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The CONSORT Statement: revised recommendations for improving the quality of reports of parallel-group randomized trials 2001.

To comprehend the result of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticism of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Comment. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage or participants through an RCT. The revised flow diagram depicts information from 4 stages of a trial (enrollment, intervention allocation, follow-up and analysis). The diagram explicitly includes the number of participants, according to each intervention group, included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting or an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.

Guidelines as Topic↗

[Fecal and urinary incontinence after delivery: risk factors and prevention].

OBJECTIVE: This study was undertaken to review the available data on urinary and fecal incontinence and their association with maternal as well as fetal per partum characteristics. METHOD: A Pubmed (Medline search performed between 1999 and 2003 using "urinary incontinence and delivery" and "fecal incontinence and delivery" identified 501 relevant papers. Most of them are retrospective analyses whereas few are randomized controlled trials (RCT). RESULTS: Two studies performed with computer-stored databases analyzed the risk factors of incontinence among 2,886,126 deliveries. Primiparity, birthweight over 4000 g and all types of assisted vaginal deliveries significantly increased the risk of anal sphincter damage. Results concerning the effect of episiotomy are conflicting. Controlled randomized trials have shown that pelvic floor muscle training during pregnancy as well as planned cesarean section significantly and moderately decrease the risk of urinary incontinence. The only RCT available has shown that planned cesarean section did not reduce significantly incontinence of flatus. Finally the only trial that compare surgical techniques used to repair the anal sphincter did not show any significant difference. CONCLUSION: Risk factors for anal sphincter damage during delivery are well known. RCT focusing on how to prevent and how to cure fecal as well as urinary incontinence are urgently needed.

Anal Canal↗

The quality of evidence in health informatics: how did the quality of healthcare IT evaluation publications develop from 1982 to 2005?

OBJECTIVE: To obtain an overview of study designs and study methods used in research evaluating IT in health care, to present a list of quality criteria by which all kinds of reported evaluation studies on IT systems in health care can be assessed, and to assess the quality of reported evaluation studies on IT in health care and its development over time (1982-2005). METHODS: A generic 10-item list of quality indicators was developed based on existing literature on quality of medical and medical informatics publications. It is applicable to all kind of IT evaluation papers and not restricted to randomized controlled trials. One hundred and twenty explanatory papers evaluating the effects of an IT system in health care published between 1982 and 2005 were randomly selected from PubMed, the study designs and study methods were extracted, and the quality indicators were used to assess the quality of each paper by two independent raters. RESULTS: The inter-rater variability of scoring the 10 quality indicators as assessed by a pre-test with nine papers was good (K=0.87). There was a trend towards more multi-centre studies and authors coming more frequently from various departments. About 70% of the studies used a design other than a randomized controlled trial (RCT). Forty percent of the studies combined at least two different data acquisition methods. The quality of IT evaluation papers, as defined by the quality indicators, was only slightly improving in time (Spearman correlation coefficient [rs]=0.19). The quality of RCTs publications was significantly higher than the quality of non-RCT studies (p<0.001). CONCLUSION: The continuous and dominant number of non-RCT studies reflects the various approaches applicable to evaluate IT systems in health care. Despite the increasing discussion on evidence-based health informatics, the quality of published evaluation studies on IT interventions in health care is still insufficient in some aspects. Journal editors and referees should take care that reports of evaluation on IT systems contain all aspects needed for a sufficient understanding and reproducibility of a paper. Publication guidelines should be developed to support more complete and better publications of IT evaluation papers.

Europe↗

Preoperative radiochemotherapy and radical resection for stages II to IV oral and oropharyngeal cancer: grade of regression as crucial prognostic factor.

The purpose of this study was to assess the prognostic value of histological response to preoperative radiochemotherapy in an established multimodal therapy concept for advanced oral and oropharyngeal cancer. Two hundred and twenty-two patients who underwent preoperative radiochemotherapy (RCT: 50 Gy, mitomycin C and fluorouracil) and radical surgery were retrospectively evaluated. Resected tumours of all patients were histologically analysed and response to RCT was classified in histopathological grades of regression (RG). In a multivariate statistical analysis, RG was compared with established factors regarding their predictive value for overall and disease-specific survival. The 5-year overall survival probability in the different groups of histopathological regression grades were: RG1 (no vital tumour): 73.4%, RG2 (minimal tumour remnants encompassing less than 5%): 72.1%, RG3 (5-50% vital tumour cells): 41.9%, RG4 (more than 50% vital tumour): 37.9%. For disease-specific survival probability no significant differences were found between both groups of "responders" (RG1 and RG2) nor between "non-responders" (RG3 and RG4), whereas responders and non-responders differed significantly from each other (log-rank test; p < 0.001). T-classification, N-classification and disease stage, histological grading, tumour site, age, and sex had less prognostic value than RG in a Cox regression model. In the neoadjuvant multimodal therapy concept, histological response to preoperative RCT is a crucial prognostic factor even when surgical R0-resection is accomplished. Thus, non-responders have to be regarded as high-risk patients for recurrence and may benefit from further therapy.

Antineoplastic Combined Chemotherapy Protocols↗

COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy.

PURPOSE: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). METHODS AND MATERIALS: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. RESULTS: Good response (TRG 1+2), moderate response (TRG 3), and poor response (TRG 4+5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3+4) to treatment than were those with normal COX-2 expression (p=0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p=0.0007, chi-square test). CONCLUSIONS: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.

Apoptosis↗

Cardiac medical therapy in patients after undergoing coronary artery bypass graft surgery: a review of randomized controlled trials.

The purpose of this paper is to review the randomized controlled trial (RCT) data investigating cardiac medical therapy for patients after coronary artery bypass grafting (CABG). We identified RCTs with > or =100 enrolled patients that examined the impact of cardiac medical therapy on outcomes > or =1 year after CABG. The MEDLINE database was searched for trials conducted between 1966 and 2004 on the following medications: aspirin, antilipid agents, beta-blockers, calcium channel blockers (CCBs), nitrates, and angiotensin-converting enzyme (ACE) inhibitors. Both aspirin and antilipid agents were found to reduce the progression of atherosclerosis and the occurrence of graft occlusion. Cardiovascular events were decreased with antilipid agents. In small trials, beta-blockers and CCBs failed to decrease the incidence of cardiovascular events. No RCTs examined nitrates, and one small RCT documented a reduction in cardiovascular events among patients treated with ACE inhibitors. We conclude that few RCTs have examined the efficacy of cardiac medical therapy in post-CABG patients. Based on current RCT evidence, aspirin and antilipid agents should be used routinely after CABG. However, current data do not support the use of beta-blockers, CCBs, and nitrates, and more evidence is needed regarding the use of ACE inhibitors.

Adrenergic beta-Antagonists↗

Back schools in occupational health care: design of a randomized controlled trial and cost-effectiveness study.

OBJECTIVE: To describe the design of a randomized controlled trial (RCT), including a cost-effectiveness analysis, comparing high-intensity and low-intensity back schools with usual care in occupational health care. DESIGN: RCT and cost-effectiveness analysis. STUDY POPULATION: Employees sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain. Interventions High-intensity back school treatment consists of a training program based on the principles of cognitive-behavioral therapy. Low-intensity back school treatment is comparable to the original Swedish Back School. Usual care is provided by the occupational physician according to the Dutch guidelines for the occupational health treatment of patients with low back pain. OUTCOME MEASURES: Primary outcome measures are return to work, pain intensity, functional status, and general improvement. Secondary outcome measures are kinesiophobia and pain coping. The cost-effectiveness analysis includes the direct and indirect costs. The outcome measures are assessed before randomization and 3, 6, and 12 months after randomization. CONCLUSION: RCTs of different methodological quality have been conducted to examine the effectiveness of back schools in occupational health care. The large variation in type, content, and intensity of back schools has led to conflicting evidence. Therefore, 2 different forms of back schools are compared. Moreover, this is the first RCT to include a cost-effectiveness analysis comparing low-intensity and high-intensity back schools with usual care in occupational health care.

Adolescent↗

Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically evaluate the effectiveness of probiotics in preventing antibiotic-associated diarrhea (AAD) in children. STUDY DESIGN: The following electronic databases up to December 2005, in any language, were searched for studies relevant to AAD and probiotics: MEDLINE, EMBASE, and The Cochrane Library. Only randomized controlled trials (RCT) were considered for study inclusion. RESULTS: Six placebo-controlled, RCTs (766 children) were included. Treatment with probiotics compared with placebo reduced the risk of AAD from 28.5% to 11.9% (relative risk, RR, 0.44, 95% CI 0.25 to 0.77, random effect model). Preplanned subgroup analysis showed that reduction of the risk of AAD was associated with the use of Lactobacillus GG (2 RCTs, 307 participants, RR 0.3, 95% CI 0.15 to 0.6), S. boulardii (1 RCT, 246 participants, RR 0.2, 95% CI 0.07-0.6), or B. lactis & Str. thermophilus (1 RCT, 157 participants, RR 0.5, 95% CI 0.3 to 0.95). CONCLUSIONS: Probiotics reduce the risk of AAD in children. For every 7 patients that would develop diarrhea while being treated with antibiotics, one fewer will develop AAD if also receiving probiotics.

Anti-Bacterial Agents↗

HRT as secondary prevention of cardiovascular disease.

OBJECTIVE: To review the evidence of the efficacy of postmenopausal hormone replacement therapy (HRT) in secondary prevention of coronary artery disease or stroke. RESULTS: Although a number of rather large and prolonged non-randomized observational studies have produced convincing and consistent evidence of the efficacy of HRT in the prevention of recurrence of cardiac events, the first randomized, placebo controlled trial (RCT) on heart disease and estrogen replacement study (HERS) reported no benefit of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) in secondary prevention of cardiac events in women with established coronary artery disease. This was supported by RCT reporting no effect of CEE or CEE + MPA on the progress of coronary sclerosis. Similarly, some nonrandomized observational studies have evaluated the risk of recurrent stroke in regard to the use of HRT, and the data are conflicting reporting a reduced or increased risk of recurrence for HRT users. One RCT has shown that low-dose estrogen treatment can only slow down the progression of carotid arteriosclerosis in high-risk postmenopausal women, whereas two other RCTs have shown no benefit (or risk) of using HRT for secondary prevention of ischemic stroke or progression of carotid atherosclerosis. CONCLUSION: The evidence accumulated so far shows that HRT has no place in secondary prevention of coronary or carotic artery disease. Its use in these patients must be based on solid nonvascular indications and expected benefits from these causes.

Cardiovascular Diseases↗

The efficacy of hypertonic saline nasal irrigation for chronic sinonasal symptoms.

OBJECTIVE: To assess quality of life (QOL) in patients with sinonasal symptoms in response to hypertonic saline nasal irrigation (HSNI), and to assess HSNI use patterns. STUDY DESIGN AND SETTING: The study was an uncontrolled 12-month follow-up to a randomized controlled trial (RCT) and used HSNI in a community setting. We included 54 participants with recurrent or chronic sinonasal symptoms. Forty participants had been in the intervention group of a previous study; 14 had been control participants. Primary outcome measures were the Rhinosinusitis Disability Index (RSDI), a sinus-symptom severity assessment (SIA), and the Sino-Nasal Outcomes Test (SNOT-20). Secondary outcome measures were frequency and pattern of HSNI use, side effects and satisfaction. RESULTS: Among participants using HSNI in the prior RCT, RSDI scores continued to improve, from 73.2 +/- 2.6 points to 80.6 +/- 2.4 points (P < 0.001). SIA and SNOT-20 scores remained stable. Former control participants reported QOL improvement similar to that of HSNI users in the prior RCT. RSDI scores improved from 62.0 +/- 3.9 points to 79.7 +/- 3.7 points (P < 0.05), SNOT-20 scores improved from 43.5 +/- 5.7 points to 28.4 +/- 4.8 points, and SIA scores improved from 4.2 +/- 0.3 points to 2.6 +/- 0.3 points (P < 0.01). Mean HSNI use for all participants was 2.4 irrigations per week; 33% of participants used HSNI regularly, 55% when symptomatic. Side effects were minor; satisfaction was high. CONCLUSIONS: Participants with chronic sinonasal symptoms reported improved QOL and frequent, satisfying use of HSNI. SIGNIFICANCE: HSNI is an effective adjunctive treatment of chronic sinonasal symptoms.

Adult↗

In vitro fracture resistance of endodontically treated central incisors with varying ferrule heights and configurations.

STATEMENT OF PROBLEM: The in vitro effectiveness of a uniform circumferential ferrule has been established in the literature; however, the effect of a nonuniform circumferential ferrule height on fracture resistance is unknown. PURPOSE: This in vitro study investigated the resistance to static loading of endodontically treated teeth with uniform and nonuniform ferrule configurations. MATERIAL AND METHODS: Fifty extracted intact maxillary human central incisors were randomly assigned to 1 of 5 groups: CRN, no root canal treatment (RCT), restored with a crown; RCT/CRN, no dowel/core, restored with a crown; 2 FRL, 2-mm ferrule, cast dowel/core and crown; 0.5/2 FRL, nonuniform ferrule (2 mm buccal and lingual, 0.5 mm proximal), cast dowel/core and crown; and 0 FRL, no ferrule, cast dowel/core and crown. The teeth were prepared to standardized specifications and stored for 72 hours in 100% humidity prior to testing. Testing was conducted with a universal testing machine with the application of a static load, and the load (N) at failure was recorded. Statistical analysis was performed with a 1-way analysis of variance and the Tukey Honestly Significant Difference test (alpha=.05). The mode of fracture was noted by visual inspection for all specimens. RESULTS: There was strong evidence of group differences in mean fracture strength ( P <.0001). Following adjustment for all pairwise group comparisons, it was found that the lack of a ferrule resulted in a significantly lower mean fracture strength (0 FRL: 264.93 +/- 78.33 N) relative to all other groups. The presence of a nonuniform (0.5 to 2-mm vertical height) ferrule (0.5/2 FRL: 426.64 +/- 88.33 N) resulted in a significant decrease ( P =.0001) in mean fracture strength when compared with the uniform 2-mm vertical ferrule (2 FRL: 587.23 +/- 110.25 N), the group without RCT (CRN: 583.67 +/- 86.09 N), and the RCT-treated tooth with a crown alone (CRN/RCT: 571.04 +/- 154.86 N). The predominant mode of failure was an oblique fracture extending from the lingual margin to the facial surface just below the insertion of the tooth into the acrylic resin. CONCLUSION: The results demonstrated that central incisors restored with cast dowel/core and crowns with a 2-mm uniform ferrule were more fracture resistant compared to central incisors with nonuniform (0.5 to 2 mm) ferrule heights. Both the 2-mm ferrule and nonuniform ferrule groups were more fracture resistant than the group that lacked a ferrule.

Crowns↗

The efficacy comparison of ibuprofen, acetaminophen-codeine, and placebo premedication therapy on the depth of anesthesia during treatment of inflamed teeth.

The purpose of this study was to elucidate whether premedication therapy with acetaminophen-codeine or ibuprofen is able to increase the depth of anesthesia in inflamed teeth. Sixty patients with the diagnosis of irreversible pulpitis in 1 mandibular tooth requiring root canal therapy (RCT) were selected. Two other teeth in the same quadrant were selected as controls. An electric pulp tester (EPT) was used to evaluate pulp sensitivity at the baseline and after drug administration and anesthesia injection. The subjects were divided into 3 groups randomly, and in each group 1 of the 3 drugs including acetaminophen-codeine, ibuprofen, and placebo were administered 1 hour before anesthesia delivery. After 1 hour, anesthesia was injected and after a waiting period, the EPT measurement was recorded. The reversed EPT scale was used to evaluate the depth of anesthesia achieved during RCT. Data were analyzed to statistically compare the results before and after intervention in cases and controls of each group and among different groups. Significanly lower tooth sensitivity levels (TSLs) were observed after intervention in acetaminophen-codeine and ibuprofen groups, which was more significant in the ibuprofen group. The comparison of inflamed teeth TSLs in the acetaminophen-codeine group and the placebo group after anesthesia and drug administration showed significant differences (P = .001). This comparison between ibuprofen and placebo groups also showed significant differences (P approximately 0). Also, significantly lower TSL of inflamed teeth was observed in the ibuprofen group in comparison with the acetaminophen-codeine group (P = .002). This study reflected preoperative administration of ibuprofen, if not contraindicated, as a drug of choice 1 hour before local anesthesia injection as an effective method for achieving a deep anesthesia during RCT of teeth with irreversible pulpitis.

Acetaminophen↗

Natural history and clinical outcome of sporadic renal cortical tumors diagnosed in the young adult.

OBJECTIVES: To determine the natural history of patients younger than 40 years (young patient [YP] group) who are diagnosed with a sporadic renal cortical tumor (RCT) and to compare the natural history of these patients with the more typical older patient (OP) with RCT. METHODS: We reviewed our database and identified 34 patients (younger than 40 years old, median age 35) who underwent surgery for a sporadic RCT. The YP group outcomes were compared with 100 patients between 41 and 85 years (median 65). We fit a Cox proportional hazards model to examine the relationship between age at presentation and recurrence risk. RESULTS: The median tumor size in the YP group was 3.8 cm (range 0.6 to 19) and in the OP group was 5.0 cm (range 0.9 to 22; P = 0.225). Tumors were discovered incidentally in 51% and 56% of the YP and OP groups, respectively (P = 0.65). The frequency of partial nephrectomy did not differ between the two groups (35% YP and 30% OP, P = 0.55). The frequency of malignant histologic subtypes did not differ between the groups (P = 0.439). In the YP group, only larger tumor size (hazard ratio 1.23, 95% confidence interval 1.02 to 1.50, P = 0.034) was associated with a statistically significant increased risk of recurrence. Those in the YP group were not more or less likely to develop recurrence than those in the OP group (hazard ratio 0.79, 95% confidence interval 0.22 to 2.85, P = 0.72). The 5-year disease-free survival rate was 73% and 80% in the YP and OP groups, respectively (P = 0.23). The 5-year disease-specific survival rate was 85% and 84% in the YP and OP groups, respectively (P = 0.88). CONCLUSIONS: The findings of our study indicate that the natural history of RCTs is similar in both younger and older patients. Young patients were neither more nor less likely to develop recurrence compared with their older counterparts.

Adolescent↗

Health-related quality of life in senior adults with epilepsy: what we know from randomized clinical trials and suggestions for future research.

OBJECTIVE: The goal of this work was to review the randomized controlled trial (RCT) literature on antiepileptic medication effects on health-related quality of life in seniors with epilepsy. METHODS: Studies published from 1998 to June 2002 were identified by searching through Medline and the Cochrane Clinical Trials Register. Pre-1998 RCTs identified by Baker et al. [Epilepsia 41 (2003) 1357] were also examined for relevance to the present review. Studies were reviewed if they included a RCT design and included epilepsy patients over the age of 60. RESULTS: A total of 85 clinical trials were reviewed. Of the 85 studies reviewed only 37 RCT studies included patients over the age of 60. However, formal quality-of-life outcome assessment was not performed in any of the RCTs that included senior adults, and only six studies provided formal quantitative analyses of AED effects in the form of adverse events incidence and participant withdrawal rates. For the most part, early study withdrawal rates were substantial for seniors and adverse events were very common. Two studies reporting on the cognitive and behavioral effects of study AEDs indicated only modest impact when AED monotherapy was kept at therapeutic levels. CONCLUSIONS: Despite growing appreciation for quality-of-life, issues in the management of epilepsy little current empirical guidance is available for elderly with epilepsy. There exists virtually no information on elderly patient preferences and goals for epilepsy treatment outcomes, and available data primarily concerns younger adults. Despite some encouraging preliminary evidence from this review suggesting that conservative AED treatment may have a more favorable quality of life-related outcome, more conclusive statements await further systematic investigation.

Aged↗

[Selective serotonin reuptake inhibitors in major depressive disorder in children and adolescents (ratio of benefits/risks)].

UNLABELLED: Major depressive disorder in children and adolescents is associated with high risk of suicide and persistent functional impairment. While psychological treatments are used as a first line treatment in mild and moderately severe depression in this age group, the number of prescriptions for antidepressant medication (SSRI) has grown in recent years. Recently, FDA and MHRA advised that most of SSRI should not be used to treat MDD under the age of 18 years. They may increase the risk of suicidal thoughts and self harm. We reviewed the recent literature on efficacy and suicide risks of SSRI in depressed young people. Conflicting findings of SSRI efficacy have been reported in clinical studies. The discrepancies could be related to the heterogeneous samples and the absence of a standard definition of treatment effectiveness. In randomised placebo-controlled antidepressant clinical trials (RCT), the assessment of treatment effectiveness is commonly made with the CDRS-R (improvement of 20% or 30% or 40%) and CGI. SSRI demonstrated significantly, but modest, improvement compared with placebo in CGI score of 1 or 2: 10% more for sertraline, 16.8% more for paroxetine and between 16 to 24% more for fluoxetine. In adults, RCT studies have shown placebo response rates of 30% to 50%, drug response rates of 45% to 50% and drug-placebo differences of 18% to 25%. The highest placebo response rates, in young people, may be related to the highly selected group not representative of the general population of depressed patients and/or to the high youths' sensibility of psychotherapy. Patients participating in antidepressant clinical trials have a low BDI and CDI in Emslie's study for example (2002). In adults, previous reports suggest that SSRI use is associated with increased suicidal risk. But the analyse of 48 277 depressed patients participating in RCT for nine FDA approved antidepressants fail to support an overall difference in suicide risk between antidepressants (SSRI) and placebo treated subjects. An inverse relationship between regional change in use of antidepressants (increased) and suicide (decreased) is found in young -people in United States from 1990 and 2000. We can not draw a conclusion from few studies with few -participants. None suicide have been reported in pharmacological studies. And the link between "suicidality" and MDD can not be excluded. The instruments of assessment in depressed young patients are based on extensions of adult procedures. Whereas clinical picture of MDD in children, adolescents and adults have some differences. Depressed youngsters have more pronounced mood lability. Depressed adolescents have more anhedonia than depressed children. Future investigations into the efficacy and safety of treatments for children and adolescents depression should use specific instruments directly built on phenomenological and clinical picture of depressed children and adolescents. Comparison studies of pharmacotherapy, specific psychotherapies (not only CBT) and combined therapies are necessary to identify the adolescents who will benefit the most from specific or combined therapies. Further studies into the factors that influence treatment outcome including clinical picture (clinical dimensions, severity, duration, co morbidity), genetic factor, age, and i-llness course may help identify appropriate treatments for children and adolescents with MDD. Studies should include patients more severely ill, with associated psychiatric troubles, treatment resistance, history of relapses... In clinical studies, the link between "suicidality" and some clinical dimensions (which take part in clinical picture or not) must be analysed by assessing anhedonia, hopelessness feel, impulsive trait, borderline personality, familial inter-action, biological indices. New treatment should be expand and their efficacy and safety must be study: St John's worth, Bright light therapy, Trans-cranial Magnetic Stimulation. IN PRACTICE: suicide and MDD have a strongest relation and it must be investigate syste-matically during the course of MDD. The suicide risk increases in the context of past history of suicide attempts, hopelessness, psychosis, impulsivity traits, substance abuse, familial dysfunction, life events, open access of arms. The use of SSRI in depressed children and adolescents is also the question of the quality and the support of the consultant and the mode of the prescription.

Adolescent↗

The views of nurses to the conduct of a randomised controlled trial of problem drinkers in an accident and emergency department.

The Trent Regional Health Authority funded a study in 1995 to train nurses in an accident and emergency (A&E) department to screen all adult attendees for alcohol problems with a view to identifying a sample of problem drinkers to participate in a randomised controlled trial (RCT). In the RCT identified drinkers were to be assigned either to health education plus brief counselling intervention or, as controls, to health education alone. Despite 16654 attendance's at A&E during the recruitment phase of the study only 20% of attendees were screened of whom a further 19% were identified as problem drinkers by the CAGE screening questionnaire. Less than half of the problem drinkers were, however, provided with feedback by the nurses, leaving a small group of 264 eligible for entry to the RCT. The great majority of this subgroup refused an initial appointment at the specialist clinic and so the trial was abandoned. A number of in-depth interviews were undertaken with the nurses in an attempt to understand ways in which the overall conduct of the study might have been improved. This paper outlines in some detail some of the reasons for the lack of success with the study which include; general environmental factors that undoubtedly led to stress and poor morale amongst the nursing team, the differences in perception between managers and clinical nurses concerning the value of research and the inadequacy of the initial training programme. The paper concludes that there are problems in the NHS which do not provide a helpful backcloth to the successful conduct of health services research.

Adult↗

Postprandial reverse cholesterol transport in type 2 diabetic patients: effect of a lipid lowering treatment.

Deterioration of reverse cholesterol transport (RCT), an important anti-atherogenic process, may contribute to the largely unexplained severity of cardiovascular risk in type 2 diabetic patients. Among other relevant metabolic perturbations is the impairment in type 2 patients of the postprandial increase in RCT which, in normal subjects, is associated with the transfer to HDL of PL from lipolyzed chylomicrons. We have explored the possibility that improvement of postprandial lipolysis by bezafibrate might also restore the stimulated level of postprandial RCT. Twelve male patients (HbA1c 7.6 +/- 1.6% triglycerides (TG) 4.5 +/- 2.4 mmol/l) were treated for 4 weeks with 400 mg bezafibrate and compared with seven age-matched controls. Lipoproteins were analyzed over 8 h after a 1000 Kcal fat load (80% lipid), serum mediated cholesterol efflux was evaluated using 3H-cholesterol labelled Fu5AH cells. Fasting efflux was lower in patients (17.9 +/- 3.3 vs 19.9 +/- 3.0 a. units, P < 0.05) and decreased postprandially in most instead of increasing, so that area under the time-curve (AUC) was 23% lower than in controls (140 +/- 23 vs 170 +/- 25 units x h, P < 0.001) The patients' HDL failed to acquire PL and gained TG in proportion to lipemia (r = 0.660, P < 0.001). Bezafibrate restored fasting efflux (19.6 +/- 3.6 units, P < 0.005 vs pretreatment) but not postprandial increase of efflux or HDL-PL. AUC of efflux was however improved to 155 +/- 23 units h (P < 0.02). Postprandial efflux related mainly to HDL-PL in controls and patients before treatment. HDL-TG emerged as a significant negative correlate common to all groups (r = -0.674, P < 0.001 8 h after the meal). Impairment of reverse cholesterol transport in diabetic patients might therefore be due to combined postprandial deficit of PL transfer and excess accumulation of TG in HDL. The significant improvement due to fibrate treatment might thus be related to the reduction of HDL-TG contents associated with the improvement of postprandial hyperlipemia.

Bezafibrate↗

Dynamics of reverse cholesterol transport: protection against atherosclerosis.

This review considers the antiatherogenic function of high density lipoprotein (HDL) from the point of view of its dynamics within the sequential steps of reverse cholesterol transport (RCT). It is postulated that the efficiency of cholesterol flux through the RCT pathways is clinically more relevant than the HDL cholesterol concentration. The particular role of pre-beta(1)-HDL is reviewed drawing attention to the relationship between its concentration and the flux of cholesterol through the RCT system.

Animals↗