Drug Interactions between Antiretroviral Medications and Medications Used in the Treatment of Drug Addiction: Research Needs

Today substance dependence is one of the major public health problems in the world with millions of people abusing legal and illegal drugs. In addition, almost one‐third of the world's population suffers with one or more infections. Both drugs of abuse and infections are associated with serious medical and health consequences, some of which may be exacerbated by the occurrence of pharmacokinetic and/or pharmacodynamic interactions between medications used in the treatment of these conditions when they co‐occur. This review briefly discusses issues surrounding clinical management related to drug interactions experienced by substance abusing patients. The emphasis of this paper is on the research needed to further study the extent, nature, and underlying molecular/genetic mechanism(s) of interactions between drugs of abuse, medications used in the treatment of drug addiction, and co‐occurring infections. (Am J Addict 2009;19:96–100)     

Validation Study of an Automated Electronic Acute Lung Injury Screening Tool

Objective

The authors designed an automated electronic system that incorporates data from multiple hospital information systems to screen for acute lung injury (ALI) in mechanically ventilated patients. The authors evaluated the accuracy of this system in diagnosing ALI in a cohort of patients with major trauma, but excluding patients with congestive heart failure (CHF).

Design

Single-center validation study. Arterial blood gas (ABG) data and chest radiograph (CXR) reports for a cohort of intensive care unit (ICU) patients with major trauma but excluding patients with CHF were screened prospectively for ALI requiring intubation by an automated electronic system. The system was compared to a reference standard established through consensus of two blinded physician reviewers who independently screened the same population for ALI using all available ABG data and CXR images. The system's performance was evaluated (1) by measuring the sensitivity and overall accuracy, and (2) by measuring concordance with respect to the date of ALI identification (vs. reference standard).

Measurements

One hundred ninety-nine trauma patients admitted to our level 1 trauma center with an initial injury severity score (ISS) ≥ 16 were evaluated for development of ALI in the first five days in an ICU after trauma.

Main Results

The system demonstrated 87% sensitivity (95% confidence interval [CI] 82.3-91.7) and 89% specificity (95% CI 84.7-93.4). It identified ALI before or within the 24-hour period during which ALI was identified by the two reviewers in 87% of cases.

Conclusions

An automated electronic system that screens intubated ICU trauma patients, excluding patients with CHF, for ALI based on CXR reports and results of ABGs is sufficiently accurate to identify many early cases of ALI.     

Medical Consequences of Drug Abuse and Co-Occurring Infections: Research at the National Institute on Drug Abuse

ABSTRACT

Substance abuse still remains one of the major problems in the world today, with millions of people abusing legal and illegal drugs. In addition, a billion people may also be infected with one or more infections. Both drugs of abuse and infections are associated with enormous burden of social, economic, and health consequences. This article briefly discusses a few medical consequences of drugs of abuse and infections such as human immunodeficiency virus, hepatitis C virus, psychiatric complications in hepatitis C infection, pharmacokinetic drug–drug interactions among medications used in the treatment of addiction and infections, and new drugs in development for the treatment of infections. Research is encouraged to study interactions between infections, drugs of abuse, and underlying pathophysiologic and molecular/genetic mechanisms of these interactions.     

Butterbur: an evidence-based systematic review by the natural standard research collaboration

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.     

Substance abuse in first-episode bipolar I disorder: indications for early intervention

OBJECTIVE: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder. METHOD: The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods. RESULTS: Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes. CONCLUSIONS: Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.     

Gene-conversion tract directionality is influenced by the chromosome environment

Spontaneous and double-strand break (DSB)-induced gene conversion in Saccharomyces cerevisiae was assayed using non-tandem chromosomal direct repeat crosses and plasmid × chromosome crosses. Each cross involved identical ura3 alleles marked with phenotypically silent restriction fragment length polymorphic (RFLP) mutations at approximately 100-bp intervals. DSBs introduced in vivo at HO sites in one allele stimulated recombination to Ura⁺ by more than two orders of magnitude. Spontaneous gene-conversion products were isolated from a related strain lacking a functional HO nuclease gene. The multiple markers did not appear to influence the frequency of direct repeat deletions for spontaneous or DSB-induced events. DSB-induced conversion reflected efficient mismatch repair of heteroduplex DNA. Conversion frequencies of equidistant markers on opposites sides of the DSB were similar in the direct repeat cross. In contrast, markers 5′ of the DSB (promoter-proximal) converted more often than 3′ markers in plasmid × chromosome crosses, a possible consequence of crossing-over associated with long conversion tracts. With direct repeats, bidirectional tracts (extending 5′ and 3′ of the DSB) occurred twice as often as in a plasmid × chromosome cross in which DSBs were introduced into the plasmid-borne allele. A key difference between the direct-repeat and plasmid×chromosome crosses is that the ends of a broken plasmid are linked, whereas the ends of a broken chromosome are unlinked. We tested whether linkage of ends influenced tract directionality using a second plasmid × chromosome cross in which DSBs were introduced into the chromosomal allele and found few bidirectional tracts. Thus, chromosome environment, but not linkage of ends, influences tract directionality. The similar tract spectra of the two plasmid × chromosome crosses suggest that similar mechanisms are involved whether recombination is initiated by DSBs in plasmid or chromosomal alleles. Received: 11 May / 24 July 1998     

Clinical and ethical implications of impaired executive control functions for patient autonomy

The authors identify the clinical and ethical implications of impaired executive control functions for patient autonomy. Executive control functions are processes that orchestrate relatively simple ideas, movements, or actions into complex goal-directed behavior, and impairments in these functions are becoming more common as the population ages. The authors examine difficulties that individuals with impaired executive control functions may have in making treatment decisions and describe a practical, ethically justified framework for making treatment decisions for patients with impairments in these functions. Three components of autonomy are identified-intentionality, understanding, and voluntariness. Intentionality and voluntariness are especially affected by impaired executive control functions. Impairments of these aspects of autonomy may often be overlooked when only traditional mental status examinations are employed, with adverse consequences for the health of patients wrongly thought to possess intact ability to make and carry out plans of care. Two case vignettes illustrate the complexities faced by clinicians intervening with patients who have deficits in decision-making capacity caused by impaired executive control functions.     

Prevalence of substance abuse in a psychiatric evaluation unit.

The prevalence of substance abuse and psychiatric illness was studied in a Psychiatric Evaluations Unit. Twenty-six percent of the subjects received a psychiatric diagnosis only with no concomitant substance use disorder. Thirty-four percent were diagnosed with a substance use disorder but with no other psychiatric disorders. Thirty-nine percent of the subjects had a history of both psychiatric and substance use disorder; 62% of these substance abusers with a psychiatric illness reported using drugs (including alcohol) the week before the interview; 56% used illicit drugs while 44% used alcohol only. Differences among substance abusers with a psychiatric illness, those with a substance abuse diagnosis alone, and those with a psychiatric diagnosis alone are presented.