Post-withdrawal Period Research Articles

Analysis of SLC6A4 (5 ‑HTTLPR) gene polymorphism depending on clinical features and efficacy of therapeutic and rehabilitation measures in patients with psychostimulant addiction

The annual increase in the number of patients with psychostimulant addiction and the low duration of remissions as a result of treatment of such disorders prompt researchers to search for new approaches to therapy. It seems relevant to search for and introduce into practice new clinical and genetic markers that increase the effectiveness of psychostimulant addiction therapy within the framework of a personalized approach. The purpose of the study is to determine the impact of a number of clinical characteristics and SLC6A4 (5‑HTTLPR) gene polymorphism on the efficacy of treatment and rehabilitation program in patients with psychostimulant addiction. Materials and methods. The study included 325 patients diagnosed with «mental and behavioral disorders due to use of psychostimulants» (F14.2, F15.2, F19.2 according to ICD-10); men and women aged 18 to 50 years, ethnically Russian, signed informed consent to participate in the study. Methods: clinical-psychopathological, anamnestic, molecular-genetic, psychometric (Montgomery — Åsberg Depression Rating Scale (MADRS)), and statistical methods. Results. All patients were divided into groups depending on the psychoactive substances used and comorbid psychiatric pathology. It was found that SSRI monotherapy (Escitalopram) for the relief of affective disorders in the post-withdrawal period was most effective in the patients who used only psychostimulants (p<0.005). Combined psychopharmacotherapy was more efficient in other groups (p<0.001). The patients with SS and SL genotypes of the SLC6A4 (5‑HTTLPR) gene tolerated Escitalopram monotherapy worse; a statistical difference was achieved for the patients with LL and SL/SS genotypes of group 2 (p<0.036). There were more patients who passed the rehabilitation program and with the longest remissions among those with the SL and SS genotypes of the SLC6A4 (5‑HTTLPR) gene in all groups. Conclusion. After analyzing the results, the conclusions about the association between a number of clinical and genetic characteristics of patients with psychostimulant addiction and the effectiveness of treatment and rehabilitation measures were drawn.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors in juvenile idiopathic arthritis.

To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients. This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9165/patient on active treatment (pre-withdrawal) and decreased significantly to €5063/patient (-44.8%) and €6569/patient (-28.3%) in the first and second year post-withdrawal, respectively (P < 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1180/patient, and €1320/patient in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first and second year post-withdrawal period, respectively. In the first two years after initiating withdrawal, the total annual costs were decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdrawal decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

Pleiotropic effects of Metadoxil in the treatment of acute and chronic alcohol intoxications

This article presents a review of modern scientific data concerning the safety and efficacy of the use of Metadoxil at different stages of the treatment of alcohol use disorder (from acute alcohol intoxication to the alcohol withdrawal syndrome, to the post-withdrawal period and remission stabilization), as well as a review of the advantages of Metadoxil use in such patients, due to the neuro- and hepatoprotective effects of this medication. Authors also describe a clinical case from their own practice. In the aforementioned case, the use of Metadoxil as a part of combination therapy contributed not only to the stabilization of remission of the alcohol use disorder, but also to diminishing of symptoms of comorbid mental (obsessive-compulsive disorder) and somatic (alcoholic fatty liver disease) diseases.

The use of Cytoflavin in the post-withdrawal period in patients with alcohol dependence

BACKGROUND: The issues of therapy of dependence on psychoactive substances remain relevant at present, focusing on the prevention, treatment, and rehabilitation of these patients in the first place.&#x0D; AIM: To evaluate the effectiveness of a course of Cytoflavin in patients with alcohol dependency during the post-abstinence period.&#x0D; MATERIALS AND METHODS: An open, double-blind, placebo-controlled clinical study of the antioxidant Cytoflavin (10 mL/day, 5 days) effectiveness to correct emotional and motivational disorders after the treatment of alcohol withdrawal syndrome was performed in 30 patients with alcohol dependency. Anamnestic information, the clinical picture of the disease, and psychological tests the Holmes and Rage method (the degree of stress tolerance and social adaptation) and alcohol consumption motivation test (ACMT) were used to verify alcohol dependency. Before and after Cytoflavin treatment, the psychological indicators and complaints were recorded. According to the alcohol intake questionnaire, the psychological state of the patients was assessed based on a package of standard psychological tests, including the Wasserman test (level of neuroticism), Spielberger test (level of anxiety), Hamilton test (level of depression), SAN test (self-assessment of well-being, activity, and mood), and degree of craving for alcohol. For pairwise conjugated variants, the significance of differences was determined using the Students t-test; statistical analysis was performed using the standard Statistica for Windows software package.&#x0D; RESULTS: In general, the course use of Cytoflavin treatment improved clinical and psychological parameters in patients with alcohol dependency in the post-abstinence period.&#x0D; CONCLUSION: It is concluded that the use of the drug as a component of a comprehensive therapeutic program for alcohol dependency is highly promising.

Hypothymia in alcohol dependence

The purpose of the work is to identify hypothymic disorders typical for patients with alcohol dependence. Material and methods. 100 male patients aged 38-53 years who were hospitalized for alcohol dependence with a typical course in the early post-withdrawal period were examined. The examination was carried out by the clinical method and using the HDRS scale. Results. Affective disorders in alcohol addicts manifested in the form of hypothymia within the asthenic (cerebro-asthenic) syndrome, which is fundamentally different from the depressive disorders that are typical for psychiatric diseases. Conclusions. The peculiarity of the hypothymic symptoms is sufficient to negate their similarity to depression in psychiatric illnesses. The use of the concept of depression in narcology is carried out with an assumption that often distorts the true state of affairs in the clinical picture.

Association of single nucleotide variants rs34532313 of the &lt;i&gt;MTNR1A&lt;/i&gt; gene and rs10830963 of the &lt;i&gt;MTNR1B&lt;/i&gt; gene with suicidal risk in alcohol dependence syndrome and insomnia

Background: Suicidal behaviour is the leading cause of mortality from external causes at all ages worldwide. More than a million people commit completed suicide each year. According to the World Health Organisation, 25-50% of suicide victims suffered from alcohol and other substance use disorders, 22% of all suicide deaths were attributable to alcohol use (WHO, 2014). Several papers have suggested potential associations of insomnia and increased suicide risk in patients with alcoholism. We hypothesise that mutations in melatonin receptor genes may be associated with suicide risk in patients with alcoholism.Methods. The Insomnia Severity Index (ISI) was used as a tool to assess the presence and severity of insomnia. The Columbia Suicide Severity Rating Scale (C-SSRS) was used as a method to examine suicidal behavior. Genotyping of MTNR1A (rs34532313), MTNR1B (rs10830963) genes was performed using real-time polymerase chain reaction (RT-PCR). A comparative genetic study of two groups of patients was carried out: the first group, patients with alcohol dependence syndrome (F10.2); the second group, patients with alcohol dependence syndrome (F10.2) and insomnia, which persisted 7-14 days after starting alcohol withdrawal therapy.Results. Suicidal thoughts and a history of auto-aggressive behaviour were more common in subjects with insomnia in the post-withdrawal period. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were more likely to have suicidal thoughts and a history of suicide attempts in a genetic study of patients with insomnia.Conclusions. Our study found that the TT genotype of the MTNR1A gene (rs34532313) is a genetic marker of suicidal behaviour risk in patients with insomnia in the post-withdrawal period. However, the same pattern was not observed in patients without insomnia.

Sensitivity to placebo therapy in patients with alcohol dependence in postwithdrawal period

40 patients with alcohol dependence in post-abstinent period was used to study the psychological peculiarities of emotional-motivational sphere during the course of placebo therapy. The placebo-reactor was 62.5%, placebo preaction – 15%, placebo-negative reactors of 22.5%. There are significant differences in the compared groups of patients. After a course of placebo-therapy all patients showed positive changes in emotional state, most pronounced in placebo-directoru. The least pronounced changes in the placebo group-negative patients (but to lessen the desire for alcohol most pronounced). The conclusion about the need for a differentiated approach to the treatment of alcohol withdrawal syndrome and postdetoxification state.

Fatal poisonings involving propoxyphene before and after voluntary withdrawal from the United States’ market: An analysis from the state of Florida

The synthetic opioid propoxyphene was a schedule IV controlled substance with multiple reported health risks before the US Food and Drug Administration issued a request for voluntary market withdrawal in November 2010. The purpose of this study is to investigate the characteristics and occurrences of propoxyphene-related deaths in Florida before and after voluntary market removal. Decedent-level toxicology data from Florida’s Medical Examiners Commission was used to compare the temporal, polysubstance use, sociodemographic, and geographic profiles associated with propoxyphene-involved deaths for a pre-withdrawal (November 2008–November 2010) and post-withdrawal (December 2010–December 2012) period. Sensitivity analyses using multiple data sources, including Florida’s Prescription Drug Monitoring Program and other states’ data, were conducted to examine potential reporting bias. Results showed that the number of propoxyphene-involved deaths declined by 84% from 580 deaths to 92 deaths after market withdrawal. The co-occurrence of other prevalent drugs, such as oxycodone (17.2% to 26.1%, p=0.0422) increased significantly in the post-withdrawal study period. A larger proportion of the propoxyphene-related deaths were reported from South Florida after the withdrawal (28.4% to 56.5%, p<0.0001). No significant changes in age and race/ethnicity were observed. Sensitivity analyses revealed that several deaths occurred in other states after market withdrawal, as recently as 2016. Our findings are consistent with previous studies that propoxyphene was still available after removal from the US market. Continued surveillance is recommended after highly abused opioids are withdrawn from the market due to on-going safety risks.

Imepitoin withdrawal in dogs with idiopathic epilepsy well-controlled with imepitoin and phenobarbital and/or potassium bromide does not increase seizure frequency

Phenobarbital or potassium bromide (KBr) add-on treatment decreases the average monthly seizure frequency in dogs with idiopathic epilepsy resistant to a maximum dose of imepitoin. The importance of continued administration of imepitoin in these dogs is currently unknown. The goal of this study was to assess whether imepitoin withdrawal would destabilize epileptic seizure control. In this prospective clinical trial epileptic seizure control was evaluated by comparing the monthly seizure frequency of 13 dogs with well-controlled idiopathic epilepsy receiving a combination of imepitoin and phenobarbital (n=4), imepitoin and KBr (n=7), and imepitoin, phenobarbital and KBr (n=2) during a period of 3–6 months (pre-withdrawal period), with a follow-up period of 9–12 months after withdrawal of imepitoin (post-withdrawal period). Adverse effects were also recorded before and after withdrawal of imepitoin. Imepitoin was tapered off over 3 months as follows: 20mg/kg twice daily for 1 month, then 10mg/kg twice daily for 1 month, then once daily for 1 month.Withdrawal of imepitoin did not increase monthly seizure frequency (P=0.9). Moreover, all owners reported improvement in the adverse effects experienced by their dog after withdrawal of imepitoin. Imepitoin withdrawal in epileptic dogs that were well-controlled with imepitoin and phenobarbital and/or KBr did not worsen epileptic seizure control, and possibly decreased antiepileptic treatment-related adverse effects. However, a worsening of seizure frequency could occur in individual cases.

Decision support during electronic prescription to stem antibiotic overuse for acute respiratory infections: a long-term, quasi-experimental study

BackgroundInterventions to support decision-making can reduce inappropriate antibiotic use for acute respiratory infections (ARI), but they may not be sustainable. The objective of the study is to evaluate the long-term effectiveness of a clinical decision-support system (CDSS) interposed at the time of electronic (e-) prescriptions for selected antibiotics.MethodsThis is a retrospective, observational intervention study, conducted within a large, statewide Veterans Affairs health system. Participants are outpatients with an initial visit for ARI. A CDSS was deployed upon e-prescription of selected antibiotics during the study period. From 01/2004 to 05/2006 (pre-withdrawal period), the CDSS targeted azithromycin and the fluoroquinolone gatifloxacin. From 05/2006 to 12/2011 (post-withdrawal period), the CDSS was retained for azithromycin but withdrawn for the fluoroquinolone. A manual record review was conducted to determine concordance of antibiotic prescription with ARI treatment guidelines.ResultsOf 1131 included ARI visits, 380 (33.6%) were guideline-concordant. For azithromycin, concordance did not change between the pre- and post-withdrawal periods, and adjusted odds of concordance was 8.8 for the full study period, compared to unrestricted antibiotics. For fluoroquinolones, guideline concordance decreased from 88.6% (39 of 44 visits) to 51.3% (59 of 115 visits), pre- vs. post-withdrawal periods (p < 0.005). The adjusted odds of concordance compared to “All Other Antibiotics” visits decreased from 24.4 (95% CI 9.0–66.3) pre-withdrawal to 5.5 (95% CI 3.5–8.8) post-withdrawal (p = .008). Concordance did not change between those same time periods for antibiotics that were never subjected to the intervention (“All Other Antibiotics”).ConclusionsA CDSS interposed at the time of e-prescription of selected antibiotics can shift their use toward ARI treatment guidelines, and this effect can be maintained over the long term as long as the CDSS remains in place. Removal of the CDSS after 3.5 years of implementation resulted in a rise in guideline-discordant antibiotic use.

Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia

BackgroundMalaria still poses one of the major threats to human health. Development of effective antimalarial drugs has decreased this threat; however, the emergence of drug-resistant Plasmodium falciparum, a cause of Malaria, is disconcerting. The antimalarial drug chloroquine has been effectively used, but resistant parasites have spread worldwide. Interestingly, the withdrawal of the drug reportedly leads to an increased population of susceptible parasites in some cases. We examined the prevalence of genomic polymorphisms in a malaria parasite P. falciparum, associated with resistance to an antimalarial drug chloroquine, after the withdrawal of the drug from Indonesia.ResultsBlood samples were collected from 95 malaria patients in North Sulawesi, Indonesia, in 2010. Parasite DNA was extracted and analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) for pfcrt and pfmdr1. In parallel, multiplex amplicon sequencing for the same genes was carried out with Illumina MiSeq. Of the 59 cases diagnosed as P. falciparum infection by microscopy, PCR–RFLP analysis clearly identified the genotype 76T in pfcrt in 44 cases. Sequencing analysis validated the identified genotypes in the 44 cases and demonstrated that the haplotype in the surrounding genomic region was exclusively SVMNT. Results of pfmdr1 were successfully obtained for 51 samples, where the genotyping results obtained by the two methods were completely consistent. In pfmdr1, the 86Y mutant genotype was observed in 45 cases (88.2%).ConclusionsOur results suggest that the prevalence of the mutated genotypes remained dominant even 6 years after the withdrawal of chloroquine from this region. Diversified haplotype of the resistance-related locus, potentially involved in fitness costs, unauthorized usage of chloroquine, and/or a short post-withdrawal period may account for the observed high persistence of prevalence.

Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine.

Cardiovascular responses to smoking cessation may differ in adolescents compared to adults. We administered nicotine by osmotic minipump infusion for 17 days to adolescent and adult rats (30 and 90 days of age, respectively) and examined cardiac norepinephrine levels during treatment, after withdrawal, and for months after cessation. In adults, nicotine evoked a significant elevation of cardiac norepinephrine and a distinct spike upon withdrawal, after which the levels returned to normal; the effect was specific to males. In contrast, adolescents did not show significant changes during nicotine treatment or in the immediate post-withdrawal period. However, beginning in young adulthood, males exposed to adolescent nicotine showed sustained elevations of cardiac norepinephrine, followed by later-emerging deficits that persisted through six months of age. We then conducted adolescent exposure using twice-daily injections, a regimen that augments stress associated with inter-dose withdrawal episodes. With the injection route, adolescents showed an enhanced cardiac norepinephrine response, reinforcing the relationship between withdrawal stress and a surge in cardiac norepinephrine levels. The relative resistance of adolescents to the acute nicotine withdrawal response is likely to make episodic nicotine exposure less stressful or aversive than in adults. Equally important, the long-term changes after adolescent nicotine exposure resemble those known to be associated with risk of hypertension in young adulthood (elevated norepinephrine) or subsequent congestive heart disease (norepinephrine deficits). Our findings reinforce the unique responses and consequences of nicotine exposure in adolescence, the period in which most smokers commence tobacco use.

Therapeutic efficacy of original anticonvulsant meta-chloro-benzhydrylurea (m-ch-BHU) in the treatment of patients with a compulsive craving for alcohol

IntroductionThe problem of the treatment of alcohol addiction is very difficult due to the reoccurrence of relapses. One of the major concepts of the formation of alcohol addiction is the concept of epileptic origin of compulsive craving for alcohol.ObjectiveWe investigated therapeutic efficacy of long-term dosing of original anticonvulsant (m-ch-BHU) on symptoms of alcohol withdrawal syndrome (AWS) in patients with a compulsive craving for alcohol.MethodsSixty-eight male alcoholic patients aged from 24 to 53 years with different levels of alcohol abuse were examined. Type of course of alcoholism in examined patients was of middle-progressing character. Clinical evaluation of state of patients was carried out with traditional clinical description. Quantitative characterization was conducted according to Hamilton Anxiety Scale and Hamilton Depression Scale. m-ch-BHU was administered to alcoholic patients at dose from 300 mg a day during 21 days against the background of conventional medication as well as in post-withdrawal period under various degrees of severity of affective disorders.ResultsAmong affective disorders dysphoric symptoms have a marked tropism for m-ch-BHU. Of the other clinical manifestations in the structure of AWS cerebral diencephalic paroxysms, cardiovascular and myofascial symptoms have the most pronounced sensitivity to the drug. In patients with complicated forms of alcoholism application of m-ch-BHU is effective also in phase of remission in spontaneously arising symptom complex of neurovegetative manifestations of primary pathological craving for ethanol called “dry abstinence”.ConclusionsOur data allows recommending the use of m-ch-BHU under outpatient conditions as an anti-recurrent and preventive agent.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Tryptophan Metabolism in Post-Withdrawal Alcohol-Dependent Patients

The aim of the study was to investigate the parameters of tryptophan and phenylalanine metabolism and their associations to immune system activation and to behavioural symptoms during medium-term withdrawal (4-12 weeks of abstinence) in alcohol-dependent patients. Biochemical assays and clinical assessments at the beginning of treatment (fourth week of alcohol abstinence in average) and prior to the discharge after 8 weeks of treatment. Kynurenine to tryptophan ratio (Kyn/Trp) slightly correlated with neopterin levels in early post-withdrawal period (Week 4 of abstinence) but this association disappeared after 12 weeks of abstinence. Phenylalanine and tyrosine concentrations as well as phenylalanine to tyrosine ratio (Phe/Tyr) decreased between Weeks 4 and 12 of abstinence. Kynurenine and Kyn/Trp increased significantly at 12th week of abstinence when compared with the beginning of the study (Week 4 of abstinence). At Week 12, Kyn/Trp significantly correlated with such behavioural symptoms as fatigue, irritability and sleep disturbances. Tryptophan breakdown in early stages may be influenced by the increased activity of indoleamine 2,3-dioxygenase but the increase of Kyn/Trp between Weeks 4 and 12 of abstinence seems to be independent of immune changes and correlates with behavioural symptoms in later stages of the post-withdrawal course. A possible role of kynurenine metabolites in mediation of the increased stress sensibility in post-withdrawal alcohol-dependent patients is discussed.

Pharmacotherapy of alcohol use disorders: seventy-five years of progress.

Modern pharmacotherapy for alcohol dependence has its roots in the failure of National Prohibition in the United States and the rise of the disease model of alcoholism (embodied in Alcoholics Anonymous). In 1948, disulfiram was the first medication approved by the U.S. Food and Drug Administration (FDA) to treat alcohol dependence, but its efficacy has not been supported by randomized controlled trials. In the 1960s, benzodiazepines replaced older treatments for alcohol withdrawal, but sedative and dependence-producing effects limit their utility in the postwithdrawal period. In the 1980s, the focus shifted to the treatment of co-occurring psychiatric disorders and medications that modify negative mood states, which contribute to relapse to heavy drinking. In the 1990s, developments in neurobiology implicated specific neurotransmitter systems underlying alcohol's effects, culminating in the 1994 approval by the FDA of the opioid antagonist naltrexone to treat alcohol dependence. In 2006, the FDA approved a long-acting formulation of naltrexone. Recently, nalmefene, another opioid receptor antagonist, was approved in Europe for as-needed use to reduce heavy drinking. Acamprosate, an amino acid derivative, first approved in France in 1989, received FDA approval in 2004. However, the beneficial effects of the approved medications are only modestly greater than those of placebo, and their use is limited. Topiramate, currently under investigation for alcohol dependence, has greater efficacy but a variety of adverse effects. In addition to the identification of novel compounds, the future of alcohol dependence pharmacotherapy will depend on developments in pharmacogenetics, in which genetic variation that moderates treatment efficacy and adverse effects is used to personalize treatment.

Effectiveness and Safety of Laropiprant on Niacin-Induced Flushing

Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (>6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) ≥4 (primary end point) and the percentage of patients with a maximum GFSS of ≥4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of ≥4 (p <0.001) and the percentage of patients with a maximum GFSS of ≥4 (p <0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.

Blood and tissue fatty acid compositions, lipoprotein levels, performance and meat flavor of broilers fed fish oil: changes in the pre- and post-withdrawal design

Administration of fish oil (FO) in broiler diets can elevate α-linolenic acid (ALA), eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) levels, which are protective against cardiovascular disease. However, optimization based solely on n-3 polyunsaturated fatty acid (n-3 PUFA) enrichment in chicken meat could lead to lower meat quality, unless the withdrawal period (plan) is applied for 1 week. The present study investigated whether the incorporation of FO in the diet for 32 days followed by its withdrawal for 1 week affected blood lipid profiles, lipoprotein particles, performance and meat flavor in male broiler chickens. Two hundred and forty birds (1-day-old, Ross 308) were assigned to 1 of 4 dietary groups: 0%, 1%, 2% or 3% FO with four replicates. Broilers were fed for 49 days according to a 4-phase feeding program. The experimental phase comprised day 11 to 42, and FO was removed on day 42. Blood samples were collected during the pre- and post-withdrawal period after the recordings before slaughter. The FO groups demonstrated decreased low-density lipoprotein (LDL) and increased high-density lipoprotein levels on day 42 (P < 0.01); however, these values were not significant after design withdrawal. Diet supplementation with FO elevated the blood levels of palmitic acid (C16:0) and n-3 PUFAs, especially long-chain (LC) PUFAs (EPA, C20:5n-3 and DHA, C22:6n-3), and caused a decline in the level of arachidonic acid (AA, C20:4n-6; P < 0.05). Application of a one-week withdrawal period resulted in a decrease in (P < 0.05) linoleic acid (C18:2n-6) and an increase in the level of AA, unlike their amounts on day 42. Although blood and tissue LC n-3 PUFA levels on day 49 were significantly higher in the FO groups compared with the control, they demonstrated a substantial decrease on day 49 compared with day 42. The best results, mainly the lowest n-6/n-3 fatty acids (FAs) and feed conversion ratio (FCRs), were observed for 3% FO (group T4), even after institution of the withdrawal design. Degradation of total n-3 FAs deposited in tissues occurred after instituting the withdrawal plan diet, but deposited levels of EPA and DHA in tissues could ensure omega-3 enrichment of broiler meat in groups 3 and 4. On the basis of the dissatisfaction of the panelists toward group 4 meats (scored as near to acceptable) and their satisfaction with cooked samples of T3 (scored as good), group 3 meats were selected as good-quality n-3-enriched broiler meat.

Abstract 8824: Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients

Extended-release niacin (ERN) produces improvements across the lipid profile in patients with dyslipidemia, but is underutilized due to flushing, a process primarily mediated by prostaglandin D 2 (PGD 2 ). The PGD 2 receptor antagonist, laropiprant (LRPT), reduces ERN-induced flushing in patients with dyslipidemia. This study tested the hypothesis that, after 20 weeks of the fixed-dose combination ERN/LRPT, patients who continued on ERN/LRPT would have less flushing than patients who had LRPT withdrawn, but continued on ERN alone. After a 2-week placebo run-in, 1152 patients with dyslipidemia were randomized 2:2:1 to one of three daily treatment groups: (1) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg for the remainder of the study; (2) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg from 5 to 20 weeks, then ERN 2g without laropiprant from 21 to 32 weeks; or (3) placebo for the duration of the study. The key endpoints were based on the Global Flushing Severity Score (GFSS) from the previously validated Flushing Symptom Questionnaire: the number of days/week with moderate or greater GFSS ≥4 (primary) and the percentage of patients with maximum GFSS ≥4 (secondary) during the post-withdrawal period of the study (weeks 21 to 32). ERN/LRPT produced significantly less flushing relative to ERN alone during the post-withdrawal period, as measured by the number of days/week with GFSS ≥4 (p&lt;0.001; see fig) and the percentage of patients with maximum GFSS ≥4 (ERN/LRPT: 19.6%; ERN: 48.9%; Placebo: 9.2%). There were fewer drug related adverse experiences during the post-withdrawal period comparing the ERN/LRPT to the ERN treatment groups. In summary, following 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less flushing than patients who had LRPT withdrawn, and continued with ERN alone. This study supports the long-term efficacy (&gt; 24 weeks) of ERN/LRPT in reducing flushing symptoms.

Some aspects of the clinical picture and dynamics of the postwithdrawal period in opium addiction patients

The psychopathological pattern of the postwithdrawal state in opium addiction patients is discussed. The pathological addiction to the drug in dependence of premorbid personality characteristics and the inverse dynamics are analyzed.

Alcohol Detoxification and Relapse Prevention Using Valproic Acid Versus Gabapentin in Alcohol-dependent Patients

Objective Acute alcohol withdrawal and the period immediately after alcohol withdrawal are of clinical importance because this is the time that patients may be most at risk for relapse to drinking. Methods The current study was a randomized double-blind, placebo-controlled trial comparing valproic acid and gabapentin as (1) treatment for the acute symptoms of alcohol withdrawal (5 d) and (2) the prevention of relapse and amelioration of psychiatric symptoms associated with protracted alcohol withdrawal (4 wk). Fifty-seven male veterans presenting for alcohol detoxification were randomized to receive valproic acid, gabapentin, or placebo for a total of 4 weeks. All subjects received benzodiazepine medication if needed based on symptoms of acute withdrawal from alcohol for the first 5 days of treatment. Outcomes Included Phase 1: symptoms of physiologic withdrawal during the first 5 days of treatment and doses of benzodiazepine required; phase 2: alcohol use and craving, symptoms of psychiatric distress, and sleep disturbances. Subjects entering the study were in mild to moderate withdrawal and the medications were well tolerated. Results The results of this randomized trial suggest that the anticonvulsants were not significantly better than placebo in treating mild withdrawal symptoms, did not influence relapse to alcohol and did not treat the symptoms of depression and sleep disturbance that occur in the postwithdrawal period. Conclusions There was some evidence that these medications were superior to placebo in alleviating anxiety. Because subjects as a group improved in all domains significantly, it suggests that supportive treatment is effective in mild to moderate withdrawal.