Gerd Antes

A systematic review and meta-analysis of pylorus-preserving versus classical pancreaticoduodenectomy for surgical treatment of periampullary and pancreatic carcinoma.

Objective:Comparison of effectiveness between the pylorus-preserving pancreaticoduodenectomy (“pylorus-preserving Whipple” [PPW]) and the classic Whipple (CW) procedure. Methods:A systematic literature search (Medline, Embase, Cochrane Library, Biosis, Science Citation Index, Ovid Journals) was performed to identify all eligible articles. Randomized controlled trials (RCTs) comparing PPW versus CW for periampullary and pancreatic carcinoma were eligible for inclusion. The methodologic quality of included studies was evaluated independently by 2 authors. Quantitative data on perioperative parameters (blood loss, transfusion, operation time, and length of hospital stay), mortality, morbidity, and survival were extracted from included studies for meta-analysis. Pooled estimates of overall treatment effect were calculated using a random effects model. Results:In total, 1235 abstracts were retrieved and checked for eligibility and 6 RCTs finally included. The critical appraisal revealed vast heterogeneity with respect to methodologic quality and outcome parameters. The comparison of overall in-hospital mortality (odds ratio, 0.49; 95% CI, 0.17 to 1.40; P = 0.18), morbidity (odds ratio 0.89; 95% CI, 0.48 to 1.62; P = 0.69), and survival (hazard ratio, 0.74; 95% CI, 0.52 to 1.07; P = 0.11) showed no significant difference. However, operating time (weighted mean difference, −68.26 minutes; 95% CI, −105.70 to −30.83; P = 0.0004), and intraoperative blood loss (weighted mean difference, −766 mL; 95% CI, −965.26 to −566.74; P = 0.00001) were significantly reduced in the PPW group. Conclusion:Hence, in the absence of relevant differences in mortality, morbidity, and survival, the PPW seems to be as effective as the CW. Given obvious clinical and methodological interstudy heterogeneity, efforts should be intensified in the future to perform high quality RCTs of complex surgical interventions on the basis of well defined outcome parameters.

Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials

Abstract Objective Open angle glaucoma is one of the most common causes of blindness in industrialised nations. Treatments to lower ocular pressure are widely used in glaucoma prevention and treatment, despite conflicting evidence. Design We performed meta-analyses to reassess the effectiveness of pressure lowering treatment to delay the development of glaucoma in ocular hypertension, as well as progression of manifest open angle glaucoma. Data sources Medline, Embase, and the Cochrane Library. Selection of studies Eligible studies were randomised controlled trials with a concurrent untreated control group and information on time to glaucomatous changes to visual field and optic disc. Trial reports were reviewed independently by two investigators in an unblinded standardised manner. Results Meta-analysis of trials in ocular hypertension showed a significant preventive effect of reducing intraocular pressure on progression to glaucoma (hazard ratio 0.56, 95% confidence interval 0.39 to 0.81, P = 0.01; number needed to treat 12). Pooled data of studies in manifest glaucoma showed a significant delay of visual field deterioration (0.65, 0.49 to 0.87, P = 0.003; NNT = 7), with subgroup analysis showing a larger effect in patients with raised pressure and a reduced effect in normal tension glaucoma (subgroup comparison: not significant). Conclusions Lowering intraocular pressure in patients with ocular hypertension or manifest glaucoma is beneficial in reducing the risk of visual field loss in the long term.

Differential Effectiveness of Placebo Treatments: A Systematic Review of Migraine Prophylaxis

IMPORTANCE When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications for the interpretation of placebo-controlled trials, the knowledge base on the subject is weak. OBJECTIVE To investigate whether different types of placebo treatments are associated with different responses using the studies of migraine prophylaxis for this analysis. DESIGN, SETTING, AND PARTICIPANTS We searched relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects estimates according to the type of placebo for the proportions of treatment response. We performed meta-regression analyses to identify sources of heterogeneity. In a network meta-analysis, direct and indirect comparisons within and across trials were combined. Additional analyses were performed for continuous outcomes. EXPOSURE Active migraine treatment and the placebo control conditions. MAIN OUTCOMES AND MEASURES Proportion of treatment responders, defined as having an attack frequency reduction of at least 50%. Other available outcomes in order of preference included a reduction of 50% or greater in migraine days, the number of headache days, or headache score or a significant improvement as assessed by the patients or their physicians. RESULTS Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI, 0.30-0.47]) and sham surgery (0.58 [0.37-0.77]) were associated with a more pronounced reduction of migraine frequency than oral pharmacological placebos (0.22 [0.17-0.28]) and were the only significant predictors of response in placebo groups in multivariable analyses (P = .005 and P = .001, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]). Corresponding analyses for continuous outcomes showed similar findings. CONCLUSIONS AND RELEVANCE Sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ between treatment modalities.

Duodenum-preserving pancreatic head resection versus pancreatoduodenectomy for surgical treatment of chronic pancreatitis: a systematic review and meta-analysis.

Objective:The optimal choice of technique for the surgical treatment of pancreatic head lesions in chronic pancreatitis is still under debate. This systematic review and meta-analysis aims to compare the effectiveness and safety of duodenum-preserving pancreatic head resection (DPPHR) versus pancreatoduodenectomy (PD) by means of parameters of mortality and morbidity and functional outcomes and quality of life. Methods:A systematic literature search (Medline, Embase, Biosis, The Cochrane Library, and Science Citation Index) was performed to identify randomized controlled trials (RCTs) comparing DPPHR and PD. Included literature was assessed and extracted by 2 independent reviewers. A meta-analysis of pain relief (primary end point), several parameters of short- and long-term measures and quality of life, was done using the random effects-model. Results:In total, 1284 citations were checked for eligibility and 4 RCTs were included. The critical appraisal revealed a heterogeneous methodological quality of included trials. Comparing DPPHR versus PD, postoperative pain relief, overall mortality, and morbidity showed no significant difference. Intraoperative blood replacement, hospital stay, weight gain, exocrine insufficiency, occupational rehabilitation, and quality of life were significantly improved in the DPPHR group. Conclusion:DPPHR and PD seem to be equally effective in terms of postoperative pain relief, overall morbidity, and incidence of postoperative endocrine insufficiency. However, the presented findings suggest superiority of DPPHR in the treatment of chronic pancreatitis with regard to several peri and postoperative outcome parameters and quality of life. Further RCTs are eagerly awaited to prove these findings.

A Safety Review and Meta-Analyses of Bevacizumab and Ranibizumab: Off-Label versus Goldstandard

Background We set out a systemic review to evaluate whether off-label bevacizumab is as safe as licensed ranibizumab, and whether bevacizumab can be justifiably offered to patients as a treatment for age-related macular degeneration with robust evidence of no differential risk. Methods and Findings Medline, Embase and the Cochrane Library were searched with no limitations of language and year of publication. We included RCTs with a minimum follow-up of one year which investigated bevacizumab or ranibizumab in direct comparison or against any other control group (indirect comparison). Direct comparison (3 trials, 1333 patients): The one year data show a significantly higher rate of ocular adverse effects (AE) with bevacizumab compared to ranibizumab (RR = 2.8; 95% CI 1.2–6.5). The proportion of patients with serious infections and gastrointestinal disorders was also higher with bevacizumab than with ranibizumab (RR = 1.3; 95% CI 1.0–1.7). Arterial thromboembolic events were equally distributed among the groups. Indirect comparison: Ranibizumab versus any control (5 trials, 4054 patients): The two year results of three landmark trials showed that while absolute rates of serious ocular AE were low (≤2.1%), relative harm was significantly raised (RR = 3.1; 95% CI 1.1–8.9). A significant increase in nonocular haemorrhage was also observed with ranibizumab (RR = 1.7; 95% CI 1.1–2.7). Bevacizumab versus any control (3 trials, 244 patients): We were unable to judge the safety profile of bevacizumab due to the poor quality of AE monitoring and reporting in the trials. Conclusions Evidence from head-to-head trials raises concern about an increased risk of ocular and multiple systemic AE with bevacizumab. Therefore, clinicians and patients should continue to carefully weight up the benefits and harms when choosing between the two treatment options. We also emphasize the need for studies that are powered not just for efficacy, but for defined safety outcomes based on the signals detected in this systematic review.

Intravitreal bevacizumab (Avastin®) versus ranibizumab (Lucentis®) for the treatment of age-related macular degeneration: a safety review

Aim To conduct a systematic review in order to compare adverse effects (AE) and the reporting of harm in randomised controlled trials (RCTs) and non-RCTs evaluating intravitreal ranibizumab and bevacizumab in age-related macular degeneration. Methods Medline, Embase and the Cochrane Library were searched with no limitations of language and year of publication. Studies which compared bevacizumab or ranibizumab as monotherapy with any other control group were included. Case series were included if they met predefined quality standards. Results The 2 year results of phase III trials evaluating ranibizumab show that the rates of serious ocular AE were low (≤2.1%) but indicate major safety concerns (RR 3.13, 95% CI 1.10 to 8.92). A possible signal with regard to thromboembolic events (RR 1.35, 95% CI 0.66 to 2.77) and a significant increase in non-ocular haemorrhage (RR 1.62, 95% CI 1.03 to 2.55) were also noted. In contrast to ranibizumab trials, the RCTs evaluating bevacizumab are of limited value. The main shortcomings are small sample sizes and an apparent lack of rigorous monitoring for AE. A critical assessment of the large number of published case series evaluating bevacizumab also shows that no reliable conclusions on safety can be drawn using this study design. Therefore, any perception that intravitreal bevacizumab injections are not associated with major ocular or systemic AE are not supported by reliable data. Conclusion The bevacizumab studies show too many methodological limitations to rule out any major safety concerns. Higher evidence from ranibizumab trials suggests signals for an increased ocular and systemic vascular and haemorrhagic risk which warrants further investigation.

Extent of Non-Publication in Cohorts of Studies Approved by Research Ethics Committees or Included in Trial Registries

Background The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. Methods and Findings Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%–52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%–65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2–3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6–2.5). The probability of publication within two years after study completion ranged from 7% to 30%. Conclusions A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased.

Does the architecture of hospital facilities influence nosocomial infection rates? A systematic review

OBJECTIVE To review the evidence regarding the effects of interventions to improve hospital design and construction on the occurrence of nosocomial infections. METHODS Systematic review of experimental and non-experimental, architectural intervention studies in intensive care units (ICUs), surgical departments, isolation units, and hospitals in general. The studies dated from 1975, and were in English, French, German, Italian, and Spanish. Regardless of format, the studies were identified through seven medical databases, reference lists, and expert consultation. RESULTS One hundred seventy-eight scientific articles were identified; however, none of these described a meta-analysis, systematic review, or randomized, controlled trial. Most of the articles were categorized at the lowest level of evidence (expert judgment or consensus statements). Only 17 described completed concurrent or historical cohort studies matching the inclusion criteria (ICUs, 9; surgical departments, 4; isolation units, 2; hospitals in general, 2). The interventions generally included a move to other premises or renovation. However, in many studies, the staff-to-patient ratio was also improved. Some studies showed lower infection rates after intervention, but this finding cannot be generalized because of confounding and frequently small study populations. CONCLUSIONS The lack of stringent evidence linking hospital design and construction with the prevention of nosocomial infection is partly attributable to the multifactorial nature of these infections, and some improvement will be seen if basic conditions such as the availability of sufficient space, isolation capacity, and facilities for handwashing are met. However, to our knowledge, other factors, especially the improper hand hygiene of medical staff, have greater impact.

Evidence-based medicine—from best research evidence to a better surgical practice and health care

BackgroundThe use of the terms evidence-based medicine (EBM) and healthcare (EBHC) has become commonplace in the medical as well as in the surgical literature. Using the best available evidence, however, is not yet a working routine among surgeons because of the large amount and complexity of published research and the lack of user-friendly tools and necessary skills for the use of research results.DiscussionThis article encourages to formulate surgically relevant questions and to answer them on the basis of high-quality research, preferably by using systematic reviews which are based on the quality criteria of the Cochrane Collaboration.ConclusionsAs currently only 77 Cochrane reviews address surgical procedures; much work remains to be done to enlarge the number of high-quality and relevant reviews. Similarly, the number and quality of randomized controlled trials need to be increased in all surgical specialties.

Hearing screening in newborns: systematic review of accuracy, effectiveness, and effects of interventions after screening

Background The authors aimed to evaluate the benefits and harms of universal newborn hearing screening programmes in the detection of hearing impairment. Objectives In the absence of randomised trials evaluating whole screening programmes, the study divided the objective into three systematic reviews of non-randomised controlled studies of diagnostic accuracy of screening tests, screening versus no screening, and therapeutic effect of early versus later treatment. Methods The authors searched 11 bibliographic databases, and included 17 studies (diagnostic: 9, screening: 2, and treatment: 6). All studies apart from one treatment study showed major quality deficits. Eight diagnostic studies comparing otoacoustic emissions with auditory brainstem response showed sensitivities (and specificities) between 50% (49.1%) and 100% (97.2%). Results The studies comparing screening versus no screening showed an improvement of speech development of children in the screening group compared with the group without screening. Early treatment was associated with better language development in comparison to children with later treatment. Conclusions The authors concluded that there is a lack of high-quality evidence regarding all elements of newborn hearing screening. Early identification and early treatment of children with hearing impairments may be associated with advantages in language development. Other patient-relevant parameters, such as social aspects, quality of life, and educational development, have not been adequately investigated.