Non-controlled Trials Research Articles

Utilisation des anti-VEGF dans la dégénérescence maculaire liée à l’âge

We provide an overview of new anti-VEGF treatments for exudative age-related macular degeneration. We reviewed the current literature on this topic (including randomized controlled trials, nonrandomized and noncontrolled trials, and case reports). The efficacy and safety of anti-VEGF therapies for AMD are reported. We discuss combined therapy approaches, treatment frequency, and emerging therapies for exudative AMD. Therapies that target VEGF greatly improve treatment for exudative AMD. However, many questions are still being debated.

Continuous Glucose Monitors: The Long-Awaited Watch Dogs?

To date, several continuous glucose sensors have been developed and launched in the U.S. and European markets, though large-scale application in standard diabetes care still awaits its breakthrough. This report offers an overview of the current applications and clinically relevant aspects of continuous glucose monitors (CGMs), e.g., the calibration procedure, interpretation of continuous glucose data, and some important limitations. It is still difficult to state with certainty that CGMs allow effective improvement in glycemic control for the majority of patients with type 1 diabetes, in view of the paucity of controlled studies showing an impact on hemoglobin A1c or frequency of hypoglycemia, even if such a tendency seems to emerge from most non-controlled intervention trials. Future controlled trials should also take into account patient-related outcomes, to evaluate the effect of CGMs on health status, treatment satisfaction, and fear of hypoglycemia. Increased accuracy and reimbursement are key to further implementation of CGMs.

Measurement of the Walking Duration With Therapeutic Shoes in Neuropathic Diabetic Patients by a Novel Device (Show-me)

Therapeutic shoes and other prophylactic interventions are used to prevent diabetic foot ulceration (1,2), but patient’s compliance to use prescribed footwear has never been investigated in primary care. Therapeutic footwear might be effective in secondary ulcer prevention, as demonstrated in two noncontrolled trials, but was only effective when worn >60% of the daytime (3) or >8 h a day (4). In a controlled clinical trial, no benefit was observed between control patients wearing their own footwear and intervention patients wearing specialized footwear (5). The aim was to measure the duration of walking with therapeutic shoes by a novel device, “Show-me” (shoe-wearing measuring equipment), in neuropathic patients without a history of …

Value and limitations of the Continuous Glucose Monitoring System in the management of type 1 diabetes

The CGMS (Continuous Glucose Monitoring System) is a portable device allowing continuous measuring of glucose. It provides recordings of at least 72 h, during which 288 measures/day are performed. Results are visualised in the form of a set of curves, illustrating the variations in blood glucose levels over time. The quality of the records has often been questioned by several authors. Some of the system's physiologically related limitations can be explained by the less than perfect coincidence of variations in glucose levels observed in the interstitial tissue, where CGMS measurings are done, and in the blood, where calibrations are performed. Other limitations, such as defects in accuracy or in reproducibility of tracings or premature curtailments of recordings, are due to technical weaknesses which were considerably improved during the past few years, particularly with regard to the quality of the electrodes providing a more stable signal over time. In clinical practice, CGMS is a tool for investigating the glycaemic patterns of diabetic patients in conjonction with SMBG. It allows the identification of overlooked hyper- or hypoglycaemia. Generally well accepted, it is a usefull tool to analyse the nocturnal period, or any situation where glucose checks are rare. The visual nature of its results provides a facilitating support in the discussion between the patient and the care-provider during consultations or educational sessions. CGMS utilisation was proposed for guiding treatment adjustment. At present, it is still difficult to state with certainty that this tool allows effective improvement in the metabolic control of patients with type 1 diabetes, in view of the paucity of controlled studies showing an impact on HbA1c values or on the frequency of hypoglycaemia, even if such a tendency emerges from most non-controlled intervention trials.

Diagnosis and Treatment of Chronic Immune-mediated Neuropathies

The chronic autoimmune neuropathies are a diverse group of disorders, whose diagnosis and classification is based on the clinical presentations and results of ancillary tests. In chronic inflammatory demyelinating polyneuropathy, controlled therapeutic trials demonstrated efficacy for intravenous gamma-globulins, corticosteroids, and plasmaphereis. In multifocal motor neuropathy, intravenous gamma-globulins have been shown to be effective. In the other immune-mediated neuropathies, there are no reported controlled therapeutic trials, but efficacy has been reported for some treatments in non-controlled trials on case studies. Choice of therapy in individual cases is based on reported efficacy, as well as severity, progression, coexisting illness, predisposition to developing complications, and potential drug interactions.

A randomized controlled study of low-dose UVA1, medium-dose UVA1, and narrowband UVB phototherapy in the treatment of localized scleroderma

In previous trials, UV therapy has been demonstrated to be effective in the treatment of localized scleroderma (LS). To date, a randomized comparison study to evaluate the efficacy and safety of different, commonly used phototherapeutic modalities in LS is still outstanding. The aim of this study was to compare the safety and efficacy of low-dose (LD) UVA1, medium-dose (MD) UVA1, and narrowband (NB) UVB phototherapy in the treatment of LS. Sixty four patients with LS were consecutively included in a prospective, open, randomized controlled 3-arm study. Severity of LS was determined by means of a clinical score, and clinical improvement was also monitored by histopathologic analysis and 20-MHz ultrasound. A total of 27 patients were treated with LD UVA1 (20 J/cm2), 18 patients received MD UVA1 (50 J/cm2), and 19 patients were treated with NB UVB dependent on their skin type. Phototherapy was performed 5 times weekly for 8 weeks. Two of the 64 patients included in this trial discontinued therapy. Skin status significantly improved in all patients who finished the treatment protocol, resulting in a reduction of the clinical score in all groups (LD UVA1, 7.6-5.0 [P < .001, 95% confidence interval 1.6-3.4]; MD UVA1, 11.1-6.6 [P < .001, 95% confidence interval 2.5-6.2]; NB UVB, 7.3-4.9 [P < .001, 95% confidence interval 1.6-3.2]). The reduction of the score was accompanied by an improvement of the visual analog scale for itching and tightness, histologic score, and 20-MHz ultrasound. MD UVA1 was significantly more effective than NB UVB (P < .05). There were no significant differences between LD UVA1 and NB UVB and the former and MD UVA1 (P > .05). We had a relatively small study sample and nonblinded assessment of primary outcome. Phototherapy, as previously reported in several noncontrolled trials, is an effective therapeutic option in LS, with a favorable risk/benefit ratio. UVA1 phototherapy should be considered among the first approaches in the management of LS.

Optimum therapeutic approaches for lupus nephritis: what therapy and for whom?

The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.

Epilepsy and quality of life in adults: A review of instruments

The aim of this report is to describe the state of the art of quality of life (QoL) instruments used for adults with epilepsy and to help those in the field to identify, select, and use the instruments most suitable for their purposes. We searched Medline and the Cochrane Database for articles in English, German, French, Spanish, Portuguese and Italian published by the end of 2002. Electronic retrieval was completed by hand-search. The final list included 203 articles reporting 205 studies. There were 62 validation studies and 143 clinical studies, including 7 population studies, 45 “pure” observational, 37 observational with aspects of validation and 54 experimental (38 randomized clinical trials and 16 non-randomized or non-controlled trials). Twenty-four generic and 21 specific QoL instruments were used. Eight were used in more than 10 studies, while 21 were used only once; 7/24 generic and 19/21 specific questionnaires were validated for epilepsy. The different domains considered in the 26 questionnaires specifically validated for epilepsy are listed. We classified questionnaires according to three aspects: validation, diffusion of use, and specificity of domains. Questionnaires covering all three aspects (WPSI, ESI-55, QOLIE-89, QOLIE-31, QOLIE-10, Liverpool Batteries) should be preferred when planning a QoL study in epilepsy. However, those covering only two aspects (SF-36, SEALS, EPSES, EOS, PESOS, QOLAS) could also be useful in selected situations or may become a first-choice instrument in the future, after more widespread use or complete validation. All the other instruments should at present be considered only for second choice.

Selective Serotonin-Reuptake Inhibitors in the Treatment of Premature Ejaculation

To review the use of selective serotonin-reuptake inhibitors (SSRIs) in the treatment of premature ejaculation. Articles were retrieved through a MEDLINE search (1966-January 2004). Search terms used to identify articles included serotonin uptake inhibitors, premature ejaculation, rapid ejaculation, and sexual behavior, as well as the generic names of currently available SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. The literature search was limited to articles published in the English language containing human subjects. Articles obtained through the literature search were evaluated, and randomized controlled trials were included in this review. Information from noncontrolled trials or case reports was considered for inclusion if it contributed to the completeness of this review and if it was the highest level of evidence available. Premature ejaculation is a commonly reported sexual difficulty. Delayed ejaculation is a widely reported sexual adverse effect of SSRIs. In some men exhibiting premature ejaculation, the ability of the SSRIs to delay ejaculation has been therapeutic. Trials evaluating the ejaculation-delaying ability of SSRIs demonstrated that paroxetine, fluoxetine, sertraline, and citalopram produce a statistically significant increase in the ejaculation latency time compared with placebo. Taking advantage of the ejaculation-delaying effects of SSRIs increases the treatment options available to prescribers and patients. Convenience and minimal adverse effect profile make these agents an alternative to previously used behavior modalities and older pharmacologic agents. Although some questions still surround the details of their use, SSRIs have the potential to improve the quality of life for men with premature ejaculation and their partners.

Guideline Watch: Practice Guideline for the Treatment of Patients With Borderline Personality Disorder

Since the 2001 publication of APA’s Practice Guideline for the Treatment of Patients With Borderline Personality Disorder (1), more studies have been published on borderline personality disorder (BPD) than on any other personality disorder (2, 3). New analyses of the validity of the DSMIV-TR criteria–defined construct of BPD have been published, new data on the prevalence of BPD are available, risk factors for and biological characteristics of BPD are being elucidated, and new studies on the treatment of BPD have been carried out. This guideline watch highlights the most important of these developments.

Drug-eluting stent: a review and update

The development of stent has been a major advance in the treatment of obstructive coronary artery disease since the introduction of balloon angioplasty. However, neointimal hyperplasia occurring within the stent leading to in-stent restenosis is a main obstacle in the long-term success of percutaneous coronary intervention (PCI). The recent introduction of drug-eluting stents (DES) contributes a major breakthrough to interventional cardiology. Many large randomized clinical trials using DES have shown a remarkable reduction in angiographic restenosis and target vessel revascularization when compared with bare metal stents. The results of these trials also appear to be supported by evidence from everyday practice and non-controlled clinical trials. However, the expanded applications of DES, especially in treating complex lesions such as left main trunk, bifurcation, saphenous vein graft lesions, or in-stent restenosis, are still under evaluation with ongoing studies. With the availability of different types of DES in the market, the issue of cost should not be a deterrent and DES will eventually be an economically viable option for all patients. The adoption of DES in all percutaneous coronary intervention may become a reality in the near future. In this review article, we summarize the recent development and progress of DES as well as compare and update the results of clinical trials.

The relationship between depression and interferon beta-1a therapy in patients with multiple sclerosis

It has been suggested that interferons (IFN) may cause depression de novo or worsen pre-existing depression. Depression data collected using validated instruments from individual clinical trials in multiple sclerosis, however, have consistently failed to identify an association. In this study, pooled data from 6 controlled studies and 17 noncontrolled clinical trials of subcutaneous IFN beta-1a were assessed to determine the relationship between IFN therapy with physician reports of depression and suicide. In distinction to the negative findings for depressive symptom ratings, pooling of physician-reported side effect data from these clinical trials identified a statistically significant association between depression and IFN use during the first six months of treatment There was an association between these reported episodes of depression and discontinuation of IFN therapy, but IFN treatment was not associated with suicide attempts. IFN beta-1a may induce a constellation of symptoms, particularly early in therapy, that may be labelled as depression by physicians. However, the lack of an increase in depression-rating scale scores and the lack of association with suicide risk suggests that the syndrome may be an atypical one.

Nonresorbable copolymer implantation for gastroesophageal reflux disease: A randomized sham-controlled multicenter trial

This aim was to determine whether endoscopic implantation of a biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA) is a more effective therapy for gastroesophageal reflux disease (GERD) than a sham procedure. In a randomized, single-blind, prospective, multicenter clinical trial, 64 patients with GERD were enrolled whose symptoms were well controlled by proton pump inhibitor (PPI) therapy and rapidly recurred after cessation of PPI therapy. Thirty-two patients were assigned to Enteryx implantation and 32 to a sham procedure consisting of standard upper endoscopy. Patients in both groups with unsatisfactory symptom relief after 3 months were eligible for re-treatment by Enteryx implantation. The primary study end point was > or =50% reduction in PPI use. Secondary end points included > or =50% improvement in GERD score and the proportion of patients not undergoing re-treatment procedure. Follow-up evaluations were performed at 3 and 6 months. The percentage of Enteryx-treated patients achieving a > or =50% reduction in PPI use (81%) was greater than that of the sham group (53%), with a rate ratio of 1.52 (confidence interval [CI], 1.06-2.28; P=.023). A higher proportion of the Enteryx (68%) than sham group (41%) ceased PPI use completely (rate ratio, 1.67; CI, 1.03-2.80; P=.033). GERD health-related quality of life heartburn score improvement > or =50% was achieved by 67% of the Enteryx group versus 22% of the sham group (rate ratio, 3.05; CI, 1.55-6.33; P <.001). More Enteryx-treated (81%) than sham-treated (19%) patients did not undergo re-treatment (rate ratio, 4.33; CI, 2.23-9.29; P <.001). Enteryx implantation more effectively reduces PPI dependency and alleviates GERD symptoms than a sham procedure.

Do Psychosocial Variables Predict Weight Loss or Mental Health after Obesity Surgery? A Systematic Review

The objective of this study was to present a systematic review of psychological and psychosocial predictors of weight loss and mental health after bariatric surgery. This systematic review included all controlled and noncontrolled trials of the last 2 decades with either a retrospective or prospective design and a follow-up period of at least 1 year. The relevant literature was identified by a search of computerized databases. All articles published in English and German between 1980 and 2002 were reviewed. Using the above inclusion/exclusion criteria, 29 articles were identified focusing on psychosocial predictors of weight loss and mental health after obesity surgery. Personality traits have no predictive value for the postoperative course of weight or mental state. Apart from serious psychiatric disorders including personality disorders, psychiatric comorbidity seems to be of more predictive value for mental and physical well-being as two essential aspects of quality of life than for weight loss postsurgery. However, depressive and anxiety symptoms as correlates of psychological stress with regard to obesity seem to be positive predictors of weight loss postsurgery. The severity of the symptoms or the disorder is more relevant for the outcome of obesity surgery than the specificity of the symptoms. It is also not solely the consumption of distinct "forbidden" foods, such as sweets or soft drinks, but rather a general hypercaloric eating behavior, either as an expression of the patient's inadequate compliance or a dysregulation in energy balance, which is associated with a poor weight loss postsurgery.

Radiofrequency surgery of the soft palate in the treatment of snoring: a review of the literature.

Radiofrequency surgery of the soft palate presents a promising alternative for the treatment of snoring. The aim of this study was to give an overview of the current literature and to quantify the results in terms of a meta-analysis of treatment efficacy. Current databases were searched for publications concerning the treatment of snoring with radiofrequency surgery up to January 2003. Only original articles published in peer-reviewed journals were taken into consideration. The review is based on 22 publications, mostly consisting of prospective noncontrolled clinical trials. Snoring was assessed with the help of visual analogue scales or snoring scores provided by the bed partner. In all these trials, a significant reduction of snoring was reported. Postoperative morbidity was low, but complication rates differed substantially. According to all of the published material, radiofrequency surgery of the soft palate leads to a significant reduction of subjective snoring, and snoring is reduced to a tolerable level. Nevertheless, these findings will have to be confirmed by controlled clinical trials.

Depression and personality disorder.

Research into the relationship between depression and personality disorder is compromised by a number of methodologic factors, including differing concepts of personality disorder, the validity of a personality disorder diagnosis, the effect of mood on diagnosis, and the overlap between some personality disorder symptoms and mood symptoms. Personality pathology is common in patients with personality disorder. Reasons for this include a "scar" effect of chronic low mood on attitudes and behaviors, as well as possible risk factors via certain personality traits. The negative effect of comorbid personality disorder on treatment outcome in depressed patients may be less than previously believed. Possible reasons include treatment bias in non-controlled trials and the increasing use of selective serotonin reuptake inhibitors rather than tricyclic antidepressants. Many personality traits and disorders may be part of the psychopathology of depression and share a common origin.

Humoral rejection of human organ transplants.

Although T-cell mediated rejection has remained the most common form of acute rejection, humoral rejection now accounts for a substantial fraction in patients with kidney or heart allografts, and probably causes the majority of acute graft losses. The frequency, variously estimated at 20-30%, is attributed to improved methods of detection, including staining for C4d in tissues, which is more sensitive and specific than histological features. Detection of circulating anti-donor reactive antibody (usually to donor HLA antigens) confirms the diagnosis. The clinico-pathological entity of acute humoral rejection is well accepted in kidney and increasingly in heart transplantation. Recent evidence points to a new category of chronic humoral rejection, which accounts for about 60% of chronic rejection of kidneys. Importantly, the hallmark of humoral rejection, C4d, can be detected in the grafts before development of histological evidence of chronic rejection. Humoral rejection is generally not responsive to the usual anti-T cell immunosuppressive agents, but small, non-controlled trials suggest humoral rejection can be reversed with plasmapheresis, intravenous immunoglobulin, anti-CD20 and other treatments, all of which deserve formal clinical evaluation. Prophylaxis for chronic rejection is expected to require donor-specific serological monitoring and protocol biopsies.

Tube digestif et toxine botulique

Introduction. – the aim of this work was to check literature to assess botulinum toxin injection efficacy in gastrointestinal motor disorders with special emphasis on controlled clinical trials. Methods. – literature was carried out with the Medline data bank. Results. – seventy three articles in French and in English including a recent general review were retained. Comparative clinical trials only concerned achalasia and anal fissure. The other gastrointestinal motor disorders only gave rise to open non-controlled trials assessed on clinical end points. Discussion. – this review of literature helps to determine usefullness and safety of Botulinum toxin injection in the treatment of esophageal achalasia and anal fissure. The main limitation is its brief duration of action. Studies concerning the others spastic motor disorders are based on unknown physiopathology and controlled trials are required to assess its efficacy. Conclusion. – botulinum toxin is increasingly used for gastrointestinal motor disorders with worthwhile results. Its efficacy has been yet established for only two disorders : it has a valuable palliative role in achalasia and may be curative for anal fissure.

Amantadine in Parkinson's disease.

Although levodopa is the most common drug prescribed to relieve the symptoms of Parkinson's disease it is associated with motor and psychiatric side-effects. Consequently, interest has turned to alternative drugs with improved side-effect profiles to replace or augment levodopa. Amantadine, originally used as an antiviral drug, has been shown to improve the symptoms of Parkinson's disease. To compare the efficacy and safety of amantadine therapy (monotherapy or adjuvant therapy) versus placebo in treating people with Parkinson's disease. Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted. Randomised controlled trials comparing amantadine with placebo in the treatment of patients with a clinical diagnosis of idiopathic Parkinson's disease. Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion. Six randomised controlled trials were found comparing amantadine monotherapy or adjuvant therapy with placebo in the treatment of idiopathic Parkinson's disease. Five examined amantadine as adjuvant therapy with optimal levels of levodopa or anticholinergics and one examined amantadine as an adjuvant therapy with minimum tolerated levels of anticholinergics or as a monotherapy. Five were double-blind cross-over studies and one was a double-blind parallel group study. In total they examined 215 patients. The parallel group study allowed the randomisation codes to be broken and allowed patients in the placebo group to then receive amantadine. This could have led to bias. One study did not present the results of the placebo arm of the trial, hence we could not determine the difference between the two treatment groups. Two cross-over studies presented the results of the combined data from both treatment and placebo arms. The risk of carry-over effect into the second arm meant that these results could not be analysed. The final two studies presented at least some of their data from the end of the first arm of the trials. However only means were given, without standard deviations, so we could not determine the statistical significance of any difference between the amantadine and placebo groups. Although the authors did report on the side-effects from amantadine (such as livido recticularis, dry mouth and blurred vision), they state that none of them were severe. A considerable amount of evidence on the effectiveness of amantadine has accrued from non-controlled trials, often in patients with Parkinsonian conditions other than idiopathic Parkinson's disease. However, rigorous analysis of the six randomised controlled trials of amantadine reveals insufficient evidence of its efficacy and safety in the treatment of idiopathic Parkinson's disease.

Ventilación mecánica no invasiva en pacientes con enfermedades neuromusculares y en pacientes con alteraciones de la caja torácica

from negative pressure ventilators was widely used to treat respiratory insufficiency in patients with poliomyelitis between 1930 and 1960, leading to dramatic decreases in mortality. The publication of various noncontrolled trials describing cases successfully treated with NIV 4-9 has meant that, for ethical reasons, hardly any controlled trials have been designed. Available reports indicate that NIV is able to reverse alveolar hypoventilation, improve quality of life and prolong survival in neurological patients, as well as provide other benefits. Nevertheless, it may be that such findings overestimate the benefits of NIV , given that negative results are seldom reported. The only controlled studies of NIV are those of Vianello et al 10 and Shonhofer et al 11 . The former observed clinical and functional benefits in patients with Duchenne muscular dystrophy and the latter reported positive results in patients with chest restriction. In this review, we discuss the underlying pathophysiology of NIV use in patients with neurological diseases, the general mechanisms of action of the technique and its indications and complications. We also analyze the mechanisms involved and results obtained with NIV in two neuromuscular diseases.