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 217 records · Page 12Linked to original sources
PubMed2004

Quetiapine for schizophrenia.

BACKGROUND: Quetiapine is an atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for the treatment of schizophrenia and other psychoses. OBJECTIVES: To determine the effects of quetiapine for schizophrenia in comparison to placebo, and other antipsychotics. SEARCH STRATEGY: Electronic searches of the Cochrane Schizophrenia Group's Register of Trials (February 2003), Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1),EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. We contacted AstraZeneca Pharmaceuticals for information regarding unpublished trials. The review was updated in February 2003. SELECTION CRITERIA: All randomised controlled trials where adults with schizophrenia or similar illnesses were assigned to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. We analysed data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI). Only homogeneous data were interpreted as favouring treatment or control. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics (NNH). We calculated relative risk (RR) for dichotomous data, and weighted mean differences (WMD) for continuous data. MAIN RESULTS: Despite the fact that 3443 people were randomised in 12 quetiapine studies, there are almost no data on service utilisation, economic outcomes, social functioning and quality of life. Over half of those within the quetiapine versus placebo comparison were lost to follow up (53% quetiapine vs 61% placebo, n=716, 4RCTs, RR 0.84 CI 0.7 to 0.9, NNT 11 CI 7 to 55) so it is impossible to interpret any ratings of global or mental state within this comparison with confidence. People allocated quetiapine, however, did not have more movement disorders than those given placebo (n=395, 2 RCTs, RR needing medication for EPSE 0.62 CI 0.3 to 1.2). The same applies to the comparison of >/= 250 mg/day quetiapine with < 250 mg/day quetiapine (49% dropout >/= 250 mg/day vs 58% < 250 mg/day, n=1066, 3 RCTs, RR 0.84 CI 0.8 to 0.9, NNT 11 CI 7 to 29). It should be noted that two deaths occurred in the higher dose group (n=618, 1 RCT, RR 0.1 CI 0.0 to 2.1). When quetiapine was compared with typical antipsychotics, about 36% of both groups failed to complete the short-term studies (n=1624, 6 RCTs, RR 0.87 CI 0.8 to 1.0). Average change in global state was heterogeneous and equivocal (n=762, 3 RCTs, WMD in short term 0.19 CI 0.00 to 0.38, I squared 76%). Mental state measures were also equivocal (n=1247, RR not improved 0.97 CI 0.9 to 1.1) including specific measures of negative symptoms (n=305, 1 RCT, MD change in SANS short term 0.94 CI -0.2 to 2.0). Movement disorders were less prevalent for those allocated quetiapine (n=1117, 4 RCTs, RR needing medication for extrapyramidal adverse effects 0.47 CI 0.4 to 0.6, NNT 4 CI 4 to 5, I squared 88%). Dry mouth (n=649, 2 RCTs, RR short term 2.85 CI 1.5 to 5.6, NNH 17 CI 7 to 65) and sleepiness (n=959, 3 RCTs, RR 1.51 CI 1.1 to 2.2, NNH 18 CI 8 to 181) may also be more prevalent for people given quetiapine compared with the older drugs. In the quetiapine versus risperidone comparison, over 30% of people left the study before completion (n=728, 1 RCT, RR 0.94 CI 0.7 to 1.2). Four people, all treated with quetiapine, died during the study (n=728, 1 RCT, RR 2.86 CI 0.2 to 52.8). Continuous mental state measures did not show clear differences between the two drugs (n=637, 1 RCT, MD PANSS 1.2 CI -2.0 to 4.4). However, considerably fewer people given quetiapine needed medication for extrapyramidal side effects compared with those allocated to risperidone (n=712, 1 RCT, RR 0.27 CI 0.2 to 0.5, NNT 11 CI 10 to 16). Quetiapine caused more dizziness (n=728, 1 RCT, RR 1.85 CI 1.0 to 3.3, NNH 18 CI 7 to 487), more dry mouth (n=728, 1 RCT, RR 2.11 CI 1.2 to 3.8, NNH 14 CI 6 to 82) and more sleepiness than risperidone (n=728, 1 RCT, RR 2.03 CI 1.4 to 2.9, NNH 7 CI 4 to 17). REVIEWERS' CONCLUSIONS: Quetiapine is effective for the treatment of schizophrenia, but it is not much different from first-generation antipsychotics and risperidone with respect to treatment withdrawal and efficacy. In comparison to first-generation antipsychotics and risperidone, quetiapine has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness. More clearly reported pragmatic randomised controlled trials should be carried out to determine its position in everyday clinical practice. Studies of medium and long-term effects, including cost-effectiveness, quality of life, social functioning and service utilisation, in comparison with the effects of typical and atypical antipsychotics should be priority areas.

Adult↗
PubMed1998

Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer.

BACKGROUND: Amifostine has reduced toxicities associated with radiation therapy and platinum-based chemotherapy. In a phase II randomized trial, we investigated the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy (RCT) in patients with head and neck cancer. PATIENTS AND METHODS: Thirty-nine patients with stage III or IV squamous cell carcinomas of the head and neck received RCT (following surgery or as primary treatment). Radiotherapy was given five days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy in conjunction with carboplatin 70 mg/m2 on days 1 through 5 and days 21 through 26. Eligible patients were randomised to receive RCT alone or preceded by a rapid infusion of amifostine (500 mg) on the days when carboplatin was administered. RESULTS: Patients receiving amifostine + RCT (n = 25) had significantly reduced mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparison with patients receiving RCT alone (n = 14). Additionally, patients receiving amifostine + RCT had significantly less thrombocytopenia (P = 0.001) and leukopenia (P = 0.001). At 12 months following therapy, 79% of patients receiving amifostine + RCT had no evidence of disease compared with 64% of those receiving RCT alone. CONCLUSIONS: Amifostine reduces the RCT-induced toxicities in patients with head and neck cancer and has no negative impact on antitumour efficacy.

Adult↗
PubMed2002

Reading the research literature. Putting randomized clinical trials into practice. 2.

Randomized clinical trials (RCT) are our best available method for determining whether a treatment works or has what we technically call efficacy. RCTs set out to demonstrate that a particular treatment regimen works better than a conventional standard treatment or placebo, for a particular type of patient, with a particular condition or indication. The results of an RCT are, generally, used by the Food and Drug Administration (FDA) as the basis for approving treatments--especially drug treatments. The approval of a drug generally indicates that at least two independently conducted, randomized clinical trials have demonstrated that the treatment has efficacy for at least one indication. Once a drug is FDA approved, a physician has the authority to prescribe it for the approved, as well as other, indications. However, if used for another indication, a physician may risk a greater liability, should the outcome not be as expected. Unfortunately, RCT conducted for one indication cannot be used to support either the efficacy or safety of the treatment for another indication. Even when used for an approved indication, it is difficult to know what to expect when a new treatment is put into practice. The most difficult part of reading medical literature is to apply or put it into practice--what we call extrapolation. Extrapolation differs from interpretation, which refers to results of patients included in the investigations, while extrapolation asks questions about those who receive the treatment in practice. This important distinction is called effectiveness--when a treatment works in practice, as opposed to efficacy, which indicates it works under the conditions of an RCT. Authors of a randomized clinical trial draw conclusions about effectiveness as well as efficacy, because they are eager to have their successful treatment used and, despite being tempered by the peer review process, are likely to encourage its widespread adoption. Even if the author is not biased toward adopting the treatment, it is important to recognize that you, as the practitioner, know your patients best. Your patients may be quite different from those included in the RCT. Therefore, we need a systematic approach in order to draw conclusions from an RCT and apply them in practice. This paper will take a look at two basic questions in order to apply the results of an RCT. It will ask how large an impact can we expect on average for patients who are different from those in the RCT, and what conclusions can we draw about safety from an RCT?

Humans↗
PubMed1987

[Mitral regurgitation due to ruptured chordae tendineae in the aged: a clinicopathologic study].

We observed 13 cases of mitral regurgitation (MR) due to ruptured chordae tendineae (RCT) among 4,000 consecutive autopsies of patients over 60 years of age (0.33%). There were four men and nine women whose average age was 79.8 yrs. Five cases had a single RCT (Group I) and eight had multiple RCT (from two to eight chordae) (Group II). The sites of RCT were in the posterior mitral leaflet (PML) in nine, the anterior leaflet in one, and both in three. All in Group I showed RCT in the PML; the posterior scallop in two and the middle scallop in three. The average heart weight was 340 g in Group I and 431 g in Group II. Sclerosis of the coronary arteries, the circumference of the mitral valve ring, and thickness of the leaflets did not differ significantly. Estimated volume of the left atrium was significantly greater in Group II than in Group I (185 ml vs 57 ml, p less than 0.05). Jet lesions were observed in 10 of the 13 cases. The etiologies of RCT were previous endocarditis in two, mitral valve prolapse in three, and spontaneous rupture in eight. Congestive heart failure was observed in three (60%) in Group I and eight (100%) in Group II (p less than 0.01). Cardiothoracic ratio more than 60% was observed in three (60%) of Group I and six (75%) of Group II. Atrial fibrillation was demonstrated in one in Group I (20%) and six (75%) in Group II (p less than 0.05), and cardiac death in one (20%) in Group I and six (75%) in Group II (p less than 0.05). Phonocardiograms showed pansystolic murmur in all cases, third heart sound in nine (69%), and fourth heart sound in four (57%). Echocardiographically, RCT was diagnosed in six of nine cases (67%). In conclusion, patients with RCT involving more than two chordae tendineae can show more severe clinical course than cases with a single RCT.

Aged↗
PubMed1982

Human prostate androgen receptor quantitation: effects of temperature on assay parameters.

When cytoplasmic extracts of human prostatic tissues were split to permit quantitation of total androgen receptor (RCT) content by saturation analysis at 15 degrees and 2 degrees, we observed that 30% (10 of 32) of the specimens yielded statistically increased values for RCT following incubation at 15 degrees as compared to 2 degrees. Considering only those specimens (13 of 32) showing statistically differentiated RCT yield, 77% (10 of 13) yielded greater RCT content following incubation at 15 degrees. The families of association constants (Ka) obtained for RCT determinations at 2 degrees and 15 degrees were not statistically differentiated. The increased yield of RCT content determined at 15 degrees was 95% (mean) and 20 to 350% (range). Nuclear androgen receptor content determined at 15 degrees was greater for 25% (2 of 8) of the patient specimens when compared to split determinations performed at 2 degrees. Incubation of nuclear extracts at 15 degrees resulted in a significant 3-fold reduction in receptor Ka for methyltrienolone (R1881). This did not appear to affect assay precision. These studies showed that incubation at 15 degrees is preferable to incubation at 2 degrees for quantitation of RCT and nuclear androgen receptor content by saturation analysis. Single saturating dose determinations of RCT consistently yielded underestimates. The extent of underestimate was variable from specimen to specimen and was both ligand concentration and assay temperature dependent. Our data suggest that results of single saturating dose determinations of RCT require cautious interpretation.

Cell Nucleus↗
PubMed1994

Randomized controlled trials in surgery.

BACKGROUND: The objective was to determine the number of randomized controlled trials (RCT) performed by surgeons, published in surgical journals, or comprising a surgical arm and to assess their characteristics and overall quality. METHODS: RCT in general surgery (including gastrointestinal, breast, surgical oncology, vascular, critical care, and trauma) published in 1990 were retrieved by MEDLINE and analyzed to determine the funding agency, type of therapy, area of surgery, journal published, country of origin, number of centers, and whether a surgeon was the principal author. The completeness of the MEDLINE search was compared to a manual search of the literature. All RCT were assessed with Chalmers' qualitative score. RESULTS: MEDLINE retrieved 202 surgical RCT (46% of those retrieved by a manual search) with a mean score of 0.40 +/- 0.13. However, surgical RCT were performed by surgeons in only one third of trials, compared surgical therapies in only one quarter of trials, and were published in surgical journals in less than one third of trials. Only 22% of surgical RCT were funded by peer reviewed granting agencies. The strongest variables determining the quality of surgical RCT were the type of therapy tested (p = 0.0001), the type of journal published (p = 0.006), and the area of general surgery (p = 0.007). CONCLUSIONS: Although surgical RCT are being performed, there are a relatively low proportion and standard of RCT performed by surgeons as the principal author, published in surgical journals, and comparing surgical therapies. This may reflect a lack of expertise by surgeons in clinical trials, lack of funding for surgical trials, methodologic problems peculiar to surgical trials, or a need for adoption of other research designs to assess surgical therapies.

Authorship↗
PubMed1993

[Randomized clinical trials in the Nederlands Tijdschrift voor Geneeskunde].

OBJECTIVE: To collect all randomized clinical trials (RCT) published in the Nederlands Tijdschrift voor Geneeskunde (Ned Tijdschr Geneeskd) in order to present them to the Cochrane Centre, Oxford, United Kingdom, to be included in the international database of RCT's, which will be used to perform meta-analyses. DESIGN: Retrospective bibliometric study. SETTING: Editorial office of Ned Tijdschr Geneeskd. METHOD: All original papers (OP), published between the May 1st, 1948 and May 1st, 1993 were studied. Papers were selected that met the criteria for RCT: randomization or the similar assignment of patients to different treatment groups. RESULTS: Of 6820 OP 259 (3.8%) were selected. In 69 (26.6%) randomization seemed to be performed correctly and in 20 (7.7%) randomization was not correct; in 170 (65.6%) there was no randomization. In the period May 1st, 1948 till May 1st, 1968 24 RCT's were published, in the period May 1st, 1973 till May 1st, 1993 60. Most RCT's (78%) describe the effects of pharmaceutical treatment. CONCLUSION: RCT's as such were difficult to recognize in Ned Tijdschr Geneeskd. Over the years there was an increase in the number of published RCT's. The problems we found with the design of RCT's and randomization are still current. An international register of published and/or planned RCT's, as envisaged by the Cochrane Centre, will make it easier to carry out meta-analyses.

Humans↗
PubMed2000

Using randomized controlled trials to evaluate socially complex services: problems, challenges and recommendations.

BACKGROUND: Following the lead of evidence-based medicine, practice based on effectiveness research has become the new gold standard of contemporary public policy. Studies of this sort are increasingly demanded to evaluate services provided by mental health, social services and criminal justice systems. AIMS: The paper questions whether the simple randomized controlled trial (RCT) paradigm as applied in clinical trials can be used "off the rack" to evaluate socially complex service (SCS) interventions. These are services that are characterized by complex, diverse and non-standardized staffing arrangements; ambiguous protocols; hard-to-define study samples and unevenly motivated subjects and dependence on broader social environments. The difficulty of ensuring precise protocols, equivalent groups (tied to a meaningful target population) and neutral and equivalent trial environments under real world conditions are explored, as are the implications of not achieving standardization and equivalence. METHODS: Limitations of effectiveness research as a research tool and information source are examined by comparing the assumptions underpinning the simple RCT to the characteristics of SCS interventions, as illustrated by programs targeted to mentally disordered offenders in Britain. RESULTS: SCSs violate the assumptions underpinning the simple RCT model in ways that draw into sharp question the validity, reliability and generalizability of inferences of SCS trials. DISCUSSION: The RCT is not a panacea. Effectiveness research of SCS interventions that is based on the RCT model is unlikely to yield valid, reliable and generalizable inferences without becoming more complex in design and more sensitive to issues of selection bias, unmeasured variables and endogeneity. Ten recommendations are offered for stylizing the RCT design to the characteristics of socially complex services. IMPLICATIONS: It remains an empirical issue whether RCT-based services effectiveness research can inform mental health policy. Without major design innovations, it is more likely that the information generated by this research will have limited practical use, especially if the RCT model is unable to control for the effect of social complexity and the interaction between social complexity and dynamic systemic change. Scientific evaluations of services make clinical and economic sense so long as they are designed to meet the challenges of the services of which they promise greater knowledge.

Journal Article↗
PubMed2005

Challenges to evidence-based medicine: a comparison of patients and treatments in randomized controlled trials with patients and treatments in a practice research network.

BACKGROUND: The practice of evidence-based medicine depends on the availability of clinically relevant research, yet questions have been raised about the generalizability of findings from randomized controlled trials (RCTs). OBJECTIVES: The aim of this study was to quantify differences between RCT patients and treatments and those in day-to-day clinical practice. RESEARCH DESIGN: Data from published reports of two key RCTs underlying recent treatment advances in psychiatry were compared with data on routine psychiatric practice collected through a Practice Research Network (PRN). SETTING: Hospital inpatient units (RCT) and the full range of psychiatric practice settings in the United States (PRN). SUBJECTS: Adults with bipolar I disorder and adults with schizophrenia. MEASURES: Demographic (age, gender, race), clinical (principal diagnoses, comorbid conditions, psychosocial functioning, and histories of hospitalization), and treatment (medication name and dosage) characteristics. RESULTS: PRN patients had more comorbid conditions and were more likely to be white, female, and older than RCT patients. In all, 38% of PRN patients with schizophrenia and 55% of PRN patients with bipolar I disorder would have been ineligible for the corresponding RCT. Most PRN patients receiving an RCT study medication were also receiving other medications not allowed by the RCT protocol. CONCLUSIONS: Findings support the assertion that RCT patients and treatments are not typical of those in clinical practice, and most patients in clinical practice are receiving treatments that do not have direct empirical support. Research is needed to determine the extent to which RCT findings should be used to guide routine clinical decisions.

Adult↗
PubMed2003

A comparison of respiratory compensation thresholds of anaerobic competitors, aerobic competitors and untrained subjects.

This study compared respiratory compensation thresholds (RCT) ( VCO(2) inflection point) of competitors in highly aerobic events (aerobic competitors, ARC) ( n=16), competitors in highly anaerobic events (anaerobic competitors, ANC) ( n=15), and untrained subjects (UT) ( n=25). Maximal oxygen consumption ( VO(2max)), respiratory compensation threshold as a percentage of VO(2max) (RCT), and VO(2) at RCT ( Vdot;O(2RCT)) were determined during a maximal Bruce treadmill protocol. VO(2max) (ml x kg(-1) min(-1)) was significantly greater ( P<0.05) for ARC [67.2 (8.5)] than for ANC [50.0 (7.8)] and UT [43.8 (5.4)]. However, the difference between ANC and UT only approached significance ( P=0.07). RCT was not significantly different between ARC [76.3 (8.7)] and ANC [80.7 (6.8)] but was significantly lower ( P<0.05) for UT [62.5 (8.8)]. VO(2RCT) (ml x kg(-1) min(-1)) was significantly greater ( P<0.05) for ARC [51.6 (11.0)] and ANC [40.2 (6.6)] than for UT [27.4 (5.4)], with a significant difference also between ARC and ANC. While used as a criterion for group assignment, greater VO(2max), as well as RCT values in ARC (vs UT), reflect chronic aerobic training adaptations. ANC demonstrated VO(2max) values intermediate to ARC and UT, with RCT very comparable to those found in ARC. The results suggest subjects competitive in highly anaerobic events do not possess excessively high VO(2max) values. These individuals, however, demonstrate a high RCT when values are expressed relative to VO(2max). Oxygen consumption at the RCT in this group is superior to that in UT but inferior to that in ARC, which likely has important implications regarding performance.

Adaptation, Physiological↗
PubMed2005

Oncocytic modifications in rectal adenocarcinomas after radio and chemotherapy.

The purpose of the study is to highlight oncocytic modifications in rectal adenocarcinomas and evaluate a possible correlation with preoperative radiochemotherapy (RCT). Twenty-eight cases of advanced rectal carcinoma, treated preoperatively by 5-fluorouracil (200-225 mg/m(2)) and 44-46 Gy in 22-23 fractions, were studied. All patients underwent biopsy before RCT. Surgery was performed within 6 weeks after RCT. In all cases oncocytic modifications were searched for on hematoxylin and eosin (H&E) and at immunohistochemistry using an antimitochondrial antibody. In addition, in two cases, both pre- and post-RCT tissues were examined at electron microscopy. All tumors were adenocarcinomas. In pre-RCT biopsies, oncocytic changes were difficult to find on H&E, while the antimitochondrial antibody strongly stained numerous neoplastic cells (mean 48.4%). In post-RCT surgical specimens, oncocytic changes were detected in 24 out of 28 cases on H&E and the antimitochondrial antibody stained most of the residual neoplastic cells (mean 76.7%). Ultrastructural examination revealed large and bizarre mitochondria inside tumor cells both in pre- and post-RCT tissues. In conclusion, the present data suggest that rectal adenocarcinomas are "mitochondrion-rich" tumors. After preoperative RCT, residual neoplastic cells acquire a definite oncocytic phenotype.

Adenocarcinoma↗
PubMed1998

Radiochemotherapy with amifostine cytoprotection for head and neck cancer.

A randomized study was conducted to evaluate the protective activity of amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT). Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week up to 60 Gy) with carboplatin 70 mg/m2 on days 1-5 and 21-25 inclusive. Patients either received RCT alone (n = 14) or RCT + A at a dose of 500 mg prior to treatment with carboplatin (n = 25). There was a significant reduction in the incidence of grade 3/4 mucositis (P < 0.0001), acute grade 2 xerostomia (P < 0.0001) and grade 3/4 thrombocytopenia (P = 0.012) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5% and 63.6% in patients who received RCT alone. There were 18 (72%) complete responses (CR) and 6 (24%) partial responses (PR) in patients who received A, compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The disease-free survival at 12 months is 85.7% in the RCT + A arm and 78.6% in the RCT alone arm. The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity.

Adult↗
PubMed2006

The challenge of recruiting patients with anterior cruciate ligament injury of the knee into a randomized clinical trial comparing surgical and non-surgical treatment.

AIMS: To determine the number of patients needed to be screened (NNS) and allocated (NNA) in order to include one participant in a randomized clinical trial (RCT), and to compare the characteristics of patients accepting or declining participation in the RCT. METHODS: The recruitment process of an ongoing multicenter RCT, comparing surgical and non-surgical interventions after acute anterior cruciate ligament (ACL) injury of the knee is described. We use the known concept Number Needed to Screen (NNS) and introduce the new concept Number Needed to Allocate (NNA) as variables to support a priori sample size calculations of future investigations. RESULTS: 560 patients were screened to identify 162 patients (29%) eligible for inclusion in the RCT. 41 of those declined participation for various reasons, the most common being unwillingness to undergo surgery (n=23) or unwillingness to risk conservative treatment (n=8). 19 patients were excluded after MRI assessment or arthroscopy. Thus, 102 (18%) patients were allocated to one of the two treatments in the RCT. The NNS was 5.5 individuals with an acute knee injury, and the NNA was 1.6 individuals eligible for inclusion, to include 1 patient in the RCT. Patients declining to participate in the RCT were more frequently self-employed and less frequently injured in sports activities than those accepting RCT participation. CONCLUSIONS: We suggest that the a priori sample size calculation needs to be multiplied by at least 5.5 to provide an estimate of the number needed to screen, or 1.6 to provide an estimate of the number needed to allocate in order to include the desired number of patients in a trial comparing surgical and non-surgical treatment of the ACL injured patient.

Adolescent↗
PubMed2006

Simulation of the Syst-Eur randomized control trial using a primary care electronic medical record was feasible.

OBJECTIVE: To determine the validity of outcome research using a primary care practice database by comparing a randomized controlled trial (RCT) with a simulated one. STUDY DESIGN AND SETTING: A cohort from the United Kingdom General Practice Research Database (GPRD) was used to simulate the Systolic Hypertension in Europe (Syst-Eur) trial, a study of antihypertensive therapy of isolated systolic hypertension, by replicating all aspects of that RCT (selection criteria, study time frame, treatment, and outcomes) except randomization. RESULTS: The exposed and unexposed groups in the GPRD study exhibited similar baseline characteristics. Stroke, the primary RCT outcome, decreased significantly in both the RCT (incidence rate ratio IRR = 0.58) and the GPRD study (IRR = 0.68). Myocardial infarction decreased nonsignificantly but similarly in both studies (RCT IRR = 0.70; GPRD IRR = 0.74). With the GPRD study extended for 3 years more, myocardial infarction decreased significantly, comparable to findings from the Systolic Hypertension in the Elderly Program (SHEP), another RCT similar to Syst-Eur. CONCLUSIONS: The findings support the potential value of clinical databases to investigate treatment effectiveness. RCT simulation using the GPRD may be the most feasible way to assess observational study validity in comparison to RCTs. The extended GPRD study shows the feasibility of using a simulated study to supplement the results of an RCT of limited duration.

Computer Simulation↗
PubMed2005

Reverse cholesterol transport and cholesterol efflux in atherosclerosis.

Reverse cholesterol transport (RCT) is a pathway by which accumulated cholesterol is transported from the vessel wall to the liver for excretion, thus preventing atherosclerosis. Major constituents of RCT include acceptors such as high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I), and enzymes such as lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), hepatic lipase (HL) and cholesterol ester transfer protein (CETP). A critical part of RCT is cholesterol efflux, in which accumulated cholesterol is removed from macrophages in the subintima of the vessel wall by ATP-binding membrane cassette transporter A1 (ABCA1) or by other mechanisms, including passive diffusion, scavenger receptor B1 (SR-B1), caveolins and sterol 27-hydroxylase, and collected by HDL and apoA-I. Esterified cholesterol in the HDL is then delivered to the liver for excretion. In patients with mutated ABCA1 genes, RCT and cholesterol efflux are impaired and atherosclerosis is increased. In studies with transgenic mice, disruption of ABCA1 genes can induce atherosclerosis. Levels of HDL are inversely correlated with incidences of cardiovascular disease. Supplementation with HDL or apoA-I can reverse atherosclerosis by accelerating RCT and cholesterol efflux. On the other hand, pro-inflammatory factors such as interferon-gamma (IFN-gamma), endotoxin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), can be atherogenic by impairing RCT and cholesterol efflux, according to in vitro studies. RCT and cholesterol efflux play a major role in anti-atherogenesis, and modification of these processes may provide new therapeutic approaches to cardiovascular disease. Further research on new modifying factors for RCT and cholesterol efflux is warranted.

ATP Binding Cassette Transporter 1↗
PubMed2004

The number, quality, and coverage of randomized controlled trials in nephrology.

Randomized controlled trials (RCT) are the optimal study design to answer intervention questions. The authors evaluated the number, quality, and coverage of RCT in nephrology. MEDLINE was searched using the relevant medical subject headings for nephrology and 12 major specialties in internal medicine, limited by "randomized controlled trial" as a publication type. A random selection of 160 RCT in nephrology (40 for each decade) published since 1966 and an additional 270 RCT from ongoing or published Cochrane systematic reviews in various areas of nephrology, dialysis, and transplantation were evaluated for quality of reporting using standard criteria. The number of RCT published in nephrology from 1966 to 2002 (2779) is fewer than all other specialties of internal medicine (range: 5335 in hematology to 27109 in cardiology) with the proportion of all citations which are RCT being the third lowest (1.15%). There has been an increase in both indices from 1966 to 1996, but not at a greater rate than other specialties, and there has been no increase over the past 5 yr. Some areas of nephrology, in particular glomerulonephritis, are clear outliers with very low numbers of RCT to guide clinical decision-making. Overall the quality of RCT reporting in nephrology is low and has not improved over the past 30 yr with unclear allocation concealment (89%), lack of reported blinding of outcome assessors (92%), and failure to perform "intention-to-treat analysis" (50%) particularly frequent. The challenges of improving the quality and quantity of trials in nephrology are substantial, but they can be overcome by using standard guidelines and checklists for trial reporting, greater attention to the trial methods and not just the results, involving experts in trial design and reporting, multicenter collaboration, and larger and simpler trials.

Humans↗
PubMed2004

Root canal treatment in a population-based adult sample: status of teeth after endodontic treatment.

The purpose of this study was to quantify treatment outcomes of endodontically treated teeth, in a representative, population-based adult sample. The "Florida Dental Care Study" was a prospective, longitudinal, cohort study of 873 subjects who had at least one tooth at baseline and who were 45 yr or older. An in-person interview and clinical examination were conducted at baseline, 24 months, and 48 months after baseline, with 6-monthly telephone interviews between those times. Dental record information was abstracted afterward. Seventy-five teeth had conventional root-canal therapy (RCT) performed and met the inclusion criteria of 1-yr of follow-up or extraction. The mean duration of follow-up after RCT was 24.8 months. The mean (SD) attachment loss (AL) on teeth receiving RCT was only 3.3 (1.4) mm. Permanent restorations were placed in 79% of teeth a mean of 4.4 months after the RCT. However, 12% of teeth did not have any restorative treatment after RCT. After RCT had been completed, 81% of teeth were retained and 19% were ultimately extracted. Taken as a whole, this community-based study of a representative sample of adults suggests a higher failure rate than reported from studies in highly controlled environments or insured populations. It also suggests that the length of time to initial restoration of RCT-treated teeth is less than optimal. RCT was almost never performed on teeth with advanced periodontal attachment loss.

Adult↗
PubMed2004

Therapeutic interventions targeted at the augmentation of reverse cholesterol transport.

PURPOSE OF REVIEW: Serum high-density lipoproteins (HDLs) and reverse cholesterol transport (RCT) are important therapeutic targets in the management of atherosclerotic disease. This review summarizes the pathway of RCT and the currently available means by which investigators are attempting to modulate HDL levels and increase rates of RCT. RECENT FINDINGS: Low levels of HDL are commonly encountered in patients with atherosclerotic disease. HDLs mediate a substantial number of antiatherogenic effects along blood vessel walls. One of the most important of these antiatherogenic mechanisms is RCT, a series of reactions by which HDL is able to facilitate the net translocation of cholesterol from peripheral cells to the liver for excretion. There is scientific evidence supporting the concept of RCT in both animals and humans. To facilitate RCT, it is important that therapeutic effort be made to raise serum levels of HDL. Statins, fibrates, niacin, thiazolidinediones, and various combinations of these drugs all raise HDL levels. However, in many high-risk patients with established atherosclerotic disease, the elevations in HDL achieved with these medications are frequently inadequate. Newer agents designed to raise HDL and promote RCT are currently being developed, including infusible bioengineered HDL, edible HDL composed of D-amino acids, and agents capable of inhibiting cholesterol ester transfer protein, among others. SUMMARY: Established therapies for raising HDL can be effective either as monotherapy or when used in combination. Newer strategies are being developed to exploit more specifically the capacity of HDL to drive RCT and either prevent or reverse the course of atherosclerotic disease.

Apolipoprotein A-I↗