Prospective Uncontrolled Trials Research Articles

OP18 Clinical Effectiveness And Safety Of Implantable Bulking Agents For Fecal Incontinence: A Systematic Review

IntroductionThe purpose of this systematic review is to evaluate whether implantable versus injectable bulking agents (second-line therapies) are equal/superior in terms of effectiveness (severity, quality of life [QoL], sustainability) and safety (adverse events) for fecal incontinence (FI).MethodsA systematic review was conducted and five databases were searched (Medline via Ovid, Embase, Cochrane Library, University of York Centre for Reviews and Dissemination, and International Network of Agencies for Health Technology Assessment database). In-/exclusion criteria were predefined according to the PICOS scheme. The Institute of Health Economics risk of bias (RoB) tool assessed studies’ internal validity. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the strength of evidence for safety outcomes was rated. A qualitative synthesis of the evidence was used to analyse the data.ResultsSix prospective uncontrolled trials (143 patients) were included. The evidence consists of six prospective single-arm, before-after studies fulfilling the inclusion criteria for assessing clinical effectiveness and safety for implantable bulking agents. FI severity (Cleveland Clinic FI Score) statistically significantly improved to three months (p<0.01) and six months (p<0.05) follow-up (five studies). Improvements in severity sustainability were reported after 12, 14 (p<0.01), and 36 (p<0.0001) months postoperatively. Improved disease-related QoL (FI QoL Score) was found (p<0.05) 12 months after surgery, and statistically significant improvements in QoL’s sustainability after 12 months (one study).Procedure-related adverse events (n=3) occurred, where prostheses extruded during surgery, and anal discomfort/pain was felt (n=11). Device-related adverse events, i.e., prostheses’ dislodgement (n=31) and removed/extruded prostheses (n=3), occurred. Studies were judged with moderate/high RoB. The strength of evidence for safety was judged to be very low.ConclusionsImplantable bulking agents might be an effective and safe minimally invasive option in FI treatment if conservative therapies fail. FI severity significantly improved, but not QoL, which needs to be explored in further studies. Due to the uncontrolled nature of the case series, comparative studies need to be awaited.

EFFECT OF VARICOCELE REPAIR ON CONVENTIONAL SPERM PARAMETERS IN INFERTILE PATIENTS WITH CLINICAL VARICOCELE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Varicocele is present in almost 35-40% of men presenting with primary infertility. Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. To the best of our knowledge, only a few systematic reviews and meta-analyses (SRMA) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility using a before-after analytic approach for analyzing 22, 17, and 5 prospective uncontrolled trials, respectively. Indeed, the majority of SRMAs have focused on pregnancy rate as an outcome. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls.

Tumescent liposuction for lipoedema: A systematic review of clinical effectiveness and safety

Abstract Background Tumescent liposuction is an established method for surgical therapy of lipoedema - a chronic, progressive, and painful fat distribution disorder. We aimed to assess the clinical effectiveness and safety of liposuction in patients with lipoedema (stage I-III) compared to any conservative treatment, concerning patient-relevant outcomes, such as reduction of pain, reduction in the size of extremities, improvement in quality of life (QoL), and safety events. Methods A systematic review was conducted, and five databases were searched. In-/exclusion criteria were predefined according to the PICOS scheme. The internal validity of the included studies was assessed using the IHE checklist; strength of evidence for safety outcomes by the GRADE approach. Results Six prospective uncontrolled trials (467 patients) were included for assessment of clinical effectiveness. Pain outcomes (patient-reported) statistically significantly improved at six-months follow-up and up to 12 years after liposuction (six studies). Reduced sizes of patients' extremities before-and-after liposuction were reported in three studies regarding reduced leg volume and circumference of lower extremities. Statistically significant improvements in lipoedema-related QoL outcomes were reported in four studies. Seventeen post-operative adverse events occurred overall (492 patients, one additional retrospective study), including five serious adverse events. Other reported procedure-related adverse events comprise, e.g., post-operative wound infections and bleedings. Studies were judged with moderate/high risk of bias. Strength of evidence for safety outcomes was judged to be very low. Conclusions The current evidence is insufficient to prove that tumescent liposuction as safe as und more effective than conservative therapy for lipoedema. However, based on the limited evidence of the included uncontrolled studies, liposuction may potentially reduce lipoedema-associated clinical symptoms and improve the QoL. Key messages Based on the limited evidence of identified uncontrolled studies, liposuction may potentially reduce lipoedema-associated clinical symptoms and improve the quality of life of affected females. High-quality comparative studies need to be awaited. The results may support and influence the effect estimates considerably.

Pyridoxine, folate and cobalamin for migraine: A systematic review.

There is a possible relationship between migraine and hypercoagulability inducing factors, such as hyperhomocysteinemia. In this context, homocysteine (Hcy)-lowering vitamins (B6-folate-B12) may prove beneficial in the management-prophylaxis of migraine. We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6, folate and B12 (alone or as adjunctive therapies) to migraine patients, as well as patients suffering from other primary headache disorders. MEDLINE, EMBASE, CENTRAL, Google Scholar, trial registries and OpenGrey were searched. Twelve relevant articles were retrieved. The management of acute migraine attacks with Hcy-lowering vitamins has not provided promising results (one randomized controlled trial-RCT-and one prospective uncontrolled trial). On the contrary, significant benefits were registered for the use of B6 alone, in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura (MA) in adults compared to placebo (five RCTs, only one did not obtain significant results). Folate supplementation alone was not more efficacious than placebo (one RCT). Limited data for the prophylaxis of migraine without aura (MO) in children (two prospective uncontrolled trials) and adults (two prospective uncontrolled trials involving both MA and MO participants) impede the extraction of safe conclusions. An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common. Overall, a potential beneficial effect regarding the administration of B6, folate and/or B12 in the prophylaxis of MA in adults was indicated. Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted.

Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders

In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 μg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (<40 years old) and 12% in older women (≥40 years old), p = 0.68. Similarly, in patients treated with the long agonist protocol younger women had an OPR of 26.7% versus 12.5% in older women, p = 0.23. Among patients treated with the short flare-up, live births rate were 15% and 4.3% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.32. Similarly, in patients treated with the long agonist protocol, live births rate were 25% and 12.9% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.41. None of the patients reported any serious adverse event related to treatment. According to our results, CFA followed by hpHMG in a short flare-up or long GnRH agonist protocol appears to be a feasible option for poor ovarian responders. Large phase III trials are mandatory prior to introduction in clinical practice.

Ablation of Barrett's esophagus using the HALO radiofrequency ablation system

The incidence of esophageal adenocarcinoma is rising at an epidemic rate. Barrett's esophagus (BE) is its only known precursor lesion and is an ideal target for endoprevention of esophageal adenocarcinoma. Recent advances in endoscopic therapy, especially radiofrequency ablation (RFA) using the HALO system have renewed interest in ablative therapies for the management of BE. RFA uses a bipolar electrode array to deliver thermal energy to the metaplastic and dysplastic Barrett's tissue for large-area circumferential and small-area focal ablation. Multiple prospective uncontrolled trials, case series, and registries have consistently shown safety and effectiveness of RFA in treating all stages of BE. A large multicenter sham-controlled trial showed that in patients with either low-grade or high-grade dysplasia, RFA is effective in ablating esophageal intestinal metaplasia and dysplasia and preventing progression to higher grades of dysplasia and cancer. In addition, cost-effectiveness models have shown ablation may be a cost-effective strategy for the management of all stages of BE. This article is a review of technical background of RFA using the HALO system and is a summary of the data on its current applications for the treatment of BE.

Pulsed Radiofrequency: A Critical Review of Its Efficacy

Pulsed radiofrequency is a growingly popular pain treatment modality. However, its clinical efficacy remains controversial. In this review, the available literature on pulsed radiofrequency is critically analysed to determine its clinical efficacy. Our search of the literature for pulsed radiofrequency yielded 341 citations; after reviewing the abstracts we found 51 relevant articles. There were 4 review articles: 44 articles pertained to the application of pulsed radiofrequency by an electrode placed in the vicinity of a neural structure. Of these only two were randomised controlled trials. Of the remaining 42 articles, one was a non-randomised controlled trial, three were prospective uncontrolled trials: there were six retrospective studies, 11 case reports, eight laboratory studies, two position papers, five editorials and seven items of correspondence, while one publication reported two studies. Three articles pertained to transcutaneous application of pulsed radiofrequency. Of the two randomised controlled trials, one reported efficacy of the pulsed radiofrequency while the other reported it to be ineffective. The majority of the uncontrolled and observational studies reported clinical efficacy of pulsed radiofrequency, however many of these studies had limitations. Further randomised controlled clinical trials are recommended in order for the practising pain physician to clearly understand the role of pulsed radiofrequency in the treatment of various chronic pain syndromes.

The effectiveness of antidepressant medication in the management of behaviour problems in adults with intellectual disabilities: a systematic review

A comprehensive systematic review was performed to establish the current evidence base regarding the effectiveness of antidepressant medication for the management of behaviour problems in adults with intellectual disabilities. An electronic search of PsycInfo, Embase, Medline and Cinahl databases was conducted spanning the time period 1990 to October 2005 for primary trials. This was supplemented by hand searching and cross-referencing of relevant reviews. Strict scientific methodology requirements were formulated that the studies had to meet in order to merit inclusion in this review. One crossover randomized controlled trial in a small cohort, seven prospective uncontrolled trials and two retrospective studies were yielded in the search. Of these, one explored the effectiveness of the tricyclic antidepressant--clomipramine, and nine considered various selective serotonin reuptake inhibitors (SSRIs). Evidence based primarily on a small number of either prospective or retrospective case studies that included a small number of participants and often used non-validated outcome measures for a short period of follow-up, suggests that antidepressants, particularly SSRIs, show improvement of aggression and self-injurious behaviour on average in less than 50% of cases and the rest show either no improvement or deterioration. The effect is most pronounced in the presence of an underlying anxiety or an associated diagnosis of obsessive-compulsive disorder. Most studies have highlighted the concern regarding adverse effects.

Malignant ascites: Systematic review and guideline for treatment

A guideline on the management of symptomatic malignant ascites by abdominal paracentesis, diuretics and peritoneovenous shunting, based on a systematic review of the literature is presented. Thirty-two relevant studies were identified. None were randomized control trials, one was a non-randomized open controlled trial, five were cohort studies or prospective uncontrolled trials, 26 studies were non-analytic studies like case series. Although paracentesis, diuretics and shunting are commonly used procedures, the evidence is weak. Available data show good, although temporary effect of paracentesis on symptom relief. Fluid withdrawal speed and concurrent intravenous hydration is not sufficiently studied. Peritoneovenous shunts can control ascites in patients with malignant ascites, but have to be balanced by the potential risks of this procedure. The available data about diuretics in treatment of malignant ascites are controversial. The use of diuretics therefore should be considered in all patients, but has to be evaluated individually.

Endoscopic management of uterine fibroids

Uterine fibroids are very common, but their relationship to fertility is still controversial. Data in relation to fibroids and fertility mainly come from retrospective case series and prospective uncontrolled trials. Although some authors advocate prospective controlled studies, it is unlikely that an easy answer will be found due to considerable variations in location, size and number of fibroids, presence of additional infertility factors and variation of surgical techniques. Submucosal fibroids are more likely to be associated with menstrual disorders and subfertility, and hysteroscopic myomectomy has been accepted as the standard treatment for them. Treatment of submucosal fibroids may be associated with better reproductive outcomes. There is bigger controversy over the impact of intramural and subserosal fibroids on fertility. Laparoscopic myomectomy is now used by a large number of groups for removal of these fibroids in selected cases, but still remains a challenging procedure which requires advanced laparoscopic skills. Its advantages over open myomectomy include reduced postoperative pain, shorter hospitalization, quicker recovery, reduced febrile morbidity and blood loss. It may also reduce the risk of postoperative adhesion formation. There are now large numbers of pregnancies following laparoscopic myomectomy and the risk of uterine rupture in future pregnancies seems to be very low with good surgical technique.

Pulsed Radiofrequency: A Neurobiologic and Clinical Reality

Pulsed Radiofrequency: A Neurobiologic and Clinical Reality

Treatment of chronic hepatitis C in patients with drug dependence: time to change the rules?

Approximately 170 million people world-wide are chronically infected with the hepatitis C virus (HCV). While the seroprevalence in the general population ranges between 0.2 and 2%, 50-90% of injection drug users are chronically HCV-infected. However, most patients who are drug abusers are still excluded from treatment of chronic HCV infection with interferon (IFN)-alpha. Due to the recent treatment advances resulting in sustained response rates between 50 and 80%, it becomes increasingly important to reflect the still existing contraindications and restrictions for IFN-alpha treatment, especially for patients with intravenous drug use (IDU) with or without psychiatric comorbidity. We reviewed clinical trials that focus on the treatment of chronic hepatitis C in patients with drug addiction published between 1987 and 2003. Only seven clinical trials investigating HCV treatment among drug users were found: four open prospective uncontrolled trials and three controlled trials. Thus far, no trials using pegylated IFN-alpha have been conducted. Data about sustained response and adherence in HCV-infected methadone substituted patients were either comparable to control groups or to representative clinically controlled trials using the same treatment regimen (IFN-alpha monotherapy or combined with ribavirin). Patients with former or present drug abuse seem more likely to discontinue treatment early. HCV-infected IDUs tended to be older with higher inflammatory activity and stage of fibrosis when interferon treatment was started. Psychiatric comorbidity did not negatively influence adherence or treatment outcome. There is no clinical evidence suggesting that HCV treatment with IFN-alpha should be limited to IDUs or methadone substituted patients. However, more prospective controlled trials on HCV treatment for patients with IDU are needed to establish and apply new rules and guidelines.