Predicting smoking cessation and its relapse in HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: The aim of the study was to assess whether prospective follow-up data within the Swiss HIV Cohort Study can be used to predict patients who stop smoking; or among smokers who stop, those who start smoking again. METHODS: We built prediction models first using clinical reasoning ('clinical models') and then by selecting from numerous candidate predictors using advanced statistical methods ('statistical models'). Our clinical models were based on literature that suggests that motivation drives smoking cessation, while dependence drives relapse in those attempting to stop. Our statistical models were based on automatic variable selection using additive logistic regression with component-wise gradient boosting. RESULTS: Of 4833 smokers, 26% stopped smoking, at least temporarily; because among those who stopped, 48% started smoking again. The predictive performance of our clinical and statistical models was modest. A basic clinical model for cessation, with patients classified into three motivational groups, was nearly as discriminatory as a constrained statistical model with just the most important predictors (the ratio of nonsmoking visits to total visits, alcohol or drug dependence, psychiatric comorbidities, recent hospitalization and age). A basic clinical model for relapse, based on the maximum number of cigarettes per day prior to stopping, was not as discriminatory as a constrained statistical model with just the ratio of nonsmoking visits to total visits. CONCLUSIONS: Predicting smoking cessation and relapse is difficult, so that simple models are nearly as discriminatory as complex ones. Patients with a history of attempting to stop and those known to have stopped recently are the best candidates for an intervention.

Sentinel lymph node involvement and a high Breslow index are independent factors of risk for early relapse of melanoma.

AIM: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated prospectively and compared with other known risk factors of relapse in early stage melanoma. METHODS: Surgery was guided by lymphoscintigraphy, blue dye and gamma probe detection. SLN were analysed by haematoxylin eosin (HE) histochemistry and multimarker immunohistochemistry (IHC). Disease free survival (DFS) was evaluated with Kaplan-Meier plots according to different parameters and Cox analyses of variance. RESULTS: From 210 patients a total of 381 SLN were excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow-up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for early relapse (p < 0.0005) were SLN positivity and a high Breslow index. CONCLUSION: SLN tumour positivity is an independent factor of high risk for early relapse with a higher power of discrimination than the Breslow index.

Blunted glucose-induced thermogenesis in 'overweight' patients: a factor contributing to relapse of obesity.

Glucose-induced thermogenesis was studied in 12 overweight patients (9F and 3M) before (mean body weight +/- s.e.m. 83 +/- 2 kg) and after weight loss (68 +/- 2 kg), and in eight of the same patients following relapse of body weight gain (84 +/- 5 kg). Expressed as a percentage of the energy content of the 100 g oral glucose load, glucose-induced thermogenesis was lower in the overweight before weight loss (6.5 +/- 0.5 per cent, P less than 0.05), after weight loss (3.9 +/- 0.6 per cent, P less than 0.01) and after weight regain (6.3 +/- 0.9 per cent, P less than 0.05) than in a group of lean control subjects, matched for sex and age (8.3 +/- 0.5 per cent). Basal energy expenditure was lower after weight reduction than before (1.16 +/- 0.04 vs 1.41 +/- 0.08 kcal/min, P less than 0.01). In the formerly overweight patients, the combined effect of a decreased basal energy expenditure and an attenuation of glucose induced thermogenesis resulted in a postprandial energy expenditure which was markedly lower than in the overweight state (P less than 0.001). Following relapse of obesity, glucose-induced thermogenesis remained attenuated compared to control subjects. These results suggest that a lowered basal energy expenditure and a reduced glucose-induced thermogenesis contribute to the positive energy balance which results in relapse of body weight gain after cessation of a hypocaloric diet.

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

BACKGROUND About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. DESIGN AND METHODS. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. RESULTS. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). CONCLUSIONS The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens.

PURPOSE: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. RESULTS: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). CONCLUSION: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis.

BACKGROUND The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. DESIGN AND METHODS Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. RESULTS Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. CONCLUSIONS This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.

The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse.

The administration of selective serotonin reuptake inhibitors (SSRIs) typically used as antidepressants increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) has not been studied. In the present work we examined the effects of a 15-d treatment with the SNRI atomoxetine (1, 3 and 10 mg/kg, i.p.) in male rats trained to drink alcohol solutions in a 4-bottle choice test. The treatment with atomoxetine (10 mg/kg, i.p.) during an alcohol deprivation period increased alcohol consumption after relapse. This effect only lasted one week, disappearing thereafter. Treatment with atomoxetine did not cause a behavioral sensitized response to a challenge dose of amphetamine (1.5 mg/kg, i.p.), indicating the absence of a supersensitive dopaminergic transmission. This effect is markedly different from that of SSRI antidepressants that produced both long-lasting increases in alcohol consumption and behavioral sensitization. Clinical implications are discussed.

Energy expenditure in obese women before and during weight loss, after refeeding, and in the weight-relapse period.

In 10 moderately obese women, 24-h energy expenditure (24EE) was measured in a respiration chamber under four conditions: 1) before weight loss (body weight = 77.9 kg), 2) during weight loss (63.9 kg), 3) after realimentation (62.5 kg), and 4) 6-15 mo after the study diet with ad libitum diet (67.7 kg). The 14 +/- 8 kg (mean +/- SD) weight loss produced a decrease in 24EE of 1498 +/- 1138 kJ/d (P < 0.001), ie, a decrease of weight of 107 kJ.kg body wt-1.d-1. The subsequent 24EE (conditions 3 and 4) remained lower than the value before weight loss. A significant correlation was found between changes before and after weight regain in basal respiratory quotient (RQ) and the spontaneous rate of body-weight gain after cessation of the period of low energy intake (r = 0.89, P < 0.01); this suggests that the value of the postabsorptive RQ may be a predictor of relapse of weight gain. After discontinuation of the low energy diet, an elevated postabsorptive RQ shows that the endogenous lipid oxidation is low, a condition favoring weight gain.

A genomewide association study of smoking relapse in four European population-based samples.

OBJECTIVES: Genomewide association studies (GWAS) have identified clear evidence of genetic markers for nicotine dependence. Other smoking phenotypes have been tested, but the results are less consistent. The tendency to relapse versus the ability to maintain long-term abstinence has received little attention in genetic studies; thus, our aim was to provide a better biological understanding of this phenotype through the identification of genetic loci associated with smoking relapse. METHODS: We carried out a GWAS on data from two European population-based collections, including a total of 835 cases (relapsers) and 990 controls (abstainers). Top-ranked findings from the discovery phase were tested for replication in two additional independent European population-based cohorts. RESULTS: Of the seven top markers from the discovery phase, none were consistently associated with smoking relapse across all samples and none reached genomewide significance. A single-nucleotide polymorphism rs1008509, within the Xylosyltransferase II (XYLT2) gene, was suggestively associated with smoking relapse in the discovery phase (β=-0.504; P=5.6E-06) and in the first replication sample (ALSPAC) (β=-0.27; P=0.004; n=1932), but not in the second sample (KORA) (β=0.19; P=0.138; n=912). We failed to identify an association between loci implicated previously in other smoking phenotypes and smoking relapse. CONCLUSION: Although no genomewide significant findings emerged from this study, we found that loci implicated in other smoking phenotypes were not associated with smoking relapse, which suggests that the neurobiology of smoking relapse and long-term abstinence may be distinct from biological mechanisms implicated in the development of nicotine dependence.

Sentinel lymph node involvement and a high Breslow index are independent factors of risk for early relapse of melanoma

Rapport de synthèse : Le ganglion sentinelle (GS) se défini comme le premier ganglion de la chaîne ganglionnaire qui draine le territoire anatomique où siège une tumeur et, par conséquent, celui ayant le plus de possibilités de recevoir des métastases. La combinaison des deux techniques de détection du GS existantes, lymphoscintigraphie et coloration, permettent de déceler le GS dans 95-100% des cas. Le taux d'attente métastatique du GS varie entre 16 et 21 % des patients. Dans 50 à 87% des cas, le GS est le seul site de métastase et la probabilité de trouver des micro-métastases dans des ganglions appartenant aux relais supérieurs sans atteinte du GS est estimée à moins de 2%. Ces chiffres relèvent l'importance de la détection du GS. L'emploi de cette technique offre de nombreux avantages par rapport à la lymphadénéctomie élective que nous décrirons. Selon Rousseau et al., il existe une probable association entre le statut du GS et la survie de la maladie. Cette interprétation et celles d'autres auteurs soulignent la pertinence clinique du statut du GS dans le mélanome. En ce qui concerne la survie sans maladie (DFS) et la survie globale (OS), aucune différence significative n'a été observée entre les patients ayant subi une résection complète immédiate des ganglions lymphatiques et ceux qui d'abord ont subi une résection chirurgicale et analyse du GS secondaire, suivies par une dissection élective en cas de positivité. L'objectif de cette étude prospective était d'évaluer la pertinence de la positivité tumorale du GS dans l'évaluation des risques de rechute du mélanome. Cette étude a confirmé l'intérêt de la scintigraphie des ganglions lymphatiques (associée à la technique de coloration par bleu et celle de détection par sonde portable) dans l'identification du GS comme approche thérapeutique au stade précoce du mélanome. Elle a montré, en autre, que le statut du GS et l'indice de Breslow sont des facteurs de risque indépendants importants de rechute chez des patients atteints d'un mélanome au stade précoce. La combinaison de ces deux paramètres a permis de créer des groupes de patients à risque de rechute différents qui pourraient conduire à l'adaptation des protocoles de thérapie en fonction de ces risques.