Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RCT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer.

PURPOSE: Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small-cell lung cancer (NSCLC), but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine, a radioprotector, could reduce the incidence of radiochemotherapy-induced acute and late toxicities. METHODS AND MATERIALS: Between October 1997 and August 1999, 73 patients with previously untreated Stage IIIa-IIIb NSCLC were randomized to treatment with RCT alone (n = 36) or RCT plus amifostine (300 mg/m(2) daily i.v. infusion, n = 37). RCT consisted of either paclitaxel (60 mg/m(2)) or carboplatin (AUC 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy/5 days/week to a total dose of 55 to 60 Gy. Blood cell counts were measured weekly; esophagitis and acute lung toxicity were evaluated during the treatment course. Treatment efficacy was assessed following World Health Organization criteria for response. Late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria. RESULTS: A total of 68 patients were evaluable for toxicity analysis (RCT group, n = 32; RCT + amifostine, n = 36). There was no significant difference between treatment arms in patient baseline characteristics. The incidence of Grade >or=3 esophagitis during RCT was significantly lower for patients receiving amifostine than for patients receiving RCT alone (38.9% vs. 84.4%%, p < 0.001). Furthermore, the incidence of Grade >or=3 acute pulmonary toxicity was significantly reduced in patients treated with RCT plus amifostine compared to patients who received RCT alone (19.4% vs. 56.3%, p = 0.002). At 3 months after RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than patients who received RCT alone (p = 0.009). Combined response rates (complete plus partial responses) were 82.2% in the RCT group and 88.8% in the RCT plus amifostine group (p = 0.498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced NSCLC without compromising antitumor efficacy.

Amifostine↗

Pain and immunologic response to root canal treatment and subsequent health outcomes.

OBJECTIVE: This study examined the effects of pain and stress associated with a dental procedure, root canal treatment (RCT), on natural killer cell cytotoxicity (NKCC) and the subsequent development of symptoms of upper respiratory illness during the following month. METHODS: Patients (N = 33) were recruited from those scheduled for RCT appointments. Subjects for a non-RCT comparison group (N = 14) were also recruited from dental clinic patients. Peripheral blood was drawn by use of an indwelling catheter three times: just before RCT, 30 minutes after injection of a local anesthetic, and 30 minutes after RCT (a parallel time course was followed for the comparison group.) Blood was assayed for cortisol and NKCC. Subjects completed a health diary in the month after RCT. RESULTS: Patients showed a significant increase in NKCC between baseline and RCT and a significant decrease from RCT to after RCT, whereas the comparison group did not. The NKCC following the RCT was negatively correlated with the pain level during RCT (r = -0.48, p < .01) and pain levels 2 and 6 hours after RCT (r = -0.43, p < .05; r = -0.44 p < .05, respectively). The patient group reported significantly more illness episodes 2 weeks after RCT than the comparison group (Wilcoxon rank sum = 4.78, p = .03). Discriminant function analysis correctly classified 88% of the subjects into the illness category using predictor variables of post-RCT NKCC, stress, and pain levels during RCT (F(3,21) = 8.23, p < .001). CONCLUSIONS: Transitory changes in NKCC associated with pain and stress may be implicated in the development of infectious disease episodes after an acute stressful event.

Adult↗

[Mitral regurgitation due to abnormal reinsertion of chordae tendineae (looping) of the posterior mitral leaflet: clinical and echocardiographic features].

Two-dimensional (2D) echocardiographic and clinical characteristics of patients with mitral regurgitation (MR) due to abnormal reinsertion of chordae tendineae (looping) in the middle scallop of the posterior leaflet were described and compared with those of patients with chordal rupture of the posterior leaflet. Twenty-five patients with posterior mitral valve prolapse who underwent mitral valve replacement were studied. They were categorized in three groups; 14 patients with MR due to ruptured chordae tendineae (RCT) of the posterior leaflet (RCT group); three patients with looping of the chordae tendineae in the middle scallop of the posterior leaflet (looping group); and eight patients with both RCT and looping (looping + RCT group). It was difficult to distinguish the looping group from the other two groups by their 2D echocardiographic findings, which were characteristic of those of RCT. However, the following findings were more frequently encountered in the patients with looping than in those without: 1) aberrant or absent systolic coaptation with salient arc of the posterior leaflet, observed in six of the RCT group (43%), two in the looping group (67%) and seven in the looping + RCT group (88%); 2) with thickened edges of the posterior leaflet, shown in three of the RCT group (21%), two of the looping group (67%) and five of the looping + RCT group (63%) in the long-axis view, and also noticed in four of the RCT group (29%), two of the looping group (67%) and six of the looping + RCT group (75%) in the short-axis view. In the clinical history, the onset of a heart murmur, congestive heart failure and surgical treatment occurred at significantly younger ages in the looping group than in the RCT group. As for hemodynamic parameters, pulmonary hypertension was significantly milder in the looping group than in the RCT group. In conclusion, although 2D echocardiographic findings of patients with looping were similar to those of patients with RCT, it seemed possible to differentiate the looping group from the RCT group by the 2D finding of a prolapsed posterior mitral valve with a salient arc and a thickened edge. It was also suggested that the looping of chordae tendineae in the middle scallop of the posterior leaflet was congenital in origin.

Adolescent↗

The prevalence of underpowered randomized clinical trials in rheumatology.

OBJECTIVE: The conduct of underpowered randomized controlled trials (RCT) has recently been criticized in medical journals. We investigated the current prevalence of underpowered RCT in rheumatology. METHODS: We searched to identify randomized, prospective RCT assessing clinical efficacy of treatments for adult rheumatic diseases published in English in 2001 and 2002. RCT were assessed as positive or negative based on the result of the primary outcome measure. For phase III RCT with negative results without power analysis, we calculated adequate sample size using beta = 0.20 and alpha = 0.05. We also examined trial quality by assessing the adequacy of reported random sequence generation, allocation concealment, and analysis, and compared the quality of reporting of RCT with adequate and inadequate sample size. RESULTS: A total of 228 RCT met inclusion criteria; of the 205 phase III trials, 119 were positive, 81 were negative. The remaining 5 trials made no statistical comparison between interventions, and did not supply enough information for a result to be calculated. Of the 86 negative or indeterminate RCT, 37 reported sample size calculations (all but 4 had adequate power). Of the 49 remaining phase III trials that did not report power calculations, we conducted sample size calculations; only 10 were adequately powered. Few of the underpowered RCT studied rare rheumatic diseases. Negative RCT with inadequate sample size were less likely to describe adequate random sequence generation or allocation concealment than positive RCT or negative RCT with adequate sample size. CONCLUSION: The conduct of underpowered trials is not an infrequent occurrence in rheumatology, with only 50% of negative or indeterminate phase III rheumatology RCT in 2001-2002 having adequate sample size.

Antirheumatic Agents↗

Primary groin irradiation vs primary groin surgery for early vulvar cancer.

BACKGROUND: Despite changes in technique, morbidity after surgical treatment for vulvar cancer is considerable and mainly related to the groin dissection. Primary radiotherapy to the groin is expected to result in lower morbidity. However, studies on the efficacy of primary radiotherapy for the groins in terms of groin recurrences and survival show conflicting results. OBJECTIVES: To determine whether the effectiveness and safety of primary radiotherapy to the inguino-femoral lymph nodes is comparable with surgery SEARCH STRATEGY: The literature search was carried out using the criteria set by the Cochrane Gynaecological Cancer Group. A MEDLINE and EMBASE search using the Mesh Heading 'vulvar neoplasms' and textword 'vulva' was performed. Publications on the effectiveness of primary radiotherapy treatment of early squamous cell carcinoma of the vulva were selected. SELECTION CRITERIA TYPE OF STUDY: Randomized clinical trials, case-control and observational studies of primary radiotherapy of the groin Type of participants: Patients with early squamous cell cancer of the vulva Type of interventions: inguino-femoral lymph node dissection and primary radiotherapy of the inguino-femoral lymph nodes. Type of outcome measurements: incidence of groin recurrences, survival and morbidity DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted results MAIN RESULTS: Out of nine reviewed papers only three met the selection criteria. From these studies, (one randomised controlled trial ¿RCT¿ one case-control and one observational study) it became clear from the RCT that the incidence of groin recurrences after primary radiotherapy is higher compared with surgery. survival was also worse in the radiotherapy group. The other two studies showed a higher than expected number of groin recurrences after primary radiotherapy. Morbidity after primary radiotherapy was lower compared with surgery. The conclusion of the RCT was criticized on the grounds of the depth of the radiotherapy administered. The depth of 3 cm used in the RCT, is too shallow to administer an optimal dose to the deeper groin nodes. REVIEWER'S CONCLUSIONS: As shown in an RCT, primary radiotherapy to the groin results in less morbidity but also in a higher number of groin recurrences compared with surgery. Although the technique of radiotherapy in the RCT was criticized, other uncontrolled data do not give evidence for a similar or better groin control for radiotherapy when compared to surgery. This means that surgery is still to be considered the cornerstone of therapy for the groin nodes in women with vulvar cancer. Individual patients not fit enough to withstand surgery can be treated with primary radiotherapy.

Carcinoma, Squamous Cell↗

Radio(chemo)therapy plus resection versus radio(chemo)therapy alone for the treatment of stage III esophageal cancer.

PURPOSE: To compare radio(chemo)therapy with 41.4-50.4 Gy (moderate dose, MD-RCT) plus resection versus radio(chemo)therapy with 59.4-66.6 Gy (higher dose, HD-RCT) alone for outcome in stage III esophageal cancer, and to investigate potential prognostic factors including preradiotherapy (pre-RT) hemoglobin. PATIENTS AND METHODS: 148 patients with stage III esophageal cancer, treated with MD-RCT plus resection (n = 41) or HD-RCT alone (n = 107), were retrospectively evaluated for age, gender, performance status, tumor location, tumor length, stage, histology, grading, number of chemotherapy courses, pre-RT hemoglobin, resection, overall survival (OS), metastases-free survival (MFS), and locoregional control (LC). RESULTS: On univariate analysis, MD-RCT plus resection resulted in better 2-year OS (57% vs. 25%; p = 0.049), 2-year MFS (71% vs. 39%; p = 0.041), and 2-year LC (76% vs. 39%; p = 0.003). On multivariate analysis, results maintained significance for LC (p = 0.021). According to multivariate analysis, pre-RT hemoglobin was associated with OS (p = 0.003), MFS (p = 0.043), and LC (p = 0.041), tumor length with OS (p = 0.002) and MFS (p = 0.017), and the number of chemotherapy courses with OS (p = 0.008). Complications were more frequent in the MD-RCT-plus-surgery group (p < 0.001). Acute (p = 0.47) and late toxicity (p = 0.86) were similar in both groups. In patients receiving surgery, R0 resection was superior to R1/2 resection for OS (p < 0.001), MFS (p = 0.030), and LC (p < 0.001). MD-RCT plus R0 resection was also superior to HD-RCT alone. CONCLUSION: MD-RCT plus resection resulted in better LC than HD-RCT alone. If R0 resection is possible, MD-RCT plus resection appears preferable, as it results in better outcome. If only R1/2 resection can be performed, HD-RCT alone appears preferable regarding outcome and the greater morbidity associated with resection.

Antineoplastic Agents↗

Localized squamous-cell cancer of the esophagus: retrospective analysis of three treatment schedules.

BACKGROUND AND PURPOSE: A retrospective study comparing chemotherapy and radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery in localized squamous-cell esophageal carcinoma. MATERIALS AND METHODS: Between 1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according to the UICC 78 TNM classification) were treated in two different institutions. They were divided into three groups according to the treatment proposed: E group (treatment by esophagectomy; n = 30), RCT+E group (treatment by preoperative radiochemotherapy and esophagectomy; n = 46), RCT group (treatment by radiochemotherapy; n = 63). Factors like age, tumor localization and stage were similar in all groups. An intention to treat analysis was made. RESULTS: The E group showed no postoperative mortality, while in the RCT+E group, the surgery mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative radiochemotherapy, a pathological complete response was observed in 25% of cases and the curative resection rate was higher (82% after RCT + E versus 60% after E). The 5-year survival difference between the three groups was not relevant (E group, 12.6%; RCT group, 25.8%; RCT + E group, 38.7%). The median survival was 29, 24 and 28.5 months, respectively. The event-free survival was identical for the E group and the RCT group. For patients treated by radiochemotherapy, local and/or distant relapses were significantly reduced by esophagectomy (relapses occurred in 51% of patients in the RCT + E group versus 75% in the RCT group, P = 0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to improve dysphagia was necessary for 38% of patients treated by exclusive radiochemotherapy versus 11% of patients treated by surgery (P = 0.001). CONCLUSIONS: Treatments by esophagectomy or radiochemotherapy were not significantly different. Preoperative radiochemotherapy and surgery lead to a higher survival rate than exclusive radiochemotherapy, however, with a high postoperative mortality rate. This study suggests the relevance of a prospective randomized trial to compare RCT+E and RCT alone.

Antineoplastic Combined Chemotherapy Protocols↗

Quality of reporting randomised clinical trials in dental and medical research.

OBJECTIVE: To assess 1) the quality of reporting randomised clinical trials in dental (RCT-Ds) and medical research (RCT-Ms), 2) the quality of RCT reports in relation to the journal impact factor, 3) the source of funding, and 4) the quality of RCT-Ds in different areas of dental research. DESIGN RANDOM: samples of 100 RCT-Ds and 100 RCT-Ms published in 1999 were evaluated for quality of reporting under blinded conditions with the Jadad quality assessment scale. In addition, correlation between the quality scores and journal impact factor or source of funding, as well as area of dental research were analysed. RESULTS: The quality of RCT-Ds and RCT-Ms published in 1999 was generally inadequate. The quality was largely equivalent in RCT-Ds and RCT-Ms. There was no correlation between the quality scores and the journal impact factor or the source of funding. Some differences were found in the quality scores between different areas of dental research. CONCLUSIONS: The results from these RCT-Ds and RCT-Ms show that most of them were imperfect in the reporting of methodology and trial conduct. There is a clear need to improve the quality of trial reporting in dental and medical research.

Dental Research↗

Randomized controlled drug trials on very elderly subjects: descriptive and methodological analysis of trials published between 1990 and 2002 and comparison with trials on adults.

BACKGROUND: Very elderly subjects (VES; aged 80 years or older) constitute a special population as they frequently present multiple diseases (polypathology). Results from trials on general adult populations therefore cannot be extrapolated to VES. We performed a census of randomized controlled trials (RCT) on VES published between 1990 and 2002, and carried out a descriptive and methodological analysis of these RCT/VES, comparing them with matched RCT on general adult populations (control RCT, RCT/C). METHODS: We searched for RCT/VES in two international databases (EMBASE and MEDLINE) and then manually. RCT/C were matched to RCT/VES for disease area and year of publication. The methodological quality of each RCT was assessed with Chalmers' scale. RESULTS: We identified 84 RCT/VES, 63 of which were conclusive and 21, inconclusive. Subjects were institutionalized in 48 RCT, and community dwelling in 11 RCT (unspecified in 25 RCT). Efficacy was the main criterion in 75 RCT; tolerance in 9 RCT. Twenty-six RCT were published by geriatrics journals, and 58 by general medical journals. The RCT/VES covered most of the disease areas of geriatrics. The 84 RCT/VES had a mean methodological quality score of 0.578 +/- 0.157. The matched 84 RCT/C had a mean methodological quality score of 0.592 +/- 0.116 (p = .466). The methodological quality score of RCT/VES increased with the number of included subjects (p = .004) and the year of publication (p = .001). CONCLUSIONS: The methodological quality of RCT/VES is equivalent to that of RCT in general adult populations. Nevertheless, RCT/VES remain very scarce, and neglect certain diseases. RCT/VES and the inclusion of very elderly subjects in RCT on adults should be strongly encouraged.

Adult↗

[Mitral regurgitation due to ruptured chordae tendineae: sensitivity and specificity of the diagnostic criteria by two-dimensional echocardiography].

The sensitivity and specificity of the two-dimensional (2D) echocardiographic criteria for diagnosing ruptured mitral chordae tendineae (RCT) were assessed in 52 cases with non-rheumatic mitral regurgitation undergoing mitral valve prostheses. At surgery, chordal rupture was confirmed in 38 cases (RCT group), but not in 14 cases (non-RCT group). Four presumptive and three definite findings for diagnosing mitral chordal rupture using 2D echo were evaluated. Mitral valve prolapse with incomplete coaptation of the mitral leaflets in the long-axis view was observed in 32 cases in the RCT group and in four cases in the non-RCT group (sensitivity 84%, specificity 80%). In the short-axis view at the level of the mitral orifice, delayed closure of the involved mitral leaflet was observed in four cases in the RCT group but in none of the non-RCT group (sensitivity 11%, specificity 100%), delayed protodiastolic opening of the involved leaflet in 15 cases of the RCT group and in one of the non-RCT group (sensitivity 39%, specificity 92%), and finally, increased excursion of the involved valve in 27 cases of the RCT group and in three cases of the non-RCT group (sensitivity 71%, specificity 79%). The following three echocardiographic findings were regarded as direct evidence of mitral chordal rupture: Fine echoes with abnormally rapid transverse and/or oblique motion around the mitral orifice in the short-axis view were observed in 13 cases of the RCT group (sensitivity 34%, specificity 100%); echoes with abnormal whip-like motion in the long-axis view in 10 cases (sensitivity 26%, specificity 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Psychological therapies for people with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a relatively common personality disorder with a major impact on health services as those affected often present in crisis, often self-harming. OBJECTIVES: To evaluate the effects of psychological interventions for people with borderline personality disorder. SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general bibliographic databases (December 2002) and searched relevant reference lists for further trials. SELECTION CRITERIA: All relevant clinical randomised controlled trials involving psychological treatments for people with BPD. The definition of psychological treatments included behavioural, cognitive-behavioural, psychodynamic and psychoanalytic. DATA COLLECTION AND ANALYSIS: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). MAIN RESULTS: We identified seven studies involving 262 people, and five separate comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as usual studies found no difference for the outcome of still meeting SCID-II criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to 1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI 0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1 RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical difference in favour of people receiving DBT compared with those allocated to treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD -15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of interviewer-assessed alcohol free days, skewed data are reported and tend to favour DBT. When a substance abuse focused DBT was compared with comprehensive validation therapy plus 12-step substance misuse programme no clear differences were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87) or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When dialectical behaviour therapy-oriented treatment is compared with client centred therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted 0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2 to 11). There were no differences for outcomes of anxiety and depression (n=24, 1 RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI 0.14 to 1.28) but people who received DBT had less general psychiatric severity than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally this one relevant study reports skewed data for suicidal ideation with considerably lower scores for people allocated to DBT. When psychoanalytically oriented partial hospitalization was compared with general psychiatric care the former tended to come off best. People who received treatment in a psychoanalytic orientated day hospital were less likely to be admitted into inpatient care when measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in psychoanalytically oriented partial hospitalization needed day hospital intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to 0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic medication by the 30 to 36 month follow-up, than those receiving psychoanalytic treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and depression scores were generally lower in the psychoanalytically oriented partial hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3 CI 3 to 6), as are global severity scores. People receiving psychoanalytic care in a day hospital had better social improvement in social adjustment using the SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD -0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR leaving the study early 1.00 CI 0.23 to 4.42). AUTHORS' CONCLUSIONS: This review suggests that some of the problems frequently encountered by people with borderline personality disorder may be amenable to talking/behavioural treatments but all therapies remain experimental and the studies are too few and small to inspire full confidence in their results. These findings require replication in larger 'real-world' studies.

Behavior Therapy↗

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.

PURPOSE: To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). METHODS AND MATERIALS: Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). RESULTS: This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072). CONCLUSION: With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.

Adult↗

Should we be performing more randomized controlled trials evaluating surgical operations?

BACKGROUND: The objective of this study was, first to determine what proportion of clinical treatment evaluation questions involving surgical operations could be answered by a randomized controlled trial (RCT). Second, for those questions not amenable to a RCT, to determine the problems that potentially preclude the initiation of RCT in an ideal clinical research setting. METHODS: A sample of treatment evaluation questions involving a surgical procedure was obtained by a computerized search of the surgical literature. Problems precluding a RCT were defined. Their face validity and interobserver and intraobserver reliability were assessed. By use of these criteria, the sample questions were evaluated to determine whether a RCT could be performed and, if not, the predominant reasons precluding RCT of surgical procedures. RESULTS: Only 38.8% of treatment evaluation questions could have been answered by a RCT in an ideal clinical research setting. Patient preference was the most common precluding problem encountered (40% of all problems). The principal precluding problem was patient preference in 23.1%, an uncommon condition in 24.2%, and lack of community (clinical) equipoise in 10%. Methodologic issues (1.2%) and surgical preference (2.3%) were infrequent precluding problems. Questions evaluating therapy for malignant disease, comparing surgical with nonsurgical therapies, and where survival was the primary outcome were more likely to have problems precluding RCT. CONCLUSIONS: In the ideal situation RCT can be performed to evaluate only 40% of treatment questions involving surgical procedures. Patient preferences, uncommon conditions, and lack of surgical community equipoise appear to be the most common reasons precluding the of RCT of surgical operations.

Humans↗

Randomised controlled trials and publication trends in periodontal research during 1980-2000.

OBJECTIVES: To study publication trends, as well as the number and proportion of randomised controlled trials covering different areas of periodontal research (RCT-Ps). MATERIAL AND METHODS: The study was based on Medline searches (MeSH terms) for the period 1980- 2000. The RCT-Ps (n = 675) were examined for relevance for different areas of periodontal research, journals of publication, and the countries of origin. RESULTS: In periodontal research the annual number of publications had increased from 162 in 1980 to 440 in 2000. Moreover, clinical trials in periodontal research (CT-Ps) had increased more than 10-fold, and RCT-Ps more than 15-fold. More than 4 out of 10 RCT-Ps covered the areas 'periodontal surgery' and 'gingivitis and plaque treatment or prevention'. More than 6 out of 10 RCT-Ps in total and more than 8 out of 10 RCT-Ps about 'periodontal surgery', were published in two different journals. U.S.A was the most common country of origin of RCT-Ps, contributing to almost 4 out of 10 RCT-Ps during 1988-2000. CONCLUSION: The annual number of RCT-Ps increased substantially during 1980-2000, and a few clinical research areas predominated. Future research should give priority to areas where clinical evidence is scarce and where high-quality RCT-Ps are most needed.

Dental Research↗

Survey of the impact of randomised clinical trials on surgical practice in France. French Associations for Research in Surgery (AURC and ACAPEM). Association Universitaire de Recherche en Chirurgie. Association des Chirurgiens de l'Assistance Publique pour l'Evaluation Médicale.

OBJECTIVE: To evaluate the impact of randomised clinical trials (RCT) on decision-making and therapeutic policies among general and gastrointestinal surgeons in France. DESIGN: Telephone questionnaire. SETTING: Multicentre study, France. SUBJECTS: A random sample of 152 surgeons, mean (SD) age 50 (8) years. INTERVENTIONS AND MAIN OUTCOME MEASURE: Surgeons were asked 12 questions about their knowledge of RCT and how trials were conducted; influence of RCT on their treatment policies; means of obtaining information about treatments; how they evaluated their own results; whether they were willing to take part in RCT; and personal details including age, speciality, and type of practice. Surgeons were stratified according to age and type of practice. RESULTS: 148 questionnaires were suitable for analysis. 83 surgeons (56%) were under 50 years old, 38 (26%) were exclusively gastrointestinal surgeons, 82 (56%) worked in private practice, and 36 (24%) worked in teaching and university hospitals. The rest undertook mixed duties. When asked to say where they obtained their knowledge about antibiotics, 91 (61%) referred to RCT; these were mainly hospital-based, gastrointestinal, and younger surgeons. Asked to name a RCT-based policy, 81 (55%) gave medical rather than operative examples. 80 (54%) had already participated in a RCT; 79 (53%) said that they were willing to participate in a RCT that included random allocation of patients (there were no statistically significant differences in answers according to speciality or type of practice, although younger surgeons answered "yes" to both questions). Specialised journals were the main source of information for 115 (78%), and surgeons read a mean of 40 issues/year. 142 (96%) read journals in French and 66 (45%) in English, but this number fell to 10 (15%) of the 65 surgeons aged 50 or more. Personal experience was considered a more important source of therapeutic knowledge by older and specialist surgeons. 109 surgeons (74%) recalled patients during the first month postoperatively to evaluate their results. CONCLUSIONS: French surgeons, particularly those aged 50 or over, are not well informed about the nature, conduct, and value of RCT. Most of their information is acquired through reading and attending scientific meetings and congresses. Surgeons tended to attach more importance to the fame of the author than to the conduct of the study. The overall impact of RCT was weak among the surgeons questioned.

Adult↗

Cholera toxin subunit B inhibits IL-12 and IFN-{gamma} production and signaling in experimental colitis and Crohn's disease.

BACKGROUND AND AIMS: Cholera toxin B subunit (CT-B) is a powerful modulator of immune responses. The authors have previously demonstrated that oral administration of recombinant CT-B (rCT-B) is able to prevent and cure the Crohn's disease (CD)-like trinitrobenzene sulfonic acid (TNBS) mediated colitis. In this study they extended their observations and examined if rCT-B interferes with the molecular signaling underlying the Th1 type response both in TNBS colitis and in ex vivo human CD explants. METHODS: TNBS treated mice were fed with rCT-B, and IFN-gamma and IL-12 production by colonic lamina propria mononuclear cells (LPMC) was examined by ELISA. In vitro culture of mucosal explants from CD patients and non-inflammatory bowel disease controls, pre-incubated with rCT-B, were examined for IFN-gamma and IL-12 production by ELISA and semiquantitative reverse transcription polymerase chain reactions. STAT-1, -4, -6 activation and T-bet expression were examined following rCT-B treatment by western blotting both in TNBS treated mice and in human mucosal explants. RESULTS: rCT-B significantly reduced IL-12 and IFN-gamma secretion by LPMC from TNBS treated mice. Consistent with this, rCT-B inhibited both STAT-4 and STAT-1 activation and downregulated T-bet expression. Inhibition of Th1 signaling by CT-B associated with no change in IL-4 synthesis and expression of active STAT-6 indicating that rCT-B does not enhance Th2 cell responses. Moreover, in vitro treatment of CD mucosal explants with rCT-B resulted in reduced secretion of IL-12/IFN-gamma and inhibition of STAT-4/STAT-1 activation and T-bet expression. CONCLUSIONS: These studies indicate that CT-B inhibits mucosal Th1 cell signaling and suggest that rCT-B may be a promising candidate for CD therapy.

Adult↗

[Study on the effects of the hypocholesteremic agents, cholestyramine and compactin on the induction of renal tumors in rats by N-ethyl-N-hydroxyethyl nitrosamine].

Male Wistar rats were administered with 0.1% N-ethyl-N-hydroxyethyl nitrosamine (EHEN)-containing diet for 2 weeks, and were then Rept for further 23 weeks on basal diet. At 25 weeks, the rats were divided into three groups. Group I was fed on basal diet to 40 weeks. Group II was fed on 2% cholestyramine-containing diet to 40 weeks. Group III was fed on 0.02% compactin-containing diet to 40 weeks. At 40 weeks after the start of experiment, the rats were sacrificed and examined histologically for the incidence of renal cell tumors (RCT) and dysplastic foci (DF) of the kidney. The serum levels of total cholesterol at 40 weeks were 108.9 +/- 23.4, 78.8 +/- 12.5, 95.6 +/- 43.4 mg/dl in Groups I, II and III, respectively. The levels were significantly lower in Groups II and III (p less than 0.01, 0.05, respectively, Wilcoxon test) than Group I. The average numbers of DF were 4.5 +/- 4.1, 1.3 +/- 0.3, 2.3 +/- 2.0 per cm2 of kidney slices in Groups I, II and III, respectively. DF were significantly less in Group II than Group I (p less than 0.025, Wilcoxon test), and less in Group III than Group I (not statistically significant). There was no statistical difference between Groups II and III. RCT were observed in 9 of 34 kidneys (26%), 2 of 18 (11%), 1 of 20 (5%) in Groups, I, II and III, respectively. The ratios of kidneys with RCT were lower in Group II than Group I (not statistically significant), and lower in Group III than Group I (p less than 0.05, qui-square test). There was no statistical difference between Groups II and III. RCT were classified into gross and microscopic lesions. Four gross RCT were found in 4 rats of Group I; no gross RCT was in Groups II and III. There were 5 microscopic RCT in 5 rats, 3 in 2, 1 in 1 in Groups I, II and III, respectively. In Group I, serum levels of total cholesterol were compared between the following subgroups; the rats with RCT and/or with more than 10 DF per kidney, and the rats without RCT and with less than 10 DF per kidney. The mean level was 120.8 +/- 21.8 mg/dl in the former subgroup, which was significantly higher than that (94.1 +/- 19.6 mg/dl) in the latter subgroup (p less than 0.025, Wilcoxon test). The serum cholesterol was suggested to act as a promoter in the development of DF and RCT.

Animals↗

Inositol for respiratory distress syndrome in preterm infants.

BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. OBJECTIVES: To assess the effectiveness/safety of supplementary inositol in preterm infants with RDS in reducing adverse neonatal outcomes. SEARCH STRATEGY: Medline, Embase, and Reference Update Databases were searched in August 1997 using key words: inositol and infant-newborn and random allocation or controlled trial or randomized trial (RCT). The reference lists of identified RCTs, personal files and Science Citation Index were searched. Unpublished additional information was obtained from the authors of one RCT published in abstract form. SELECTION CRITERIA: All randomized controlled trials of inositol supplementation to preterm infants with a control group that received a placebo or no intervention were included. Outcomes of interest were bronchopulmonary dysplasia (BPD), death, BPD or death, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis. DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted independently by the two researchers and any discrepancy was resolved through consensus. Revman was used for analysis of the data. MAIN RESULTS: Four reports of three RCTs were identified. One report was a duplicate publication. The outcome of death or bronchopulmonary dysplasia was reported in two trials, and was found to be significantly reduced (RR 0.56, 95% CI 0.42, 0.77; RD -0.215, 95% CI -0.323, -0.107). The outcome of death was reported in two trials and was found to be significantly reduced (RR 0.48, 95% CI 0.28, 0.80; RD -0.131, 95% CI -0.218, -0.043). Retinopathy of prematurity, stage 4 or needing therapy, was reported in two trials, and was found to be significantly reduced (RR 0.09, 95% CI 0.01, 0.67; RD -0.078, 95% CI -0.128, -0.027). Intraventricular hemorrhage, grade III-IV, was significantly decreased (RR 0.55, 95% CI 0.32, 0.95; RD -0.090, 95% CI -0.170, -0.010). Neither sepsis nor necrotizing enterocolitis outcomes were increased. When a secondary analysis was done excluding a study published in abstract form, the results differed only in that there was a significant reduction in retinopathy of prematurity, any stage (RR 0.53, 95% CI 0.29, 0.97; RD -0.082, 95% CI -0.159,-0.005). REVIEWER'S CONCLUSIONS: Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multi-center RCT of appropriate size is justified to confirm these findings.

Dietary Supplements↗