End Of Treatment Week Research Articles

Effect of Varenicline Added to Counseling on Smoking Cessation Among African American Daily Smokers

African American smokers have among the highest rates of tobacco-attributable morbidity and mortality in the US, and effective treatment is needed for all smoking levels. To evaluate the efficacy of varenicline vs placebo among African American adults who are light, moderate, and heavy daily smokers. The Kick It at Swope IV (KIS-IV) trial was a randomized, double-blind, placebo-controlled clinical trial conducted at a federally qualified health center in Kansas City. A total of 500 African American adults who were daily smokers of all smoking levels were enrolled from June 2015 to December 2017; final follow-up was completed in June 2018. Participants were provided 6 sessions of culturally relevant individualized counseling and were randomized (in a 3:2 ratio) to receive varenicline (1 mg twice daily; n = 300) or placebo (n = 200) for 12 weeks. Randomization was stratified by sex and smoking level (1-10 cigarettes/d [light smokers] or >10 cigarettes/d [moderate to heavy smokers]). The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26. The secondary outcome was 7-day point prevalence smoking abstinence at week 12, with subgroup analyses for light smokers (1-10 cigarettes/d) and moderate to heavy smokers (>10 cigarettes/d). Among 500 participants who were randomized and completed the baseline visit (mean age, 52 years; 262 [52%] women; 260 [52%] light smokers; 429 [86%] menthol users), 441 (88%) completed the trial. Treating those lost to follow-up as smokers, participants receiving varenicline were significantly more likely than those receiving placebo to be abstinent at week 26 (15.7% vs 6.5%; difference, 9.2% [95% CI, 3.8%-14.5%]; odds ratio [OR], 2.7 [95% CI, 1.4-5.1]; P = .002). The varenicline group also demonstrated greater abstinence than the placebo group at the end of treatment week 12 (18.7% vs 7.0%; difference, 11.7% [95% CI, 6.0%-17.7%]; OR, 3.0 [95% CI, 1.7-5.6]; P < .001). Smoking abstinence at week 12 was significantly greater for individuals receiving varenicline compared with placebo among light smokers (22.1% vs 8.5%; difference, 13.6% [95% CI, 5.2%-22.0%]; OR, 3.0 [95% CI, 1.4-6.7]; P = .004) and among moderate to heavy smokers (15.1% vs 5.3%; difference, 9.8% [95% CI, 2.4%-17.2%]; OR, 3.1 [95% CI, 1.1-8.6]; P = .02), with no significant smoking level × treatment interaction (P = .96). Medication adverse events were generally comparable between treatment groups, with nausea reported more frequently in the varenicline group (163 of 293 [55.6%]) than the placebo group (90 of 196 [45.9%]). Among African American adults who are daily smokers, varenicline added to counseling resulted in a statistically significant improvement in the rates of 7-day point prevalence smoking abstinence at week 26 compared with counseling and placebo. The findings support the use of varenicline in addition to counseling for tobacco use treatment among African American adults who are daily smokers. ClinicalTrials.gov Identifier: NCT02360631.

Additive Analgesic Effect of Transcranial Direct Current Stimulation Together with Mirror Therapy for the Treatment of Phantom Pain.

Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation. Following ethical approval, eligible patients provided informed consent and were randomly assigned to a study treatment group that continued for 2weeks (once daily): 1) mirror therapy; 2) mirror therapy and sham tDCS; or 3) mirror therapy and tDCS. Assessments were done before treatment; at the end of treatment weeks 1 and 2; and at 1week, 1month, and 3months following treatment. The primary outcome measure was pain intensity. Secondary measures were derived from the Short Form McGill Pain Questionnaire and the Brief Pain Inventory. Thirty patients were recruited, and 29 patients completed the study. Three months following treatment, pain intensity was significantly (P<0.001) reduced in the combined treatment group (reduction of 5.4±3.3 points) compared with the other study arms (mirror therapy, 1.2±1.1; mirror therapy and sham tDCS, 2.7±3.2). All secondary outcome results were in line with these findings. Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain.

Monitoring anatomical changes of individual patients using statistical process control during head-and-neck radiotherapy.

Reduced toxicity while maintaining loco-regional control rates have been reported after reducing planning target volume (PTV) margins for head-and-neck radiotherapy (HNRT). In this context, quantifying anatomical changes to monitor patient treatment is preferred. This retrospective feasibility study investigated the application of deformable image registration (DIR) and Exponentially Weighted Moving Average (EWMA) Statistical Process Control (SPC) charts for this purpose. DIR between the computed tomography for treatment planning (pCT) images of twelve patients and their daily on-treatment cone beam computed tomography (CBCT) images quantified anatomical changes during treatment. EWMA charts investigated corresponding trends. Uncertainty analysis provided 90% confidence limits which were used to confirm whether a trend previously breached a threshold. Trends in patient positioning reproducibility occurred before the end of treatment week four in 54% of cases. Using SPC process limits, only 24% of these were confirmed at a 90% confidence level before the end of treatment. Using an a priori clinical limit of 2 mm, absolute changes in patient pose were detected in 39% of cases, of which 82% were confirmed. Soft tissue trends outside SPC process limits occurring before the end of treatment week four were confirmed in 90% of cases. Structure specific action thresholds enabled detection of systematic anatomical changes during the first four weeks of treatment. Investigation of the dosimetric impact of the observed deviations is needed to show the efficacy of SPC to timely indicate required treatment adaptation and provide a safety net for PTV margin reduction.

Oral haloperidol or olanzapine intake produces distinct and region-specific increase in cannabinoid receptor levels that is prevented by high fat diet

Clinical studies show higher levels of cannabinoid CB1 receptors (CB1R) in the brain of schizophrenic patients while preclinical studies report a significant functional interaction between dopamine D2 receptors and CB1Rs as well as an upregulation of CB1Rs after antipsychotic treatment. These findings prompted us to study the effects of chronic oral intake of a first and a second generation antipsychotic, haloperidol and olanzapine, on the levels and distribution of CB1Rs in the rat brain. Rats consumed either regular chow or high-fat food and drank water, haloperidol drinking solution (1.5mg/kg), or olanzapine drinking solution (10mg/kg) for four weeks. Motor and cognitive functions were tested at the end of treatment week 3 and upon drug discontinuation. Two days after drug discontinuation, rats were euthanized and brains were processed for in vitro receptor autoradiography. In chow-fed animals, haloperidol and olanzapine increased CB1R levels in the basal ganglia and the hippocampus, in a similar, but not identical pattern. In addition, olanzapine had unique effects in CB1R upregulation in higher order cognitive areas, in the secondary somatosensory cortex, in the visual and auditory cortices and the geniculate nuclei, as well as in the hypothalamus. High fat food consumption prevented antipsychotic-induced increase in CB1R levels in all regions examined, with one exception, the globus pallidus, in which they were higher in haloperidol-treated rats. The results point towards the hypothesis that increased CB1R levels could be a confounding effect of antipsychotic medication in schizophrenia that is circumveneted by high fat feeding.

Effects of fenofibrate on hepatocyte apoptosis in nonalcoholic fatty liver

To use a rat model of nonalcoholic liver disease (NAFLD) to observe effects of the peroxisome proliferator-activated receptor-a (PPAR-a) agonist fenofibrate on hepatic steatosis in nonalcoholic fatty liver and to investigate the underlying mechanism. Sixty-six Sprague-Dawley rats were given adaptive feeding for 1 week and then randomly allocated into the following three groups: unmodeled control (group C,n =18), untreated NAFLD model (group M, n =24), and fenofibrate-treated NAFLD model (group F, n =24).Group C rats were given a normal diet, while group M and group F rats were given a high-fat diet. After model establishment, the group F rats were treated with fenofibrate (10 mg/kg/d, intraperitoneal) and the group C and group M rats were given sham-treatment with cosolvent (5 mL/kg/d, intraperitoneal). At the end of treatment weeks 4, 6 and 8, one-third of rats in each group were euthanized.Liver tissues were assessed by hematoxylin-eosin (HE) staining to determine level of steatosis and inflammaion activity, and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling to measure changes in hepatocyte apoptosis index. Changes in expression levels of the PPAR-a receptor and apoptosis factors (bcl-2, bax and caspase-3) were assessed by reverse transcription-PCR and immunohistochemistry. The NAFLD modeled rats showed appropriate induction of hepatic steatosis, hepatic inflammation, and hepatocyte apoptosis. Compared to the group M rats, the group F rats showed lower expression of PPAR-and bcl-2 and higher expression of bax and caspase-3 at both the mRNA and protein level. Fenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD, and the mechanism may be associated with inhibition of hepatocyte apoptosis.

Can a one-weekend group therapy reduce fear of blushing? Results of an open trial

Fear of blushing is a specific syndrome generally subsumed under the diagnostic category of social anxiety disorder (SAD). This study aims at gathering preliminary data about an intensive weekend intervention specifically designed for individuals with fear of blushing as the predominant complaint. Treatment consisted of a combination of attention training and behavioral therapy. Thirty-one blushing-fearful individuals meeting the criteria for SAD following the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) were treated in three groups. The study was conducted as an open trial. Full assessments were performed before treatment, six weeks after treatment, and at six-month follow-up. Only fear of blushing, the main outcome criterion, was assessed immediately before and after the treatment weekend. The intensive therapy program was well accepted. Fear of blushing and SAD were significantly reduced and reductions remained stable. At follow-up, nearly two-thirds of the participants achieved significant changes in fear of blushing. Despite the preliminary nature of this study, the condensed format of weekend therapy for treating fear of blushing calls for further investigation.

Combination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery After a Focal Cortical Infarct in Rats

Although myelin-associated neurite outgrowth disinhibitors have shown promise in restoring motor function after stroke, their interactive effects with motor training have rarely been investigated. The present study examined whether a combinatorial treatment (NEP 1-40+motor rehabilitation) is more effective than either treatment alone in promoting motor recovery after focal ischemic injury. Adult rats were assigned to one of 3 treatment groups (infarct/NEP 1-40+motor training, infarct/NEP 1-40 only, infarct/motor training only) and 2 control groups (infarct/no treatment, intact/no treatment). A focal ischemic infarct was induced by microinjecting endothelin-1 into the motor cortex. Therapeutic treatments were initiated 1 week postinfarct and included intraventricular infusion of the pharmacological agent NEP 1-40 and motor training (skilled reach task). Behavioral assessments on skilled reach, foot fault, and cylinder tests were conducted before the infarct and for 5 weeks postinfarct. Rats demonstrated significant forelimb impairment on skilled reach and foot fault tests after the infarct. Although all infarct groups improved over time, motor training alone and NEP 1-40 alone facilitated recovery on the skilled reach task at the end of treatment Weeks 2 and 4, respectively. However, only NEP 1-40 paired with motor training facilitated recovery after 1 week of treatment in addition to treatment at Weeks 2 and 4. Finally, only the NEP 1-40+motor training group maintained a performance level equivalent to that of the intact group over the entire period of posttreatment assessment. This study suggests that behavioral training interacts with the effects of the axonal growth promoter, NEP 1-40, and may accelerate behavioral recovery after focal cortical ischemia.

Intensive Sleep Retraining treatment for chronic primary insomnia: a preliminary investigation

The aim of this study was to assess the effectiveness of Intensive Sleep Retraining, a novel, short duration behavioural therapy in treating chronic primary insomnia. Seventeen consecutive volunteers from the general public (mean age = 39.1 years), meeting selection criteria for chronic primary insomnia participated in the treatment study. The study was performed as a case replication series. Assessment involved sleep diary, actigraph and questionnaire measures of sleep and daytime functioning for a period of 2 weeks prior to, immediately after, and 6 weeks following the treatment. Treatment involved a single night of sleep deprivation, facilitating short sleep latencies (mean: 6.9 min) to a series of 50 brief nap opportunities. Following treatment, Sleep Onset Latency significantly decreased by a mean of 30.5 min (SD = 28.3), Wake Time after Sleep Onset significantly decreased by a mean of 28 min (SD = 34.0), and Total Sleep Time significantly increased by 64.6 min (SD = 45.5). Significant improvements were also seen in the daytime functioning and psychological measures of fatigue and vigour, cognitive sleep anticipatory anxiety and self-efficacy for sleep. This brief therapy was effective in improving sleep and some daytime functioning and psychological questionnaire measures. These improvements were maintained up to 2 months following the treatment weekend. Further exploration of this brief therapy is needed, with larger, randomized, placebo-controlled trials over longer follow-up periods, and in comparison to other traditional therapies for insomnia.

Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients—a double-blind, randomized study

Classical hormone replacement therapy for hot flashes is contraindicated in breast cancer especially in endocrine responsive disease. In a double-blind, randomized phase III study, breast cancer patients suffering from hot flashes at least twice a day, who were not taking any medication against hypertension and depression received either clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks. The primary end point was defined as the frequency of hot flashes after 4 weeks of treatment. A self-reported 1-week hot flash and other symptom questionnaire were kept before the start of treatment until the end of treatment course. From April 2002 to October 2004, 80 patients were recruited of whom 64 were assessable for efficacy analyses. Thirty-three received clonidine and 31 venlafaxine, nine patients stopped early because of side-effects and seven withdrew consent. At the end of treatment week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes per day for those receiving clonidine (P = 0.025). Venlafaxine is significantly more effective in reducing the frequency of hot flashes in breast cancer patients than clonidine.

Effect of Topiramate on Plasma Concentrations of Clozapine, Olanzapine, Risperidone, and Quetiapine in Patients With Psychotic Disorders

To investigate the effect of topiramate on the steady-state plasma concentrations of the second-generation antipsychotics--clozapine, olanzapine, risperidone, and quetiapine--in patients with schizophrenia or bipolar disorder. Thirty-eight outpatients on long-term treatment with clozapine (250-500 mg/d, n = 10), olanzapine (10-20 mg/d, n = 12), risperidone (3-6 mg/d, n = 9), or quetiapine (200-600 mg/d, n = 7) received adjunctive topiramate, gradually titrated up to a final dosage of 200 mg/d for 6 weeks. Pharmacokinetic assessments were made at baseline and at the end of treatment weeks 4 and 8 at topiramate dosages of 100 and 200 mg/d, respectively. Plasma concentrations of clozapine and its metabolite (norclozapine), olanzapine, risperidone and its metabolite (9-hydroxy-risperidone), and quetiapine were not significantly modified during concomitant administration of topiramate. Adjunctive topiramate therapy was well tolerated in all groups. These findings indicate that topiramate, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of the new antipsychotics-clozapine, olanzapine, risperidone, and quetiapine.

Ribavirin induced hemolysis is haptoglobin dependent

sponsive to or relapsing after a minimum of 12 weeks of TIW interferon were enrolled in the North American RIBAHEP Study Group. Study subjects were randomized into the following treatment groups: DTIW received 1000 mgm ribavirin daily with 3 million units (MU) Intron A for 28 days followed by Intron A 3 MU for 44 additional weeks or TIW received 1000 mgm ribavirin daily with 3 MU Intron A TIW for 48 weeks. Results: Two hundred nine (209) of the enrolled patients have competed 48 weeks of treatment. Eighty-one (81) patients were HCV RNA negative at end of treatment week 12 (WI2R) and remained so at end of treatment week 48. Of this group twenty-five patients have completed follow-up week 24 with a sustained response rate (SR) of 80% (20/25). Twelve (12) patients who were HCV RNA positive at end of week 12 were negative at end of week 48 (LR). Eight (8) of these patients have completed follow-up week 24 with an SR of 50% (4/8). The following table compares characteristics of the above mentioned groups. Table: Observation: Comparison of week 12 responders and late responders suggests that LRs are more likely than WI2Rs to be patients with genotype I, who were not treated with daily interferon induction and/or who had no reduction of ribavirin dose. Though the number of patients evaluated for SR is small, it appears that LRs are less likely than WI2Rs to sustain their non-detectable HCV RNA status. Conclusions: eWeek 24 HCV RNA level is a better marker than week 12 HCV RNA level to identify patients who will clear HCV RNA after 48 weeks of combination therapy. eThe cumulative doses of interferon andlor ribavirin appear to be critical determinants in HCV RNA clearance, particularly in difficult to treat patients (i.e. those who are previous treatment non-responders or have HCV genotype I). elndividualization of treatment protocols based on the above observations may improve the individual outcome and over-all cost effectiveness of interferonlribavirin treatment.

Continuous accelerated irradiation (CAIR) of head and neck cancer – treatment technique, toxicity and 2-year results

Purpose Evaluation of preliminary (2-year) treatment results of 7 days a week continuous accelerated irradiation (CAIR) in compare to convectional and concomitant radiotherapy. Methods One hundred and twenty eight patients with squamous cell carcinoma of oral cavity, oroand hypopharynx and supraglottic larynx in stage T2-4 NO-1 MO were randomized between 3 groups: A (study-CAIR) – 51 pts, B (control-2) – 28 pts and treated by radiation therapy alone in 1994–96. In majority (81%) there were the patients in advanced clinical stage (T3+T4). Patient and tumour characteristic, radiation technique and volumes, total and fraction doses were exactly the same in 3 groups of patients. Only the overall treatment time was shorter by about 2 weeks in CAIR group comparing to control-1 because of the lack of weekend breaks. The overall treatment time in CAIR and control-2 group was exactly the same because in control-2 group the “CAIR weekend fractions” were given through the Tuesday and Fridays as a concomitant boost. Results One hundred twenty five patients (98%) completed the whole designed radiotherapy. Generally, 2-year local tumour control rate (LTCR) in CAIR arm was 87% and in control-1 and control-2 arms respectively 40% and 67% (p 75% vs 10% and 33% in oral cavity, 86% vs 36% and 70% in oropharynx, 88% vs 50% and 80% in hypopharynx and supraglottis; 100% vs 64% and 78% forT2, 94% vs 39% and 67% for T3, 66% vs 26% and 56% for T4. There were 14% of grade III and IV radiation morbidity in CAIR arm and 4% and 10% in control-1 arms respectively. Conclusion The hight effectivness of CAIR fractionation reflects the net effect of not only the simple shortening the overall treatment time by 2 weeks but also the exclusion treatment weekend breaks.

Prediction of attrition from day hospital treatment in lower socioeconomic cocaine-dependent men

This study attempted to identify predictors of completion of a 27 h/week 4-week day hospital program for cocaine dependence. The research subjects were 95 lower socioeconomic, primarily African American male veterans. Of a wide range of predictor variables available at baseline, including sociodemographic and historical information, Addiction Severity Index data, psychiatric diagnoses, SCL-90 measures, and measures of craving and familial alcoholism, only the cocaine urine toxicology result and self report of days of cocaine use in the past 30 days (log transformed) were significant predictors. The urine toxicology result was the more powerful predictor with 73% with a negative urine completing treatment, as contrasted with 36% with a positive urine. Three additional measures obtained at the end of treatment week 1 further increased ability to predict treatment completion/attrition. Two of these measures were based on counsellor ratings and one was based on the patient's report of psychiatric treatment services received during the first treatment week. Thus, patients at high risk for dropout can be identified fairly early. Whether treatments can be adapted to retain such patients is an important question for the field.

Relationship Between Concentrations of Adinazolam and Its Primary Metabolite in Plasma and Therapeutic/Untoward Effects in the Treatment of Panic Disorder

Adinazolam mesylate, a triazolobenzodiazepine with antidepressant and anxiolytic activity, has been shown in several studies to treat panic disorder effectively. This report presents the results of analysis of concentrations in plasma of adinazolam and its primary metabolite, N-desmethyladinazolam (NDMAD), determined as a part of a flexible-dose, double-blind study of the efficacy of adinazolam mesylate sustained release tablets in the treatment of panic disorder with agoraphobia. Dosages administered in the study were titrated from 30 mg/day up to a maximum of 120 mg/day. Concentrations in plasma were determined by high-performance liquid chromatography at clinical evaluations at the end of treatment weeks 1, 2, and 4. The concentrations of both compounds were proportional to the administered dose. An inverted U-shaped concentration-response curve was apparent, where response was based on a priori definitions contained in the study protocol. However, this was probably a result of the flexible-dose study design used. By use of the post hoc definitions of response, as measured by the Clinician's Global Improvement Scale and the total panic attack frequency, logistic regression analysis resulted in more adequate predictions of actual response frequencies. Results indicate that NDMAD contributes to the therapeutic effects of adinazolam mesylate sustained release tablets in the treatment of panic disorder. The exact contributions of adinazolam and NDMAD to response in panic disorder could not be determined, because of the correlation between adinazolam and NDMAD concentrations on multiple dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a Church-Based Sexuality Education Program for Adolescents

This study examines the effects of a shortterm church-based sex education program in relation to 3 program goals: increased sex information; heightened self-esteem; and clarity of personal sexual values. This church program was designed for adolescents in grades 9-12. Approximately 10 hours of information and discussion of sexual issues were contained in the shortterm program which can be implemented during a weekend. The programs purpose was to present a holistic view of sexuality that affirms the importance of people as sexual beings and encourages consideration of varying opinions values and consequences regarding sexual issues. The adolescents were encouraged to challenge sexual steroetypes and myths and to make responsible decisions regarding their own sexual choices. Experimental group subjects were selected from a population of high school age youth who attended a large Protestant church in a Dallas Texas suburb. All program participants taking the pretests and posttests were included in the experimental group for a total of 74 adolescents -- 49 females and 25 males. Control subjects were selected from a church of the same denomination and from the same geographic area as well as of similar size. All high school youth who attended Sunday school on the designated pretest date were asked to take the test. Posttests were adminstered to control group subjects on a Sunday afternoon 3 weeks after the treatment weekend. 41 control group subjects returned to take the posttest -- 26 females and 15 males. No significant change in the self-esteem variable was found. There was significant positive change in sex information and clarity of personal sexual values. Follow-up assessment would ascertain if the positive effects are maintained over time. The study data indicate that a shortterm church-based sexuality program for high school adolescents can have positive effects on sexual learning and clarity of personal sexual values.