Calcium channel blockers for tocolysis: a review of their role and safety following reports of serious adverse events

The use of nifedipine and other calcium channel blockers has become commonplace in the management of preterm labour. Several relatively small randomised trials have compared calcium channel blockers with beta-agonists and the meta-analyses of these studies have demonstrated superior or comparable efficacy and a superior adverse events profile. The safety of calcium channel blockers in pregnancy has not been rigorously evaluated and they remain unlicensed for use as tocolytics. Indeed, there is concern following a number of recent case studies that have reported serious adverse events after the administration of a calcium channel blocker as a tocolytic. In this article all these recently reported cases are critically reviewed and the pros and cons of tocolytic treatment options are discussed. Based on the findings of this review the following recommendations can be made with regard to tocolysis with calcium channel blockers: firstly, calcium channel blockers should not be combined with intravenous beta-agonists; secondly, intravenous nicardipine or high oral doses of nifedipine should not be used in cases where the mother is cardiovascular compromised or in cases of multiple gestation; finally, blood pressure should be monitored and cardiotocography recorded during the administration of immediate release tablets and patients should be advised to avoid chewing them. To truly establish the safety of tocolytics, all serious adverse effects of tocolytics should be reported to a central point and be critically reviewed.     

Cognitive change process during group cognitive behaviour therapy for depression

BACKGROUND: This study extended that of Kwon and Oei [Kwon, S.M., Oei, T.P.S., 2003. Cognitive change processes in a group cognitive behavior therapy of depression. J. Behav. Ther. Exp. Psychiatry, 3, 73-85], which outlined a number of testable models based on Beck's cognitive theory of depression. Specifically, the current study tested the following four competing models: the causal, consequential, fully and partially interactive cognitive models in patients with major depressive disorder. METHODS: A total of 168 clinically depressed outpatients were recruited into a 12-week group cognitive behaviour therapy program. Data was collected at three time points: baseline, mid- and at termination of therapy using the ATQ, DAS and BDI. The data were analysed with Amos 4.01(Arbuckle, J.L., 1999. Amos 4.1. Smallwaters, Chicago.) structural equation modelling. RESULTS: Results indicated that dysfunctional attitudes, negative automatic thoughts and symptoms of depression reduced significantly during treatment. Both the causal and consequential models equally provided an adequate fit to the data. The fully interactive model provided the best fit. However, after removing non-significant pathways, it was found that reduced depressive symptom contributed to reduced depressogenic automatic thoughts and dysfunctional attitudes, not the reverse. CONCLUSION: These findings did not fully support Beck's cognitive theory of depression that cognitions are primary in the reduction of depressed mood.     

Dose response effects of avian influenza (H7N7) vaccination of chickens: Serology,clinical protection and reduction of virus excretion

Knowledge of the relation between the antigen content of inactivated avian influenza (AI) vaccines, the serological response after vaccination and protection of vaccinated animals is important for the choice of optimal vaccines and vaccination regimes as well as for the assessment of criteria for the licensing of new AI-vaccines. We studied this relation in a dose response study using inactivated H7N7 avian influenza vaccines with varying antigen content. The serological response depended on the antigen content of the vaccines. Anti-AI antibodies were detected most frequently with ELISA, followed by the virus neutralisation test and the haemagglutination inhibition (HI) assay. Chickens with measurable HI-antibody titers, using homologous H7N7 antigen, were all protected against clinical disease after challenge with highly pathogenic A/chicken/Netherlands/621557/03 H7N7 virus. However, in these chickens high levels of virus could still be present on days 2–4 after challenge. The reduction of virus titers after challenge, depended on the antigen content of the vaccines as well as on the serum antibody titers. While 10 haemagglutinating units (HAU), equivalent to 0.8 μg haemagglutinin (HA) protein, per vaccine dose was sufficient for prevention of clinical disease, 128 HAU (9 μg HA) per dose was required for reduction of virus titers in all chickens to 10³ egg-infectious dose 50% (EID₅₀) or less. In order to reduce virus titers below 10³ EID₅₀ per swab a HI-antibody titer of 64 was required. After use of the vaccine with the highest antigen content, challenge still induced a booster of antibody titers which is indicative of replication of challenge virus.     

Estimation of internal uterine pressure by joint amplitude and frequency analysis of electrohysterographic signals

Monitoring the uterine contraction provides important prognostic information during pregnancy and parturition. The existing methods employed in clinical practice impose a compromise between reliability and invasiveness. A promising technique for uterine contraction monitoring is electrohysterography (EHG). The EHG signal measures the electrical activity which triggers the contraction of the uterine muscle. In this paper, a non-invasive method for intrauterine pressure (IUP) estimation by EHG signal analysis is proposed. The EHG signal is regarded as a non-stationary signal whose frequency and amplitude characteristics are related to the IUP. After acquisition in a multi-channel configuration, the EHG signal is therefore analyzed in the time-frequency domain. A first estimation of the IUP is then derived by calculation of the unnormalized first statistical moment of the frequency spectrum. The estimation accuracy is finally increased by identification of a second-order polynomial model. The proposed method is compared to root mean squared analysis and optimal linear filtering and validated by simultaneous measurement of the IUP on nine women during labor. The results suggest that the proposed EHG signal analysis provides an accurate estimate of the IUP.     

Factors Associated with the Severity of Gambling Problems in a Community Gambling Treatment Agency

Factors (demographics, gambling behaviors and comorbid problems) that may be related to the severity of gambling problems were investigated among 440 problem gamblers seeking treatment in an Australian outpatient treatment agency. The participants were divided into sub-threshold pathological gamblers (SPGs; N = 104) and pathological gamblers (PGs; N = 336) using Diagnostic Statistical Manual (DSM) IV diagnosis of pathological gambling. SPGs were more likely to be separated/divorced, while PGs were more likely to be single. PGs tended to be younger than SPGs. Participation in lottery games was the only form of gambling that could distinguish between the two severity groups. No significant differences were found in participation in more than one gambling session per week and average amount spent per session on various gambling activities between the two groups. PGs were more likely to report financial, relationship, employment, physical, intrapersonal, other excessive behaviors (e.g., substance problems), leisure (e.g., loneliness, boredom) and legal problems than SPGs. Implications and limitations of these findings are discussed.     

Laparoscopic correction of umbilical hernias using a transabdominal preperitoneal approach: results of a pilot study

Background  Laparoscopic repair of umbilical hernias is usually based on the open underlay procedure in which the mesh is placed intra-abdominally. To prevent complications such as adhesions, bowel obstruction and fistula formation we developed a new laparoscopic approach, placing the mesh in the preperitoneal space. Methods  Our laparoscopic approach concerns a standardised procedure with introduction of three intra-abdominally placed trocars. The ventral abdominal wall is incised in a lengthwise manner approximately 5 cm from the umbilical defect, followed by development of the preperitoneal space, reposition of the umbilical peritoneal sac and placement and fixation of a Prolene^TM mesh. The mesh is secured using transfascial Prolene^TM sutures; the peritoneal defect is closed with a running Vicryl^TM suture. Data on 17 patients with primary umbilical hernias laparoscopically operated on between April 2002 and March 2006 are presented. Results  The 11 men and 6 women had a mean age of 57.8 years (range 37–91 years) and a mean body mass index (BMI) of 30.6 kg/m² (range 23.7–37.9 kg/m²). Mean hernia size was 1.95 cm (range 1–3 cm), average mesh size was 110 cm² (range 100–150 cm²). Mean operating time was 85.6 min (range 60–120 min). Mean hospital stay was 2.2 days (range 1–3 days). No major complications were seen. No recurrences were observed during a mean follow-up of 36.2 months (range 13–62 months). Conclusions  The preperitoneal laparoscopic technique for umbilical hernia repair combines the advantages of a laparoscopic, minimally invasive, approach, avoiding the potential complications related to intra-abdominal mesh position.     

Dopamine modulates reward system activity during subconscious processing of sexual stimuli

Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive-compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the 'reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate 'wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.     

Endogenous cortisol is associated with functional connectivity between the amygdala and medial prefrontal cortex

Whether glucocorticoids mediate medial prefrontal cortex (mPFC) regulation of the amygdala in humans remains unclear. In the current study we investigated whether cortisol levels under relatively stress-free circumstances are related to amygdala resting-state functional connectivity with the mPFC. Resting-state fMRI data were acquired from 20 healthy male participants. Salivary cortisol was sampled at multiple times throughout the experiment. The cortisol area under the curve increase (AUCi) was calculated as a measure of cortisol dynamics. Next, seed based correlations were employed on the resting-state fMRI data to reveal regions of amygdala functional connectivity related to variations in cortisol AUCi. The resulting statistical maps were corrected for multiple comparisons using cluster based thresholding (Z>2.3, p<.05). Two regions in the mPFC showed decreasing negative functional connectivity with the amygdala when a lesser decrease in cortisol AUCi was observed: the perigenual anterior cingulate cortex and medial frontal pole (BA10). Although we initially showed a relation with cortisol AUCi, it seemed that the baseline cortisol levels were actually driving this effect: higher baseline cortisol levels related to stronger negative functional connectivity with the mPFC. Endogenous cortisol levels may modulate amygdala functional connectivity with specific regions in the mPFC, even under relatively stress-free circumstances. Our results corroborate previous findings from both animal and human studies, suggesting cortisol-mediated regulation of the amygdala by the mPFC. We propose that through this feedback mechanism the stress response might be adjusted, pointing to the putative role of cortisol in modulating stress- and, more generally, emotional responses.     

Negligible influence of comorbidity on prognosis of patients with small cell lung cancer: a population-based study in the Netherlands

Management of small cell lung cancer (SCLC) among elderly is complex because of decreased organ functions and interactions with comorbidity. Since elderly patients are often excluded from clinical trials, little is known about the way they are treated and outcome.We evaluated the prognostic effects of rising age and comorbidity in unselected Dutch SCLC patients (Eindhoven Cancer Registry). Elderly patients received chemotherapy less often and the dose was also reduced more often. Cardiovascular diseases, hypertension or diabetes lowered the proportion receiving combined chemotherapy and radiotherapy among patients with limited disease. About 80% of the patients receiving chemotherapy suffered from a side effect, which was not related to age. After adjustment for age, gender, stage and treatment modality, comorbidity had a negligible prognostic effect. Chemotherapy (in combination with radiotherapy) seemed to improve survival, however, toxicity and quality of life in these patients should be evaluated thoroughly in future randomized studies.     

A comparison of general self-efficacy and drinking refusal self-efficacy in predicting drinking behavior

A number of studies have suggested that task specific self-efficacy has more influence over behavior than general self-efficacy. However, little research has compared the impact of task-specific self-efficacy beliefs to the impact of general self-efficacy in predicting alcohol consumption. This study aimed to compare the contribution of general self-efficacy and drinking refusal self-efficacy (a form of task-specific self-efficacy) to volume and frequency of alcohol consumption. Regression analyses were performed in samples of community (n = 298) and clinical (n = 296) drinkers. Overall, drinking refusal self-efficacy was found to be a significant predictor of alcohol consumption in the community sample, while general self-efficacy was found to be a significant predictor of drinking in the clinical sample. These differences highlight the differential roles of general and task specific self-efficacy in governing drinking behavior and suggest future directions for prevention and treatment of alcohol problems.