Stefanie Schmidt

Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis - a systematic review.

Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence‐based clinical recommendations in a systematic review.

Efficacy and safety of pharmacological treatments for neuroborreliosis—protocol for a systematic review

BackgroundNeuroborreliosis is a tick-borne infectious disease of the nervous system caused by Borrelia burgdorferi. Common clinical manifestations of neuroborreliosis are cranial nerve dysfunctions, polyradiculoneuritis, and meningitis. Diagnosis is usually based on clinical presentation, serologic testing, and analysis of cerebrospinal fluid. Many aspects of pharmacological treatment, such as choice of drug, dosage, and duration are subject of intense debate, leading to uncertainties in patients and healthcare providers alike. To approach the questions regarding pharmacological treatment of neuroborreliosis, we will perform a systematic review.MethodsWe will perform a comprehensive systematic literature search for potentially eligible studies that report outcomes after pharmacological interventions. To adequately consider the wealth of research that has been conducted so far, this review will evaluate randomized controlled trials (RCTs) and non-randomized studies on treatment of neuroborreliosis. We will assess potential risk of bias for each RCT meeting our selection criteria using the Cochrane risk of bias tool for RCTs. For non-randomized studies, we will use the Newcastle-Ottawa Scale and the recently piloted Cochrane risk of bias tool for non-randomized studies. Our primary outcome of interest will be neurological symptoms and the secondary outcomes will be disability, patient-reported outcomes (quality of life, and, if reported separately from other neurological symptoms, pain, fatigue, depression, cognition, and sleep), adverse events, and cerebrospinal fluid pleocytosis. Pooling of data and meta-analysis will only be deemed justified between studies with similar design (e.g., RCTs are only combined with other RCTs), characteristics (e.g., similar populations), and of acceptable heterogeneity (I2u2009<u200980%). Pooled estimates will be calculated using RevMan software. Prespecified subgroup analyses will evaluate groups of antibiotics, length of antibiotic treatment, and different doses of doxycycline. We will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.DiscussionThis systematic review will summarize the available evidence from RCTs and non-randomized studies regarding pharmacological treatment of neuroborreliosis. The available evidence will be summarized and discussed to provide a basis for decision-making for patients and healthcare professionals.Systematic review registrationPROSPERO registration number: CRD42014008839

Gonadotropin-releasing hormone antagonists versus standard androgen suppression therapy for advanced prostate cancer A systematic review with meta-analysis.

Objectives To evaluate efficacy and safety of gonadotropin-releasing hormone (GnRH) antagonists compared to standard androgen suppression therapy for advanced prostate cancer. Setting The international review team included methodologists of the German Cochrane Centre and clinical experts. Participants We searched CENTRAL, MEDLINE, Web of Science, EMBASE, trial registries and conference books for randomised controlled trials (RCT) for effectiveness data analysis, and randomised or non-randomised controlled studies (non-RCT) for safety data analysis (March 2015). Two authors independently screened identified articles, extracted data, evaluated risk of bias and rated quality of evidence according to GRADE. Results 13 studies (10 RCTs, 3 non-RCTs) were included. No study reported cancer-specific survival or clinical progression. There were no differences in overall mortality (RR 1.35, 95% CI 0.63 to 2.93), treatment failure (RR 0.91, 95% CI 0.70 to 1.17) or prostate-specific antigen progression (RR 0.83, 95% CI 0.64 to 1.06). While there was no difference in quality of life related to urinary symptoms, improved quality of life regarding prostate symptoms, measured with the International Prostate Symptom Score (IPSS), with the use of GnRH antagonists compared with the use of standard androgen suppression therapy (mean score difference −0.40, 95% CI −0.94 to 0.14, and −1.84, 95% CI −3.00 to −0.69, respectively) was found. Quality of evidence for all assessed outcomes was rated low according to GRADE. The risk for injection-site events was increased, but cardiovascular events may occur less often by using GnRH antagonist. Available evidence is hampered by risk of bias, selective reporting and limited follow-up. Conclusions There is currently insufficient evidence to make firm conclusive statements on the efficacy of GnRH antagonist compared to standard androgen suppression therapy for advanced prostate cancer. There is need for further high-quality research on GnRH antagonists with long-term follow-up. Trial registration number CRD42012002751.

Prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance—protocol for a systematic review

BackgroundTesticular cancer is primarily treated with the surgical removal of the affected testis. About 50xa0% of testicular cancer patients present with a stage I seminoma. If no chemo- or radiotherapy as adjuvant treatment is initiated after orchiectomy, 15–20xa0% of these patients will develop metastases. Although adjuvant treatment is effective in reducing the relapse risk, there is rising concern about overtreatment of these patients. Prognostic factors at primary diagnosis might have the potential to identify patients at higher risk of tumor relapse, allowing to guide individual therapy and to avoid overtreatment. Therefore, we aim to synthesize the available evidence on tumor or patient characteristics as possible prognostic factors for cancer recurrence in patients with clinical stage I seminoma.Methods/designWe will conduct a broad systematic review to analyze what prognostic factors predict cancer recurrence in patients with a first time diagnosis of clinical stage I seminoma, who received no adjuvant chemo- or radiotherapy after orchiectomy. The literature search will comprise MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the conference proceedings of the American Society of Clinical Oncology (ASCO), American Urologic Association (AUA), and European Urologic Association (EAU) Annual Meetings. Prospective and retrospective longitudinal studies reporting on prognostic factors for cancer recurrence will be considered. We will consider the wealth of any candidate clinical or pathological prognostic factor reported in the literature. Our outcome of interest will be tumor recurrence at a minimum of 2xa0years follow-up. Study screening, data extraction, and quality assessment will be done by two reviewers independently. Hazard ratios will be used to measure the relationship between the potential prognostic factor and tumor recurrence. Meta-analyses will be conducted with sufficiently homogeneous studies and separately with respect to study design, by using the random-effects generic inverse variance model.DiscussionLimitations and strengths will be discussed in our review, and the results will be put into context with other studies in this field. Our results will help to guide evidence-based decision-making on patients with clinical stage I seminoma, allowing a better adjustment of therapies with regard to the individual patient’s risk. Our findings will furthermore help to formulate recommendations for future research.Systematic review registrationPROSPERO CRD42014009434

Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis in children: a systematic review.

BackgroundMany aspects of pharmacological treatment of Lyme neuroborreliosis in children, such as choice of drug, dosage, and duration are subject to intense debates, leading to uncertainties in patients’ parents and healthcare providers alike. To assess the available evidence for pharmacological treatment for children with Lyme neuroborreliosis we conducted a systematic review.MethodsThe comprehensive systematic literature search included randomized-controlled trials (RCTs) and non-randomized studies (NRS) on treatment of Lyme neuroborreliosis in children (age <18xa0years). Our primary outcome was neurological symptoms after treatment. Risk of bias was assessed with the Cochrane risk of bias tools for RCTs and NRS. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsTwo RCTs and four NRS were eligible for inclusion. Risk of bias in RCTs and NRS was generally high. Reporting of studies was generally poor. Regarding the primary outcome neurological symptoms at 1–3 months, no statistically significant difference could be found in cohort studies between doxycycline and beta-lactam antibiotics. In two RCTs comparing penicillin G and ceftriaxone, no patient experienced residual neurological symptoms at the last reported time points. Quality of evidence according to GRADE was judged very low.ConclusionsData is scarce and with limited quality. Several issues could not be addressed due to scarcity of information. No eligible study compared different treatment durations. According to the available evidence, there seems to be no difference between different antibiotic agents for the treatment of Lyme neuroborreliosis in children regarding neurological symptoms. We found no evidence that supports extended antibiotic regimes.Review registrationSystematic review registration: CRD42014008839.