentation of current alcohol/drug disorder (DSM-III-R) and lifetime diagnosis of major depressive syndrome; structured interviews were conducted prospectively at 6- and 12-month follow-up periods. The prevalence rate of lifetime diagnosis of major depression in the sample was 39%. Comorbidity varied according to gender and substance of choice. Lifetime depressive symptoms did not correlate with differential length-of-stay, treatment completion, or follow-up consent and, at best, were very weakly associated with follow-up contact. Patients diagnosed with lifetime depression showed the same frequency of participation in posttreatment continuing care: they also showed statistically significant reductions in job absenteeism, inpatient hospitalizations, and arrest rates pre- vs. posttreatment comparable to those of patients without lifetime depression diagnosis. Lifetime major depressive syndrome was not a predictor of outcome in response to abstinence-based treatment. Involvement in posttreatment continuing care accounted for far greater outcome variance. Posttreatment vs. pretreatment factors may be more decisive in influencing risk for relapse.

The integration of pharmacological therapy for comorbid psychiatric and addictive disorders.

The integration of pharmacological therapies for comorbid disorders requires an acceptance of independence and interactions of respective addictive and psychiatric disorders. At the same time, alcohol and other drugs induce psychiatric states that are indistinguishable from psychiatric disorders. On the other hand, while psychiatric disorders do not induce addictive use of alcohol and drugs, they do pose vulnerabilities to the development of addictive disorders. Generally, the treatment of comorbid disorders begins with abstinence and evaluation of the effects of alcohol and other drugs in contributing to the psychiatric picture. In the case of comorbid disorders, stabilization and standard treatments can be employed with certain cautions, namely, to avoid the use of addicting medications such as benzodiazepines and opiates beyond the detoxification stage. High potency neuroleptics and antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) can be used to treat continuing psychiatric states after the exclusionary criteria in DSM-IV for substance-related disorders have been applied to the clinical case. If the psychiatric symptoms clear with sustained abstinence, little or no medications may be required. Specific treatment of the addictive disorders will often determine the extent that addictive disorders are responsible for psychiatric symptomatology. Alternatively, treatment of the psychiatric disorder will enhance compliance with addiction treatment.

Integration of treatment and posttreatment variables in predicting results of abstinence-based outpatient treatment after one year.

A multi-site, longitudinal study of patients undergoing outpatient alcohol and drug dependence treatment was conducted in private outpatient facilities, consisting of 2,029 subjects from 33 independent programs enrolled in a national addiction treatment outcomes registry. Pretreatment demographic and substance variables, treatment utilization variables, and post-treatment continuum of care variables were examined simultaneously in a multivariate prediction context for association with outcome. Upon admission patients provided history information to treatment staff trained in the collection of data for the evaluation efforts. Trained interviewers conducted consecutive structured interviews prospectively for treatment outcome at six- and 12-month follow-up periods. Multivariate analysis with stepwise multiple regression indicated that, relatively speaking, the most powerful predictors of treatment outcome were posttreatment variables: namely, support group attendance and involvement in a continuing care program. Pretreatment and treatment variables contributed proportionately little to the prediction of outcome. Additional sequential-stage analysis showed that the incremental contribution to prediction by posttreatment attendance at Alcoholics Anonymous and involvement in a treatment program following discharge far exceeded the initial predictive validity of the 14 pretreatment and treatment variables examined. Participation in posttreatment continuing care correlated with statistically significant reductions in job absenteeism, inpatient hospitalizations, and arrest rates. Posttreatment more than pretreatment factors may be decisive in influencing risk for relapse.