Large Well-designed Clinical Trials Research Articles

An Algorithm Approach to Phantom Limb Pain.

Phantom limb pain (PLP) is a common condition that occurs following both upper and lower limb amputation. First recognized and described in 1551 by Ambroise Pare, research into its underlying pathology and effective treatments remains a very active and growing field. To date, however, there is little consensus regarding the optimal management of phantom limb pain. With few large well-designed clinical trials of which to make treatment recommendations, as well as significant heterogeneity in clinical response to available treatments, the management of PLP remains challenging. Below we summarize the current state of knowledge in the field, as well as propose an algorithm for the approach to the treatment of PLP.

Effect of Citrullus colocynthis on glycemic factors and lipid profile in type II diabetic patients: a systematic review and meta-analysis.

In this systematic review and meta-analysis, we investigated the effect and side effects of Citrullus colocynthis on glycemic factors and lipid profile in diabetic patients. We systematically searched English and Persian databases from inception till August 2021 using Medical Subject Headings (MeSH). Two authors independently extracted data and assessed the quality of studies. The standardized mean differences were pooled using fixed-effect models, and statistical heterogeneity was assessed using the I squared (I²) index. Of the 321 articles searched in the databases, 136 related articles were screened, 14 relevant full-text articles were assessed for eligibility; finally, four articles were included in the study, three articles were entered into the meta-analysis. The results of the meta-analysis indicated that Citrullus colocynthis does not have a significant effect on fasting blood sugar (FBS), hemoglobin A1c (HBA1c), low-density lipoprotein (LDL), total cholesterol, and triglyceride indices but increases high-density lipoprotein (HDL) (Mean Difference: 5.76; 95% CI: 1.69 to 9.84; P = 0.006; I2 = 0%). The meta-analysis results showed that Citrullus colocynthis has no significant effect on glycemic and metabolic indices of diabetes - except HDL. Due to the relatively low quality and the small number of included trials, conducting further large scale well-designed randomized clinical trials to determine the effect of Citrullus colocynthis on glycemic and metabolic indices seems essential. The online version contains supplementary material available at 10.1007/s40200-022-01045-9.

Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.

Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting. We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data. Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting. This study is registered as PROSPERO CRD42020201953. This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.

Abstract PS9-01: Consumer and patient reactions to trials of chemotherapy reductions reveal an urgent need to name and explain the concept

Abstract Introduction: A growing trend in cancer research is the study of de-escalation of treatment, particularly chemotherapy. The hope is that eliminating or reducing drug(s) from treatment regimens will reduce toxicity burden and increase quality of life without increasing risk of recurrence and death. Large well-designed clinical trials are needed to ensure this hope is a reality. One such trial is EA1181 CompassHER2 pCR, which has an accrual goal of 1,250 patients. Methods: This qualitative study included: (A) 2 focus groups with patients diagnosed with HER2+ breast cancer 3-5 years ago, for their ability to draw on their experience and react to the trial and (B) 3 focus groups with consumers who have never had a cancer diagnosis, for their ability to provide the “cancer-naïve” perspective that may more closely match that of newly diagnosed patients (the EA1181 population). One of the consumer groups was composed of Black women and moderated by a Black facilitator to allow issues to surface that may be specific to this group. Patients were identified via Living Beyond Breast Cancer; consumers were identified via a nationwide market research panel. Groups took place online in April and May 2020, after the COVID pandemic had begun. After a brief introduction to the trial, questions focused on: Reactions and questions, motivations, concerns, and descriptive language. Results: A total of 30 women (11 patients and 19 consumers) participated, representing a mix of age groups, educational attainment, and racial and ethnic social identities. The trial description raised many questions in participants’ minds. Some of the more frequent responses from both patients and consumers related to the rationale for reducing treatment and the side effects and benefits of each drug. Consumers demonstrated confusion between what is to be tested in the trial versus what is part of the neoadjuvant process. Patients questioned the timeline and length of each step. Motivations for participation centered on avoiding some chemotherapy and the associated side effects, costs, and recovery time. Some discussed taking only what is needed. Concerns were significant and centered on: (A) Fear and the feeling that it is best to take everything, (B) Possible lengthened duration of treatment since chemotherapy may be needed after surgery (versus the certainly of having all chemo prior to surgery). The duration issue generated strongly negative reactions among patients who felt they would prefer chemo and its side effects all at once. Some motivations and barriers also seemed tied to the likelihood of not needing post-surgical chemo, with participants expecting thresholds (unaided) of 50% to 80% of the perceived desirable outcome. Language around the concept is a critical issue. Participants expressed many ideas related to possible milder treatment that is modified. The word, de-escalation, garnered very negative reactions including many comparisons to military action. Toxicity is also a term that was less familiar to consumers and disliked by many as it elicits additional fear; “side effects” seems more familiar and palatable. Conclusion: Communication about trials with reduced chemotherapy will need to be effective to lead to successful accrual. Providing tools to oncologists and patients to enhance two-way communication may be necessary to ensure concepts are understood. Since de-escalation is already becoming a term commonly used by researchers, replacing it with a more effective descriptor that is clear and connects to the benefits appears time-critical. Quantifying reactions to language options and other qualitative findings via a survey with a larger sample of consumers and patients is advised. Including patient voices in trial design, as well as consumers particularly for trials for the newly-diagnosed, sheds light on communication needs. Citation Format: Mary L Smith, Elda Railey, Carol B White, Janine Hill, Courtney J Andrews, Gabrielle B Rocque. Consumer and patient reactions to trials of chemotherapy reductions reveal an urgent need to name and explain the concept [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-01.

The effects of probiotics, prebiotics and synbiotics on the reduction of IBD complications, a periodic review during 2009-2020.

To perform a systematic review on randomized controlled trials to examine the efficacy of probiotics, prebiotics and synbiotics in the treatment of IBD. PubMed, Web of science, Scopus and Google Scholar were systematically searched from January 2009 to January 2020 using the following keywords: 'Inflammatory Bowel Disease', 'Probiotics' and 'Clinical trial'. The statistical analysis was performed using SPSS software version 24.0. A total of 1832 articles were found during the initial search and 21 clinical trials were eligible. Studies comparing the effects of probiotics and placebo among patients with active ulcerative colitis (UC) showed a significant difference in clinical outcomes. Moreover, probiotics improved the overall induction of remission rates among patients with Crohn's disease (CD). Probiotics significantly decreased the IL-1β, TNF-α and IL-8 levels. Also, the need for systemic steroids, hospitalization, surgery, as well as histological score and disease activity index significantly decreased in patients who used probiotic or pro-/synbiotics. The use of probiotics, as food supplements, can induce anti-inflammatory reactions, balance the intestinal homeostasis and induce remission in IBD. The efficacy of probiotics on remission induction is more reported in UC rather than CD. Larger well-designed clinical trials are needed to further determine whether probiotics are of clear benefits for remission in IBD.

Assessment of platelet function utilizing viscoelastic testing.

Assessment of platelet function utilizing viscoelastic testing.

The way forward to understand aortic disease.

Content List ‐ Read more articles from the symposium: “Uppsala Aortic summit”.

The Efficacy and Safety of Acellular Matrix Therapy for Diabetic Foot Ulcers: A Meta-Analysis of Randomized Clinical Trials.

Background Acellular matrix (AM) therapy has shown promise in the treatment of diabetic foot ulcers (DFUs) in several studies. The clinical effects of AM therapy were not well established. Therefore, we conducted a meta-analysis of randomized clinical trials (RCTs) to examine the efficacy and safety of AM therapy for patients with DFUs. Methods A literature search of 5 databases was performed to identify RCTs comparing AM therapy to standard therapy (ST) in patients with DFUs. The primary outcome was the complete healing rate and the secondary outcomes mainly included time to complete healing and adverse events. Results Nine RCTs involving 897 patients were included. Compared with ST group, patients allocated to AM group had a higher complete healing rate both at 12 weeks (risk ratio (RR) = 1.73, 95% confidence interval (CI): 1.31 to 2.30) and 16 weeks (RR = 1.56, 95% CI: 1.28 to 1.91), a shorter time to complete healing (mean difference (MD) = −2.41; 95% CI: -3.49 to -1.32), and fewer adverse events (RR = 0.64, 95% CI: 0.44 to 0.93). Conclusion The present study suggests that AM therapy as an adjuvant treatment could further promote the healing of full-thickness, noninfected, and nonischemia DFUs. AM therapy also has a safety profile. More large well-designed randomized clinical trials with long follow-up duration are needed to further explore the efficacy and safety of AM therapy for DFUs.

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex.

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and long-term consequences of unresolved pain or excessive analgosedation, adequate nociceptive monitoring remains challenging in non-communicative, critically ill adults. In the intensive care unit (ICU), routine nociceptive evaluation is carried out by the attending nurse using the Behavior Pain Scale (BPS) in mechanically ventilated patients. This assessment is limited by medication use (e.g., neuromuscular blocking agents) and the inherent subjective character of nociceptive evaluation by third parties. Here, we describe the use of two nociceptive reflex testing devices as tools for objective pain evaluation: the pupillary dilation reflex (PDR) and nociception flexion reflex (NFR). These measurement tools are non-invasive and well tolerated, providing clinicians and researchers with objective information regarding two different nociceptive processing pathways: (1)the pain-related autonomic reactivityand (2) the ascending component of the somatosensory system. The use of PDR and NFR measurements are currently limited to specialized pain clinics and research institutions because of impressions that these are technically demanding or time-consuming procedures, or even because of a lack of knowledge regarding their existence. By focusing on the two abovementioned nociceptive reflex assessments, this study evaluated their feasibility as a physiological pain measurement method in daily practice. Pursuing novel technologies for evaluating the analgesia level in unconscious patients may further improve individual pharmacological treatment and patient related outcome measures. Therefore, future research must include large well-designed clinical trials in a real-life environment.

Collagenase clostridium histolyticum: a novel medical treatment for Peyronie's disease.

Peyronie's disease (PD) affects up to 9% of the male population. PD causes scarring of the tunica albuginea of the penis which leads to penile deformity making sexual intercourse difficult or impossible. PD also causes significant psychological, emotional and relationship difficulties for both patient and partner. Up until the licencing of Collagenase clostridium histolyticum (CCH) (Xiapex®, Xiaflex®), surgical correction of the penile deformity was the mainstay of treatment. Many conservative treatment options had been previously tried, however, the safety and efficacy of these options has not been demonstrated in large well-designed clinical trials. Intra-lesional CCH is now the gold standard option for the non-surgical management of PD. It is the first and only treatment approved by the Food and Drug Administration and the European Medicines Agency for PD. In this review article, we will discuss the pharmacology, clinical efficacy, safety and future of CCH intralesional injection. MEDLINE and PubMed search (from 1946). The search terms ("Collagenase Clostridium Histolyticum" OR "Xiapex" OR "Xiaflex") AND "Peyronie's disease" were used. The safety and efficacy of intra-lesional CCH in the management of PD has been demonstrated in 2 large-scale multicenter, randomized, double-blind placebo-controlled clinical trials; the investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II (IMPRESS I and IMPRESS II). A new study published by our group suggests a new modified shortened protocol that will reduce the cost and duration of treatment without compromising the safety or efficacy of treatment. CCH is the gold standard non-surgical option in the management of PD. The safety and efficacy of CCH has been demonstrated in large well-designed clinical trials. The new modified protocol, developed by our group, reduces the cost and inconvenience to patients whilst maintaining the efficacy. This will allow more men to benefit and will reduce the number of men undergoing surgical correction for their PD.

Diffusion-weighted imaging in identifying breast cancer pathological response to neoadjuvant chemotherapy: A meta-analysis.

BackgroundDiffusion-weighted imaging (DWI) is increasingly used to identify pathological complete responses (pCRs) to neoadjuvant chemotherapy (NAC) in breast cancer. The aim of the present study was to assess the utility of DWI using a pooled analysis.Materials and MethodsLiterature databases were searched prior to July 2017. Fifteen studies with a total of 1181 patients were included. The data were extracted to perform pooled analysis, heterogeneity testing, threshold effect testing, sensitivity analysis, publication bias analysis and subgroup analyses.ResultThe methodological quality was moderate. Remarkable heterogeneity was detected, primarily due to a threshold effect. The pooled weighted values were a sensitivity of 0.88 (95% confidence interval (CI): 0.81, 0.92), a specificity of 0.79 (95% CI: 0.70, 0.86), a positive likelihood ratio of 4.1 (95% CI: 2.9, 5.9), a negative likelihood ratio of 0.16 (95% CI: 0.10, 0.24), and a diagnostic odds ratio of 26 (95% CI: 15, 46). The area under the receiver operator characteristic curve was 0.91 (95% CI: 0.88, 0.93). In the subgroup analysis, the pooled specificity of change in the apparent diffusion coefficient (ADC) subgroup was higher than that in the pre-treatment ADC subgroup (0.80 [95% CI: 0.71, 087] vs. 0.63 [95% CI: 0.52, 0.73], P = 0.027).ConclusionsDWI may be an accurate and nonradioactive imaging technique for identifying pCRs to NAC in breast cancer. Nonetheless, there are a variety of issues when assessing DWI techniques for estimating breast cancer responses to NAC, and large scale and well-designed clinical trials are needed to assess the technique's diagnostic value.

Collagenase Clostridium histolyticum in the Treatment of Peyronie's Disease-A Review of the Literature and a New Modified Protocol.

Peyronie's disease (PD) is a common condition that results in penile deformity, which makes sexual intercourse difficult or impossible, and causes psychological, emotional, and relationship difficulties for the man affected and his partner. Collagenase Clostridium histolyticum (CCH; Xiapex, Xiaflex) is the first licensed non-surgical treatment option for PD. The safety and efficacy have been demonstrated in two large phase III randomized controlled trials (IMPRESS I and IMPRESS II). To review the safety and efficacy of CCH and to introduce a new shortened modified protocol for CCH that was developed by the authors to decrease the cost and duration of treatment. A review of the medical literature on CCH for inclusion in this review was obtained by searching the PubMed (from 1946) and Medline (from 1946) medical databases and from the screening of relevant bibliographies. The search terms Xiapex, Xiaflex, collagenase Clostridial histolyticum, and Peyronie's disease were used. Clinical trials in men with PD and scientific articles relating to pharmacologic data were included in the review. When possible, large, randomized, and well-designed trials were selected. Changes in the angle of penile curvature and in the Peyronie's Disease Questionnaire domains. The clinical trials demonstrate the safety and efficacy of CCH in the treatment of PD. The new modified protocol developed by the authors is as safe and effective as the protocol used in the clinical trials. CCH is the first licensed non-surgical treatment for PD. Its safety and efficacy have been demonstrated in large well-designed clinical trials. The new shortened modified protocol decreases the cost andduration of the treatment without compromising the safety and efficacy of the drug. This alteration will allow more patients to benefit from CCH. Abdel Raheem A, Johnson M, Abdel-Raheem T, etal. Collagenase Clostridium histolyticum in the Treatment of Peyronie's Disease-A Review of the Literature and a New Modified Protocol. Sex Med Rev 2017;5:529-535.

Treatment of acute pouchitis

Acute pouchitis is a common disease that affects many patients with an ileal pouch-anal anastomosis. The management of acute pouchitis remains largely empiric with the mainstay of therapy being the antibiotics ciprofloxacin and metronidazole. Probiotics may have a role in the primary and secondary prophylaxis of acute pouchitis. In addition, there are modest data that probiotics are effective in the treatment of mild acute pouchitis. There are limited data for other treatments of acute pouchitis including oral and rectal budesonide and glutamine suppositories. Diet plays a largely undefined role in the development and management of acute pouchitis, and, although many have been studied, no specific diet can currently be recommended. Larger well-designed clinical trials are necessary to confirm the efficacy of current treatments and to investigate new treatments for the management of acute pouchitis.

Deep Brain Stimulation for Treatment-Refractory Mood and Obsessive-Compulsive Disorders

Deep brain stimulation (DBS) is an invasive therapy in which electrodes are surgically placed into the brain and deliver continuous electrical stimulation. It was originally developed for Parkinson’s disease and other movement disorders. As evidence emerged that certain mental disorders involved abnormal function of specific brain nuclei, multiple investigators launched trials of DBS for mental disorders, particularly major depression (MDD) and obsessive-compulsive disorder (OCD). While open-label results were promising, recent large well-designed clinical trials in MDD have failed. We review the result of major DBS studies to date in psychiatry and what they have taught us about DBS’ safety and efficacy. We further review a variety of animal and human neuroscience studies that have started to shed light on DBS’ mechanisms of action at multiple brain targets. From these, we identify major trends that are likely to drive psychiatric DBS development in the coming decade, including “closed-loop” responsive stimulation, biomarker-based patient selection, and a better modeling of phenotypic heterogeneity within mental disorders. We conclude that on balance, DBS remains promising as a psychiatric treatment, but recent evidence highlights a clear need for further development and a better understanding of mechanisms.

Vitamin D as a novel therapy in inflammatory bowel disease: new hope or false dawn?

There is increasing scientific interest in the field of vitamin D research, moving the focus beyond bone health to other disease processes. Low circulating vitamin D levels have been reported as a risk factor for several pathophysiologically divergent diseases, including cancers, diabetes, CVD, multiple sclerosis and inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease (IBD). But, therein, remains the challenge: can any single nutrient contribute to multiple complex disease mechanisms and, ultimately, have therapeutic potential? The aim of this review is to critically evaluate several strands of scientific evidence surrounding vitamin D and inflammation, primarily focusing on IBD. Epidemiological studies suggest an increased incidence of IBD and rheumatoid arthritis in countries of more northern latitudes, mirroring sunlight patterns. A considerable body of evidence supports the anti-inflammatory effects of vitamin D, at least in animal models of IBD. Although it is accepted that suboptimal vitamin D status is common in IBD, some studies suggest that this associates with more severe disease. With regard to treatment, the data are only beginning to emerge from randomised controlled trials to suggest that people with IBD may remain in remission longer when treated with oral vitamin D. In conclusion, several strands of evidence suggest that vitamin D may modify the immune response in IBD. There is a continued need for large well-designed clinical trials and mechanistic studies to determine if, and how, this emerging promise translates into tangible clinical benefits for people with chronic debilitating diseases such as IBD.

Evaluation and Treatment of Functional Constipation in Infants and Children

Constipation is a pediatric problem commonly encountered by many health care workers in primary, secondary, and tertiary care. To assist medical care providers in the evaluation and management of children with functional constipation, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition were charged with the task of developing a uniform document of evidence-based guidelines. Nine clinical questions addressing diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to October 2011 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials, and PsychInfo databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. For therapeutic questions, quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Grading the quality of evidence for the other questions was performed according to the classification system of the Oxford Centre for Evidence-Based Medicine. During 3 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation, using the nominal voting technique. Expert opinion was used where no randomized controlled trials were available to support the recommendation. This evidence-based guideline provides recommendations for the evaluation and treatment of children with functional constipation to standardize and improve their quality of care. In addition, 2 algorithms were developed, one for the infants <6 months of age and the other for older infants and children. This document is intended to be used in daily practice and as a basis for further clinical research. Large well-designed clinical trials are necessary with regard to diagnostic evaluation and treatment.

Intravenous Tocilizumab: A Review of Its Use in Adults with Rheumatoid Arthritis

Tocilizumab (Actemra®, RoActemra®) is a humanized monoclonal antibody that acts as an interleukin-6 receptor antagonist. Intravenous tocilizumab as monotherapy or in combination with disease-modifying anti-rheumatic drugs (DMARDs) is indicated for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA) who had an inadequate response to one or more DMARDs or tumor necrosis factor (TNF) α antagonists (the specific indication varies between countries); it may also be used as monotherapy in patients for whom continued methotrexate use is inappropriate. This article reviews the efficacy and tolerability of tocilizumab in these patients and briefly summarizes its pharmacology. Several large well-designed clinical trials and routine clinical practice studies showed that tocilizumab was an effective and generally well tolerated biologic for the treatment of adults with RA, including those with an inadequate response to DMARDs or TNFα antagonists. In these studies, tocilizumab as monotherapy or in combination with DMARDs (including methotrexate) had beneficial effects on the signs and symptoms of disease, health-related quality of life/physical function, and/or radiologic disease progression. In addition, tocilizumab monotherapy was more effective than adalimumab monotherapy in improving the signs and symptoms of disease in patients for whom continued methotrexate use was inappropriate. As with other biologic DMARDS, infections were the most common adverse event associated with tocilizumab therapy. Pooled and meta-analyses demonstrated that the efficacy and tolerability profile of tocilizumab was sustained during long-term (up to 9 years) therapy. Although additional comparative data are needed to position tocilizumab more definitively with respect to other biologic DMARDs, current evidence indicates that tocilizumab is effective as a first- or subsequent-line biologic in patients with moderate to severe RA.

Stem Cell Transplantation for Ischemic Stroke

Studies in animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. However, to date, evidence for the benefits of stem cell transplantation in patients with ischemic stroke is lacking. Our objective was to assess the efficacy and safety of stem cell transplantation compared with conventional treatments in patients with ischemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2010), the Cochrane Central Register of Controlled Trials (CENTRAL; The …

Etanercept: An Evolving Role in Psoriasis and Psoriatic Arthritis

Tumor necrosis factor alpha (TNFalpha) plays a key pathophysiological role in psoriasis and psoriatic arthritis (PsA). Recent interest has thus focused on the clinical potential of TNFalpha antagonists (e.g. etanercept) in these settings. In psoriasis, several large pooled analyses and well-designed clinical trials documented the significant clinical efficacy and generally favorable tolerability of etanercept for up to 96 weeks. Similarly, in PsA, a large phase III trial showed that, etanercept significantly reduced arthritic symptoms and inhibited radiographic disease progression; sustained clinical benefit was again evident for up to 2 years. Etanercept is at the forefront of psoriatic disease management, and continued evolution and evaluation of the compound - for example, in detailed comparative studies and economic analyses - is likely to confirm a key role for etanercept in the treatment of psoriasis and PsA.

Total body irradiation plus cyclophosphamide versus busulphan with cyclophosphamide as conditioning regimen for patients with leukemia undergoing allogeneic stem cell transplantation: a meta-analysis

The aim of the study was to compare the therapeutic efficacy of total body irradiation (TBI)/cyclophosphamide (CY) versus BU/CY as conditioning regimen for leukemia. We electronically searched the Cochrane Central Register of Controlled Trials, Medline, Embase, CIBMTR and critically appraised all relevant articles (1990.01–2009.04). Comparative studies were evaluated on clinical therapeutic effects of TBI/CY and busulphan BU/CY regimens with assessement of engraftment, relapse, complications, and disease-free survival (DFS). Eighteen trials totaling 3172 patients have been assessed. Pooled comparisons of studies indicated that for patients with acute leukemia (ALL and AML), the TBI/CY regimen lead to lower rates of leukemia relapse, lower transplant-related mortality (TRM), and higher DFS, while for chronic myeloid leukemia (CML), the TBI/CY regimen had a higher rate of leukemia relapse, lower TRM, and similar DFS. The TBI/CY regimen was associated with similar occurrence of engraftment, acute and chronic graft-versus-host disease (GVHD), but with higher rates of cataract [odds ratio (OR) 12.69, p = 0.01], interstitial pneumonitis, later growth or development problems [OR 5.04, p = 0.008]. BU/CY regimen was associated with higher rates of complications like liver veno-occlusive disease [OR 0.43, p < 0.00001], hemorrhagic cystitis, and TRM. Our meta-analysis confirmed that different regimens and type of leukemia may affect the complications and outcome. An analysis of the effects of other regimens need to be carried out by large sample and well-designed clinical trials.