Kathrin Grummich

Antibiotics Versus Surgical Therapy for Uncomplicated Appendicitis: Systematic Review and Meta-analysis of Controlled Trials (PROSPERO 2015: CRD42015016882).

Objective: The aim was to investigate available evidence regarding effectiveness and safety of surgical versus conservative treatment of acute appendicitis. Summary of Background Data: There is ongoing debate on the merits of surgical and conservative treatment for acute appendicitis. Methods: A systematic literature search (Cochrane Library, Medline, Embase) and hand search of retrieved reference lists up to January 2016 was conducted to identify randomized and nonrandomized studies. After critical appraisal, data were analyzed using a random-effects model in a Mantel-Haenszel test or inverse variance to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results: Four trials and four cohort studies (2551 patients) were included. We found that 26.5% of patients in the conservative group needed appendectomy within 1 year, resulting in treatment effectiveness of 72.6%, significantly lower than the 99.4% in the surgical group, (RR 0.75; 95% CI 0.7–0.79; P = 0.00001; I2 = 62%). Overall postoperative complications were comparable (RR 0.95; 95% CI 0.35–2.58; P = 0.91; I2 = 0%), whereas the rate of adverse events (RR 3.18; 95% CI 1.63–6.21; P = 0.0007; I2 = 1%) and the incidence of complicated appendicitis (RR 2.52; 95% CI 1.17–5.43; P = 0.02; I2 = 0%) were significantly higher in the antibiotic treatment group. Randomized trials showed significantly longer hospital stay in the antibiotic treatment group (RR 0.3 days; 95% CI 0.07–0.53; P = 0.009; I2 = 49%). Conclusions: Although antibiotics may prevent some patients from appendectomies, surgery represents the definitive, one-time only treatment with a well-known risk profile, whereas the long-term impact of antibiotic treatment on patient quality of life and health care costs is unknown. This systematic review and meta-analysis helps physicians and patients in choosing between treatment options depending on whether they are risk averse or risk takers.

Industry Bias in Randomized Controlled Trials in General and Abdominal Surgery: An Empirical Study.

Background: Industry sponsorship has been identified as a source of bias in several fields of medical science. To date, the influence of industry sponsorship in the field of general and abdominal surgery has not been evaluated. Methods: A systematic literature search (1985–2014) was performed in the Cochrane Library, MEDLINE, and EMBASE to identify randomized controlled trials in general and abdominal surgery. Information on funding source, outcome, and methodological quality was extracted. Association of industry sponsorship and positive outcome was expressed as odds ratio (OR) with 95% confidence interval (CI). A &khgr;2 test and a multivariate logistic regression analysis with study characteristics and known sources of bias were performed. Results: A total of 7934 articles were screened and 165 randomized controlled trials were included. No difference in methodological quality was found. Industry-funded trials more often presented statistically significant results for the primary endpoint (OR, 2.44; CI, 1.04–5.71; P = 0.04). Eighty-eight of 115 (76.5%) industry-funded trials and 19 of 50 (38.0%) non–industry-funded trials reported a positive outcome (OR, 5.32; CI, 2.60–10.88; P < 0.001). Industry-funded trials more often reported a positive outcome without statistical justification (OR, 5.79; CI, 2.13–15.68; P < 0.001). In a multivariate analysis, funding source remained significantly associated with reporting of positive outcome (P < 0.001). Conclusions: Industry funding of surgical trials leads to exaggerated positive reporting of outcomes. This study emphasizes the necessity for declaration of funding source. Industry involvement in surgical research has to ensure scientific integrity and independence and has to be based on full transparency.

Mobile phones and health: Media coverage study of German newspapers on possible adverse health effects of mobile phone use

The scientific debate about potential risks from the radio frequency electromagnetic fields (RF-EMFs) of mobile telecommunication is ongoing, accompanied by considerable media discussion about whether electromagnetic fields from mobile phones cause adverse health effects. Since most people do not make use of scientific databases, the print media are key actors in informing the public about scientific developments concerning potential health risks from mobile telecommunication. In order to analyse the kind of information German print media provide to the public, a media analysis of a sample of German newspapers during the years 2002–2007 was performed: 17 regional and national daily newspapers were analysed along with weekly journals. The results indicate that, besides ambiguous media coverage, there are remarkable differences among the various newspapers in their approach to the topic. Most newspapers highlight unspecified, potentially adverse effects and link mobile phone use to the development of cancer, which is not supported by current scientific knowledge. However, in recent years, a slight shift in the foci of reporting can be observed. As these results show, newspapers increasingly acknowledge the existence of scientific uncertainty and provide more detailed information on the topic.

Percutaneous versus surgical strategy for tracheostomy: protocol for a systematic review and meta-analysis of perioperative and postoperative complications

BackgroundTracheostomy is one of the most frequently performed procedures in intensive care medicine. The two main approaches to form a tracheostoma are the open surgical tracheotomy (ST) and the interventional strategy of percutaneous dilatational tracheotomy (PDT). It is particularly important to the critically ill patients that both procedures are performed with high success rates and low complication frequencies. Therefore, the aim of this systematic review is to summarize and analyze existing and relevant evidence for peri- and postoperative parameters of safety.Methods/designA systematic literature search will be conducted in The Cochrane Library, MEDLINE, LILACS, and Embase to identify all randomized controlled trials (RCTs) comparing peri- and postoperative complications between the two strategies and to define the strategy with the lower risk of potentially life-threatening events. A priori defined data will be extracted from included studies, and methodological quality will be assessed according to the recommendations of the Cochrane Collaboration.DiscussionThe findings of this systematic review with proportional meta-analysis will help to identify the strategy with the lowest frequency of potentially life-threatening events. This may influence daily practice, and the data may be implemented in treatment guidelines or serve as the basis for planning further randomized controlled trials. Considering the critical health of these patients, they will particularly benefit from evidence-based treatment.Systematic review registrationPROSPERO CRD42015021967

Prophylactic mesh placement for the PREvention of paraSTOmal hernias: The PRESTO systematic review and meta-analysis

Background Parastomal hernia (PH) is the most common complication after ostomy formation. Prophylactic mesh placement may be effective in reducing the rate of PH at the stoma site. The aims of this systematic review were to summarize the evidence with regard to the safety and effectiveness in comparison with the standard procedure without mesh placement and to identify important risk constellations. Method A systematic literature search was performed in PubMed, EMBASE and the Cochrane library with no language or date restrictions. Randomized (RCTs) and non-randomized controlled trials (nRCTs) were included. The main outcomes of interest were PH (primary outcome) rate and stoma-related complications (secondary outcomes) such as stenosis or fistula. Statistical analysis included meta-analyses of pooled data and subgroup analyses. Results Eleven trials (eight RCTs; three nRCTs) with a total of 755 patients were included. PH rate varied from 0% to 59% in the intervention and from 20% to 94% in the control group. RCTs showed a significant reduction of PH rate in the mesh group (OR 0.24; 95% CI 0.10 to 0.58, p = 0.034), whereas included nRCTs did not. No significant differences were observed in postoperative complication rates. Subgroup analyses showed superiority of non-absorbable meshes and sublay mesh positioning in open surgery. Conclusion Prophylactic mesh placement is safe and reduces PH rate. A recommendation for prophylactic non-absorbable meshes in a sublay position can be made for patients undergoing open colorectal operations with end-ostomies. Further research endeavors should focus on patient-oriented outcomes, not only PH rate, with respect to tailored treatment in specific patient populations.

Optimal literature search for systematic reviews in surgery

BackgroundThe aim of the present study was to determine empirically which electronic databases contribute best to a literature search in surgical systematic reviews.MethodsFor ten published systematic reviews, the systematic literature searches were repeated in the databases MEDLINE, Web of Science, CENTRAL, and EMBASE. On the basis of these reviews, a gold standard set of eligible articles was created. Recall (%), precision (%), unique contribution (%), and numbers needed to read (NNR) were calculated for each database, as well as for searches of citing references and of the reference lists of related systematic reviews (hand search).ResultsCENTRAL yielded the highest recall (88.4%) and precision (8.3%) for randomized controlled trials (RCT), MEDLINE for non-randomized studies (NRS; recall 92.6%, precision 5.2%). The most effective combination of two databases plus hand searching for RCT was MEDLINE/CENTRAL (98.6% recall, NNR 97). Adding EMBASE marginally increased the recall to 99.3%, but with an NNR of 152. For NRS, the most effective combination was MEDLINE/Web of Science (99.5% recall, NNR 60).ConclusionsFor surgical systematic reviews, the optimal literature search for RCT employs MEDLINE and CENTRAL. For surgical systematic reviews of NRS, Web of Science instead of CENTRAL should be searched. EMBASE does not contribute substantially to reviews with a surgical intervention.

Placebo-Controlled Trials in Surgery: A Systematic Review and Meta-Analysis

AbstractThis systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. “Surgical procedure” was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92–2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.

Association of industry sponsorship and positive outcome in randomised controlled trials in general and abdominal surgery: protocol for a systematic review and empirical study

BackgroundIndustry sponsorship has been identified as a factor correlating with positive research findings in several fields of medical science. To date, the influence of industry sponsorship in general and abdominal surgery has not been fully studied. This protocol describes the rationale and planned conduct of a systematic review to determine the association between industry sponsorship and positive outcome in randomised controlled trials in general and abdominal surgery.Methods/designA literature search in the Cochrane Library, MEDLINE and EMBASE and additional hand searches in relevant citations will be conducted. In order to cover all relevant areas of general and abdominal surgery, a new literature search strategy called multi-PICO search strategy (MPSS) has been developed. No language restriction will be applied. The search will be limited to publications between January 1985 and July 2014. Information on funding source, outcome, study characteristics and methodological quality will be extracted.The association between industry sponsorship and positive outcome will be tested by a chi-squared test. A multivariate logistic regression analysis will be performed to control for possible confounders, such as number of study centres, multinational trials, methodological quality, journal impact factor and sample size.DiscussionThis study was designed to clarify whether industry-sponsored trials report more positive outcomes than non-industry trials. It will be the first study to evaluate this topic in general and abdominal surgery. The findings of this study will enable surgical societies, in particular, to give advice about cooperation with the industry and disclosure of funding source based on empirical evidence.Systematic review registrationPROSPERO CRD42014010802

Closed cannulation of subclavian vein vs open cut-down of cephalic vein for totally implantable venous access port (TIVAP) implantation: protocol for a systematic review and proportional meta-analysis of perioperative and postoperative complications

BackgroundTotally implantable venous access port (TIVAP) implantation is one of the most often performed operations in general surgery (over 100,000/year in Germany). The two main approaches for TIVAP placement are insertion into the cephalic vein through an open cut-down technique (OCD) or closed cannulation technique of the subclavian vein (CC) with Seldinger technique. Both procedures are performed with high success rates and very low complication frequencies. Because of the low incidence of complications, no single interventional trial is able to report a valid comparison of peri- and postoperative complication frequencies between both techniques. Therefore, the aim of this systematic review is to summarize evidence for peri- and postoperative complication rates in patients undergoing OCD or CC.Methods/DesignA systematic literature search will be conducted in The Cochrane Library, MEDLINE, and Embase to identify randomized controlled trials (RCTs), observational clinical studies (OCS), or case series (CS) reporting peri- and/or postoperative complications of at least one implantation technique. A priori defined data will be extracted from included studies, and methodological quality will be assessed. Event rates with their 95% confidence intervals will be derived taking into account the follow-up time per study by patient-months where appropriate. Pooled estimates of event rates with corresponding 95% confidence intervals will be calculated on the base of the Freeman-Tukey double arcsine transformation within a random effect model framework.DiscussionThe findings of this systematic review with proportional meta-analysis will help to identify the procedure with the best benefit/risk ratio for TIVAP implantation. This may have influence on daily practice, and data may be implemented in treatment guidelines. Considering the impact of TIVAP implantation on patients’ well being together with its socioeconomic relevance, patients will benefit from evidence-based treatment and health-care costs may also be reduced.Systematic review registrationPROSPERO CRD42013005180.

Conflicts of interest in randomised controlled surgical trials: systematic review and qualitative and quantitative analysis

Abstract Conflicts of interest may lead to biased trial designs and unbalanced interpretation of study results. We aimed to evaluate the reporting of potential conflicts of interest in full publications of surgical randomised controlled trials (RCTs). A systematic literature search was performed in CENTRAL, MEDLINE and EMBASE (1985–2014) to find all surgical RCTs of medical devices and perioperative pharmacological or nutritional interventions. The information on conflicts of interest was evaluated both quantitatively and qualitatively, and the development of stated conflicts over time was studied. Of 7934 articles, 444 met the inclusion criteria. In 93 of 444 trials (20.9%), conflicts of interest were disclosed. In half of the cases, the information provided was insufficient to permit conclusions regarding possible influence on the trials. Information about conflicts of interest has increased continuously during the last decades (1985–1994: 0%, 1995–2004: 2.8% and 2005–2014: 33.0%; p<0.001). Among the 115 industry-funded trials, industry participation was considered as a potential conflict of interest in 24 cases (20.9%). Over the past three decades, only every 10th trial has provided appropriate information on conflicts of interest. However, transparency is crucial for the reliability of evidence-based medicine. There is an urgent need for the full disclosure of all conflicts of interest in surgical publishing and for transparency regarding cooperation between academia and industry.