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Randomized Clinical Trials (randomized + clinical_trials)
Selected AbstractsSystematic review of randomized controlled trials of pharmacological interventions to reduce ischaemia-reperfusion injury in elective liver resection with vascular occlusionHPB, Issue 1 2010Mahmoud Abu-Amara Abstract Background:, Vascular occlusion during liver resection results in ischaemia-reperfusion (IR) injury, which can lead to liver dysfunction. We performed a systematic review and meta-analysis to assess the benefits and harms of using various pharmacological agents to decrease IR injury during liver resection with vascular occlusion. Methods:, Randomized clinical trials (RCTs) evaluating pharmacological agents in liver resections conducted under vascular occlusion were identified. Two independent reviewers extracted data on population characteristics and risk of bias in the trials, and on outcomes such as postoperative morbidity, hospital stay and liver function. Results:, A total of 18 RCTs evaluating 17 different pharmacological interventions were identified. There was no significant difference in perioperative mortality, liver failure or postoperative morbidity between the intervention and control groups in any of the comparisons. A significant improvement in liver function was seen with methylprednisolone use. Hospital and intensive therapy unit stay were significantly shortened with trimetazidine and vitamin E use, respectively. Markers of liver parenchymal injury were significantly lower in the methylprednisolone, trimetazidine, dextrose and ulinastatin groups compared with their respective controls (placebo or no intervention). Discussion:, Methylprednisolone, trimetazidine, dextrose and ulinastatin may have protective roles against IR injury in liver resection. However, based on the current evidence, they cannot be recommended for routine use and their application should be restricted to RCTs. [source] Techniques for liver parenchymal transection: a meta-analysis of randomized controlled trialsHPB, Issue 4 2009Viniyendra Pamecha Abstract Background:, Different techniques of liver parenchymal transection have been described, including the finger fracture, sharp dissection, clamp,crush methods and, more recently, the Cavitron ultrasonic surgical aspirator (CUSA), the hydrojet and the radiofrequency dissection sealer (RFDS). This review assesses the benefits and risks associated with the various techniques. Methods:, Randomized clinical trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Odds ratio (ORs), mean difference (MDs) and standardized mean differences (SMDs) were calculated with 95% confidence intervals based on intention-to-treat analysis or available-case analysis. Results:, We identified seven trials including a total of 556 patients. Blood transfusion requirements were lower with the clamp,crush technique than with the CUSA or hydrojet. The clamp,crush technique was quicker than the CUSA, hydrojet or RFDS. Infective complications and transection blood loss were greater with the RFDS than with the clamp,crush method. There was no significant difference between techniques in mortality, morbidity, liver dysfunction or intensive therapy unit and hospital stay. Conclusions:, The clamp,crush technique is more rapid and is associated with lower rates of blood loss and otherwise similar outcomes when compared with other methods of parenchymal transection. It represents the reference standard against which new methods may be compared. [source] Amitriptyline treatment of chronic pain in patients with temporomandibular disordersJOURNAL OF ORAL REHABILITATION, Issue 10 2000O. Plesh Randomized clinical trials of amitriptyline will require data from pilot studies to be used for sample size estimates, but such data are lacking. This study investigated the 6-week and 1-year effectiveness of low dose amitriptyline (10,30 mg) for the treatment of patients with chronic temporomandibular disorder (TMD) pain. Based on clinical examination, patients were divided into two groups: myofascial and mixed (myofascial and temporomandibular joint disorders). Baseline pain was assessed by a Visual Analogue Scale (VAS) for pain intensity and by the McGill Pain Questionnaire (MPQ). Depression was assessed by the Beck Depression Inventory (BDI) short form. Patient assessment of global treatment effectiveness was obtained after 6 weeks and 1 year of treatment by using a five-point ordinal scale: (1) worse, (2) unchanged, (3) minimally improved, (4) moderately improved, (5) markedly improved. The results showed a significant reduction for all pain scores after 6 weeks and 1 year post-treatment. The depression scores changed in depressed but not in non-depressed patients. Global treatment effectiveness showed significant improvement 6 weeks and 1 year post-treatment. However, pain and global treatment effectiveness were less improved at 1 year than at 6 weeks. [source] Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: The nuclear medicine perspectiveJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2004Giuliano Mariani MD Abstract The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. 99mTc-labeled colloids with most of the particles in the 100,200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94,97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T1a-b breast cancers, with size ,1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients. J. Surg. Oncol. 2004;85:112,122. © 2004 Wiley-Liss, Inc. [source] Histidine-tryptophan-ketoglutarate solution vs.LIVER TRANSPLANTATION, Issue 8 2007University of Wisconsin solution for liver transplantation: A systematic review University of Wisconsin (UW) solution has been recognized as the gold standard in liver preservation, but its limitations are becoming obvious, such as risk of biliary complications and its high cost. Alternatively, the effects of histidine-tryptophan-ketoglutarate (HTK), such as improved biliary protection and low cost, have been observed. This systematic review is conducted to compare the efficacy and safety of these 2 solutions. Databases from 1966 to June 2006 were searched. Randomized clinical trials (RCTs) and cohort studies comparing HTK and UW solutions for liver transplantation were included. Ten articles including 11 comparisons (1,200 patients) met the inclusion criteria, containing 2 RCTs and 9 cohort studies. No marked differences existed between the 2 groups in patient and graft survival rates, acute rejection, primary nonfunction, primary dysfunction, delayed graft function, and ALT and AST levels after transplantation. The only positive result was observed in the bile production after deceased donor liver transplantation (DDLT), which was statistically significantly higher in HTK group than that of UW group (95% confidence interval, 18.65-57.47; P = 0.0001). Although the difference in biliary complications between the 2 groups did not reach statistical significance, HTK was thought to be more effective for biliary tract flush and prevention of biliary complications in some studies. There was no statistically significant difference of effects (except bile production) between HTK and UW. But trends were documented in some studies for the superiority of HTK in biliary tract flush, prevention of biliary complications, and cost saving. Adequately powered RCTs with longer follow-up periods are required to evaluate the long-term effect of these 2 solutions. Liver Transpl 13:1125,1136, 2007. © 2007 AASLD. [source] Evidence-Based Medicine and NeuromodulationNEUROMODULATION, Issue 3 2008John D. Loeser MD ABSTRACT Evidence-based medicine is gaining increasing penetrance in the United States. Neuromodulation providers need to know how to use this resource and how to get what we do appropriately evaluated and included in structured reviews and meta-analyses. Randomized clinical trials are not the only form of evidence for patient care activities; other, equally valid strategies are available and should be used for interventions that may preclude blinding and randomization. Those who determine payment are going to use evidence-based medicine to make decisions that may not be in the best interests of our patients or our profession. [source] Is Rhythm-Control Superior to Rate-Control in Patients with Atrial Fibrillation and Diastolic Heart Failure?ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010Melissa H. Kong M.D. Background: Although no clinical trial data exist on the optimal management of atrial fibrillation (AF) in patients with diastolic heart failure, it has been hypothesized that rhythm-control is more advantageous than rate-control due to the dependence of these patients' left ventricular filling on atrial contraction. We aimed to determine whether patients with AF and heart failure with preserved ejection fraction (EF) survive longer with rhythm versus rate-control strategy. Methods: The Duke Cardiovascular Disease Database was queried to identify patients with EF > 50%, heart failure symptoms and AF between January 1,1995 and June 30, 2005. We compared baseline characteristics and survival of patients managed with rate- versus rhythm-control strategies. Using a 60-day landmark view, Kaplan-Meier curves were generated and results were adjusted for baseline differences using Cox proportional hazards modeling. Results: Three hundred eighty-two patients met the inclusion criteria (285 treated with rate-control and 97 treated with rhythm-control). The 1-, 3-, and 5-year survival rates were 93.2%, 69.3%, and 56.8%, respectively in rate-controlled patients and 94.8%, 78.0%, and 59.9%, respectively in rhythm-controlled patients (P > 0.10). After adjustments for baseline differences, no significant difference in mortality was detected (hazard ratio for rhythm-control vs rate-control = 0.696, 95% CI 0.453,1.07, P = 0.098). Conclusions: Based on our observational data, rhythm-control seems to offer no survival advantage over rate-control in patients with heart failure and preserved EF. Randomized clinical trials are needed to verify these findings and examine the effect of each strategy on stroke risk, heart failure decompensation, and quality of life. Ann Noninvasive Electrocardiol 2010;15(3):209,217 [source] Repeated peribulbar injections of triamcinolone acetonide: a successful and safe treatment for moderate to severe Graves' ophthalmopathyACTA OPHTHALMOLOGICA, Issue 1 2009Marcela Bordaberry Abstract. Purpose:, In this study, we aimed to evaluate the efficacy of peribulbar triamcinolone injections to treat inflammatory signs of Graves' ophthalmopathy (GO) in patients with moderate to severe GO and associated optic neuropathy (ON). Methods:, Twenty-one patients with active GO [clinical activity score (CAS) , 4] and systemic thyroid disease under control were enrolled in this prospective pilot study. Peribulbar triamcinolone acetonide was injected in each orbit (42 eyes), in four doses of 20 mg at 2-week intervals. Ophthalmological examination including CAS evaluation, visual field, computerized tomography (CT) scan and digital photography were performed before and after treatment. Results:, Twenty-one patients (11 with moderate disease, 10 with ON) were enrolled in this study and followed for at least 14 months. Initial mean CAS was 6.38 ± 1.49, which dropped to 1.8 ± 1.12 after 6 months of treatment (P = 0.01; mean difference of 4.57 ± 1.56; range 1,8 score points). ON was diagnosed in 10 patients. Of these, 66% improved with peribulbar triamcinolone exclusively. A transitory increase in intraocular pressure in two patients was controlled with topic medication. Conclusion:, Peribulbar triamcinolone injections reduce the inflammatory signs of moderate GO, as measured by the CAS, and could also be used as an alternative treatment for ON. Randomized clinical trials are needed to compare the results of triamcinolone peribulbar injections to those of other treatment modalities. [source] The Late Open Infarct-related Artery Hypothesis: Evidence-based Medicine or Not?CLINICAL CARDIOLOGY, Issue 11 2007Martin Brueck M.D. Abstract Randomized clinical trials have clearly shown that early reperfusion of coronary arteries is the established treatment of myocardial infarction preserving left ventricular function and reducing mortality. However, late patency of the infarct-related artery is an independent predictor of survival leading to the late open-artery hypothesis. This concept implies restoration of antegrade blood flow of the infarct-related artery in patients with myocardial infarction to improve survival by mechanisms less time-dependent or even time-independent. Possible explanations for this benefit include improved left ventricular function and electrical stability by perfusion of hibernating myocardium, accelerated infarct healing and limitation of ventricular remodeling. This review focuses on the evidence of late recanalization of occluded infarct-related arteries in patients with coronary artery disease. Copyright © 2007 Wiley Periodicals, Inc. [source] Cost-effectiveness of sirolimus therapy with early cyclosporin withdrawal vs. long-term cyclosporin therapy in AustraliaCLINICAL TRANSPLANTATION, Issue 4 2006Adam Gordois Abstract:, Cyclosporin (CsA) is Australia's most widely used immunosuppressant following renal transplantation. Randomized clinical trials demonstrate that sirolimus use for immunosuppression is associated with significantly lower incidence rates of nephrotoxicity and chronic graft rejection, and lower serum creatinine levels, suggesting long-term benefits if used as a replacement therapy for CsA. The cost-effectiveness of replacing CsA with sirolimus after 2,4 months (as approved by Australian regulatory authorities) was assessed relative to continued CsA plus low-dose sirolimus. A Markov model simulated outcomes over a patient's lifetime from initial transplant. Costs, measured in Australian dollars from the perspective of the Australian healthcare system, included immunosuppressants, dialysis, and inpatient and outpatient treatment. In a cohort with a mean age of 45 yr, the mean lifetime cost per patient is $39 052 greater with the study therapy. However, an average of 272 chronic graft rejections and 91 regrafts are prevented per 1000 patients. The mean predicted survival benefit is 2.086 life-years, or 0.938 quality-adjusted life-years (QALYs) when utility weights and discounting are incorporated. The incremental cost per QALY gained with the study therapy was $41 613. Cost-effectiveness was most sensitive to model duration and dialysis cost. Sirolimus is a cost-effective alternative to CsA for the long-term treatment of patients undergoing renal transplantation. [source] Early intervention in patients at ultra high risk of psychosis: benefits and risksACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009M. B. De Koning Objective:, Prediction of transition to psychosis in the prodromal phase of schizophrenia has raised interest in intervention prior to the onset of frank psychosis. The aim of this review was to examine whether interventions in the prodromal phase have a favourable benefit/risk ratio. Method:, A literature search in PubMed, EMBASE and PsycINFO was performed. Results:, Three randomized clinical trials with antipsychotic medication and/or cognitive behavioural therapy as clinical intervention suggested a positive effect at the end of treatment, but no significant differences were found at the end of follow-up periods from 1 to 4 years. Naturalistic studies present a hypothesis about a possible preventive effect of antidepressive medication. The results of eight other studies are more difficult to interpret. Side-effects of antipsychotic medication and non-adherence with medication are essential problems. Conclusion:, At the present time, the data concerning the benefits and risks do not justify prodromal intervention as standard clinical practice. [source] Appraising the mitogenicity of insulin analogues relative to human insulin,response to: Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activity in cultured cancer cells.DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2010Diabetes Metab Res Rev 2009; 25(1): 4 Abstract Interest in mitogenic and potentially carcinogenic effects of insulin and insulin analogues has been renewed by several recent publications that have examined the relationship between cancer and insulin analogues. Actions mediated through the insulin-like growth factor-I receptor in a hyperinsulinaemic state have been implicated mechanistically. Both type 2 diabetes and endogenously elevated insulin-like growth factor-I have been epidemiologically linked to malignancies. Therefore, in vitro mitogenic effects and binding affinities of the various analogues have been analysed. A recent publication by Weinstein et al. studied the in vitro mitogenic and anti-apoptotic activities of insulin analogues, and their conclusion asserts that insulins glargine, detemir, and lispro displayed proliferative and anti-apoptotic effects in a number of malignant cell lines. However, their conclusions are not supported by the data which are not complete and lack clear statistical significance. This data should be interpreted cautiously in light of all other presently available scientific evidence. Prospective, randomized clinical trials will best address any direct relationship between insulin analogues and cancer. Until those studies are designed and completed, clinicians should consider the demonstrated strong benefit of glycaemic control in balance with any alleged risk. Copyright © 2010 John Wiley & Sons, Ltd. [source] Results from two randomized clinical trials evaluating the impact of quarterly recovery management checkups with adult chronic substance usersADDICTION, Issue 6 2009Christy K Scott ABSTRACT Aims Post-discharge monitoring and early reintervention have become standard practice when managing numerous chronic conditions. These two experiments tested the effectiveness of recovery management checkup (RMC) protocols for adult chronic substance users. Intervention RMC included quarterly monitoring; motivational interviewing to provide personalized feedback and to resolve ambivalence about substance use; treatment linkage, engagement and retention protocols to increase the amount of treatment received. Participants and setting Recruited from sequential addiction treatment admissions, participants in the two experiments were, on average, 36 and 38 years of age, mainly female (59% versus 46%), African American (85% versus 80%) and met past-year criteria for dependence (87% versus 76%). Design Participants in both experiments were assigned randomly to the RMC or control condition and interviewed quarterly for 2 years. Measurement The Global Appraisal of Individual Needs (GAIN) was the main assessment instrument. Findings RMC participant outcomes were better than control participants in both experiments. Effect sizes were larger in the second experiment in terms of reducing days to readmission (Cohen's d = 0.41 versus d = 0.22), successive quarters in the community using substances (d = ,0.32 versus ,0.19), past-month symptoms of abuse/dependence (d = ,0.23 versus ,0.02) and increasing the days of abstinence over 2 years (d = +0.29 versus 0.04). Conclusion RMC, which provided ongoing monitoring and linkage, is feasible to conduct and is effective for adults with chronic substance dependence. [source] Evaluating the validities of different DSM-IV-based conceptual constructs of tobacco dependence,ADDICTION, Issue 7 2008Peter S. Hendricks ABSTRACT Aim To compare the concurrent and predictive validities of two subsets of DSM-IV criteria for nicotine dependence (tolerance and withdrawal; withdrawal; difficulty controlling use; and use despite harm) to the concurrent and predictive validity of the full DSM-IV criteria. Design Analysis of baseline and outcome data from three randomized clinical trials of cigarette smoking treatment. Setting San Francisco, California. Participants Two samples of cigarette smokers (n = 810 and 322), differing with regard to baseline characteristics and treatment received, derived from three randomized clinical trials. Measurements DSM-IV nicotine dependence criteria were measured at baseline with a computerized version of the Diagnostic Interview Schedule for DSM-IV (DIS-IV). Additional baseline measures included the Fagerström Test of Nicotine Dependence (FTND), number of cigarettes smoked per day, breath carbon monoxide (CO) level, the Minnesota Nicotine Withdrawal Scale (MNWS), the Michigan Nicotine Reinforcement Questionnaire (M-NRQ) and the Profile of Mood States (POMS). Seven-day point-prevalence abstinence was assessed at week 12. Findings Full DSM-IV criteria displayed greater concurrent validity than either of the two subsets of criteria. However, DSM-IV symptoms accounted for only a nominal amount of the variance in baseline smoking-related characteristics and were unrelated to smoking abstinence at week 12. Cigarettes smoked per day was the only significant predictor of abstinence at week 12. Conclusions Although the findings do not provide a compelling alternative to the full set of DSM-IV nicotine dependence criteria, its poor psychometric properties and low predictive power limit its clinical and research utility. [source] REVIEW: Norepinephrine and stimulant addictionADDICTION BIOLOGY, Issue 2 2009Mehmet Sofuoglu ABSTRACT No pharmacotherapies are approved for stimulant use disorders, which are an important public health problem. Stimulants increase synaptic levels of the monoamines dopamine (DA), serotonin and norepinephrine (NE). Stimulant reward is attributable mostly to increased DA in the reward circuitry, although DA stimulation alone cannot explain the rewarding effects of stimulants. The noradrenergic system, which uses NE as the main chemical messenger, serves multiple brain functions including arousal, attention, mood, learning, memory and stress response. In pre-clinical models of addiction, NE is critically involved in mediating stimulant effects including sensitization, drug discrimination and reinstatement of drug seeking. In clinical studies, adrenergic blockers have shown promise as treatments for cocaine abuse and dependence, especially in patients experiencing severe withdrawal symptoms. Disulfiram, which blocks NE synthesis, increased the number of cocaine-negative urines in five randomized clinical trials. Lofexidine, an ,2 -adrenergic agonist, reduces the craving induced by stress and drug cues in drug users. In addition, the NE transporter (NET) inhibitor atomoxetine attenuates some of d-amphetamine's subjective and physiological effects in humans. These findings warrant further studies evaluating noradrenergic medications as treatments for stimulant addiction. [source] Surgical treatment of migraine headaches.HEADACHE, Issue 3 2003B Guyuron Plast Reconstr Surg. 2002 Jun;109(7):2183-2189 This prospective study was conducted to investigate the role of removal of corrugator supercilii muscles, transection of the zygomaticotemporal branch of the trigeminal nerve, and temple soft-tissue repositioning in the treatment of migraine headaches. Using the criteria set forth by the International Headache Society, the research team's neurologist evaluated patients with moderate to severe migraine headaches, to confirm the diagnosis. Subsequently, the patients completed a comprehensive migraine headaches questionnaire and the team's plastic surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator supercilii muscle. The patients were asked to maintain an accurate diary of their migraine headaches and to complete a monthly questionnaire documenting pertinent information related to their headaches. Patients in whom the injection of Botox resulted in complete elimination of the migraine headaches then underwent resection of the corrugator supercilii muscles. Those who experienced only significant improvement underwent transection of the zygomaticotemporal branch of the trigeminal nerve with repositioning of the temple soft tissues, in addition to removal of the corrugator supercilii muscles. Once again, patients kept a detailed postoperative record of their headaches. Of the 29 patients included in the study, 24 were women and five were men, with an average age of 44.9 years (range, 24 to 63 years). Twenty-four of 29 patients (82.8 percent, p < 0.001) reported a positive response to the injection of Botox, 16 (55.2 percent, p < 0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced significant improvement (at least 50 percent reduction in intensity or severity), and five (17.2 percent, not significant) did not notice a change in their migraine headaches. Twenty-two of the 24 patients who had a favorable response to the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001) observed a postoperative improvement. Ten patients (45.5 percent, p < 0.01) reported elimination of migraine headaches and 11 patients (50.0 percent, p < 0.004) noted a considerable improvement. For the entire surgical group, the average intensity of the migraine headaches reduced from 8.9 to 4.1 on an analogue scale of 1 to 10, and the frequency of migraine headaches changed from an average of 5.2 per month to an average of 0.8 per month. For the group who only experienced an improvement, the intensity fell from 9.0 to 7.5 and the frequency was reduced from 5.6 to 1.0 per month. Only one patient (4.5 percent, not significant) did not notice any change. The follow-up ranged from 222 to 494 days, the average being 347 days. In conclusion, this study confirms the value of surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited significantly from the surgery. It is also evident that injection of Botox is an extremely reliable predictor of surgical outcome. Comment: Many small placebo-controlled studies and much anecdotal literature suggests that botulinum toxin may be effective in prevention of migraine, perhaps to the same extent as conventional prophylactic treatment. Larger, randomized clinical trials are underway to resolve this issue. In the meantime, those who believe in the effectiveness of botulinum toxin prophylaxis argue about how it works, that is whether its antinociceptive properties are due to peripheral effects, central or presynaptic effects, or both. Dr. Guyuron's group favors the idea that botulinum toxin interrupts a reflex arc between the central nervous system (CNS) and peripheral musculature, and that after establishing efficacy by low dose botulinum injection in the corrugator supercilii muscles, surgical resection of these muscles results in prolonged and effective prophylaxis. The idea is radical but intriguing and should not be dismissed out of hand. However, a trial is necessary in which both the botulinum toxin injections are blinded with vehicle, and the study of the surgery involves a sham surgery control group with extended long-term follow-up, before these forms of prophylaxis can be recommended to patients. SJT [source] Antiretroviral effects on HIV-1 RNA, CD4 cell count and progression to AIDS or death: a meta-regression analysisHIV MEDICINE, Issue 10 2008EJ Mills Objective Governments, clinicians and drug-licensing bodies have adopted changes in CD4 cell counts and HIV-1 RNA levels as evidence of effectiveness for new therapeutic interventions. We aimed to determine the strength of the association between the magnitude of the effect of changes in CD4 cell count and HIV-1 RNA and progression to AIDS or death in the highly active antiretroviral therapy (HAART) era. Methods We identified all randomized clinical trials (RCTs) evaluating the effect of HAART on both clinical and surrogate endpoints (1994 to September 2006). We performed a meta-regression and weighted linear regression. We additionally estimated potential RCT sample sizes that would be required to assess the effectiveness of new interventions in terms of clinical endpoints. Results We included data from 178 RCTs. We were unable to demonstrate a strong relationship at any time-point. Specifically, this was the case when CD4 T-cell change and clinical outcomes were examined at week 24 [coefficient ,0.01, 95% confidence interval (CI) ,0.03 to 0.001, P=0.54], week 48 (coefficient ,0.01, 95% CI ,0.02 to 0.001, P=0.83) and week 96 (coefficient 0.00, 95% CI ,0.03 to 0.04, P=0.76). This was also the case when viral load was examined as a surrogate marker. Given the small number of clinical events occurring in new interventional RCTs, any RCT aiming to evaluate clinical endpoints within these time-points would require an exceptionally large sample size. Conclusions Our findings indicate that, within short-term clinical trial settings, it is not possible to estimate the proportion of treatment effect associated with surrogate endpoints. [source] Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a comprehensive review of their clinical efficacyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2010Bernardo Dell'Osso Abstract Anxiety disorders are common psychiatric conditions that typically require long-term treatment. This review summarizes current knowledge of the pharmacological treatment of anxiety disorders with serotonin norepinephrine reuptake inhibitors (SNRIs) with specific emphasis on the findings of recent randomized clinical trials and relevant neurobiological investigations. It is now well established that gabaergic, noradrenergic and serotonergic systems play a critical role in the pathophysiology of anxiety disorders, abnormalities in these systems being related to structural and functional alterations in specific brain areas such as the amygdala, prefrontal cortex, locus coeruleus and hippocampus, as repeatedly shown by neuroimaging studies. SNRIs selectively inhibit norepinephrine and serotonin reuptake and have shown to be efficacious and generally well tolerated treatments in patients with anxiety disorders, with some potential clinical advantages over selective serotonin reuptake inhibitors (SSRIs), which are considered by many to represent first-line pharmacological treatments in patients with anxiety disorders. Anxiety disorders are characterized by a typically chronic course, high rates of comorbidity and frequent partial response to standard treatments, and the increasing use of SNRIs reflects currently unmet clinical need, in terms of overall response, remission rates and treatment tolerability. Copyright © 2009 John Wiley & Sons, Ltd. [source] Un-promoted issues in inflammatory bowel disease: opportunities to optimize careINTERNAL MEDICINE JOURNAL, Issue 3 2010J. M. Andrews Abstract Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gut, which lead to significant morbidity and impaired quality of life (QoL) in sufferers, without generally affecting mortality. Despite CD and UC being chronic, life-long illnesses, most medical management is directed at acute flares of disease. Moreover, with more intensive medical therapy and the development of biological therapy, there is a risk that management will become even more narrowly focused on acute care, and be directed only at those with more severe disease, rather than encompassing all sufferers and addressing important non-acute issues. This imbalance of concentration of medical attention on ,high-end' care is in part driven by the need to perform and publish randomized clinical trials of newer therapies to obtain registration and licensing for these agents, which thus occupy a large proportion of the recent IBD treatment literature. This leads to less attention on relatively ,low-technology' issues including: (i) the psychosocial burden of chronic disease, QoL and specific psychological comorbidities; (ii) comorbidity with functional gastrointestinal disorders (FGIDs); (iii) maintenance therapy, monitoring and compliance; (iv) smoking (with regard to CD); (v) sexuality, fertility, family planning and pregnancy; and (vi) iron deficiency and anaemia. We propose these to be the ,Un-promoted Issues' in IBD and review the importance and treatment of each of these in the current management of IBD. [source] Tumor metastasis and the lymphatic vasculatureINTERNATIONAL JOURNAL OF CANCER, Issue 12 2009Jonathan P. Sleeman Abstract Tumor-associated lymphatic vessels act as a conduit by which disseminating tumor cells access regional lymph nodes and form metastases there. Lymph node metastasis is of major prognostic significance for many types of cancer, although lymph node metastases are themselves rarely life-threatening. These observations focus our attention on understanding how tumor cells interact with the lymphatic vasculature, and why this interaction is so significant for prognosis. Tumors interact with the lymphatic vasculature in a number of ways, including vessel co-option, chemotactic migration and invasion into lymphatic vessels and induction of lymphangiogenesis. Tumor-induced lymphangiogenesis both locally and in regional lymph nodes has been correlatively and functionally associated with metastasis formation and poor prognosis. The investigation of the molecular regulation of lymphangiogenesis has identified ways of interfering with prolymphangiogenic signaling. Blockade of tumor-induced lymphangiogenesis in preclinical models inhibits metastasis formation in lymph nodes and often also in other organs, suggesting that blocking the lymphatic route of dissemination might suppress metastasis formation not only in lymph nodes but also in other organs. However, randomized clinical trials that have investigated the efficacy of therapeutic removal of lymph nodes have concluded that lymph node metastases act only as indicators that primary tumors have developed metastatic potential, and do not govern the further spread of metastatic cells. To reconcile these apparently paradoxical observations we suggest a model in which tumor-induced lymphangiogenesis and lymph node metastasis formation act as indicators that tumors are producing factors that can act systemically to promote metastasis formation in distant organs. © 2009 UICC [source] The role of diet and nutrition in cervical carcinogenesis: A review of recent evidenceINTERNATIONAL JOURNAL OF CANCER, Issue 4 2005Reina García-Closas Abstract Our objective was to provide an update on recent epidemiologic evidence about the role of diet and nutrition on the risk of human papillomavirus (HPV) persistence and cervical neoplasia, taking HPV into account. We conducted a systematic review and qualitative classification of all observational studies controlling for HPV infection published between March 1995 and November 2003 and of all randomized clinical trials published between January 1991 and November 2003. Scientific evidence was classified as convincing, probable, possible or insufficient, as used in a previous study on diet and cancer. Thirty-three studies were eligible for this review (10 clinical trials, 8 observational prospective studies and 15 case-control studies). The few studies on HPV persistence showed a possible protective effect of fruits, vegetables, vitamins C and E, beta- and alpha-carotene, lycopene, luterin/zeaxanthin and cryptoxanthin. Evidence for a protective effect of cervical neoplasia was probable for folate, retinol and vitamin E and possible for vegetables, vitamins C and B12, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin and cryptoxanthin. Evidence for an increased risk of cervical neoplasia associated with high blood homocysteine was probable. Results did not differ between studies looking at preneoplastic and invasive lesions or between retrospective and prospective studies. The available evidence for an association between diet and nutritional status and cervical carcinogenesis taking HPV infection into account is not yet convincing. Large cohort studies are needed to adequately assess the role of foods and nutrients in cervical HPV carcinogenesis. © 2005 Wiley-Liss, Inc. [source] The transversus abdominis plane block: a valuable option for postoperative analgesia?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2010A topical review The transversus abdominis plane (TAP) block is a newly described peripheral block involving the nerves of the anterior abdominal wall. The block has been developed for post-operative pain control after gynaecologic and abdominal surgery. The initial technique described the lumbar triangle of Petit as the landmark used to access the TAP in order to facilitate the deposition of local anaesthetic solution in the neurovascular plane. Other techniques include ultrasound-guided access to the neurovascular plane via the mid-axillary line between the iliac crest and the costal margin, and a subcostal access termed the ,oblique subcostal' access. A systematic search of the literature identified a total of seven randomized clinical trials investigating the effect of TAP block on post-operative pain, including a total of 364 patients, of whom 180 received TAP blockade. The surgical procedures included large bowel resection with a midline abdominal incision, caesarean delivery via the Pfannenstiel incision, abdominal hysterectomy via a transverse lower abdominal wall incision, open appendectomy and laparoscopic cholecystectomy. Overall, the results are encouraging and most studies have demonstrated clinically significant reductions of post-operative opioid requirements and pain, as well as some effects on opioid-related side effects (sedation and post-operative nausea and vomiting). Further studies are warranted to support the findings of the primary published trials and to establish general recommendations for the use of a TAP block. [source] Results, Rhetoric, and Randomized Trials: The Case of DonepezilJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2008John R. Gilstad MD Whether donepezil provides meaningful benefit to patients with Alzheimer's disease (AD) is controversial, but drug sales annually total billions of dollars. A review of data from published randomized clinical trials (RCTs) found rhetorical patterns that may encourage use of this drug. To create a reproducible observation, the sentences occurring at five specific text sites in all 18 RCTs of donepezil for AD were tabulated, as were study design, sources of financial support, and outcomes that could be compared between trials. Rhetoric in the 13 vendor-supported trials (15 publications) was strongly positive. Three early trials used the motif "efficacious (or effective) , treating , symptoms" four times. "Well-tolerated and efficacious" or an equivalent motif appeared 11 times in five RCTs. Nine RCTs referred 15 times to previously proven effectiveness. Seven trials encourage off-label use, for "early" cognitive impairment, severe dementia in advance of the Food and Drug Administration labeling change, or behavioral symptoms. These rhetorical motifs and themes appeared only in the vendor-supported trials. Trials without vendor support described the drug's effects as "small" or absent; two emphasized the need for better treatments. RCT results were highly consistent in all trials; the small differences do not explain differences in rhetoric. At these text sites in the primary research literature on donepezil for AD, uniformly positive rhetoric is present in all vendor-supported RCTs. Reference to the limited benefit of donepezil is confined to RCTs without vendor support. Data in the trials are highly consistent. This observation generates the hypothesis that rhetoric in vendor-supported published RCTs may promote vendors' products. [source] Effect of Metoprolol on Quality of Life in the Prevention of Syncope TrialJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2009Ph.D., ROBERT S. SHELDON M.D. Introduction: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope. Methods: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients <42 and ,42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively. Results: There were 208 patients, mean age 42 ± 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either <42 or ,42 years of age. Conclusion: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test. [source] ,Liberal' vs. ,restrictive' perioperative fluid therapy , a critical assessment of the evidenceACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009M. BUNDGAARD-NIELSEN Background: Several studies have assessed the effect of a ,liberal' vs. a ,restrictive' perioperative fluid regimen on post-operative outcome. The literature was reviewed in order to provide recommendations regarding perioperative fluid regimens. Methods: A PubMed search identified randomized clinical trials and cited studies, comparing two different fixed fluid volumes on post-operative clinical outcome in major surgery. Studies were assessed for the type of surgery, primary and secondary outcome endpoints, the type and volume of administered fluid and the definition of the perioperative period. Also, information regarding perioperative care and type of anaesthesia was assessed. Results: In the seven randomized studies identified, the range of the liberal intraoperative fluid regimen was from 2750 to 5388 ml compared with 998 to 2740 ml for the restrictive fluid regimen. The period for fluid therapy and outcome endpoints were inconsistently defined and only two studies reported perioperative care principles and discharge criteria. Three studies found an improved outcome (morbidity/hospital stay) with a restrictive fluid regimen whereas two studies found no difference and two studies found differences in the selected outcome parameters. Conclusion: Liberal vs. restrictive fixed-volume regimens are not well defined in the literature regarding the definition, methodology and results, and lack the use of or information on evidence-based standardized perioperative care-principles (fast-track surgery), thereby precluding evidence-based guidelines for procedure-specific perioperative fixed-volume regimens. Optimization of perioperative fluid management may include a combination of fixed crystalloid administration to replace extra-vascular losses and avoiding fluid excess, together with individualized goal-directed colloid administration to maintain a maximal stroke volume. [source] Examination of the analytic quality of behavioral health randomized clinical trialsJOURNAL OF CLINICAL PSYCHOLOGY, Issue 1 2007Bonnie Spring Adoption of evidence-based practice (EBP) policy has implications for clinicians and researchers alike. In fields that have already adopted EBP, evidence-based practice guidelines derive from systematic reviews of research evidence. Ultimately, such guidelines serve as tools used by practitioners. Systematic reviews of treatment efficacy and effectiveness reserve their strongest endorsements for treatments that are supported by high-quality randomized clinical trials (RCTs). It is unknown how well RCTs reported in behavioral science journals fare compared to quality standards set forth in fields that pioneered the evidence-based movement. We compared analytic quality features of all behavioral health RCTs (n = 73) published in three leading behavioral journals and two leading medical journals between January 2000 and July 2003. A behavioral health trial was operationalized as one employing a behavioral treatment modality to prevent or treat an acute or chronic physical disease or condition. Findings revealed areas of weakness in analytic aspects of the behavioral health RCTs reported in both sets of journals. Weaknesses were more pronounced in behavioral journals. The authors offer recommendations for improving the analytic quality of behavioral health RCTs to ensure that evidence about behavioral treatments is highly weighted in systematic reviews. © 2006 Wiley Periodicals, Inc. J Clin Psychol 63: 53,71, 2007. [source] CLINICAL TRIALS ON THE USE OF WHITENING STRIPS IN CHILDREN AND ADOLESCENTSJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 6 2005K.J. Donly ABSTRACT Objective: This article reported the cumulative findings from three controlled, randomized clinical trials evaluating the efficacy and tolerability of tooth whitening in children and adolescents using disposable polyethylene strip systems. Materials and Methods: The study population included 132 children and adolescents, ages 10 to 18 years. (Please note that 71 of these subjects were identified in the previous review.) Fifty-three percent of the subjects were female and 47% were male, with a mean age of 14.4 years. Subjects were divided into experimental treatment groups by balancing groups with respect to demographic characteristics and baseline tooth colors. Subiects were treated with either 5.3% or 6.5% hydrogen peroxide gel polyethylene strips. All subjects had to have all permanent anterior teeth erupted, a baseline Vita shade (Vita Zahnfabrik, Bad Säckingen, Germany) score of A2 or darker, and a desire that their teeth be whitened. One study included subjects who had previously received comprehensive orthodontic treatment. Digital images were collected for all subjects at baseline, 2 weeks, and 4 weeks. Oral examinations and interviews were conducted at each appointment to evaluate adverse events. Color change was calculated from the digital images in the same manner previously described. Results: The 5.3% and 6.5% hydrogen peroxide strips used for 30 minutes twice a day yielded significant tooth whitening (p < .0001) after 14 days. For the primary whitening parameter, ,b*, continued treatment during the 14- to 28-day period resulted in significant additional reduction in yellowness (p < .0001). Subjects treated with 6.5% hydrogen peroxide strips experienced significantly (p < .03) greater reduction in yellowness (approximately 0.8 ,b* units) compared with those who used the 5.3 hydrogen peroxide strips. The hydrogen peroxide strips were tolerated well in all of these studies, with minor tooth sensitivity and oral irritation being the primary complaints. Eighteen subjects (14%) reported oral irritation, whereas 30 subjects (23%) reported tooth sensitivity. All adverse events were relieved upon discontinuance of product use. Conclusion: The 5.3% and 6.5% hydrogen peroxide gel strips used for 30 minutes twice a day effectively whitened teeth, and both regimens were well tolerated. [source] An Overview of the TAXUS® Express®, Paclitaxel-Eluting Stent Clinical Trial ProgramJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2006JOHN M. LASALA M.D., Ph.D. Restenosis remains a problem following percutaneous coronary intervention in patients with coronary artery disease. Drug-eluting stents (DES), which combine mechanical and pharmacologic properties, have been shown to prevent or reduce neointimal growth after deployment. This review describes the TAXUS paclitaxel-eluting stent clinical trial expansion program (TAXUS® Express®, Boston Scientific, Natick, MA). This program comprises the largest data set of randomized controlled trials (RCTs) of DES to date, with over 6,200 patients enrolled since 2000. The program includes treatment of de novo lesions, as well as higher-risk lesion and patient populations. In this review, we discuss the results from the TAXUS family of randomized clinical trials, and compare the findings with data from TAXUS registries. The data from the randomized clinical trials suggest that the paclitaxel-eluting stent provides consistent and durable benefits across multiple lesion and patient types. Evidence from peri-and postapproval registries, where patient populations are more heterogeneous than those eligible and included in the RCTs, corroborate these findings, with overall low rates of cardiac events, including reinterventions. [source] Short-term effects of a mandibular advancement device on obstructive sleep apnoea: an open-label pilot trialJOURNAL OF ORAL REHABILITATION, Issue 8 2005G. AARAB summary, Obstructive sleep apnoea (OSA) is a common sleep disorder, which is, among others, associated with snoring. OSA has a considerable impact on a patient's general health and daily life. Nasal continuous positive airway pressure (nCPAP) is frequently used as a ,gold standard' treatment for OSA. As an alternative, especially for mild/moderate cases, mandibular advancement devices (MADs) are prescribed increasingly. Their efficacy and effectiveness seem to be acceptable. Although some randomized clinical trials (RCTs) have been published recently, most studies so far are case studies. Therefore, our department is planning a controlled RCT, in which MADs are compared with both nCPAP and a control condition in a parallel design. As a first step, an adjustable MAD was developed with a small, more or less constant vertical dimension at different mandibular positions. To test the device and the experimental procedures, a pilot trial was performed with 10 OSA patients (six mild, four moderate; one women, nine men; mean age = 47·9 ± 9·7 years). They all underwent a polysomnographic recording before as well as 2,14 weeks after insertion of the MAD (adjusted at 50% of the maximal protrusion). The apnoea,hypopnoea index (AHI) was significantly reduced with the MAD in situ (P = 0·017). When analysed as separate groups, the moderate cases showed a significantly larger decrease in AHI than the mild cases (P = 0·012). It was therefore concluded from this pilot study that this MAD might be an effective tool in the treatment of, especially, moderate OSA. [source] Four "lessons learned" while implementing a multi-site caries prevention trialJOURNAL OF PUBLIC HEALTH DENTISTRY, Issue 3 2010James D. Bader DDS Abstract As the number of dental-related randomized clinical trials (RCTs) increases, there is a need for literature to help investigators inexperienced in conducting RCTs design and implement studies. This commentary describes four "lessons learned" or considerations important in the planning and initial implementation of RCTs in dentistry that, to our knowledge, have not been discussed in the general dental literature describing trial techniques. These considerations are a) preparing or securing a thorough systematic review; b) developing a comprehensive set of study documents; c) designing and testing multiple recruitment strategies; and d) employing a run-in period prior to enrollment. Attention to these considerations in the planning phases of a dental RCT can help ensure that the trial is clinically relevant while also maximizing the likelihood that its implementation will be successful. [source] | ||||||||||||||||||||||||||||||||||