Patient interest in acupuncture for smoking cessation: a survey.

BACKGROUND/OBJECTIVE: Tobacco use remains the leading cause of preventable death in the United States. The most widely available treatment options to assist patients in smoking cessation are limited by side effects and moderate efficacy at best. Acupuncture may be an effective option for smoking cessation. The goal of this study was to establish the need for and interest in acupuncture therapy to potentially assist with smoking cessation from a patient perspective. METHODS: We conducted a cross-sectional survey study among patients aged 18 years or older whose medical record reported current tobacco use with English as their preferred language. REDCap surveys were administered to patients during office visits and included questions regarding opinions and use of all treatments available for smoking cessation (including acupuncture) as well as perceived barriers to acupuncture treatment. RESULTS: A total of 57 surveys were distributed, and 42 (74%) were completed. Most patients reported previous attempts at quitting (76%) and had tried a variety of treatments including nicotine replacement (45%), Chantix (varenicline; 23%), Wellbutrin (bupriopion; 19%), "cold turkey" (65%) and hypnosis (3%). No respondents reported having tried acupuncture for smoking cessation. CONCLUSION: When comparing treatment options, patients reported more interest in acupuncture than other treatment options with a statistically significant difference in the level of interest between acupuncture and bupropion. All barriers (cost, time and effectiveness) were equally rated on a Likert-type scale with a median of 50 on a 101-point scale.

Kami-shoyo-san improves ASD-like behaviors caused by decreasing allopregnanolone biosynthesis in an SKF mouse model of autism.

Dysfunctions in the GABAergic system are associated with the pathogenesis of autism spectrum disorder (ASD). However, the mechanisms by which GABAergic system dysfunctions induce the pathophysiology of ASD remain unclear. We previously demonstrated that a selective type I 5α-reductase inhibitor SKF105111 (SKF) induced ASD-like behaviors, such as impaired sociability-related performance and repetitive grooming behaviors, in male mice. Moreover, the effects of SKF were caused by a decrease in the endogenous levels of allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor. In this study, we used SKF-treated male mice as a putative animal model of ASD and examined the effects of Kami-shoyo-san (KSS) as an experimental therapeutic strategy for ASD. KSS is a traditional Kampo formula consisting of 10 different crude drugs and has been used for the treatment of neuropsychiatric symptoms. KSS dose-dependently attenuated sociability deficits and suppressed an increase in grooming behaviors in SKF-treated mice without affecting ALLO content in the prefrontal cortex. The systemic administration of the dopamine D1 receptor antagonist SCH23390 reversed the ameliorative effects of KSS. On the other hand, the dopamine D2 receptor antagonist sulpiride and GABAA receptor antagonist bicuculline only attenuated the ameliorative effect of KSS on repetitive self-grooming behaviors. The present results indicate that KSS improves SKF-induced ASD-like behaviors by facilitating dopamine receptor-mediated mechanisms and partly by neurosteroid-independent GABAA receptor-mediated neurotransmission. Therefore, KSS is a potential candidate for the treatment of ASD.

Effects of varenicline, nicotine or placebo on depressive symptoms in postmenopausal smokers.

BACKGROUND: Varenicline carries a black box warning for neuropsychiatric adverse events. OBJECTIVE: We examined varenicline use and past history of major depressive disorder (MDD) on depressive symptoms during smoking cessation. METHOD: This is a secondary analysis of two smoking cessation studies in 152 postmenopausal women who received placebo or nicotine patch, or 78 women who received varenicline with relaxation. Lifetime history of MDD (LH-MDD) was assessed at baseline and women with current MDD were excluded. Center for Epidemiologic Study Depression scale (CESD) measured depressive symptoms at baseline, 6 and 12 weeks. RESULTS: Baseline CESD scores were 5.3 + 4.4. Those with a LH-MDD reported higher CESD scores (p > .001). Those taking varenicline reported lower scores over all time periods compared to nicotine or placebo (p < .01). The differences between varenicline and the other treatments remained when controlling for LH-MDD, indicating an independent effect. CESD scores were associated with concurrent smoking status (p < .001), and with withdrawal symptoms (p < .001). CONCLUSION: CESD score were lower in those receiving varenicline, whether this is due to an anti-depressant effect, subject selection, use of relaxation or another cause is unknown. Varenicline does not increase depressive symptoms during smoking cessation in postmenopausal women without current MDD. Subjects with a LH-MDD are susceptible to developing depressive symptoms during smoking cessation, regardless of pharmacologic aid. SCIENTIFIC SIGNIFICANCE: Pharmacologic aids did not increase depression symptoms in this select population of postmenopausal women without current depression. Smoking cessation does increase depressive symptoms in those with LH-MDD, though the degree of increase was not clinically meaningful.

Ivabradine in combination with metoprolol succinate in the treatment of inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or a disproportional increase in HR during exercise. ß-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to ß-blockers but in some patients its efficacy to resolve all IST-related symptoms is limited. The aim of the study was to assess the efficacy and safety of combining ivabradine with metoprolol succinate in patients with refractory highly symptomatic IST. METHODS: Twenty patients (36 ± 10 years; 16 women) with IST were enrolled. All patients received metoprolol succinate 95 mg single dose during the first month of the study. After 4 weeks of treatment with metoprolol, ivabradine was administered as adjuvant therapy up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed at baseline, after 4, and 8 weeks of the study, respectively. RESULTS: We observed significant and similar reduction in resting HR both for metoprolol and for combined therapy compared to the baseline. The mean HR during daily activity was significantly lower on ivabradine and metoprolol compared to monotherapy with ß-blocker. The combined treatment yielded a significant increase in exercise capacity as assessed by treadmill stress test. After 4 weeks of combined therapy a significant reduction in IST-related symptoms, measured by means of the European Heart Rhythm Association score, was observed. CONCLUSION: Combining ivabradine with metoprolol is an effective and well-tolerated treatment option for IST in patients with refractory to monotherapy.

Promoting smoking cessation.

Cigarette smoking causes significant morbidity and mortality in the United States. Physicians can use the five A's framework (ask, advise, assess, assist, arrange) to promote smoking cessation. All patients should be asked about tobacco use and assessed for motivation to quit at every clinical encounter. Physicians should strongly advise patients to quit smoking, and use motivational interviewing techniques for patients who are not yet willing to stop smoking. Clinical contacts with unmotivated patients should emphasize the rewards and relevance of quitting, as well as the risks of smoking and anticipated barriers to abstinence. These messages should be repeated at every opportunity. Appropriate patients should be offered pharmacologic assistance in quitting, such as nicotine replacement therapies, bupropion, and varenicline. Use of pharmacologic support during smoking cessation can double the rate of successful abstinence. Using more than one type of nicotine replacement therapy ("patch plus" method) and combining these therapies with bupropion provide additional benefit. However, special populations pose unique challenges in pharmacotherapy for smoking cessation. Nicotine replacement therapies increase the risk of birth defects and should not be used during pregnancy. They are usually safe in patients with cardiovascular conditions, except for those with unstable angina or within two weeks of a coronary event. Varenicline may increase the risk of coronary events. Nicotine replacement therapies are safe for use in adolescents; however, they are less effective than in adults. Physicians also should arrange to have repeated contact with smokers around their quit date to reinforce cessation messages.

[Alternative therapy with ivabradine in patients with functional class III chronic heart failure].

Aim of the study - to determine efficacy of therapy with the use of ivabradine in patients with functional class (FC) III chronic heart failure (CHF) on the basis of assessment of its action on regulatory adaptive status (RAS). We included into the study 100 patients with FC III CHF at the background of ischemic heart disease (IHD) and/or stage III hypertensive disease (HD) receiving complex therapy (quinapril, torasemide, spironolactone). After randomization group 1 comprised 56 patients (age 62.9+/-1.8 years) who were prescribed slow release metoprolol succinate (59.1+/-4.5 mg/day). Group 2 comprised 44 patients (age 59.4+/-1.3 years) who were prescribed If channel inhibitor ivabradine (12.1+/-2.3 mg/day) if beta-blocker use was not possible. Examination at baseline and in 6 months included treadmillometry with assessment of maximal oxygen consumption (VO2 max) at exercise, echocardiography, 24-hour blood pressure monitoring, measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood plasma. For objective qualitative assessment of the state of RAS we used a test of cardio-respiratory synchronism. Therapy with the use of ivabradine improved structural and functional state of the myocardium, elevated tolerance to exercise, caused positive changes of NT-proBNP concentration in blood plasma and VO2 max at exercise. Thus ivabradine probably can serve as alternative to -adrenoblockers when their use is not possible patients with FC III CHF at the background of IHD and/or stage III HD.

Tolvaptan for the treatment of hyponatremia and congestive heart failure.

Vasopressin plays a central role in regulating body fluid homeostasis, serum osmolality and vascular tone. In response to elevated serum osmolality, vasopressin acts on V2 renal receptors increasing water reabsorption and causing serum sodium to decrease. Pathological conditions characterized by abnormally elevated vasopressin levels such as heart failure (HF) or syndrome of inappropriate antidiuretic hormone (SIADH) can result in hyponatremia. Tolvaptan is a new selective nonpeptide vasopressin V2 receptor antagonist that has shown to rapidly normalize serum sodium concentrations in hyponatremic patients. In patients with congestive heart failure (CHF) and symptoms of volume overload, tolvaptan prompted rapid free water elimination and improved short-term signs and symptoms of HF, although no effect on long-term mortality or HF-related morbidity was observed. Data from phase III studies including over 5,000 patients have demonstrated that tolvaptan is a safe and well tolerated vasopressin receptor antagonist, whose long-term use is not associated with adverse outcomes. Tolvaptan has been recently approved for the treatment of hyponatremia and a marketing authorization application has been filed for the treatment of CHF.

Cross-validation of a new procedure for early screening of smoking cessation medications in humans.

Brief procedures for evaluating medication efficacy may reveal which candidate drugs warrant further testing in clinical trials and which do not. We previously carried out a study of smoking abstinence, involving the nicotine patch, and established the sensitivity of our procedure. In this study, we sought to cross-validate our earlier work by comparing short-term smoking abstinence due to varenicline (relative to placebo) in smokers with high intrinsic quit interest (n = 57) and those with low intrinsic quit interest (n = 67). All the subjects were randomly assigned to either abstinence reinforcement ($12/day) or no reinforcement. In a crossover design, all the subjects participated in two 3-week phases: ad libitum smoking (week 1), dose run-up of varenicline (1.0 mg b.i.d.) or placebo (week 2), and quit attempt on medication verified daily by carbon monoxide <5 ppm (week 3). As with the nicotine patch in the previous study, varenicline (relative to placebo) increased abstinence more effectively in those with high intrinsic quit interest than in those with low quit interest but did not affect abstinence due to reinforcement. These data confirm the feasibility of a brief, sensitive test of the efficacy of cessation medications in smokers with high quit interest.

Are nicotine replacement therapy, varenicline or bupropion options for pregnant mothers to quit smoking? Effects on the respiratory system of the offspring.

Nicotine occurs in tobacco smoke. It is a habit-forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the antioxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastically increased AMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mother's milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals exposed to nicotine via the placenta and mother's milk, and thus during phases of lung development characterized by rapid cell division, is likely due to 'programming' induced by nicotine. Since varenicline, a partial nicotine agonist, has basically the same structure as nicotine, and also binds to acetylcholine receptors in competition with nicotine (but with largely the same effect), it is not advisable to use nicotine or varenicline during gestation and lactation. Furthermore, the use of individual vitamin supplements is also not advisable because of the negative impact on the program that controls maintenance of lung structural and functional integrity and aging. A more appropriate smoking cessation program will also include a mixture of antioxidant nutrients such as in tomato juice.

The effects of high-dose amlodipine/benazepril combination therapies on blood pressure reduction in patients not adequately controlled with amlodipine monotherapy.

BACKGROUND: This study compared the efficacy and safety of amlodipine/benazepril (10/40 mg/day and 10/20 mg/day) with amlodipine 10 mg/day in patients whose blood pressure (BP) was not adequately controlled with amlodipine monotherapy. METHODS: After a lead-in period with amlodipine monotherapy, 812 non-responder patients (mean sitting diastolic BP > or =95 mmHg) were randomized to one of three treatment groups. Ambulatory BP monitoring was conducted in 276 patients. RESULTS: Treatment with amlodipine/benazepril 10/40 mg/day and 10/20 mg/day resulted in a decrease of mean sitting systolic and mean sitting diastolic BP by 13.3/12.7 mmHg and 12.1/11.6 mmHg, respectively, compared with monotherapy (6.6/8.5 mmHg) (p < 0.0001). Both combinations resulted in more responders than monotherapy (74% and 65% vs. 54%; p < 0.0001 and p < 0.0085, respectively). Amlodipine/benazepril 10/40 mg/day and 10/20 mg/day decreased ambulatory systolic and diastolic BP by 9.9/6.7 mmHg and 7.4/5.2 mmHg compared with monotherapy (p < 0.0001). The incidence of pedal edema was lower in the amlodipine/benazepril combinations compared with monotherapy (4.5%, 5.5% vs. 9.2%, respectively, p=NS). No significant metabolic side-effects were noted among the combination groups. CONCLUSION: Amlodipine/benazepril combinations were well tolerated and resulted in significant BP reductions and better BP responder rates than amlodipine monotherapy.

An open-label, randomized, controlled, 4-week comparative clinical trial of barnidipine hydrochloride, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in Chinese patients with renal parenchymal hypertension.

This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

BACKGROUND: Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. OBJECTIVE: The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. METHODS: A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. RESULTS: Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. CONCLUSIONS: Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination of amlodipine/ benazepril can be successfully accomplished in the majority of patients.

Effect of obesity and feeding on the growth hormone (GH) response to the GH secretagogue L-692,429 in young men.

GH secretion and the response to GH secretagogues are significantly diminished in obese individuals. Previous studies have shown that L-692,429 (L), a nonpeptide mimetic of GH-releasing peptide, selectively stimulates GH release in normal young men and in the elderly, who also have diminished GH secretion. A paired, two-site study examined the effects of L on GH release in 12 healthy obese (part A; mean +/- SD: age, 26.1 +/- 3.3 yr; body mass index, 35.0 +/- 3.1 kg/m2) and 10 nonobese (part B; age, 22.2 +/- 2.3 yr; body mass index, < or = 27.0) young men. In part A, placebo, low dose L (0.2 mg/kg), or high dose L (0.75 mg/kg) was administered iv over 15 min on 3 separate occasions after an overnight fast. Samples for GH, PRL, and cortisol determinations were obtained every 15 min. GH release (mean +/- SE) was significantly increased by both doses of L compared to the effect of placebo: 12.6 +/- 1.8 micrograms/L (low dose), 18.5 +/- 2.7 micrograms/L (high dose), and 0.84 +/- 0.1 microgram/L (placebo), respectively (P < 0.05). In a subset of 6 obese men, in samples collected every 5 min, the GH response to both doses of L was significantly greater than that to 1 microgram/kg GHRH. To compare the response to low dose L in the obese and to determine the effects of feeding on this response, 0.2 mg/kg L was administered as described in part A to nonobese young men after an overnight fast (fasted) or a standardized breakfast (fed; part B). Low dose L was an effective GH secretagogue in nonobese young men; however, this effect was attenuated with feeding [43.6 +/- 7.9 (fasted) vs. 17.7 +/- 4.8 (fed) micrograms/L]. Of note, the response to low dose L in fasted obese individuals was similar to that in fed nonobese individuals. The administration of L was well tolerated in both groups. We conclude that L is an effective GH secretagogue in obese and nonobese young men and may have therapeutic benefits when administered to relative (obese or elderly) or absolute GH-deficient individuals.

Effects of benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, on blood pressure in patients with hypertension.

OBJECTIVE: To assess the efficacy and safety of several combinations of benazepril, an angiotensin-converting enzyme inhibitor, and hydrochlorothiazide, as compared with placebo, in the treatment of patients with essential hypertension. DESIGN: A 6-week, randomized, double-blind, parallel study conducted at 24 centers. A placebo run-in period of 1 to 4 weeks preceded the double-blind phase. PARTICIPANTS AND SETTING: Male and female outpatients, aged 18 years and older, were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase. Among the 334 patients who entered the double-blind phase, 17% were aged 65 years or older and 26% were black. Eleven patients withdrew because of adverse experiences, including two patients receiving placebo. INTERVENTIONS: Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg; or combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg, 10/12.5 mg, 20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks. MAIN OUTCOME MEASURES: The mean change from baseline in sitting diastolic blood pressure at end point (last postrandomization measurement carried forward) in the double-blind phase. Combination therapy with benazepril/hydrochlorothiazide, 20/25 mg, was compared with benazepril, 20 mg alone, and hydrochlorothiazide, 25 mg alone. Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated. RESULTS: Compared with placebo, all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point. In the benazepril/hydrochlorothiazide, 20/25 mg, group, the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups (benazepril, 20 mg, P < or = .05; hydrochlorothiazide, 25 mg, P < or = .001) alone. All therapies were generally well tolerated. Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy. CONCLUSION: Benazepril in combination with hydrochlorothiazide, including a low-dose combination of 5/6.25 mg, is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension.

Addition of zatebradine, a direct sinus node inhibitor, provides no greater exercise tolerance benefit in patients with angina taking extended-release nifedipine: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The Zatebradine Study Group.

OBJECTIVES: We examined the antianginal and anti-ischemic effects of oral zatebradine, a direct sinus node inhibitor that has no blood pressure-lowering or negative inotropic effects in patients with chronic stable angina pectoris taking extended-release nifedipine. BACKGROUND: Heart rate reduction is considered an important pharmacologic mechanism for providing anginal pain relief and anti-ischemic action in patients with chronic stable angina, suggesting a benefit for sinus node-inhibiting drugs. METHODS: In a single-blind placebo run-in, randomized double-blind, placebo-controlled, multicenter study, patients already receiving extended-release nifedipine (30 to 90 mg once a day) were randomized to receive zatebradine (5 mg twice a day [n = 64]) or placebo (n = 60). All subjects had reproducible treadmill exercise-induced angina at baseline, and after randomization they performed a serial exercise test 3 h after each dose for 4 weeks. RESULTS: Zatebradine reduced rest heart rate both at 4 weeks ([mean +/- SEM] 12.9 +/- 1.23 vs. 2.3 +/- 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 +/- 1.2 vs. 3.4 +/- 1.2 [placebo] beats/min, p < 0.0001). Despite the significant effects on heart rate at rest and exercise, there were no additional benefits of zatebradine from placebo baseline in measurements of total exercise duration, time to 1-mm ST segment depression or time to onset of angina. Subjects taking zatebradine also had more visual disturbances as adverse reactions. CONCLUSIONS: Zatebradine seems to provide no additional antianginal benefit to patients already receiving nifedipine, and it raises questions regarding the benefit of heart rate reduction alone as an antianginal approach to patients with chronic stable angina.