Introduction. Treatment of locally advanced prostate cancer is under discussion. Differences between clinical and pathological staging and risk factors such as positive surgical margins and seminal vesicle involvement challenge the individual treatment decisions. Case Presentation. Clinical tumor stage before treatment was assessed to be T2. After radical prostatectomy, pathological examination revealed the stage pT3b N0 M0 including positive surgical margin and seminal vesicle involvement. Early adjuvant androgen deprivation therapy and late adjuvant radiation therapy were added in response to the pathological risk factors. No evidence of disease was observed for 15 years after the treatment. The unexpected pathological findings were not explained by the physicians in charge. Discussion. A narrative review of the recent literature showed that multiple treatment modalities including adjuvant radiotherapy following radical prostatectomy are consistent with current recommendations. The multimodal approach has possibly cured a high-risk patient and may also work successfully in other patients. An alternative treatment option with better preservation of health-related quality of life might have also achieved a similar good overall survival.

Background: Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis.

Objectives: We investigated the association of SHS with coronary artery calcification (CAC).

Methods: In this cross-sectional analysis, we used baseline data (2000–2003) from 1,766 never-smokers without clinically manifested coronary heart disease, 45–75 years of age, from the Heinz Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in Germany. Self-reported frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC scores were derived based on electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS as the explanatory variable and ln(CAC+1) as the response variable. We conducted logistic regression to estimate the odds ratio (OR) for presence of any CAC.

Results: Frequent exposure to SHS was reported by 21.5% of participants. After adjustment for age, sex, and socioeconomic status, CAC + 1 was 21.1% [95% confidence interval (CI): –5.5%, 55.2%] higher in exposed than in unexposed participants. After adjusting for other cardiovascular risk factors, the association was attenuated (15.4%; 95% CI: –9.6%, 47.2%). SHS exposure was also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03, 1.84).

Conclusions: Self-reported frequent exposure to SHS was associated with subclinical coronary atherosclerosis in our cross-sectional study population. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is of public health importance.

Introduction

Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials.

Methods

A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival.

Results

26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies.

Conclusions

Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies.

Introduction

Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy.

Methods

Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations.

Results

A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws.

Conclusions

HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.

Background

Primary study selection between systematic reviews is inconsistent, and reviews on the same topic may reach different conclusions. Our main objective was to compare systematic reviews on negative pressure wound therapy (NPWT) regarding their agreement in primary study selection.

Methods

This retrospective analysis was conducted within the framework of a systematic review (a full review and a subsequent rapid report) on NPWT prepared by the Institute for Quality and Efficiency in Health Care (IQWiG).

For the IQWiG review and rapid report, 4 bibliographic databases (MEDLINE, EMBASE, The Cochrane Library, and CINAHL) were searched to identify systematic reviews and primary studies on NPWT versus conventional wound therapy in patients with acute or chronic wounds. All databases were searched from inception to December 2006.

For the present analysis, reviews on NPWT were classified as eligible systematic reviews if multiple sources were systematically searched and the search strategy was documented. To ensure comparability between reviews, only reviews published in or after December 2004 and only studies published before June 2004 were considered.

Eligible reviews were compared in respect of the methodology applied and the selection of primary studies.

Results

A total of 5 systematic reviews (including the IQWiG review) and 16 primary studies were analysed. The reviews included between 4 and 13 primary studies published before June 2004. Two reviews considered only randomised controlled trials (RCTs). Three reviews considered both RCTs and non-RCTs. The overall agreement in study selection between reviews was 96% for RCTs (24 of 25 options) and 57% for non-RCTs (12 of 21 options). Due to considerable disagreement in the citation and selection of non-RCTs, we contacted the review authors for clarification (this was not initially planned); all authors or institutions responded. According to published information and the additional information provided, most differences between reviews arose from variations in inclusion criteria or inter-author study classification, as well as from different reporting styles (citation or non-citation) for excluded studies.

Conclusion

The citation and selection of primary studies differ between systematic reviews on NPWT, particularly with regard to non-RCTs. Uniform methodological and reporting standards need to be applied to ensure comparability between reviews as well as the validity of their conclusions.

Background

Negative pressure wound therapy (NPWT) is widely applied, although the evidence base is weak. Previous reviews on medical interventions have shown that conclusions based on published data alone may no longer hold after consideration of unpublished data. The main objective of this study was to identify unpublished randomised controlled trials (RCTs) on NPWT within the framework of a systematic review.

Methods

RCTs comparing NPWT with conventional wound therapy were identified using MEDLINE, EMBASE, CINAHL and The Cochrane Library. Every database was searched from inception to May 2005. The search was updated in December 2006. Reference lists of original articles and systematic reviews, as well as congress proceedings and online trial registers, were screened for clues to unpublished RCTs. Manufacturers of NPWT devices and authors of conference abstracts were contacted and asked to provide study information. Trials were considered nonrandomised if concealment of allocation to treatment groups was classified as "inadequate". The study status was classified as "completed", "discontinued", "ongoing" or "unclear". The publication status of completed or discontinued RCTs was classified as "published" if a full-text paper on final study results (completed trials) or interim results (discontinued trials) was available, and "unpublished" if this was not the case. The type of sponsorship was also noted for all trials.

Results

A total of 28 RCTs referring to at least 2755 planned or analysed patients met the inclusion criteria: 13 RCTs had been completed, 6 had been discontinued, 6 were ongoing, and the status of 3 RCTs was unclear. Full-text papers were available on 30% of patients in the 19 completed or discontinued RCTs (495 analysed patients in 10 published RCTs vs. 1154 planned patients in 9 unpublished RCTs). Most information about conference abstracts and unpublished study information referring to trials that were unpublished at the time these documents were generated was obtained from the manufacturer Kinetic Concepts Inc. (KCI) (19 RCTs), followed by The Cochrane Library (18) and a systematic review (15). We were able to obtain some information on the methods of unpublished RCTs, but results data were either not available or requests for results data were not answered; the results of unpublished RCTs could therefore not be considered in the review. One manufacturer, KCI, sponsored the majority of RCTs (19/28; 68%). The sponsorship of the remaining trials was unclear.

Conclusion

Multi-source comprehensive searches identify unpublished RCTs. However, lack of access to unpublished study results data raises doubts about the completeness of the evidence base on NPWT.