Search

Purpose To assess the methodological quality of all relevant and recent European clinical practice guidelines (CPGs) for advanced oesophageal and gastric cancers, and to synthesise their recommendations on the use of chemotherapy. Methods We searched PubMed, EMBASE, guidelines repositories, and other sources from 2010 onwards. We appraised quality using AGREE-II and AGREE-REX. Results 11 CPGs were included (five high, five low, and one moderate quality). Most guidelines showed deficiencies in the domain "applicability", with only three scoring above 60%. Nine did not report having sought the views and preferences of the target population. The lowest scores for AGREE-REX were item Values and Preferences of Target Users (1.6; SD 1.3), and item Values and Preferences of Policy/Decision-Makers (1.8; SD 1.7). The domain Clinical Applicability got the highest score and the domain Implementability got the lowest. Conclusions An urgent area of research is how to develop credible and implementable recommendations on the clinical use of CT for advanced oesophageal and gastric cancer. Systematic review registration: PROSPERO (CRD42021236753).

Background: Patients with advanced pancreatic cancer (PC) have a high risk of dying in the short or medium-term. This overview aimed to assess the evidence regarding systemic oncological treatments (SOT) versus supportive care for advanced PC. Methods: We searched for systematic reviews (SRs) in MEDLINE, Embase, The CochraneLibrary, Epistemonikos, and PROSPERO. Two authors assessed eligibility independently. Data extraction and methodological quality assessment were conducted by one author and cross-checked by another one. We evaluated the overlap of primary studies, performed a de novo meta-analysis, and assessed the certainty of evidence. Primary outcomes were overall survival (OS), quality of life (QoL), functional status (FS), and toxicity. Results: We identified three SRs that assessed SOT versus supportive care in patients with advanced PC. All SRs had critically low methodological quality. At 12 months, OS improved with chemotherapy, radiotherapy followed by chemotherapy, and immunotherapy, but the certainty of the evidence supporting these findings is very low. The evidence on chemotherapy is very uncertain about its effects on QoL; it suggests a slight increase in toxicity and little to no difference in FS. The evidence on immunotherapy is very uncertain about its effects in toxicity. Conclusions: The identified evidence is very uncertain about the benefits of oncological treatments on OS and QoL in patients with advanced PC with a high risk of dying in the short or medium-term, so its use should be proposed only to selected patients. Further studies that include a thorough assessment of patient-centred outcomes are needed. (C) 2021 Published by Elsevier Ltd.

Background: Esophageal and gastric cancers are a significant public health problem worldwide, with most patients presenting with advanced-stage disease and, consequently, poor prognosis. Systemic oncological treatments (SOT) have been widely used over more conservative approaches, such as supportive care. Nevertheless, its effectiveness in this scenario is not sufficiently clear. This paper provides an overview of systematic reviews that assessed the effectiveness of SOT compared with the best supportive care (BSC) or placebo in patients with advanced esophageal or gastric cancers in an end-of-life context. Methods: We searched MEDLINE, EMBASE, The Cochrane Library, Epistemonikos, and PROSPERO for eligible systematic reviews (SRs) published from 2008 onwards. The primary outcomes were overall survival (OS), progression-free survival (PFS), functional status, and toxicity. Two authors assessed eligibility and extracted data independently. We evaluated the methodological quality of included SRs using the AMSTAR-2 tool and the overlap of primary studies (corrected covered area, CCA). Also, we performed a de novo meta-analysis with data reported for each primary study when it was possible. We assessed the certainty of evidence using the GRADE approach. Results: We identified 16 SRs (19 included trials) for inclusion within this overview. Most reviews had a critically low methodological quality, and there was a very high overlap of primary studies. It is uncertain whether SOT improves OS and PFS over more conservative approaches due to the very low certainty of evidence. Conclusions: The evidence is very uncertain about the effectiveness of SOT for advanced esophageal or gastric cancers. High-quality SRs and further randomized clinical trials that include a thorough assessment of patient-centered outcomes are needed.

Background Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the Legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. Objectives To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. Search methods The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. Selection criteria We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centeila asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. Data collection and analysis Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (as) and percentage of heterogeneity (12). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. Main results We identified three new studies for this update. In total, 69 RCTs of oral phiebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 950/0 CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 950/0 CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate -certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have littEe or no effect on ulcer healing (RR 0.94,95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phiebotonics probably increase adverse events sEightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate -certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. Authors' conclusions There is moderate-certainty evidence that phiebotonics probably reduce oedema slightly, compared to placebo; moderate -certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate -certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

BackgroundHealthcare-associated infections (HAIs) are common and increase morbidity, mortality, and healthcare costs. Their control continues to be an unresolved issue worldwide. HAIs epidemiology shows sex/gender differences. Thus the lack of consideration of sex/gender in Cochrane reviews will limit their applicability and capacity to support informed decisions. This study aims to describe the extent to which Cochrane reviews of interventions for preventing HAIs consider sex and gender.MethodsMethodology study appraising Cochrane reviews of interventions to prevent HAIs. Search methods: Cochrane Database of Systematic Reviews from 1995 (launch of the journal) to 31 December 2016. Two authors independently extracted data with EPPI-Reviewer 4 software, and independently appraised the sex/gender content of the reviews with the Sex and Gender Appraisal Tool for Systematic Reviews (SGAT-SR).ResultsThis study included 113 reviews assessing the effects of interventions for preventing HAIs. 100 reviews (88%) used at least one sex or gender-related term. The terminology used was heterogeneous, being sex the term used in more reviews (51%). No review defined neither sex nor gender. Thus we could not assess the definitions provided. Consideration of sex and gender was practically absent in the included reviews; in fact, no review met all the applicable items of the SGAT-SR, and 51 reviews (50%) fulfilled no item. No review provided a complete description of the sex and the gender of the samples of the included studies. Only ten reviews (10%) planned to perform sex- and gender-based analysis and only three (3%) could complete the analysis. The method chosen was always the subgroup analysis based on sex (one review) or gender (two reviews). Three reviews (3%) considered sex or gender-related findings in the conclusions.ConclusionConsideration of sex and gender in Cochrane reviews of interventions for preventing HAIs was practically absent. This lack of attention to sex and gender reduces the quality of Cochrane reviews, and their applicability for all people: women and men, boys and girls, and people of diverse gender identities. Cochrane should attempt to address the shortfalls detected.

Purpose: This evidence mapping aims to describe and assess the quality of available evidence in systematic reviews (SRs) on treatments for oral cancer. Materials and methods: We followed the methodology of Global Evidence Mapping. Searches in MEDLINE, EMBASE, Epistemonikos and The Cochrane Library were conducted to identify SRs on treatments for oral cancer. The methodological quality of SRs was assessed using the Assessing the Methodological Quality of Systematic Reviews-2 tool. We organized the results according to identified Population-Intervention-Comparison-Outcome (PICO) questions and presented the evidence mapping in tables and a bubble plot. Results: Fifteen SRs met the eligibility criteria, including 118 individual reports, of which 55.1% were randomized controlled clinical trials. Ten SRs scored "Critically low" methodological quality. We extracted 30 PICOs focusing on interventions such as surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy; 18 PICOs were for resectable oral cancer, of which 8 were reported as beneficial. There were 12 PICOs for unresectable oral cancer, of which only 2 interventions were reported as beneficial. Conclusion: There is limited available evidence on treatments for oral cancer. The methodological quality of most included SRs scored "Critically low". The main beneficial treatment reported by authors for patients with resectable oral cancer is surgery alone or in combination with radiotherapy or chemotherapy. Evidence about the benefits of the treatments for unresectable oral cancer is lacking. These findings highlight the need to address future research focused on new treatments and knowledge gaps in this field, and increased efforts are required to improve the methodology quality and reporting process of SRs on treatments for oral cancer.

Background Early enteral nutrition support (within 48 hours of admission or injury) is frequently recommended for the management of patients in intensive care units (ICU). Early enteral nutrition is recommended in many clinical practice guidelines, although there appears to be a lack of evidence for its use and benefit. Objectives To evaluate the efficacy and safety of early enteral nutrition (initiated within 48 hours of initial injury or ICU admission) versus delayed enteral nutrition (initiated later than 48 hours after initial injury or ICU admission), with or without supplemental parenteral nutrition, in critically ill adults. Search methods We searched CENTRAL (2019, lssue4), MEDLINE Ovid (1946 to April 2019), Embase Ovid SP (1974 to April 2019), CINAHL EBSCO (1982 to April 2019), and ISI Web of Science (1945 to April 2019). We also searched Turning Research Into Practice (TRIP), trial registers (ClinicatTrials.gov, ISRCTN registry), and scientific conference reports, including the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. We applied no restrictions by language or publication status. Selection criteria We included all randomized controlled trials (RCTs) that compared early versus delayed enteral nutrition, with or without supplemental parenteral nutrition, in adults who were in the ICU for longer than 72 hours. This included individuals admitted for medical, surgical, and trauma diagnoses, and who required any type of enteral nutrition. Data collection and analysis Two review authors extracted study data and assessed the risk of bias in the included studies, We expressed results as risk ratios (RR) for dichotomous data, and as mean differences (MD) for continuous data, both with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE. Main results We included seven RCTs with a total of 345 participants. Outcome data were limited, and we judged many trials to have an unclear risk of bias in several domains. Early versus delayed enterat nutrition Six trials (318 participants) assessed early versus delayed enteral nutrition in general, medical, and trauma ICUs in the USA, Australia, Greece, India, and Russia. Primary outcomes Five studies (259 participants) measured mortality. It is uncertain whether early enteral nutrition affects the risk of mortality within 30 days (RR 1.00, 95% CI 0.16 to 6.38; 1 study, 38 participants; very low-quality evidence). Four studies (221 participants) reported mortality without describing the timeframe; we did not pool these results. None of the studies reported a clear difference in mortality between groups. Three studies (156 participants) reported infectious complications. We were unable to pool the results due to unreported data and sub-stantiat clinical heterogeneity. The results were inconsistent across studies. One trial measured feed intolerance or gastrointestinal complications; it is uncertain whether early enteral nutrition affects this outcome (RR 0.84, 95% CI 0.35 to 2.01; 59 participants; very low quality evidence). Secondary outcomes One trial assessed hospital length of stay and reported a longer stay in the early enteral group (median 15 days (interquartile range (IQR) 9.5 to 20) versus 12 days (IQR 7.5 to15); P = 0.05; 59 participants; very low-quality evidence). Three studies (125 participants) reported the duration of mechanical ventilation. We did not pool the results due to clinical and statistical heterogeneity. The results were inconsistent across studies. It is uncertain whether early enteral nutrition affects the risk of pneumonia (RR 0.77, 95% CI 0.55 to 1.06; 4 studies, 192 participants; very low-quality evidence). Early enteral nutrition with supplemental parenterat nutrition versus delayed enteral nutrition with supplemental parenterat nutrition We identified one trial in a burn ICU in the USA (27 participants). Primary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition affects the risk of mortality (RR 0.74, 95% CI 0.25 to 2.18; very low-quality evidence), or infectious complications (MD 0.00,95% CI -1.94 to 1.94; very low-quality evidence). There were no data available for feed intolerance or gastrointestinal complications. Secondary outcomes It is uncertain whether early enteral nutrition with supplemental parenteral nutrition reduces the duration of mechanical ventilation (MD 9.00, 95% CI 10.99 to 28.99; very low quality evidence). There were no data available for hospital length of stay or pneumonia. Authors' conclusions Due to very low-quality evidence, we are uncertain whether early enteral nutrition, compared with delayed enteral nutrition, affects the risk of mortality within 30 days, feed intolerance or gastrointestinal complications, or pneumonia. Due to very low-quality evidence, we are uncertain if early enteral nutrition with supplemental parenteral nutrition compared with delayed enteral nutrition with supplemental parenteral nutrition reduces mortality, infectious complications, or duration of mechanical ventilation. There is currently insufficient evidence; there is a need for large, multicentred studies with rigorous methodology, which measure important clinical outcomes.

Background Brain metastases occur when cancer cells spread from their original site to the brain and are a frequent cause of morbidity and death in people with cancer. They occur in 20% to 40% of people during the course of their disease. Brain metastases are also the most frequent type of brain malignancy. Single and solitary brain metastasis is infrequent and choosing the most appropriate treatment is a clinical challenge. Surgery and stereotactic radiotherapy are two options. For surgery, tumour resection is performed using microsurgical techniques, while in stereotactic radiotherapy, external ionising radiation beams are precisely focused on the brain metastasis. Stereotactic radiotherapy may be given as a single dose, also known as single dose radiosurgery, or in a number of fractions, also known as fractionated stereotactic radiotherapy. There is uncertainty regarding which treatment (surgery or stereotactic radiotherapy) is more effective for people with single or solitary brain metastasis. Objectives To assess the effectiveness and safety of surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2018), MEDLINE and Embase up to 25 March 2018 for relevant studies. We also searched trials databases, grey literature and handsearched relevant literature. Selection criteria We included randomised controlled trials (RCTs) comparing surgery versus stereotactic radiotherapy, either a single fraction (stereotactic radiosurgery) or multiple fractions (fractionated stereotactic radiotherapy) for treatment of single or solitary brain metastasis. Data collection and analysis Two review authors screened all references, evaluated the quality of the included studies using the Cochrane tool for assessing risk of bias, and performed data extraction. The primary outcomes were overall survival and adverse events. Secondary outcomes included progression-free survival and quality of life . We analysed overall survival and progression-free survival as hazard ratios (HRs) with 95% confidence intervals (CIs), and analysed adverse events as risk ratios (RRs). For quality of life we used mean difference (MD). Main results Two RCTs including 85 participants met our inclusion criteria. One study included people with single untreated brain metastasis (n = 64), and the other included people with solitary brain metastasis (22 consented to randomisation and 21 were analysed). We identified a third trial reported as completed and pending results this may be included in future updates of this review. The two included studies were prematurely closed due to poor participant accrual. One study compared surgery plus whole brain radiotherapy (WBRT) versus stereotactic radiosurgery alone, and the second study compared surgery plus WBRT versus stereotactic radiosurgery plus WBRT. Meta-analysis was not possible due to clinical heterogeneity between trial interventions. The overall certainty of evidence was low or very low for all outcomes due to high risk of bias and imprecision. We found no difference in overall survival in either of the two comparisons. For the comparison of surgery plus WBRT versus stereotactic radiosurgery alone: HR 0.92, 95% CI 0.48 to 1.77; 64 participants, very low-certainty evidence. We downgraded the certainty of the evidence to very low due to risk of bias and imprecision. For the comparison of surgery plus WBRT versus stereotactic radiosurgery plus WBRT: HR 0.53, 95% CI 0.20 to 1.42; 21 participants, low-certainty evidence. We downgraded the certainty of the evidence to low due to imprecision. Adverse events were reported in both trial groups in the two studies, showing no differences for surgery plus WBRT versus stereotactic radiosurgery alone (RR 0.31, 95% CI 0.07 to 1.44; 64 participants) and for surgery plus WBRT versus stereotactic radiosurgery plus WBRT (RR 0.37, 95% CI 0.05 to 2.98; 21 participants). Most of the adverse events were related to radiation toxicities. We considered the certainty of the evidence from the two comparisons to be very low due to risk of bias and imprecision. There was no difference in progression-free survival in the study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT (HR 0.55, 95% CI 0.22 to 1.38; 21 participants, low-certainty evidence). We downgraded the evidence to low certainty due to imprecision. This outcome was not clearly reported for the other comparison. In general, there were no differences in quality of life between the two studies. The study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT found no differences after two months using the QLQ-C30 global scale (MD -10.80, 95% CI -44.67 to 23.07; 14 participants, very low-certainty evidence). We downgraded the certainty of evidence to very low due to risk of bias and imprecision. Authors' conclusions Currently, there is no definitive evidence regarding the effectiveness and safety of surgery versus stereotactic radiotherapy on overall survival, adverse events, progression-free survival and quality of life in people with single or solitary brain metastasis, and benefits must be decided on a case-by-case basis until well powered and designed trials are available. Given the difficulties in participant accrual, an international multicentred approach should be considered for future studies.

Background: The applicability of clinical practice guidelines (CPGs) on treatments for oral cancer remains unknown since there are no systematic assessments of their quality. Thus, the objective of this study is to identify and assess the quality of them. Methods: We conducted a systematic search to identify CPGs that provided recommendations on treatments for oral cancer. The quality of each included CPG was determined using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, by four appraisers independently. The inter-appraisers agreement was assessed. Results: Twelve CPGs met the eligibility criteria. Overall agreement among appraisers was very good (ICC: 0.865; 95% CI: 0.835-0.889). The mean scores for each AGREE domain were the following: "scope and purpose" 88.4% +/- 12.4%; "stakeholder involvement" 60.4% +/- 25%; "rigor of development" 60.9% +/- 25.3%; "clarity of presentation" 76.5% +/- 19.8%; "applicability" 32.2% +/- 30.7%; and "editorial independence" 61.6% +/- 35.5%. Three CPGs were rated as "recommended"; six as "recommended with modifications"; and three as "not recommended". Conclusions: Overall, the quality of CPGs on treatments for oral cancer is suboptimal. These findings highlight the need to improve CPG development processes and their applicability in this field. Thus, increased efforts are required to enable the development of high-quality evidence-based CPGs for oral cancer.

Background: Traffic accidents (TA) are a global problem with mortality of 1.25 million each year. The objective of this study was to compare adjusted mortality rates (AMR) by AT of Colombia, with Spain and the United States (US). The selection is justified because Colombia is a country with less development in road safety, Spain a nation that has adhered to European guidelines and US for having little adherence to international guidelines. Methods: A descriptive cross-sectional study was carried out for five-year periods, by calculating the AMRs by the direct method of standardization according to sex and age groups, as well as the adjustment of the motorization index. The mean values, the 95% confidence interval for each country and the relative change between the periods studied were calculated. Results: The AMR of periods P1 and P2 in all countries decreased significantly (p

Background The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. Objectives To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions. Selection criteria Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy. Data collection and analysis Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI). Main results Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC. 1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2. modern chemotherapy (FOLFOX (5-fluorouracil plus leucovorin plus oxaliplatin), irinotecan) is more effective than outdated chemotherapy (5-fluorouracil) (HR for PFS: 0.59, 95% CI 0.49 to 0.73; 2 RCTs; high-quality evidence) (HR for OS: 0.69, 95% CI 0.51 to 0.94; 1 RCT; moderate-quality evidence); 3. irinotecan-based combinations were more effective than irinotecan alone (HR for PFS: 0.68, 95% CI 0.60 to 0.76; 6 RCTs; moderate-quality evidence); 4. targeted agents improved the efficacy of conventional chemotherapy both when considered together (HR for OS: 0.84, 95% CI 0.77 to 0.91; 6 RCTs; high-quality evidence) and when bevacizumab was used alone (HR for PFS: 0.67, 95% CI 0.60 to 0.75; 4 RCTs; high-quality evidence). With regard to secondary endpoints, tumour response rates generally paralleled the survival results; moreover, higher anticancer efficacy was generally associated with worse treatment-related toxicity, with the important exception of bevacizumab-containing regimens, where the addition of the targeted agent to chemotherapy did not result in a significant increase in the rate of SAE. Finally, we found that oral (instead of intravenous) fluoropyrimidines significantly reduced the incidence of adverse effects (without compromising efficacy) in people treated with oxaliplatin-based regimens. We could not draw any conclusions on other debated aspects in this field of oncology, such as ranking of treatments (not all possible comparisons have been tested and many comparisons were based on single trials enrolling a small number of participants) and quality of life (virtually no data available). Authors' conclusions Systemic therapy offers a survival benefit to people with metastatic CRC who did not respond to first-line treatment, especially when targeted agents are combined with conventional chemotherapeutic drugs. Further research is needed to define the optimal regimen and to identify people who most benefit from each treatment.

Background F-18-florbetapir uptake by brain tissue measured by positron emission tomography (PET) is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using amyloid biomarkers tests like F-18-florbetapir. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of F-18-florbetapir to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. Objectives To determine the DTA of the F-18-florbetapir PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD), or any form of dementia at follow-up. Search methods This review is current to May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials. gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches. Selection criteria We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of F-18-florbetapir scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Data collection and analysis We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Main results We included three studies, two of which evaluated the progression from MCI to ADD, and one evaluated the progression from MCI to any form of dementia. Progression from MCI to ADD was evaluated in 448 participants. The studies reported data on 401 participants with 1.6 years of follow-up and in 47 participants with three years of follow-up. Sixty-one (15.2%) participants converted at 1.6 years follow-up; nine (19.1%) participants converted at three years of follow-up. Progression from MCI to any form of dementia was evaluated in five participants with 1.5 years of follow-up, with three (60%) participants converting to any form of dementia. There were concerns regarding applicability in the reference standard in all three studies. Regarding the domain of flow and timing, two studies were considered at high risk of bias. MCI to ADD; Progression from MCI to ADD in those with a follow-up between two to less than four years had a sensitivity of 67% (95% CI 30 to 93) and a specificity of 71% (95% CI 54 to 85) by visual assessment (n = 47, 1 study). Progression from MCI to ADD in those with a follow-up between one to less than two years had a sensitivity of 89% (95% CI 78 to 95) and a specificity of 58% (95% CI 53 to 64) by visual assessment, and a sensitivity of 87% (95% CI 76 to 94) and a specificity of 51% (95% CI 45 to 56) by quantitative assessment by the standardised uptake value ratio (SUVR)(n = 401, 1 study). MCI to any form of dementia; Progression from MCI to any form of dementia in those with a follow-up between one to less than two years had a sensitivity of 67% (95% CI 9 to 99) and a specificity of 50% (95% CI 1 to 99) by visual assessment (n = 5, 1 study). MCI to any other forms of dementia (non-ADD); There was no information regarding the progression from MCI to any other form of dementia (non-ADD). Authors' conclusions Although sensitivity was good in one included study, considering the poor specificity and the limited data available in the literature, we cannot recommend routine use of F-18-florbetapir PET in clinical practice to predict the progression from MCI to ADD. Because of the poor sensitivity and specificity, limited number of included participants, and the limited data available in the literature, we cannot recommend its routine use in clinical practice to predict the progression from MCI to any form of dementia. Because of the high financial costs of F-18-florbetapir, clearly demonstrating the DTA and standardising the process of this modality are important prior to its wider use.

Background & aims: Nutritional support in the acutely ill is a complex topic. Clinical practice guidelines (CPGs) have been developed to assist healthcare professionals working in this field. However, the quality of these clinical guidelines has not yet been systematically assessed. The objective of our study was to identify and assess the quality of CPGs on nutrition in critically ill adult patients. Methods: We performed a systematic search to identify CPGs on nutrition in critically ill adult patients. Three independent appraisers assessed six domains (scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence) of the eligible CPGs using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument. Results: Nine CPGs were selected. Overall agreement among appraisers was very good (ICC: 0.853; 95% CI: 0.820-0.881). The mean scores for each AGREE domain were the following: "scope and purpose" 76.2% +/- 13.7%; "stakeholder involvement" 42.8% +/- 16.5%; "rigour of development" 57.9% +/- 18.1%; "clarity of presentation" 76.9% +/- 13.7%; "applicability" 30.1% +/- 22.8%; and 42.1% +/- 23.9% for "editorial independence". Four CPGs were deemed "Recommended"; three "Recommended with modifications"; and two "Not recommended". We did not observe improvement over time in the overall quality of the CPGs. Conclusions: The overall quality of CPGs on nutrition in critically ill adults is suboptimal, with only four CPGs being recommended for clinical use. Our results highlight the need to revise and improve CPG development processes in this field. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I-2 statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB.

Background Chorioamnionitis is a common infection that affects both mother and infant. Infant complications associated with chorioamnionitis include early neonatal sepsis, pneumonia, and meningitis. Chorioamnionitis can also result in maternal morbidity such as pelvic infection and septic shock. Clinical chorioamnionitis is estimated to occur in 1% to 2% of term births and in 5% to 10% of preterm births; histologic chorioamnionitis is found in nearly 20% of term births and in 50% of preterm births. Women with chorioamnionitis have a two to three times higher risk for cesarean delivery and a three to four times greater risk for endomyometritis, wound infection, pelvic abscess, bacteremia, and postpartum hemorrhage. Objectives To assess the effects of administering antibiotic regimens for intra-amniotic infection on maternal and perinatal morbidity and mortality and on infection-related complications. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2014), CENTRAL, MEDLINE, Embase, LILACS, and the WHO ICTRP (September 2014). We also searched reference lists of retrieved studies and contacted experts in the field. Selection criteria Randomized controlled trials (RCTs) that included women who experienced intra-amniotic infection. Trials were included if they compared antibiotic treatment with placebo or no treatment (if applicable), treatment with different antibiotic regimens, or timing of antibiotic therapy (intrapartumand/orpostpartum). Therefore, this review assesses trials evaluating intrapartum antibiotics, intrapartum and postpartum antibiotic regimens, and postpartum antibiotics. Diagnosis of intra-amniotic infection was based on standard criteria (clinical/test), and no limit was placed on gestational age. Data collection and analysis Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data and checked them for accuracy. We assessed the quality of the evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and included a 'Summary of findings' table. Main results Our prespecified primary outcomes were maternal and neonatal mortality, maternal and neonatal severe infection, and duration of maternal and neonatal hospital stay. We included 11 studies (involving 1296 women) and assessed them as having low to moderate risk of bias -mainly because allocation concealment methods were not adequately reported, most studies were open, and outcome reporting was incomplete. The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. The following antibiotics were assessed in the included trials: ampicillin, ampicillin/sulbactam, gentamicin, clindamycin, and cefotetan. During labor: meta-analysis of two studies found no clear differences in rates of neonatal sepsis (163 neonates; risk ratio (RR) 1.07, 95% confidence interval (CI) 0.40 to 2.86; I-2 = 9%; low quality of evidence), treatment failure (endometritis) (163 participants; RR 0.86, 95% CI 0.27 to 2.70; I-2 = 0%; low quality of evidence), and postpartum hemorrhage (RR 1.39, 95% CI 0.76 to 2.56; I-2 = 0%; low quality of evidence) when two different dosages/regimens of gentamicin were assessed. No clear differences between groups were found for any reported maternal or neonatal outcomes. The review did not identify data for a comparison of antibiotics versus no treatment/placebo. Postpartum: meta-analysis of two studies that evaluated use of antibiotics versus placebo after vaginal delivery showed no significant differences between groups in rates of treatment failure or postpartum endometritis. No significant differences were found in rates of neonatal death and postpartum endometritis when use of antibiotics was compared with no treatment. Four trials assessing two different dosages/regimens of gentamicin or dual-agent therapy versus triple-agent therapy, or comparing antibiotics, found no significant differences in most reported neonatal or maternal outcomes; the duration of hospital stay showed a difference in favor of the group of women who received short-duration antibiotics (one study, 292 women; mean difference (MD) -0.90 days, 95% CI -1.64 to -0.16; moderate quality of evidence). Intrapartum versus postpartum: one small study (45 women) evaluating use of ampicillin/gentamicin during intrapartum versus immediate postpartum treatment found significant differences favoring the intrapartum group in the mean number of days of maternal postpartum hospital stay (one trial, 45 women; MD -1.00 days, 95% CI -1.94 to -0.06; very low quality of evidence) and the mean number of neonatal hospital stay days (one trial, 45 neonates; MD-1.90 days, 95% CI -3.91 to -0.49; very low quality of evidence). Although no significant differences were found in the rate of maternal bacteremia or early neonatal sepsis, for the outcome of neonatal pneumonia or sepsis we observed a significant difference favoring intrapartum treatment (one trial, 45 neonates; RR 0.06, 95% CI 0.00 to 0.95; very low quality of evidence). Author's conclusions This review included 11 studies (having low to moderate risk of bias). The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. Only one outcome (duration of hospital stay) was considered to provide moderate quality of evidence when antibiotics (short duration) were compared with antibiotics (long duration) during postpartum management of intraamniotic infection. Our main reasons for downgrading the quality of evidence were limitations in study design or execution (risk of bias), imprecision, and inconsistency of results. Currently, limited evidence is available to reveal the most appropriate antimicrobial regimen for the treatment of patients with intraamniotic infection; whether antibiotics should be continued during the postpartum period; and which antibiotic regimen or wh

Objective: To identify and describe randomized controlled trials (RCTs) and systematic reviews (SRs) on patient safety published from 1973 onward. Materials and Methods: We handsearched a total of 12 medical journals published in English with contents related to patient safety to identify RCTs and SRs published between 1973 and the end of 2010. The results obtained from this search were complemented with an additional search in MEDLINE. The documents were classified by area of specialty or service in which the intervention was applied, level of preventive action, and type of patient safety incident, the latter in accordance with the International Classification for Patient Safety proposed by the World Health Organization (WHO). The main features of the identified studies are also described. Results: A total of 787 issues of 12 journals published between 1973 and 2010 were handsearched. This procedure yielded 10,162 references, of which, 131 corresponded to RCTs and 127 to SRs. A parallel MEDLINE search identified only about two-thirds of these articles. Of all the studies identified, 83 RCTs and 64 SRs addressed interventions related to patient safety. The types of incident related to patient safety that were included most often in RCTs involved the clinical process, and for SRs, those related to resources/organizational management. On average, only 3.5 RCTs and 3.4 SRs were published per year, many of which had significant deficiencies in the reported information, such as, for instance, a lack of details on the methodology used. Conclusions: The number of RCTs and SRs on patient safety published in specialized journals is scarce. No studies on interventions to improve the safety of the handling of blood and derivatives, infections related to health care, nutrition, or infrastructure were identified as a result of our search. Handsearching plays a key role in the identification of all the clinical trials that could be included in SRs on patient safety interventions. Knowing the content of RCTs and SRs published on patient safety can better target future research.

Background Combination chemotherapy has been the mainstay of treatment for extensive stage small cell lung cancer (SCLC) over the last 30 years even though it only gives a short prolongation in median survival time. The main goal for these patients should be palliation with the aim of improving their quality of life. Objectives To evaluate the effectiveness of chemotherapy in extensive SCLC compared with best supportive care (BSC) or placebo treatment. Search strategy MEDLINE (1966 to July 2008), EMBASE (1974 to week 31, 2008), and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2008). Experts in the field were contacted. Selection criteria Randomised controlled trials in which any chemotherapy treatment was compared with placebo or BSC in patients with extensive SCLC, as first or second therapy at relapse. Data collection and analysis Two authors independently extracted data and assessed study quality. We resolved disagreements by discussion. Additional information was obtained from one study author. Main results Two studies were included for first-line chemotherapy. A total of 65 patients were randomised to receive either placebo or ifosfamide. Ifosfamide gave an extra mean survival of 78.5 days compared with placebo. Partial tumour response was greater with the active treatment. Toxicity was only seen in the chemotherapy group. Two studies were included for second-line chemotherapy at relapse. A total of 531 patients were randomised to receive either methotrexate-doxorubicin or symptomatic treatment, or to receive oral topotecan versus BSC. The methotrexate-doxorubicin treatment gave a median survival of 63 days longer than in the symptomatic treatment group, and 21 days longer for patients allocated to receive four or eight cycles of first-line chemotherapy, respectively. Treatment with topotecan gave a median survival of 84 days longer than in the BSC group (log-rank P = 0.01). The adjusted hazard ratio for overall survival was 0.61 (95% CI, 0.43 to 0.87). Partial or complete response in the methotrexate-doxorubicin group was 22.3%. Five patients (7%, 95% CI, 2.33 to 15.67) showed a partial response with topotecan. Toxicity was worst in the chemotherapy group. Quality of life was better in the topotecan group. Authors' conclusions Chemotherapeutic treatment prolongs survival in comparison with placebo in patients with advanced SCLC. Nevertheless, the impact of first-line chemotherapy on quality of life and in patients with poor prognosis is unknown. Well-designed, controlled trials are needed to further evaluate the risks and benefits of different chemotherapeutic schedules in patients with advanced SCLC.

Background: The Spanish Back Pain Research Network (REIDE) brings together teams of researchers and clinicians who are interested in nonspecific neck and back pain (BP). Its objective is to improve the efficacy, safety, effectiveness, and efficiency of the clinical management of BP. Method: The Network welcomes clinicians and researchers interested in BP. The only requirement to become a member of REIDE is to take part in one of its research projects, and any member can propose a new one. The Network supports those projects that are of interest to two or more groups by assuming their administration and management, which allows the researchers to focus on their task. Its working method ensures methodological quality, a multidisciplinary approach, and the clinical relevance of those projects that are carried out. Results: 179 researchers from 11 areas in Spain are involved in REIDE, including experts in all of the relevant fields of BP research. Most Spanish studies on BP that have been published in international scientific journals come from the teams involved in REIDE, and it currently has 13 ongoing research projects. Conclusions: The Network can help to enhance research among rehabilitation specialists who are interested in BP, and can contribute to the development of research projects which are of interest to the specialty. © 2005 Sociedad Española de Rehabilitación y Medicina Física (SERMEF) y Elsevier España, S.L.