Single-fraction stereotactic radiosurgery versus microsurgical resection for the treatment of vestibular schwannoma: a systematic review and meta-analysis.

BACKGROUND: Vestibular schwannomas are benign tumours for which various treatments are available. We performed a systematic review of prospective controlled trials comparing the patient-relevant benefits and harms of single-fraction stereotactic radiosurgery (sfSRS) with microsurgical resection (MR) in patients with vestibular schwannoma. METHODS: We searched for randomized controlled trials (RCTs) and non-randomized prospective controlled trials in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: 09/2021) and also screened reference lists of relevant systematic reviews. Manufacturers were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome. We assessed the risk of bias (high or low) at the study and outcome level. If feasible, meta-analyses were performed. We graded the results into different categories (hint, indication, or proof of greater benefit or harm). RESULTS: We identified three non-randomized prospective controlled trials of generally low quality with evaluable data on 339 patients with unilateral vestibular schwannoma. There was an indication of greater benefit of sfSRS compared with MR for facial palsy (OR 0.06, 95% CI 0.02-0.21, p < 0.001, 2 studies), hearing function (no pooled estimate available, 2 studies), and length of hospital stay (no pooled estimate available, 2 studies). We found no clinically relevant differences for mortality, vertigo, headaches, tinnitus, balance function, work disability, adverse events, and health-related quality of life. CONCLUSIONS: Our systematic review indicates that sfSRS has greater benefits than MR in patients with unilateral vestibular schwannoma. However, it is unclear whether this conclusion still holds after 2 years, as long-term studies are lacking. It is also unclear whether the effects of sfSRS are similar in patients with bilateral vestibular schwannomas. Long-term prospective studies including patients with this condition would therefore be useful. SYSTEMATIC REVIEW REGISTRATION: The full (German language) protocol and report (Commission No. N20-03) are available on the institute's website: www.iqwig.de/en/projects/n20-03.html.

Laparoscopic versus open surgery for suspected appendicitis.

BACKGROUND: The removal of the acute appendix is one of the most frequently performed surgical procedures. Open surgery associated with therapeutic efficacy has been the treatment of choice for acute appendicitis. However, in consequence of the evolution of endoscopic surgery, the operation can also be performed with minimally invasive surgery. Due to smaller incisions, the laparoscopic approach may be associated with reduced postoperative pain, reduced wound infection rate, and shorter time until return to normal activity.This is an update of the review published in 2010. OBJECTIVES: To compare the effects of laparoscopic appendectomy (LA) and open appendectomy (OA) with regard to benefits and harms. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE and Embase (9 February 2018). We identified proposed and ongoing studies from World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and EU Clinical Trials Register (9 February 2018). We handsearched reference lists of identified studies and the congress proceedings of endoscopic surgical societies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing LA versus OA in adults or children. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted data. We performed the meta-analyses using Review Manager 5. We calculated the Peto odds ratio (OR) for very rare outcomes, and the mean difference (MD) for continuous outcomes (or standardised mean differences (SMD) if researchers used different scales such as quality of life) with 95% confidence intervals (CI). We used GRADE to rate the quality of the evidence. MAIN RESULTS: We identified 85 studies involving 9765 participants. Seventy-five trials included 8520 adults and 10 trials included 1245 children. Most studies had risk of bias issues, with attrition bias being the largest source across studies due to incomplete outcome data.In adults, pain intensity on day one was reduced by 0.75 cm on a 10 cm VAS after LA (MD -0.75, 95% CI -1.04 to -0.45; 20 RCTs; 2421 participants; low-quality evidence). Wound infections were less likely after LA (Peto OR 0.42, 95% CI 0.35 to 0.51; 63 RCTs; 7612 participants; moderate-quality evidence), but the incidence of intra-abdominal abscesses was increased following LA (Peto OR 1.65, 95% CI 1.12 to 2.43; 53 RCTs; 6677 participants; moderate-quality evidence).The length of hospital stay was shortened by one day after LA (MD -0.96, 95% CI -1.23 to -0.70; 46 RCTs; 5127 participant; low-quality evidence). The time until return to normal activity occurred five days earlier after LA than after OA (MD -4.97, 95% CI -6.77 to -3.16; 17 RCTs; 1653 participants; low-quality evidence). Two studies showed better quality of life scores following LA, but used different scales, and therefore no pooled estimates were presented. One used the SF-36 questionnaire two weeks after surgery and the other used the Gastro-intestinal Quality of Life Index six weeks and six months after surgery (both low-quality evidence).In children, we found no differences in pain intensity on day one (MD -0.80, 95% CI -1.65 to 0.05; 1 RCT; 61 participants; low-quality evidence), intra-abdominal abscesses after LA (Peto OR 0.54, 95% CI 0.24 to 1.22; 9 RCTs; 1185 participants; low-quality evidence) or time until return to normal activity (MD -0.50, 95% CI -1.30 to 0.30; 1 RCT; 383 participants; moderate-quality evidence). However, wound infections were less likely after LA (Peto OR 0.25, 95% CI 0.15 to 0.42; 10 RCTs; 1245 participants; moderate-quality evidence) and the length of hospital stay was shortened by 0.8 days after LA (MD -0.81, 95% CI -1.01 to -0.62; 6 RCTs; 316 participants; low-quality evidence). Quality of life was not reported in any of the included studies. AUTHORS' CONCLUSIONS: Except for a higher rate of intra-abdominal abscesses after LA in adults, LA showed advantages over OA in pain intensity on day one, wound infections, length of hospital stay and time until return to normal activity in adults. In contrast, LA showed advantages over OA in wound infections and length of hospital stay in children. Two studies reported better quality of life scores in adults. No study reported this outcome in children. However, the quality of evidence ranged from very low to moderate and some of the clinical effects of LA were small and of limited clinical relevance. Future studies with low risk of bias should investigate, in particular, the quality of life in children.

Challenges in Cost-Effectiveness Analysis Modelling of HPV Vaccines in Low- and Middle-Income Countries: A Systematic Review and Practice Recommendations.

BACKGROUND: Low- and middle-income countries (LMICs) face a number of challenges in implementing cervical cancer prevention programmes that do not apply in high-income countries. OBJECTIVE: This review assessed how context-specific challenges of implementing cervical cancer prevention strategies in LMICs were accounted for in existing cost-effectiveness analysis (CEA) models of human papillomavirus (HPV) vaccination. METHODS: The databases of MEDLINE, EMBASE, NHS Economic Evaluation Database, EconLit, Web of Science, and the Center for the Evaluation of Value and Risk in Health (CEA) Registry were searched for studies published from 2006 to 2015. A descriptive, narrative, and interpretative synthesis of data was undertaken. RESULTS: Of the 33 studies included in the review, the majority acknowledged cost per vaccinated girl (CVG) (26 studies) and vaccine coverage rate (21 studies) as particular challenges for LMICs, while nine studies identified screening coverage rate as a challenge. Most of the studies estimated CVG as a composite of different cost items. However, the basis for the items within this composite cost was unclear. The majority used an assumption rather than an observed rate to represent screening and vaccination coverage rates. CVG, vaccine coverage and screening coverage were shown by some studies through sensitivity analyses to reverse the conclusions regarding cost-effectiveness, thereby significantly affecting policy recommendations. CONCLUSIONS: While many studies recognized aspects of the particular challenges of HPV vaccination in LMICs, greater efforts need to be made in adapting models to account for these challenges. These include adapting costings of HPV vaccine delivery from other countries, learning from the outcomes of cervical cancer screening programmes in the same geographical region, and taking into account the country's previous experience with other vaccination programmes.

Assessing cost-effectiveness of HPV vaccines with decision analytic models: what are the distinct challenges of low- and middle-income countries? A protocol for a systematic review.

BACKGROUND: Cervical cancer poses a huge health burden, both to developed and developing nations, making prevention and control strategies necessary. However, the challenges of designing and implementing prevention strategies differ for low- and middle-income countries (LMICs) as compared to countries with fully developed health care systems. Moreover, for many LMICs, much of the data needed for decision analytic modelling, such as prevalence, will most likely only be partly available or measured with much larger uncertainty. Lastly, imperfect implementation of human papillomavirus (HPV) vaccination may influence the effectiveness of cervical cancer prevention in unpredictable ways. This systematic review aims to assess how decision analytic modelling studies of HPV cost-effectiveness in LMICs accounted for the particular challenges faced in such countries. Specifically, the study will assess the following: (1) whether the existing literature on cost-effectiveness modelling of HPV vaccines acknowledges the distinct challenges of LMICs, (2) how these challenges were accommodated in the models, (3) whether certain parameters systemically exhibited large degrees of uncertainty due to lack of data and how influential were these parameters on model-based recommendations, and (4) whether the choice of modelling herd immunity influences model-based recommendations, especially when coverage of a HPV vaccination program is not optimal. METHODS: We will conduct a systematic review to identify suitable studies from MEDLINE (via PubMed), EMBASE, NHS Economic Evaluation Database (NHS EED), EconLit, Web of Science, and CEA Registry. Searches will be conducted for studies of interest published since 2006. The searches will be supplemented by hand searching of the most relevant papers found in the search. Studies will be critically appraised using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We will undertake a descriptive, narrative, and interpretative synthesis of data to address the study objectives. DISCUSSION: The proposed systematic review will assess how the cost-effectiveness studies of HPV vaccines accounted for the distinct challenges of LMICs. The gaps identified will expose areas for additional research as well as challenges that need to be accounted for in future modelling studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017870.

Laparoscopic versus open appendectomy in patients with suspected appendicitis: a systematic review of meta-analyses of randomised controlled trials.

BACKGROUND: Several systematic reviews (SRs) of randomised controlled trials (RCTs) comparing laparoscopic versus open appendectomy have been published, but there has been no overview of SRs of these two interventions. This overview (review of review) aims to summarise the results of such SRs in order to provide the most up to date evidence, and to highlight discordant results. METHODS: Medline, Embase, Cinahl, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects were searched for SRs published up to August 2014. Study selection and quality assessment using the AMSTAR tool were carried out independently by two reviewers. We used standardised forms to extract data that were analysed descriptively. RESULTS: Nine SRs met the inclusion criteria. All were of moderate to high quality. The number of randomized controlled trials (RCTs) they included ranged from eight to 67. The duration of surgery pooled by eight reviews was 7.6 to 18.3 minutes shorter using the open approach. Pain scores on the first postoperative day were lower after laparoscopic appendectomy in two out of three reviews. The risk of abdominal abscesses was higher for laparoscopic surgery in half of six meta-analyses. The occurrence of wound infections pooled by all reviews was lower after laparoscopic appendectomy. One review showed no difference in mortality. The laparoscopic approach shortened hospital stay from 0.16 to 1.13 days in seven out of eight meta-analyses, though the strength of the evidence was affected by strong heterogeneity. CONCLUSION: Laparoscopic and open appendectomy are both safe and effective procedures for the treatment of acute appendicitis. This overview shows discordant results with respect to the magnitude of the effect but not to the direction of the effect. The evidence from this overview may prove useful for the development of clinical guidelines and protocols.

Efficacy and safety of sclerotherapy with polidocanol foam in comparison with fluid sclerosant in the treatment of first-grade haemorrhoidal disease: a randomised, controlled, single-blind, multicentre trial.

PURPOSE: Sclerotherapy is the treatment of choice for first-grade haemorrhoidal disease. Numerous studies have shown that sclerotherapy with foamed sclerosants is more efficacious than liquid in the treatment of varicose veins. The aim of this study was to assess the efficacy and safety of polidocanol foam in comparison with liquid for haemorrhoidal disease. METHODS: A total of 130 patients were randomised to foam or liquid sclerotherapy (polidocanol 3%). Patients with first-grade haemorrhoidal disease were included and blinded to treatment assignment. The primary endpoint was the stopping of perianal bleeding after one sclerotherapy session. Sclerotherapy was repeated until patients were free of bleeding (2-week intervals). The final follow-up was 12 weeks after the last sclerotherapy session. RESULTS: In the foam group, significantly more patients (88%) were treated successfully after one sclerotherapy session compared to the liquid group (69%; p = 0.01). There was high patient satisfaction in both groups, but significantly more patients were satisfied with their treatment in the foam group than in the liquid group (99 vs. 84%; p = 0.009). Additionally, in the foam group, significantly less treatment sessions were required (p < 0.001), and the total amount of injected polidocanol was reduced (p < 0.001). CONCLUSION: In the therapy of first-grade haemorrhoidal disease, polidocanol 3 % foam is more effective and equally safe compared to liquid polidocanol. The results of this trial show that foam sclerotherapy is a new, innovative, effective and safe non-surgical treatment option for haemorrhoidal disease.

Helicobacter pylori eradication in gastric mucosa-associated lymphoid tissue lymphoma: Results of a 196-patient series.

Prospective studies have reported ongoing remissions in most patients with localized Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma after curing the infection. Using specific selection criteria, the outcome of 196 patients treated in routine clinical practice was analysed. Complete remission rates, stability of remissions and frequency of relapse and histologic residual disease were in accordance with previous prospective clinical trials, whereas the median age was higher. Only a minority had a complete staging, and it may be expected that there is a significant group of patients with an unrecognized higher stage in this cohort. The frequency of follow-up investigations was also not considered as recommended in a considerable number of patients. Nevertheless, the outcome of patients was favourable regardless of limited staging and follow-up procedures. Amended recommendations and special guidelines for elderly and patients with concomitant disease should be considered.