HIV in young people: characteristics and predictors for late diagnosis of HIV.

Late diagnosis of human immunodeficiency virus (HIV) infection remains a challenging issue, especially in young population, which accounts for approximately half of new HIV infections. This study aimed to assess factors associated with late diagnosis of HIV infection in young people. It employed a hospital-based case-control design, conducted during January 2012 through August 2013. A total of 193 patients aged 18-25 years old from 21 hospitals across Thailand were studied. Late diagnosis was defined as presentation when the CD4 cell count was less than 350 cells/µL within 12 months of the first HIV diagnosis, or AIDS-defining event is present within 12 months of the first HIV diagnosis. Factors associated with the late diagnosis of HIV were those who: did not live with their parent (OR 3.87; 95% CI 1.40-10.66), had no children (OR 3.25; 95% CI 1.27-8.31), had their first sexual intercourse at age older than 18 years (OR 4.25; 95% CI 1.27-14.22), had same-age or older partners (OR 3.36; 95% CI 1.39-8.08), were substance users (OR 3.65; 95% CI 1.22-10.88), believed they changed their behaviors after receiving HIV education (OR 2.48; 95% CI 1.02-5.99), and sought care at regional (OR 3.19; 95% 1.31-7.79) or general hospitals (OR 3.34; 95% 1.07-10.35). Strategies for early HIV detection in young people should be reconsidered; particularly the involvement of parents and targeting the right population.

Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients.

BACKGROUND: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. METHODS: Alcohol-dependent patients (n = 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. RESULTS: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. CONCLUSIONS: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin.

Prospective matching of alcoholic clients to cognitive-behavioral or interactional group therapy.

OBJECTIVE: In earlier work, client sociopathy and global psychopathology were effective variables for treatment matching: clients low on both sociopathy and severity of psychopathology were likely to benefit from interactional group therapy, whereas those scoring high on either of these dimensions benefited more from a coping skills intervention. The present study assessed whether outcomes improve further when clients are assigned to group treatments prospectively based on a matching strategy derived from the previous findings. METHOD: All participants (N = 250, 66% men) met criteria for alcohol dependence or abuse. About half were prospectively assigned to either cognitive-behavioral (CB) coping skills training or interactional therapy, those with higher levels of psychiatric severity or sociopathy were given CB and those who were low on both dimensions were given interactional therapy. The other half were randomly assigned to those treatments, replicating the procedure of the earlier study. Outcome data were collected at the conclusion of treatment and at 3-month intervals for 1 year following. RESULTS: Prospective matching of clients to treatment did not produce superior drinking outcomes compared to random treatment assignment. Randomly assigned clients were more likely to be abstinent at the end of treatment, but this effect disappeared at later follow-ups. Prospectively matched clients had fewer negative consequences of drinking than did those assigned randomly (unmatched). Neither sociopathy nor psychiatric severity was particularly effective for matching. CONCLUSIONS: The matching effects from our previous study were not replicated. Nevertheless, prospective matching did reduce the negative consequences of drinking, consistent with our previous results.

The role of craving in alcohol use, dependence, and treatment.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer and chair was Barbara A. Flannery, and the co-chairs were Barbara A. Flannery and Helen Pettinati. The presentations were (1) Animal models of alcohol craving and relapse, by Amanda Roberts; (2) Real-time field assessment of alcohol craving, by Ned Cooney; (3) Medications and alcohol craving, by Robert Swift; (4) The assessment of craving: Insights from the clinic and clinical laboratory studies, by Raymond Anton; (5) A comparison of three alcohol craving questionnaires, by Barbara Flannery; (6) and Assessing posttreatment urge to drink, by Damaris Rohsenow.

Reactivity to alcohol-related stimuli in the laboratory and in the field: predictors of craving in treated alcoholics.

AIMS: (1) To search for predictors of alcohol craving in treated alcoholics; (2) to evaluate the relationship between craving and drinking immediately after treatment. DESIGN: Alcoholic patients in treatment underwent cue-reactivity trails in the laboratory and then recorded craving in the field using hand-held computers. Laboratory craving was correlated with craving in the field, and moods and situations recorded in the field were correlated with contemporaneous craving ratings using a multi-level correlational design. SETTING: A VA Medical Center substance abuse treatment program provided the treatment and laboratory settings. The patients' home environment was the field setting. PARTICIPANTS: Male alcohol-dependent veterans (N = 26) treated in a VA inpatient or intensive outpatient program. INTERVENTION: Participants underwent two cue-reactivity laboratory sessions prior to discharge to measure craving. Following discharge, participants recorded drinking and cravings eight times per day for 21 consecutive days. MEASUREMENTS: Craving ratings in the laboratory and multiple recordings per day of surroundings, craving and mood state in the field. FINDINGS: Desire to drink in the laboratory accounted for 8-10% of the variance in later drinking and urges to drink recorded in the field--a modest correlation. Frequency of positive urges in the field was significantly correlated with drinking frequency. Those who reported urges in the field had greater alcohol dependence and higher trait anger and anxiety scores than non-reporters. CONCLUSIONS: Craving is related to drinking immediately following treatment, and is most likely in those who have more severe dependence and greater mood disturbance. These individuals may benefit most from interventions for coping with cravings after treatment.

Usefulness of Doppler sonography in the diagnosis of ovarian torsion.

OBJECTIVE: To assess the predictive value of Doppler sonography in the diagnosis of ovarian torsion and to correlate Doppler results with surgical findings and various clinical characteristics. DESIGN: Retrospective study of discharged inpatients. SETTING: An academic community hospital. PATIENT(S): Twenty-one patients with surgically confirmed ovarian torsion over an 8-year period. INTERVENTION(S): Data were collected on Doppler flow results, ultrasound and surgical findings, patient characteristics, and associated morbidity. MAIN OUTCOME MEASURE(S): Accuracy of Doppler diagnosis as to presence of ovarian torsion. RESULT(S): Twenty-one patients had surgically confirmed ovarian torsion. Doppler sonography was performed in 10 of the 21 patients. Doppler sonographic findings were normal in 60% (6 of 10), and abnormal (decreased or absent) in 40% suggestive of torsion. In cases involving ovulation induction, Doppler sonography findings were normal in 25% (1 of 4). Furthermore, the time to diagnosis of ovarian torsion (mean = 5.3 hours) and the time to hospital discharge (mean = 2 days) were both decreased when compared with instances when normal flow was detected by Doppler sonography (59 hours and 2.7 days, respectively). CONCLUSION(S): Abnormal flow detected by Doppler sonography is highly predictive of adnexal torsion and is therefore useful in the diagnosis of ovarian torsion. However, when normal flow is detected by Doppler sonography, it does not necessarily exclude an ovarian torsion; in fact, torsion is missed in 60% of cases, and time to diagnosis in these cases is delayed. In cases of ovulation induction, sensitivity is increased to 75%.

CSF monoamine metabolite and beta endorphin levels in recently detoxified alcoholics and healthy controls: prediction of alcohol cue-induced craving?

BACKGROUND: Abnormalities in central neurotransmitter systems have been described in alcohol-dependent individuals and may contribute to alcohol craving. This study compared cerebrospinal fluid (CSF) levels of monoamine metabolites and beta endorphin levels in samples from early-onset alcohol-dependent patients (n = 20), late-onset alcohol-dependent patients (n = 14), and healthy controls (n = 23). It also evaluated whether these CSF measures levels predicted the degree of craving experienced in response to an alcohol cue. METHODS: Individuals meeting DSM-III and -IV R-criteria for alcohol dependence, 1 to 3 months postdetoxification, and healthy controls underwent a lumbar puncture. Patients also completed a cue exposure test day between 3 and 15 days later. RESULTS: Alcohol-dependent patients had lower CSF levels of the norepinephrine metabolite MHPG compared with the healthy subjects, but this difference disappeared when differences in age between the groups were accounted for. No other group comparisons between patients and healthy subjects reached significance. CSF levels of the dopamine metabolite HVA were significantly higher in the early-onset patients compared with the late-onset patients and controls. The CSF measures did not predict the precue levels of craving, or the increase in craving after alcohol cue exposure. CONCLUSIONS: These results are inconclusive about the role of monoaminergic dysregulation in recovering alcoholics. They also question the utility of these CSF measures to predict alcohol cue reactivity in patients who have been sober at least 1 month.

Health outcomes for people who use palliative care services.

Health outcomes are being promoted as a necessary evaluation measure in health care services. Less often discussed is the notion that health outcomes are artificially designated endpoints and that different people in the health system have different ideas of what the outcomes ought to be. Whose evidence is acceptable and relevant in constructing a framework of health outcomes in palliative care? This paper presents the findings of a research project undertaken in New South Wales, Australia, on health outcomes as evaluated by patients and caregivers. A wide range of health care professionals also participated. Patients and caregivers valued outcomes or endpoints in palliative care that were not necessarily brought about by expert clinical intervention. By adopting too narrow an interpretation of outcomes we risk sacrificing that which is uniquely valuable in palliative care services.

Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

OBJECTIVE: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. METHOD: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. RESULTS: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. CONCLUSIONS: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

Inducing craving for alcohol in the laboratory.

Research on the mechanisms of craving often involves inducing craving in subjects in controlled settings. This article describes techniques that have been used to induce craving for alcohol, including (1) exposing subjects to actual alcoholic beverages, (2) exposing subjects to visual representations of alcoholic beverages, (3) manipulating the subjects' mood states, and (4) controlling environmental settings. The intensity of craving can be rated by the subjects themselves or can be assessed by clinicians through behavioral observations or the measurement of certain physiological responses. Success in inducing craving in the laboratory, however, has been inconsistent. Ultimately, researchers may need to monitor subjects' craving responses in actual environmental settings.

Compliance with treatment and follow-up protocols in project MATCH: predictors and relationship to outcome.

Treatment and follow-up session attendance data from Project MATCH, a multisite clinical trial investigating patient-treatment matching, were analyzed to study compliance. High rates of compliance to both therapy and research protocols were achieved, enhancing treatment integrity and data quality. Strong baseline predictors of compliance did not emerge, and the small relationships found were consistent with reports from previous studies. Attendance at therapy sessions was moderately correlated with research follow-up participation. Treatment compliance predicted drinking outcome, underscoring the importance of retaining patients in treatment. Future studies should examine the associations between compliance and structural features of the treatment environment, treatment delivery, and context-features that are often under the control of the clinician/investigator.

Internal validity of Project MATCH treatments: discriminability and integrity.

Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) is a multisite collaborative project designed to evaluate patient-treatment interactions in alcoholism treatment. To evaluate whether major threats to the internal validity of the independent (treatment) variable in Project MATCH could be ruled out, we investigated several aspects of treatment integrity and discriminability. In this study, 1,726 alcohol-dependent participants at 10 sites were randomized to 3 treatments: cognitive-behavioral treatment (CBT), motivational enhancement therapy (MET), and 12-step facilitation (TSF). Participants received treatment either as outpatients or as aftercare following a more intensive inpatient or day hospital treatment. For both the outpatient and aftercare arms of the study, treatments were discriminable in that therapists implemented each of the treatments according to manual guidelines and rarely used techniques associated with comparison approaches. Participants received a high level of exposure to their study treatments, and the intended contrast in treatment dose between MET and the 2 more intensive treatments (CBT and TSF) was obtained. Alcoholics Anonymous involvement was significantly higher for participants assigned to TSF versus MET or CBT, whereas the treatments did not differ in utilization of other nonstudy treatments. Nonspecific aspects of treatment such as therapist skillfulness and level of the therapeutic alliance were comparable across treatment conditions.

Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics.

BACKGROUND: This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics. METHODS: Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving. RESULTS: Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol. CONCLUSION: The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.

Ecological momentary assessment (EMA) with treated alcoholics: methodological problems and potential solutions.

Ecological Momentary Assessment, a methodology by which information can be obtained about phenomena as they occur in a person's natural environment, was used to assess the antecedents to relapse in treated alcohol abusers. Alcoholic participants (N = 27) were asked to record their urge to drink alcohol and their mood state, situation, and alcohol use on 5- x 7-in. record cards in response to 8 random prompts per day for 21 consecutive days after discharge from a Veterans Affairs inpatient treatment center. The purpose of the research was to determine the extent to which drinking urges occurred in the patient's home environment after treatment and to identify the mood states and alcohol-related stimuli associated with urges. Field recordings were prompted by a programmable wrist watch. Results suggested that compliance with procedures was excellent and that the occurrence of drinking and of drinking urges was relatively rare. However, significant methodological problems were brought to light that may have compromised the results. These problems are presented and potential solutions are proposed.

Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-chlorophenylpiperazine (mCPP).

Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated the effects of intravenous infusion of the alpha 2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.1 mg/kg), and placebo administered to 22 male patients meeting DSM-III-R criteria for alcohol dependence and 13 male healthy subjects. Patients and healthy subjects completed 3 test days under double-blind conditions in a randomized order. Patients were sober for 12-26 days prior to testing. On each test day, participants completed startle testing 80 min following drug infusion. Stimuli with varying intensities (90, 96, 102, 108, 114 dB) were presented in a randomized order balanced across four blocks. Stimuli consisted of 40-ms bursts of white noise administered every 45-60 s for 15-20 min through headphones. Analyses indicated that patients exhibited elevated acoustic startle magnitudes on the placebo day relative to healthy subjects. In patients, the magnitude of startle amplitudes elicited at 90 dB, but not 114 dB, correlated significantly with the number of previous alcohol detoxifications. Yohimbine increased startle magnitudes and reduced startle latencies relative to placebo and mCPP in both patients and healthy subjects. mCPP did not alter startle magnitude in either group. Yohimbine also increased the probability that a 90-dB stimulus produced a startle response in healthy subjects, but not in patients. Blunting of yohimbine effects on startle probability may reflect the baseline elevations in startle probability levels in patients, but may also be consistent with other evidence of reduced postsynaptic, but not presynaptic, noradrenergic function in these same patients. These data replicate and extend previous reports indicating that yohimbine facilitates the acoustic startle response in humans. They also further implicate the number of episodes of ethanol withdrawal as a factor influencing subsequent neurobiological responsivity in chronic alcoholic patients. Based on the current data, future research should explore whether measurement of the acoustic startle response provides an objective quantitative severity measure of ethanol withdrawal.

Use of ondansetron in palliative medicine.

Ondansetron was the first of several selective 5-hydroxytryptamine (5-HT3) antagonists to be available as an antiemetic. Its uses in the setting of highly and moderately emetogenic chemotherapy and radiotherapy are well established. Ondansetron has also been used to manage nausea and vomiting in other patients. We report a retrospective analysis of its use in all 16 patients who were commenced on ondansetron after admission to our institution for nausea and/or vomiting over a 4-year period. Nine patients had advanced human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and seven had malignancy. These patients were not undergoing disease-modifying treatment and had inadequate responses to therapeutic doses of standard antiemetics, used either singly or in combination. Responses were independently reviewed and graded by two investigators. Response was judged at 48 hr after commencing therapy. Potential causes of nausea were also reviewed. Overall, 13 of 16 [81%, 95% confidence interval (CI) 54%-96%] derived benefit. Twelve of 15 patients (80%) with nausea had a demonstrable improvement, and ten of 14 patients (71%) with vomiting also improved. Eight of ten patients (80%) admitted with nausea and/or vomiting as one of their presenting problems had the symptom controlled within 48 hr of ondansetron therapy. Treatment with ondansetron was well tolerated, onset of action was rapid, and response rates were high and sustained over time. Seven of the 16 patients continued ondansetron therapy for more than 10 days. With minimal reductions in inpatient bed stays, the total costs of ondansetron could be met while at the same time better supporting patients remaining in the community.

Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men.

Relapsed alcoholic individuals frequently report that negative emotional states trigger their return to drinking. A parametric laboratory study was conducted to assess the separate and combined effects of exposure to alcohol-related stimuli and induced negative moods in abstinent alcoholic persons. The authors also sought to determine if reactivity to alcohol cues or reactivity to negative mood induction predicted relapse soon after treatment. Men with alcoholism (N = 50) undergoing inpatient treatment participated in a guided imagery procedure designed to induce negative moods and were then exposed to either their favorite alcoholic beverage or to spring water. Results indicated that both alcoholic beverage presentation and negative affect imagery led to increased subjective reporting of desire to drink. These effects were additive but not multiplicative (i.e., the interaction of mood state with beverage type was not significant). Reported urge to drink during the trial that combined negative mood imagery with alcoholic beverage exposure predicted time to relapse after inpatient discharge.

Managing HIV. Part 5: Treating secondary outcomes. 5.19 HIV and palliative care.

The goals of palliative care are the relief of pain and suffering in advanced disease and the support of the patient's carers. In HIV medicine, good palliative care often includes active treatment, and the palliative care team may work in support of the primary care doctor.

Serotonergic and noradrenergic dysregulation in alcoholism: m-chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects.

OBJECTIVE: This study compared serotonergic (5-HT) and noradrenergic reactivity in recently detoxified alcoholic patients and healthy comparison subjects. METHOD: Participants were 22 male inpatients who met DSM-III-R criteria for alcohol dependence and who were abstinent for 12-26 days and 13 male healthy comparison subjects. Subjects completed 3 days of testing over 2 weeks under double-blind conditions that involved the intravenous infusions of m-chlorophenylpiperazine (mCPP), yohimbine, or a saline placebo. Drug effects on mood, physiologic responses, and plasma levels of cortisol, prolactin, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. RESULTS: Both mCPP and yohimbine infusion increased nervousness, vital signs, and plasma cortisol, prolactin, and MHPG levels relative to placebo Cortisol responses to mCPP were blunted in the alcoholic patients relative to the comparison subjects. Cortisol and prolactin responses to yohimbine were greater in the alcoholic patients, whereas their pulse increases after yohimbine infusion were blunted. No group differences emerged in MHPG, nervousness, or blood pressure responses to either drug. CONCLUSIONS: This study documents persistent alterations in neuroendocrine responsivity of both 5-HT and noradrenergic systems in alcoholic patients after detoxification. Blunted cortisol responses to mCPP in these recently detoxified patients may reflect reductions in 5-HT2 receptor function. The absence of altered MHPG responses to yohimbine in the alcoholic patients suggests that presynaptic noradrenergic responsivity is not persistently altered in these patients. In contrast, the enhanced cortisol responses and reduced pulse responses to yohimbine in alcoholic patients may reflect down-regulation of postsynaptic noradrenergic receptors.

Differences between responders and nonresponders to cocaine cues in the laboratory.

Previous research has shown that a majority of drug-dependent subjects respond to drug cues in the laboratory with increased craving; however, approximately one-third are not cue responsive. The current study examined differences between responders and nonresponders to cocaine cues in a sample of 69 cocaine-dependent methadone patients. Subjects completed questionnaires assessing selected dimensions of addiction and participated in a cue-reactivity protocol that assessed both cocaine craving and cocaine aversion in response to cues. Four groups of subjects were identified on the basis of their cue responses: (a) increased craving plus decreased aversion; (b) increasing craving only; (c) decreased aversion only; (d) no increase in craving and no decrease in aversion ("nonresponders"). No group differences were found in severity of cocaine dependence, depression, or on any demographic variable, with the exception of parental status. Group differences were found on measures of cocaine expectancies and self-efficacy. There is a discussion of the bearing of these findings upon explanations offered in the literature for nonreactivity to drug cues.