Clearing the air: microcosting the carbon impact of drug-susceptible pulmonary TB treatment.

More than 10 million individuals develop active TB each year. The diagnosis and treatment of TB create greenhouse gas emissions, contributing to climate change. This study estimates the carbon footprint (CF) of successfully treating one person with drug-susceptible pulmonary TB (DS-PTB) in India.We defined the cascade of care for DS-PTB using national guidelines, interviews, and direct observation. We estimated the inputs for TB diagnosis and treatment in United States dollars, kilowatts per hour, and kilometres travelled; we converted them into carbon dioxide emissions equivalents (CO2e) using an appropriate calculator.The CF of diagnosing and treating one person with DS-PTB in India is 103.8 kg CO2e: 31.9% attributable to diagnosis and 68.1% to treatment. Emissions came primarily from first-line drugs (21.2%), hospitalisations (17.4%), and laboratory processes.We conservatively estimate that treating all persons with TB in India would produce at least 290,640 metric tonnes of CO2e per year, approximately the same emissions as 63,182 passenger cars in the United States. It is evident that one of India's leading public health challenges also contributes meaningfully to climate change..

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.

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.

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.

Primary and secondary depression in alcoholic men: an important distinction?

The primary-secondary depression distinction was investigated in male alcoholic patients from five Veterans Administration Medical Centers. The Psychiatric Diagnostic Interview, a DSM-III-compatible, criterion-referenced, structured interview, was administered to 565 patients admitted to the Alcoholism and Drug Treatment Units. Seventy-eight patients (13.8%) who exhibited only alcoholism and depression were divided into three subgroups based on the temporal onset of depression relative to the onset of alcoholism. Although few statistical differences were found, observed trends suggested more impairment in alcoholic patients with primary depression than in those with concurrent or secondary depression. The findings indicate that the primary-secondary depression distinction may have important clinical relevance and should be made whenever possible.

Fungal infection associated with intravenous drug abuse: a case of localized cerebral phycomycosis.

The authors present a case of confusion and mood disturbance caused by a focal cerebral fungal (phycomycosis) infection in an otherwise healthy intravenous drug addict. A review of the literature found only 9 cases of phycomycosis with localized cerebral involvement. This report describes the sixth occurrence of phycomycosis in an intravenous drug addict (the fifth to localize in the basal ganglia). In addition to the human immunodeficiency virus, unusual infectious causes of confusion and mood disturbance may be increasing as the intravenous drug-using population expands. Recognition of the clinical features of a fungal infection in a high-risk population may lead to earlier diagnosis and more effective treatment of this uniformly fatal disease. The clinician should consider localized cerebral phycomycosis as a cause of confusion and mood disturbance in intravenous drug addicts, especially when there is evidence of basal ganglia involvement.

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.

Current epidemiology of comorbidity of psychiatric and addictive disorders.

Some major epidemiologic studies have assumed that treatment of the psychiatric symptoms will result in a lowered morbidity and mortality from the addictive disorders or, more specifically, that the addictive disorders are dependent on the psychiatric disorders and etiologically linked to them as an effect or secondary consequence. There is little systematic evidence beyond anecdotal and intuitive supposition to support this popular and only hypothetic position. The consequence is that to insist on the priority of the psychiatric disorder in diagnosis and treatment is to perpetuate artifactual prevalence rates for psychiatric comorbidity in addictive disorders, and to preclude the definitive treatment to reduce the psychiatric morbidity and mortality caused by addictive disorders.

A hypothesis for a common neurochemical basis for alcohol and drug disorders.

Research findings clearly support a uniform theory for a neurochemical basis of drug and alcohol addiction. Data are available that document final common pathways for addictive behaviors in the limbic system in which neurotransmitters modulate the drive states, mood, and instinctual behaviors. The specific areas in the brain implicated in the loss of control inherent in the addictive use of multiple drugs and alcohol are the ventral tegmentum, nucleus accumbens, locus ceruleus, dorsal raphe nuclei, and the periaquaductal grey area. These sites contain cell bodies and receptors for dopamine, norepinephrine, serotonin, and endogenous opiates respectively, where multiple drugs and alcohol can often produce their effects. The acquired drive of addiction that arises spontaneously, repetitively, and relentlessly is manifested in the addictive behaviors of preoccupation, compulsivity, and relapse to drugs and alcohol.

Perspectives of effective treatment for alcohol and drug disorders.

Of the 1918 patients in the follow-up sample used for illustration, 63% reported total abstinence for the year after treatment, and an additional 24% reported at least 6 months of abstinence out of 12. Most relapses occurred during the first 6-month interval; 88% of patients who were abstinent the first 6 months maintained this status for the full year. Patients abusing drugs other than alcohol had much poorer outcomes than those abusing alcohol only, and this finding held up even when drug choice was controlled for sex and age of patients. Intravenous drug use was an important predictor of relapse, as was a history of antisocial behavior. A strong relationship to outcome was seen for patient participation in an aftercare program, and for weekly attendance at peer support group meetings. Emotional distress, relationship difficulties and family problems, financial difficulties, craving, and being around others who use alcohol and drugs are all seen as making the commitment to abstinence more difficult. There is clear evidence also that increased difficulty in these areas is predictive of later relapse. Comparisons of pretreatment and posttreatment measures of patient functioning revealed a decreased need for expensive health care services, such as hospitalization and emergency room care. The motor vehicle accident rate, traffic arrest rate, and criminal offense arrest rate all showed posttreatment declines. On-the-job problems also decreased dramatically following treatment. Posttreatment difficulties were disproportionately higher among patients who had returned to substance use than among patients who remained abstinent, documenting that successful treatment can have an affect in many areas that improve the quality of life for patients themselves (along with their families and communities) as well as reduce the high economic costs associated with alcohol and drug abuse in our society. Cost offsets for chemical dependency treatment are substantial and of broad scope; they also are related directly to the recovery rate. In general, the findings for outpatient programs tend to parallel those of the inpatients. Initial chemical severity and range of other clinical problems are lower, but significant reductions are noted. For both inpatients and outpatients monitored by CATOR, the posttreatment improvement in health care utilizations, reductions in work-related problems, and fewer arrests are related directly to recovery status. That is to say that recovering patients show significantly better improvement than relapsed patients. This means that treatment efficacy must be considered as a key element in estimating treatment benefits.

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.

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.

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.

Family history and diagnosis of alcohol dependence in cocaine dependence.

Genetic research in alcoholism has made major advances in recent decades. Twin, adoption, high-risk, and familial studies have demonstrated an inheritance factor in alcoholism. No studies have demonstrated a genetic or familial disposition to cocaine and marijuana dependence. Two hundred sixty-three inpatients were given a structured psychiatric interview retrospectively (150) and prospectively (113) to obtain a DSM-III-R diagnosis of substance dependence disorders in the probands and of alcohol dependence in family members. Our study reveals a large number of probands with cocaine dependence with a positive family history for alcohol dependence. Approximately 50% of probands with cocaine dependence had at least a first or second degree relative with a diagnosis of alcohol dependence when studied by the family history and study methods. As many as 89% of probands who met DSM-III-R criteria for cocaine dependence qualified for other substance dependence diagnoses. Our study finds a high prevalence of alcohol (68% and 89%) and cannabis dependence (53% and 46%) in patients with cocaine dependence. Furthermore, the age of onset of alcohol and other drug dependence is early for those with cocaine dependence and precedes the onset of cocaine dependence. The diagnoses of other alcohol and drug dependence in cocaine dependence and in family members of probands with cocaine dependence have important implications for etiology, prognosis, and treatment.

Comparison of the bladder response to indole and sodium saccharin ingestion by male rats.

To ascertain whether the bladder mass increase and epithelial hyperplasia induced by 5% dietary sodium saccharin (NaS) in short-term experiments with rats are caused by increased urinary excretion of indican associated with this treatment, the responses of the urine and bladder induced by 1.5% indole (Id) ingestion were compared with those induced by 5% NaS and 1.5% Id + 5% NaS. Id and NaS, when fed alone, produced equivalent increases in bladder mass and both compounds induced epithelial hyperplasia, but Id ingestion was associated with much greater urinary indican excretion (5 mg/g diet ingested) than was NaS (0.3 mg/g diet ingested). When Id and NaS were ingested together, the bladder mass increase was additive, but the epithelial hyperplasia was not exacerbated over that observed with each alone, and the urinary indican was equivalent to that produced by Id alone. These findings suggest that a high level of urinary indican excretion is associated with an increase in bladder mass and epithelial hyperplasia (Id treatment) but indicate that the relatively low urinary indican level obtained by NaS feeding alone is unlikely to be responsible for the bladder responses noted with this compound.

A blood marker for pharmacodynamic tolerance to alcohol.

The treatment of alcoholism may be delayed because of the difficulty in confirming a diagnosis. There are currently no direct blood tests to objectively determine the presence of pharmacodynamic tolerance to alcohol. The state of the membrane fluidity of the peripheral blood erythrocyte may provide a biophysical measurement of the pharmacodynamic tolerance to alcohol. This discussion proposes methods that potentially may be applied to the clinical purpose of diagnosing alcoholism in humans. The methods have been used to successfully measure pharmacodynamic tolerance in animals and humans. The development of the physiologic state of acquired tolerance and dependence is related to alcohol intake. Chronic alcohol consumption that leads to pharmacodynamic tolerance may be assessed by measuring the membrane fluidity of the peripheral blood erythrocyte. Physiologic recovery from tolerance and dependence to alcohol may also be assessed during withdrawal in which the reversal of changes in membrane fluidity is measured in the abstinent state. Relapse to drinking may be detected in the state of the membrane fluidity of the peripheral blood erythrocytes that reflect the return of tolerance and dependence. Tolerance to alcohol may be a manifestation of the inheritability to alcoholism. Alcoholics and high risk individuals appear to have an increased, innate (genetic) tolerance to alcohol. High risk individuals are nonalcoholic, blood relatives of alcoholics. Animal studies suggest that innate (genetic) tolerance and dependence to alcohol may be related to the biophysical state of erythrocyte membrane fluidity. The assessment of these changes in membrane fluidity of the erythrocyte may be performed in the peripheral blood in humans. A trait marker (in the genetically predisposed) for high risk individuals and a state (in the actively drinking) marker for pharmacodynamic tolerance in the erythrocyte might be developed. In this way, a blood test may be used to detect the inheritability for alcoholism and the development of pharmacodynamic tolerance to alcohol. No blood test for pharmacodynamic tolerance is currently available. This article represents an extrapolation from animal and human research data. The proposals contained therein may not be considered readily, clinically applicable.

Benzodiazepines: a major problem. Introduction.

Benzodiazepine use is prevalent. Moreover, benzodiazepine abuse, addiction, tolerance, and dependence occur commonly with benzodiazepine use. Confusion arises in assessing the nature and magnitude of benzodiazepine use and its consequences. Abuse, addiction, tolerance, and dependence occur in medical and nonmedical populations, but the studies do not clearly differentiate the benzodiazepine use between these two populations. The nonmedical use in medical populations is underestimated and underdiagnosed. The nonmedical use is also misdiagnosed in nonmedical populations as medical use. Clearer definitions and usage of the terms of abuse, addiction, tolerance, and dependence would result in accurate diagnosis and proper treatment of the disorders associated with benzodiazepine use, that is, anxiety and depressive disorders, alcoholism, and other drug addictions.

Addiction to and dependence on benzodiazepines. Diagnostic confusion in clinical practice and research studies.

Considerable confusion continues to surround basic concepts for abuse, addiction, tolerance, and dependence. Clinicians may be making decisions about prescribing these medications without clear definitions and distinctions. The terms are not equivalent in meaning and should not be used interchangeably in clinical application. Moreover, they may occur together or independently and are not etiologically related. Abuse is improper use outside the standard norms. Abuse implies a violation component and a control over the use of the drug. Addiction is a preoccupation with the acquisition and compulsive use of and a pattern of relapse to drugs is spite of adverse consequences. Pervasive to the criteria is a loss of control over drug use and a lack of volitional component in the drug use. In spite of problems in definitions, studies have clearly shown that abuse, addiction, tolerance, and dependence develop commonly in benzodiazepine use.

The diagnosis of marijuana (cannabis) dependence.

The definition of marijuana (Cannabis) dependence (addiction) contains three critical elements. These are (a) preoccupation with the acquisition of marijuana, (b) compulsive use of marijuana, (c) relapse to or recurrent use of the marijuana. The manifestations of abnormal marijuana use may assume many forms. Medical, psychiatric, neurological, traumatic, and sociological sequelae occur commonly in acute and chronic marijuana use. Marijuana dependence must be diagnosed primarily as the etiological or precipitating agent to adequately prevent and treat these conditions. The central role of marijuana addiction can be identified. The consequences of the marijuana addiction should be separated from the marijuana addict's actual motivation or craving to use marijuana. Marijuana addicts use abnormally because of what marijuana does to them and not for them. Marijuana reinforces its own use. Psychosocial stressors are not required to produce a marijuana addiction in biologically susceptible individuals. Consequences that result from an addiction to marijuana do not produce the abnormal use. A presumptive diagnosis of marijuana dependence (addiction) can be established by detecting significant consequences associated with marijuana use. A definitive diagnosis entails confirming the presence of addictive behavior by identifying a preoccupation, compulsivity and relapse relative to the drug, marijuana.