Lenalidomide and dexamethasone in treatment of patients with relapsed and refractory multiple myeloma - analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies.

Lenalidomide (LEN) is an immunomodulator with clinical activity against myeloma cells. Based on the pivotal phase 3 trials MM-009 and MM010, the combination of lenalidomide and dexamethasone(DEX) was approved for patients with multiple myeloma who received at least one prior therapy. Here, we evaluated LEN/DEX therapy in unselected population and subsequently in selected sub-groups of patients with relapsed/refractory multiple myeloma followed in the Registry of Monoclonal Gammopathies of the Czech Myeloma Group. Altogether 858 patients were treated with LEN/DEX in the Czech Republic and Slovakia until end of 2017. The analyzed sub-groups were defined as patients with high risk cytogenetic aberrations and patients with relapsed and refractory MM. The overall response rate (ORR; partial remission or better response, PR) in the whole group of patients was 46.3% for all lines of therapy, 26.4% for high-risk group and 32.1% for relapsed and refractory group. Medians of overall survival (OS) in the same cohorts were as follows: 25.6, 15.7 and 18.5 months, progression free survival (PFS) was: 11.2, 6.4 and 9.0 months respectively. The most common adverse events were hematologic and infectious. In conclusion we found that our results correlated with those found in other studies in terms of response rates, survival measures, and also of treatment toxicity.

SNPs within CHRNA5-A3-B4 and CYP2A6/B6 are associated with smoking dependence but not with tobacco dependence treatment outcomes in the Czech population.

PURPOSE: Tobacco/nicotine dependence has a significant heritable component. Genome-wide association studies have associated the single nucleotide polymorphisms (SNPs) rs578776, rs16969968, rs6474412, rs3733829 and rs4105144 with nicotine dependence in Western European populations. We examined whether these SNPs influence nicotine dependence and successful treatment of tobacco dependence in the Czech middle-European population. MATERIALS AND METHODS: Variants were analysed by PCR-RFLP or by TaqMan assay in 807 adult heavy tobacco-dependent smokers - patients of the Centre for Treatment of Tobacco Dependence (Prague) as well as 1,362 self-reported non-smokers. RESULTS AND DISCUSSION: Except for rs3733829, association with tobacco dependence was confirmed for all other genetic variants. In agreement with previous studies, the strongest determinant of tobacco dependence was rs16969968 with OR (95%CI) 1.32 (1.08-1.62) for A allele carriers vs. GG comparison (P=0.003). In contrast, none of the analysed variants reached significance with respect to a 1-year course of successful tobacco dependence treatment (all P over 0.18) in a subset of 525 patients. CONCLUSION: We confirmed the association between variants within genes that code nicotinic-acetylcholine receptors (-A3, -A5 and -B3), CYP2A6/B6 and tobacco dependence development in the Czech population. The success of the tobacco dependence treatment was not influenced by the analysed SNPs.

No change in serum incretins levels but rise of leptin levels after smoking cessation: a pilot study.

The mechanisms behind the changes of body weight after smoking cessation are only partially understood. To this end, we explored the possible effects of smoking cessation on incretin hormones, leptin and selected anthropometric, biochemical and other hormonal parameters. Twenty-two non-obese male adult smokers attending an ambulatory smoking cessation program in Prague, Czech Republic, were examined at the baseline. Thirteen patients (mean age 37.92+/-2.66 years, mean body mass index 25.56+/-0.69 kg/m(2)) successfully quit smoking and were examined three months after smoking cessation; relapsed smokers were not followed up. The patients underwent 2-h liquid meal test with Fresubin and repeated blood sampling for measurements of blood glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide 1 (GLP-1), amylin, insulin, leptin, peptide-YY (PYY) and pancreatic polypeptide (PP). Three months after smoking cessation, body weight increased (4.35+/-3.32 kg, p<0.001). Leptin levels increased significantly in all repeated samples, while levels of GIP, GLP-1, amylin, insulin, PYY and PP remained unchanged. In conclusions, smoking cessation increased leptin levels probably owing to weight gain while it did not influence incretin levels.

The steroid spectrum during and after quitting smoking.

Addiction to tobacco results in an imbalance of endocrine homeostasis in both sexes. This can also have impacts on fertility problems. The male reproductive system is less susceptible than that of females, with a worsening spermiogram in smokers, the most cited effect in the literature. However, the literature is inconsistent as to the effects of smoking on steroid hormone levels in men, and there is very little data on the effects of quitting smoking in men. In this study we followed 76 men before quitting smoking, and then after 6, 12, and 24 weeks and 1 year of abstinence. We measured basic anthropomorphic data and steroid hormone levels along with steroid neuroactive metabolites using GC-MS. We demonstrate lower androgen levels in men who smoke, and these changes worsened after quitting smoking. There was a drop in SHBG already in the first week of non-smoking, and levels continued to remain low. Male smokers have lower androgen levels compared to non-smokers. The lower the initial level of androgen, the lower the likelihood of success in quitting smoking. Changes in steroid hormones proved to be a promising marker for the prediction of success in quitting smoking.

Tobacco dependence, the most important cardiovascular risk factor: treatment in the Czech Republic.

Smoking is the most important cardiovascular (CV) risk factor. Stopping smoking halves the CV risk. Every clinician should provide a brief intervention with smokers. Intensive treatment should be available to those who need it. There are 37 Centers for Tobacco Dependence in the Czech Republic, which offer treatment including a psychobehavioral intervention and pharmacotherapy (varenicline, nicotine, bupropion). Czech physicians, pharmacists and nurses are regularly educated about smoking cessation. We describe the results of intensive treatment offered by our centers. Treatment includes screening (1 h), an intervention (2 h), and follow-up visits during the next 12 months. Among 3532 patients, 34.3 % had CO-validated abstinence at 12-months (including 489 patients who attended the screening visit + only the 12-month follow up visit). Among patients who underwent the intervention, the abstinence rate was 38.2 %. The majority of patients who underwent the intervention (N=2470) used some form of pharmacotherapy. After one year, the abstinence rate was 43.4 %, compared to 15.9 % (N=573) without pharmacotherapy. Only 28 % of patients came on the recommendation of a physician. Despite the decrease in CV risk following smoking cessation and the effectiveness of treatment, centers are underutilized.

[Smoking and postoperative complications]. / Kourení a pooperacní komplikace.

INTRODUCTION: Smoking has a negative impact on the outcome of surgical procedures. Smoking leads to higher risk of postoperative complications and it delays wound healing. MATERIALS AND METHODS: We observed pulmonary complications, wound healing complications, and the length of the postoperative hospitalization period of 877 patients admitted for elective surgery.. Patients were divided according to their smoking status in to 3 groups: the current smokers were 32% (279/877), the former smokers 31% (274/877) and the non-smokers 37% (324/877). RESULTS: Pulmonary complications occurred more frequently in the smoking group (3.9%) compared to the non-smoking group (0.9%), p<0,001. The incidence of wound infections was 7.5% in the smoking group compared to 4.6% in the non-smoking group. Wound dehiscence occurred in 3.6% patients in the smoking group, respectively 2.8% in the non-smoking group, without statistical significance. The number of postoperative hospitalisation days was 3 days for both smokers and non-smokers, but it decreased inversely to number of smoke-free days before the surgery for those who stopped smoking: those abstinent for 31-90 days were hospitalized for 7.0 days, those abstinent for 91-183 were hospitalized for 5.5 days, and for those abstinent over 184 days the postoperative hospitalization was, again, 3 days. Among the current smokers, 93% preferred to stay smoke-free after the surgery. CONCLUSIONS: Our results support better surgery outcomes for non-smokers. However, our sample was not large enough to assess the impact of the number of preoperative smoke-free days. An elective surgery seems to be an unused occasion to motivate smokers to stop smoking, preferably, as soon as possible before the surgery date.

Czech adolescent smokers: unhappy to smoke but unable to quit.

OBJECTIVE: To assess the prevalence of tobacco dependence among adolescents in the Czech Republic in 2010, their willingness to quit and knowledge about quitting options. METHODS: Primary, intermediate and secondary school students completed an anonymous questionnaire on tobacco use during a smoking prevention class, with a response rate of 100%. RESULTS: Of 1420 anonymous questionnaires analysed, 66.8% (n = 949) of respondents had ever tried smoking. More were from smoking (50.4%) than non-smoking (49.6%) families; there were no differences in sex. Most student smokers had experimented with cigarettes (94.6%), cigars (8%), marihuana cigarettes (4.6%) and water pipes (1.9%). At the time of the survey, 52.9% (520/949) of those who had ever tried smoking were current smokers, 30.3% smoked daily, 18.3% weekly and 4.2% less frequently. Only 20.5% of smokers had not considered quitting, and 66.9% had tried unsuccessfully to quit. Withdrawal symptoms were experienced by 24.5% (123/502) of the current smokers, indicating a high level of nicotine dependence in this age group. The majority (346/467, 74.1%) of the current smokers said they would stop smoking immediately on their own. Only a few would seek help at a pharmacy (4.9%), 3.4% would ask their doctor and 1.7% their parents. CONCLUSIONS: Tobacco dependence is prevalent among Czech adolescents. The majority of smokers wanted to stop, but knowledge about smoking cessation and quitting assistance offered to smokers was low.

Effects of smoking cessation on hormonal levels in men.

Chronic smoking can cause imbalance in endocrine homeostasis and impairment of fertility in both sexes. The male reproductive system is more resilient, still the literature provides conflicting results about the influence of smoking on the steroid hormone levels. The data about smoking cessation are limited; there has not yet been a study primarily focused on changes in steroids levels. In our study, we analyzed levels of testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), cortisol and sex hormone-binding globulin (SHBG) in male smokers and during smoking cessation. Monitored analytes were determined by RIA. The free testosterone index was calculated. Basal samples of men successful and unsuccessful in smoking cessation did not differ and monitored hormones could hardly predict success of smoking cessation. After one year without smoking, a significant BMI increase and SHBG decrease in former smokers was observed. The decrease in total testosterone was non-significant. Changes in SHBG and testosterone did not correlate with BMI, presumably due to the direct effect of smoking cessation.

Chronic cigarette smoking alters circulating sex hormones and neuroactive steroids in premenopausal women.

Chronic smoking alters the circulating levels of sex hormones and possibly also the neuroactive steroids. However, the data available is limited. Therefore, a broad spectrum of free and conjugated steroids and related substances was quantified by GC-MS and RIA in premenopausal smokers and in age-matched (38.9+/-7.3 years of age) non-smokers in the follicular (FP) and luteal phases (LP) of menstrual cycle (10 non-smokers and 10 smokers, in the FP, and 10 non-smokers and 8 smokers in the LP). Smokers in both phases of the menstrual cycle showed higher levels of conjugated 17-hydroxypregnenolone, 5alpha-dihydroprogesterone, conjugated isopregnanolone, conjugated 5alpha-pregnane-3beta,20alpha-diol, conjugated androstenediol, androstenedione, testosterone, free testosterone, conjugated 5alpha-androstane-3alpha/beta,17beta-diols, and higher free testosterone index. In the FP, the smokers exhibited higher levels of conjugated pregnenolone, progesterone, conjugated pregnanolone, lutropin, and a higher lutropin/follitropin ratio, but lower levels of cortisol, allopregnanolone, and pregnanolone. In the LP, the smokers exhibited higher levels of free and conjugated 20alpha-dihydropregnenolone, free and conjugated dehydroepiandrosterone, free androstenediol, 5alpha-dihydrotestosterone, free and conjugated androsterone, free and conjugated epiandrosterone, free and conjugated etiocholanolone, 7alpha/beta-hydroxy-dehydroepiandrosterone isomers, and follitropin but lower levels of estradiol and sex hormone binding globulin (SHBG) and lower values of the lutropin/follitropin ratio. In conclusion, chronic cigarette smoking augments serum androgens and their 5alpha/beta-reduced metabolites (including GABAergic substances) but suppresses the levels of estradiol in the LP and SHBG and may induce hyperandrogenism in female smokers. The female smokers had pronouncedly increased serum progestogens but paradoxically suppressed levels of their GABA-ergic metabolites. Further investigation is needed concerning these effects.

Higher levels of salivary alpha-amylase predict failure of cessation efforts in male smokers.

The ability to predict the success or failure of smoking cessation efforts will be useful for clinical practice. Stress response is regulated by two primary neuroendocrine systems. Salivary cortisol has been used as a marker for the hypothalamus-pituitary-adrenocortical axis and salivary alpha-amylase as a marker for the sympathetic adrenomedullary system. We studied 62 chronic smokers (34 women and 28 men with an average age of 45.2+/-12.9 years). The levels of salivary cortisol and salivary alpha-amylase were measured during the period of active smoking, and 6 weeks and 24 weeks after quitting. We analyzed the men separately from the women. The men who were unsuccessful in cessation showed significantly higher levels of salivary alpha-amylase over the entire course of the cessation attempt. Before stopping smoking, salivary cortisol levels were higher among the men who were unsuccessful in smoking cessation. After quitting, there were no differences between this group and the men who were successful in cessation. In women we found no differences between groups of successful and unsuccessful ex-smokers during cessation. In conclusions, increased levels of salivary alpha-amylase before and during smoking cessation may predict failure to quit in men. On the other hand, no advantage was found in predicting the failure to quit in women. The results of our study support previously described gender differences in smoking cessation.

Home and workplace smoking bans in Italy, Ireland, Sweden, France and the Czech Republic.

The purpose of this study was to report predictors and prevalence of home and workplace smoking bans in five European countries. We conducted a population-based telephone survey of 4,977 females, ascertaining factors associated with smoking bans. Odds ratios and 95% confidence intervals were derived using unconditional logistic regression. A complete home smoking ban was reported by 59.5% of French, 63.5% of Irish, 61.3% of Italian, 74.4% of Czech and 87.0% of Swedish females. Home smoking bans were associated with younger age and being bothered by secondhand smoke, and among smokers, inversely associated with greater tobacco dependence. Among nonsmokers, bans were also related to believing smoking is harmful (OR 1.20, 95% CI 1.11-1.30) and having parents who smoke (OR 0.62, 95% CI 0.52-0.73). Workplace bans were reported by 92.6% of French, 96.5% of Irish, 77.9% of Italian, 79.1% of Czech and 88.1% of Swedish females. Workplace smoking bans were reported less often among those in technical positions (OR 0.64, 95% CI 0.50-0.82) and among skilled workers (OR 0.53, 95% CI 0.32-0.88) than among professional workers. Workplace smoking bans are in place for most workers in these countries. Having a home smoking ban was based on smoking behaviour, demographics, beliefs and personal preference.

Smoking prevention at Prague basic schools.

Tobacco smoking is the most prevalent preventable cause of morbidity and mortality worldwide. Tobacco dependence is a paediatric disease: the majority of smokers light their first cigarette before they reach the age of 18. The paper evaluates anonymous questionnaires collected during 55 seminars at basic schools in Prague during 2006, where 776 students of the 3rd-9th classes took part. Lectors were specially trained medical students (4th and higher year of study) from three Medical Faculties in Prague, who additionally had experiences working as consultants of the Czech Quitline. The given structure of smoking prevention seminars is described. Almost half of children in the age of 8-15 years had some experience with smoking: 45.6% of girls (170/372) and a 47.9% of boys (189/394). Mean age of the first cigarette was 9.95 (SD 3.6) years. Those alarming data should lead to adoption of effective tobacco control measures in the society.

[New tobacco dependence drug: Varenicline, partial agonist of alpha4beta2 acetylcholine-nicotine receptors]. / Nový lék závislosti na tabáku: varenicline, parciální agonista alpha4beta2 acetylcholin-nikotinových receptoru.

Most of adult smokers, up to 80 % in the Czech Republic, would prefer to stop smoking and about 40 % of them try to stop each year. Most often they stop just cold turkey and this means 98 % of them relapsing until one year. Maximum efficacy of intensive currently available treatment is about 20-25 %, so also 75-80 % intensive treated smokers relaps within one year. Available and effective treatment of tobacco dependence would influence significantly morbidity and mortality. Although we cannot expect miracle, new medication varenicline, parcial agonist of alpha4beta2 acetylcholin-nicotine receptors, seems to contribute to both to a bit higher efficacy, as well as to "medicalization" of tobacco dependence and increased availability of specialized treatment services.

[Scale for tobacco evaluation in different countries]. / Skála hodnocení kontroly tabáku v jednotlivých zemích.

Tobacco causes worldwide over five millions of death, in 2050 it is expected to die over five hundred millions, in the Czech Republic eighteen thousand people die for diseases related to tobacco, in average 15 years earlier then no smokers. Systematic tobacco control is therefore necessary both in individual countries and worldwide. Tle desribed scale serves to its comparison in different countries.

Smoking and pregnancy: prevalence, knowledge, anthropometry, risk communication.

Information about smoking impact on pregnancy as well as clear advice to stop and a treatment offer should be included into the health care of pregnant women. We contacted them within the first 3 days after delivery. In the sample of 265 women 23.8% (63/265) smoked during their pregnancy (51.9% with basic education only, 25.8% with high school and 5.0% with university education), and 7% of the sample (19/265) did not quit by the delivery. Only 68% of smokers (43/63) were asked about their smoking habits during the pregnancy by their gynaecologist, and both smokers and non-smokers had insufficient information about the impact of smoking on their baby (40% of smokers and 32% of non-smokers had no idea at all), the doctor was the source of this kind of information only in 5% (13/265) cases. Smokers' children had a lower average birth weight (3.084 g in smokers vs. 3.325 g in non-smokers, p=0.02) and were smaller (49.3 cm vs. 50.5 cm respectively, p=0.02). Smokers' bodyweight increased more than non-smokers' during their pregnancy (gaining 14.8 kg vs. 12.9 kg respectively, p=0.02), they also underwent the delivery at a lower age (27.6 vs. 30.0 years respectively, p<0.01) and after a non-significantly shorter duration of pregnancy (38.7 weeks vs. 39.0 weeks respectively, p=0.53). If 23.8% of pregnant women smoke and 90.6% of them would like to stop, it is a missed opportunity for education and treatment of tobacco dependence by their physicians.

[Czech medical doctors and World No Tobacco Day on May 31, 2005]. / Cestí lékari a Svetový den bez tabáku--31.kvetna 2005.

WHO declares the 31st May each year as the World No Tobacco Day. This year "Health Professionals and Tobacco Control" paid attention to prevention and effective treatment of the pandemic of tobacco dependence. Concerning the treatment, the role of physicians is crucial. At this occasion and in cooperation with the Czech Medical Association J.E.P. new treatment guidelines were published, support of all seven Medical Faculties to the Code of Practice in Tobacco Control was declared and the Czech version of the database www.treatobacco.net was introduced.

[Telephone hotlines as a part of complex services for tobacco dependence treatment]. / Telefonní linky jako soucást komplexní nabídky sluzeb pro odvykání kourení.

Telephone quitlines for smoking cessation should be included into the available tobacco dependence treatment and should be included into smoking cessation guidelines. Telephone quitlines does not mean only the help to the calling smoker, but also can increase the number of quit attempts in the general population. Especially minorities that not so often take part in the classic smoking cessation treatment, use quitlines more often (e.g. pregnant women). Quitlines are economically effective, although the most expensive form - individual counselling - should be reserved for those really willing to stop. Quitlines should be given governmental financial support (compared to other medical interventions, any smoking cessation treatment is economically more cost effective).

[Recommendations for the treatment of tobacco dependence]. / Doporucení pro lécbu závislosti na tabáku.

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

[ABC of smoking cessation. Use of simple advice and behavioural support]. / Abeceda odvykání kourení. Krátká rada a behaviorální podpora.

The most effective methods of helping smokers to quit smoking combine pharmacotherapy (such as nicotine or bupropion) with advice and behavioural support. These two components contribute about equally to the success of the intervention. Doctors and other health professionals should therefore be familiar with what these strategies offer, encourage smokers to use them, and be able at least to provide simple advice and behavioural support to smokers. They also need to be familiar with other sources of support, such as written materials, telephone help-lines, and strategies for preventing relapses. This article focuses on non-pharmacological interventions.

[The doctors' guide to the WHO framework convention on tobacco control]. / Lékaruv pruvodce Rámcovou úmluvou o kontrole tabáku.

Tobacco is one of the greatest threats to human health. Doctors and their professional associations have a vital role in reducing illness and death from tobacco. But tobacco control is not just an issue for doctors. Meaningful regulation of the tobacco industry is needed. The WHO Framework Convention on Tobacco Control aims to protect the public against the global spread of tobacco. This review sets out the main provisions of the Framework Convention, and its implications for governments and for the medical profession.