Microwave coagulation for liver metastases.

BACKGROUND: Liver metastases (i.e. secondary hepatic malignancies) are significantly more common than primary liver cancer. Long-term survival after radical surgical treatment is approximately 50%. For people in whom resection for cure is not feasible, other treatments must be considered. One treatment option is microwave coagulation utilising electromagnetic waves. It involves placing an electrode into a lesion under ultrasound or computed tomography guidance. OBJECTIVES: To evaluate the beneficial and harmful effects of microwave coagulation versus no intervention, other ablation methods, or systemic treatments in people with liver metastases regardless of the location of the primary tumour. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest date of search was 14 April 2023. SELECTION CRITERIA: Randomised clinical trials assessing beneficial or harmful effects of microwave coagulation and its comparators in people with liver metastases, irrespective of the location of the primary tumour. We included trials no matter the outcomes reported. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. Our primary outcomes were: all-cause mortality at the last follow-up and time to mortality; health-related quality of life (HRQoL); and any adverse events or complications. Our secondary outcomes were: cancer mortality; disease-free survival; failure to clear liver metastases; recurrence of liver metastases; time to progression of liver metastases; and tumour response measures. We used risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) to present the results. Two review authors independently extracted data and assessed the risk of bias using the Cochrane RoB 1 tool. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS: Three randomised clinical trials fulfilled the inclusion criteria. The control interventions differed in the three trials; therefore, meta-analyses were not possible. The trials were at high risk of bias. The certainty of evidence of the assessed outcomes in the three comparisons was very low. Data on our prespecified outcomes were either missing or not reported. Microwave coagulation plus conventional transarterial chemoembolisation (TACE) versus conventional TACE alone One trial, conducted in China, randomised 50 participants (mean age 60 years, 76% males) with liver metastases from various primary sites. Authors reported that the follow-up period was at least one month. The trial reported adverse events or complications in the experimental group only and for tumour response measures. There were no dropouts in the trial. The trial did not report on any other outcomes. Microwave ablation versus conventional surgery One trial, conducted in Japan, randomised 40 participants (mean age 61 years, 53% males) with multiple liver metastases of colorectal cancer. Ten participants were excluded after randomisation (six from the experimental and four from the control group); thus, the trial analyses included 30 participants. Follow-up was three years. The reported number of deaths from all causes was 9/14 included participants in the microwave group versus 12/16 included participants in the conventional surgery group. The mean overall survival was 27 months in the microwave ablation and 25 months in the conventional surgery group. The three-year overall survival was 14% with microwave ablation and 23% with conventional surgery, resulting in an HR of 0.91 (95% CI 0.39 to 2.15). The reported frequency of adverse events or complications was comparable between the two groups, except for the required blood transfusion, which was more common in the conventional surgery group. There was no intervention-related mortality. Disease-free survival was 11.3 months in the microwave ablationgroup and 13.3 months in the conventional surgery group. The trial did not report on HRQoL. Microwave ablation versus radiofrequency ablation One trial, conducted in Germany, randomised 50 participants (mean age 62.8 years, 46% males) who were followed for 24 months. Two-year mortality showed an RR of 0.62 (95% CI 0.26 to 1.47). The trial reported that, by two years, 76.9% of participants in the microwave ablationgroup and 62.5% of participants in the radiofrequency ablation group survived (HR 0.63, 95% CI 0.23 to 1.73). The trial reported no deaths or major complications during the procedures in either group. There were two minor complications only in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial reported technical efficacy in 100% of procedures in both groups. Distant recurrence was reported for 10 participants in the microwave ablation group and nine participants in the radiofrequency ablation group (RR 1.03, 95% CI 0.50 to 2.08). No participant in the microwave ablation group demonstrated local progression at 12 months, while that occurred in two participants in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial did not report on HRQoL. One trial reported partial support by Medicor (MMS Medicor Medical Supplies GmbH, Kerpen, Germany) for statistical analysis. The remaining two trials did not provide information on funding. We identified four ongoing trials. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of microwave ablation in addition to conventional TACE compared with conventional TACE alone on adverse events or complications. We do not know if microwave ablation compared with conventional surgery may have little to no effect on all-cause mortality. We do not know the effect of microwave ablation compared with radiofrequency ablation on all-cause mortality and adverse events or complications either. Data on all-cause mortality and time to mortality, HRQoL, adverse events or complications, cancer mortality, disease-free survival, failure to clear liver metastases, recurrence of liver metastases, time to progression of liver metastases, and tumour response measures were either insufficient or were lacking. In light of the current inconclusive evidence and the substantial gaps in data, the pursuit of additional good-quality, large randomised clinical trials is not only justified but also essential to elucidate the efficacy and comparative benefits of microwave ablation in relation to various interventions for liver metastases. The current version of the review, in comparison to the previous one, incorporates two new trials in two additional microwave ablation comparisons: 1. in addition to conventional TACE versus conventional TACE alone and 2. versus radiofrequency ablation.

Transarterial (chemo)embolisation versus systemic chemotherapy for colorectal cancer liver metastases.

BACKGROUND: The liver is affected by two groups of malignant tumours: primary liver cancers and liver metastases. Liver metastases are significantly more common than primary liver cancer, and five-year survival after radical surgical treatment of liver metastases ranges from 28% to 50%, depending on primary cancer site. However, R0 resection (resection for cure) is not feasible in most people; therefore, other treatments have to be considered in the case of non-resectability. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the peripheral branches of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents and can lead to selective necrosis of the cancer tissue while leaving normal liver parenchyma virtually unaffected. The entire procedure can be performed without infusion of chemotherapy and is then called bland transarterial embolisation (TAE). These procedures are usually applied over a few sessions. Another possible treatment option is systemic chemotherapy which, in the case of colorectal cancer metastases, is most commonly performed using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) and FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) regimens applied in multiple sessions over a long period of time. These therapies disrupt the cell cycle, leading to death of rapidly dividing malignant cells. Current guidelines determine the role of TAE and TACE as non-curative treatment options applicable in people with liver-only or liver-dominant metastatic disease that is unresectable or non-ablatable, and in people who have failed systemic chemotherapy. Regarding the treatment modalities in people with colorectal cancer liver metastases, we found no systematic reviews comparing the efficacy of TAE or TACE versus systemic chemotherapy. OBJECTIVES: To evaluate the beneficial and harmful effects of transarterial embolisation (TAE) or transarterial chemoembolisation (TACE) compared with systemic chemotherapy in people with liver-dominant unresectable colorectal cancer liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three additional databases up to 4 April 2024. We also searched two trials registers and the European Medicines Agency database and checked reference lists of retrieved publications. SELECTION CRITERIA: We included randomised clinical trials assessing beneficial and harmful effects of TAE or TACE versus systemic chemotherapy in adults (aged 18 years or older) with colorectal cancer liver metastases. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality; overall survival (time to mortality); and any adverse events or complications. Our secondary outcomes were cancer mortality; health-related quality of life; progression-free survival; proportion of participants dying or surviving with progression of the disease; time to progression of liver metastases; recurrence of liver metastases; and tumour response measures (complete response, partial response, stable disease, and progressive disease). For the purpose of the review and to perform necessary analyses, whenever possible, we converted survival rates to mortality rates, as this was our primary outcome. For the analysis of dichotomous outcomes, we used the risk ratio (RR); for continuous outcomes, we used the mean difference; and for time to event outcomes, we calculated hazard ratios (HRs), all with 95% confidence intervals (CI). We used the standardised mean difference with 95% CIs when the trials used different instruments. We used GRADE to assess the certainty of evidence for each outcome. We based our conclusions on outcomes analysed at the longest follow-up. MAIN RESULTS: We included three trials with 118 participants randomised to TACE versus 120 participants to systemic chemotherapy. Four participants were excluded; one due to disease progression prior to treatment and three due to decline in health. The trials reported data on one or more outcomes. Two trials were performed in China and one in Italy. The trials differed in terms of embolisation techniques and chemotherapeutic agents. Follow-up ranged from 12 months to 50 months. TACE may reduce mortality at longest follow-up (RR 0.86, 95% CI 0.79 to 0.94; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. TACE may have little to no effect on overall survival (time to mortality) (HR 0.61, 95% CI 0.37 to 1.01; 1 trial, 70 participants; very low-certainty evidence), any adverse events or complications (3 trials, 234 participants; very low-certainty evidence), health-related quality of life (2 trials, 154 participants; very low-certainty evidence), progression-free survival (1 trial, 70 participants; very low-certainty evidence), and tumour response measures (presented as the overall response rate) (RR 1.81, 95% CI 1.11 to 2.96; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. No trials reported cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases. We found no trials comparing the effects of TAE versus systemic chemotherapy in people with colorectal cancer liver metastases. AUTHORS' CONCLUSIONS: The evidence regarding effectiveness of TACE versus systemic chemotherapy in people with colorectal cancer liver metastases is of very low certainty and is based on three trials. Our confidence in the results is limited due to the risk of bias, inconsistency, indirectness, and imprecision. It is very uncertain whether TACE confers benefits with regard to reduction in mortality, overall survival (time to mortality), reduction in adverse events or complications, improvement in health-related quality of life, improvement in progression-free survival, and tumour response measures (presented as the overall response rate). Data on cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases are lacking. We found no trials assessing TAE versus systemic chemotherapy. More randomised clinical trials are needed to strengthen the body of evidence and provide insight into the benefits and harms of TACE or TAE in comparison with systemic chemotherapy in people with liver metastases from colorectal cancer.

Needs Expressed in Peer-to-Peer Web-Based Interactions Among People With Depression and Anxiety Disorders Hospitalized in a Mental Health Facility: Mixed Methods Study.

BACKGROUND: Hospitalization in psychiatric wards is a necessary step for many individuals experiencing severe mental health issues. However, being hospitalized can also be a stressful and unsettling experience. It is crucial to understand and address the various needs of hospitalized individuals with psychiatric disorders to promote their overall well-being and support their recovery. OBJECTIVE: Our objectives were to identify and describe individual needs related to mental hospitals through peer-to-peer interactions on Polish web-based forums among individuals with depression and anxiety disorders and to assess whether these needs were addressed by peers. METHODS: We conducted a search of web-based forums focused on depression and anxiety and selected samples of 160 and 176 posts, respectively, until we reached saturation. A mixed methods analysis that included an in-depth content analysis, the Pearson χ2 test, and φ coefficient was used to evaluate the posts. RESULTS: The most frequently identified needs were the same for depression and anxiety forums and involved informational (105/160, 65.6% and 169/393, 43%, respectively), social life (17/160, 10.6% and 90/393, 22.9%, respectively), and emotional (9/160, 5.6% and 66/393, 16.8%, respectively) needs. The results show that there is no difference in the expression of needs between the analyzed forums. The needs were directly (42/47, 89% vs 98/110, 89.1% of times for depression and anxiety, respectively) and not fully (27/47, 57% vs 86/110, 78.2% of times for depression and anxiety, respectively) addressed by forum users. In quantitative analysis, we found that depression-related forums had more posts about the need for informational support and rectification, the expression of anger, and seeking professional support. By contrast, anxiety-related forums had more posts about the need for emotional support; social life; and information concerning medications, hope, and motivation. The most common co-occurrence of expressed needs was between sharing own experience and the need for professional support, with a strong positive association. The qualitative analysis showed that users join web-based communities to discuss their fears and questions about psychiatric hospitals. The posts revealed 4 mental and emotional representations of psychiatric hospitals: the hospital as an unknown place, the ambivalence of presumptions and needs, the negative representation of psychiatric hospitals, and the people associated with psychiatric hospitals. The tone of the posts was mostly negative, with discussions revolving around negative stereotypes; traumatic experiences; and beliefs that increased anxiety, shock, and fright and deterred users from hospitalization. CONCLUSIONS: Our study demonstrates that web-based forums can provide a platform for individuals with depression and anxiety disorders to express a wide range of needs. Most needs were addressed by peers but not sufficiently. Mental health professionals can benefit from these findings by gaining insights into the unique needs and concerns of their patients, thus allowing for more effective treatment and support.

Datasets for Automated Affect and Emotion Recognition from Cardiovascular Signals Using Artificial Intelligence- A Systematic Review.

Our review aimed to assess the current state and quality of publicly available datasets used for automated affect and emotion recognition (AAER) with artificial intelligence (AI), and emphasising cardiovascular (CV) signals. The quality of such datasets is essential to create replicable systems for future work to grow. We investigated nine sources up to 31 August 2020, using a developed search strategy, including studies considering the use of AI in AAER based on CV signals. Two independent reviewers performed the screening of identified records, full-text assessment, data extraction, and credibility. All discrepancies were resolved by discussion. We descriptively synthesised the results and assessed their credibility. The protocol was registered on the Open Science Framework (OSF) platform. Eighteen records out of 195 were selected from 4649 records, focusing on datasets containing CV signals for AAER. Included papers analysed and shared data of 812 participants aged 17 to 47. Electrocardiography was the most explored signal (83.33% of datasets). Authors utilised video stimulation most frequently (52.38% of experiments). Despite these results, much information was not reported by researchers. The quality of the analysed papers was mainly low. Researchers in the field should concentrate more on methodology.

Similarities, reliability and gaps in assessing the quality of conduct of systematic reviews using AMSTAR-2 and ROBIS: systematic survey of nutrition reviews.

BACKGROUND: AMSTAR-2 ('A Measurement Tool to Assess Systematic Reviews, version 2') and ROBIS ('Risk of Bias in Systematic Reviews') are independent instruments used to assess the quality of conduct of systematic reviews/meta-analyses (SR/MAs). The degree of overlap in methodological constructs together with the reliability and any methodological gaps have not been systematically assessed and summarized in the field of nutrition. METHODS: We performed a systematic survey of MEDLINE, EMBASE, and the Cochrane Library for SR/MAs published between January 2010 and November 2018 that examined the effects of any nutritional intervention/exposure for cancer prevention. We followed a systematic review approach including two independent reviewers at each step of the process. For AMSTAR-2 (16 items) and ROBIS (21 items), we assessed the similarities, the inter-rater reliability (IRR) and any methodological limitations of the instruments. Our protocol for the survey was registered in PROSPERO (CRD42019121116). RESULTS: We found 4 similar domain constructs based on 11 comparisons from a total of 12 AMSTAR-2 and 14 ROBIS items. Ten comparisons were considered fully overlapping. Based on Gwet's agreement coefficients, six comparisons provided almost perfect (> 0.8), three substantial (> 0.6), and one a moderate level of agreement (> 0.4). While there is considerable overlap in constructs, AMSTAR-2 uniquely addresses explaining the selection of study designs for inclusion, reporting on excluded studies with justification, sources of funding of primary studies, and reviewers' conflict of interest. By contrast, ROBIS uniquely addresses appropriateness and restrictions within eligibility criteria, reducing risk of error in risk of bias (RoB) assessments, completeness of data extracted for analyses, the inclusion of all necessary studies for analyses, and adherence to predefined analysis plan. CONCLUSIONS: Among the questions on AMSTAR-2 and ROBIS, 70.3% (26/37 items) address the same or similar methodological constructs. While the IRR of these constructs was moderate to perfect, there are unique methodological constructs that each instrument independently addresses. Notably, both instruments do not address the reporting of absolute estimates of effect or the overall certainty of the evidence, items that are crucial for users' wishing to interpret the importance of SR/MA results.

Electrocoagulation for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are two of the most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the people with metastatic liver disease will die from metastatic complications. Electrocoagulation by diathermy is a method used to destroy tumour tissue, using a high-frequency electric current generating high temperatures, applied locally with an electrode (needle, blade, or ball). The objective of this method is to destroy the tumour completely, if possible, in a single session. With the time, electrocoagulation by diathermy has been replaced by other techniques, but the evidence is unclear. OBJECTIVES: To assess the beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, CINAHL, ClinicalTrials.gov, ICTRP, and FDA to October 2020. SELECTION CRITERIA: We considered all randomised trials that assessed beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus comparators, in people with liver metastases, regardless of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed risk of bias of the included trial using predefined risk of bias domains, and presented the review results incorporating the certainty of the evidence using GRADE. MAIN RESULTS: We included one randomised clinical trial with 306 participants (175 males; 131 females) who had undergone resection of the sigmoid colon, and who had five or more visible and palpable hepatic metastases. The diagnosis was confirmed by histological assessment (biopsy) and by carcinoembryonic antigen (CEA) level. The trial was conducted in Iraq. The age of participants ranged between 38 and 79 years. The participants were randomised to four different study groups. The liver metastases were biopsied and treated (only once) in three of the groups: 75 received electrocoagulation by diathermy alone, 76 received electrocoagulation plus allopurinol, 78 received electrocoagulation plus dimethyl sulphoxide. In the fourth intervention group, 77 participants functioning as controls received a vehicle solution of allopurinol 5 mL 4 x a day by mouth; the metastases were left untouched. The status of the liver and lungs was followed by ultrasound investigations, without the use of a contrast agent. Participants were followed for five years. The analyses are based on per-protocol data only analysing 223 participants. We judged the trial to be at high risk of bias. After excluding 'nonevaluable patients', the groups seemed comparable for baseline characteristics. Mortality due to disease spread at five-year follow-up was 98% in the electrocoagulation group (57/58 evaluable people); 87% in the electrocoagulation plus allopurinol group (46/53 evaluable people); 86% in the electrocoagulation plus dimethyl sulphoxide group (49/57 evaluable people); and 100% in the control group (55/55 evaluable people). We observed no difference in mortality between the electrocoagulation alone group versus the control group (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.94 to 1.03; 113 participants; very low-certainty evidence). We observed lower mortality in the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus the control group (RR 0.87, 95% CI 0.80 to 0.95; 165 participants; low-certainty evidence). We are very uncertain regarding post-operative deaths between the electrocoagulation alone group versus the control group (RR 1.03, 95% CI 0.07 to 16.12; 152 participants; very low-certainty evidence) and between the electrocoagulation combined with allopurinol or dimethyl sulphoxide groups versus the control group (RR 1.00, 95% CI 0.09 to 10.86; 231 participants; very low-certainty evidence). The trial authors did not report data on number of participants with other adverse events and complications, recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life. Data on failure to clear liver metastases were not provided for the control group. There was no information on funding or conflict of interest. We identified no ongoing trials. AUTHORS' CONCLUSIONS: The evidence on the beneficial and harmful effects of electrocoagulation alone or in combination with allopurinol or dimethyl sulphoxide in people with liver metastases is insufficient, as it is based on one randomised clinical trial at low to very low certainty. It is very uncertain if there is a difference in all-cause mortality and post-operative mortality between electrocoagulation alone versus control. It is also uncertain if electrocoagulation in combination with allopurinol or dimethyl sulphoxide may result in a slight reduction of all-cause mortality in comparison with a vehicle solution of allopurinol (control). It is very uncertain if there is a difference in post-operative mortality between the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus control. Data on other adverse events and complications, failure to clear liver metastases or recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life were most lacking or insufficiently reported for analysis. Electrocoagulation by diathermy is no longer used in the described way, and this may explain the lack of further trials.

Transarterial (chemo)embolisation versus no intervention or placebo for liver metastases.

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of people; therefore, other treatments have to be considered. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents, and can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. This can also be performed without chemotherapy, which is called bland transarterial embolisation (TAE). OBJECTIVES: To assess the beneficial and harmful effects of TAE or TACE compared with no intervention or placebo in people with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and four more databases (December 2019). We also searched two trials registers and the US Food and Drug Administration database (September 2019). SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of TAE or TACE compared with no intervention or placebo for liver metastases. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence with GRADE. We resolved disagreements by discussion. MAIN RESULTS: We included one randomised clinical trial with 61 participants (43 male and 18 female) with colorectal cancer with liver metastases: 22 received transarterial embolisation (TAE; hepatic artery embolisation), 19 received transarterial chemoembolisation (TACE; 5-fluorouracil hepatic artery infusion chemotherapy with degradable microspheres), and 20 received 'no active therapeutic intervention' as a control. Most tumours were synchronous, unresectable metastases involving up to 75% of the liver. Participants were followed for a minimum of seven months. The trial was at high risk of bias. Very-low-certainty evidence found inconclusive results for mortality at 44 months between the TAE and TACE versus no intervention groups (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06; 61 participants). Local recurrence was reported in 10 participants without any details about the group allocation. Very-low-certainty evidence found little or no difference in mortality between the TAE and no intervention groups (RR 0.91, 95% CI 0.75 to 1.10; 42 participants). Median survival was 7 months from trial entry (range 2 to 44 months) in the TAE group and 7.9 months (range 1 to 26 months) in the control group, and 8.7 months after diagnosis (range 2 to 49 months) in the TAE group and 9.6 months (range 1 to 27 months) in the control group. The trial authors reported the differences were not statistically significant. There were no reported side effects in the control group. In the TAE group, 18 participants experienced short-term symptoms of 'post-embolisation syndrome', which were relieved with symptomatic treatment; one participant also had a local puncture site haematoma. Very-low-certainty evidence found little or no difference in mortality between the TACE and no intervention groups (RR 0.83, 95% CI 0.65 to 1.07; 39 participants). Median survival in the TACE group was 10.7 months (range 3 to 38 months) from trial entry, and 13.0 months (range 3 to 38 months) after diagnosis. The trial authors reported that differences between groups were not statistically significant. All participants experienced short-term nausea, with or without vomiting, immediately after treatment; one participant developed a wound infection, and one developed deep vein thrombosis. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Cancer Research Campaign, a non-profit organisation, provided a grant for the trial; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. We identified one ongoing trial comparing TACE plus chemotherapy versus chemotherapy alone in people with unresectable colorectal liver metastases who failed with first-line chemotherapy (NCT03783559). AUTHORS' CONCLUSIONS: Based on one, small randomised trial at high risk of bias, the evidence is very uncertain about the effect of TAE or TACE versus no active therapeutic intervention on mortality for people with liver metastases as the true effect may be substantially different. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Short-term, minor adverse events were recorded in the intervention groups only. Large trials, following current standards of conduct and reporting, are required to explore the benefits and harms of TAE or TACE compared with no intervention or placebo in people with resectable and unresectable liver metastasis.

Percutaneous ethanol injection for liver metastases.

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and the reported long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients; therefore, other treatments have to be considered. One of these is percutaneous ethanol injection (PEI), which causes dehydration and necrosis of tumour cells, accompanied by small-vessel thrombosis, leading to tumour ischaemia and destruction of the tumour. OBJECTIVES: To assess the beneficial and harmful effects of percutaneous ethanol injection (PEI) compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched the following databases up to 10 September 2019: the Cochrane Hepato-Biliary Group Controlled Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE Ovid; Embase Ovid; Science Citation Index Expanded; Conference Proceedings Citation Index - Science; Latin American Caribbean Health Sciences Literature (LILACS); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched clinical trials registers such as ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the US Food and Drug Administration (FDA) (17 September 2019). SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of percutaneous ethanol injection and its comparators (no intervention, other ablation methods, systemic treatments) for liver metastases. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures as outlined by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors performed data extraction and assessed risk of bias independently. We assessed the certainty of evidence by using GRADE. We resolved disagreements by discussion. MAIN RESULTS: We identified only one randomised clinical trial comparing percutaneous intratumour ethanol injection (PEI) in addition to transcatheter arterial chemoembolisation (TACE) versus TACE alone. The trial was conducted in China and included 48 trial participants with liver metastases: 25 received PEI plus TACE, and 23 received TACE alone. The trial included 37 male and 11 female participants. Mean participant age was 49.3 years. Sites of primary tumours included colon (27 cases), stomach (12 cases), pancreas (3 cases), lung (3 cases), breast (2 cases), and ovary (1 case). Seven participants had a single tumour, 15 had two tumours, and 26 had three or more tumours in the liver. The bulk diameter of the tumour on average was 3.9 cm, ranging from 1.2 cm to 7.6 cm. Participants were followed for 10 months to 43 months. The trial reported survival data after one, two, and three years. In the PEI + TACE group, 92%, 80%, and 64% of participants survived after one year, two years, and three years; in the TACE alone group, these percentages were 78.3%, 65.2%, and 47.8%, respectively. Upon conversion of these data to mortality rates, the calculated risk ratio (RR) for mortality at last follow-up when PEI plus TACE was compared with TACE alone was 0.69 (95% confidence interval (CI) 0.36 to 1.33; very low-certainty evidence) after three years of follow-up. Local recurrence was 16% in the PEI plus TACE group and 39.1% in the TACE group, resulting in an RR of 0.41 (95% CI 0.15 to 1.15; very low-certainty evidence). Forty-five out of a total of 68 tumours (66.2%) shrunk by at least 25% in the PEI plus TACE group versus 31 out of a total of 64 tumours (48.4%) in the TACE group. Trial authors reported some adverse events but provided very few details. We did not find data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases. The single included trial did not provide information on funding nor on conflict of interest. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of PEI plus TACE versus TACE in people with liver metastases is of very low certainty and is based on one small randomised clinical trial at high risk of bias. Currently, it cannot be determined whether adding PEI to TACE makes a difference in comparison to using TACE alone. Evidence for benefits or harms of PEI compared with no intervention, other ablation methods, or systemic treatments is lacking.

Health-Related Values and Preferences Regarding Meat Consumption: A Mixed-Methods Systematic Review.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: A person's meat consumption is often determined by their values and preferences. Purpose: To identify and evaluate evidence addressing health-related values and preferences regarding meat consumption. Data Sources: MEDLINE, EMBASE, Web of Science, Centre for Agriculture and Biosciences Abstracts, International System for Agricultural Science and Technology, and Food Science and Technology Abstracts were searched from inception to July 2018 without language restrictions. Study Selection: Pairs of reviewers independently screened search results and included quantitative and qualitative studies reporting adults' health-related values and preferences regarding meat consumption. Data Extraction: Pairs of reviewers independently extracted data and assessed risk of bias. Data Synthesis: Data were synthesized into narrative form, and summaries were tabulated and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Of 19 172 initial citations, 41 quantitative studies (38 addressed reasons for meat consumption and 5 addressed willingness to reduce meat consumption) and 13 qualitative studies (10 addressed reasons for meat consumption and 4 addressed willingness to reduce meat consumption) were eligible for inclusion. Thirteen studies reported that omnivores enjoy eating meat, 18 reported that these persons consider meat an essential component of a healthy diet, and 7 reported that they believe they lack the skills needed to prepare satisfactory meals without meat. Omnivores are generally unwilling to change their meat consumption. The certainty of evidence was low for both "reasons for meat consumption" and "willingness to reduce meat consumption in the face of undesirable health effects." Limitation: Limited generalizability of findings to lower-income countries, low-certainty evidence for willingness to reduce meat consumption, and limited applicability to specific types of meat (red and processed meat). Conclusion: Low-certainty evidence suggests that omnivores are attached to meat and are unwilling to change this behavior when faced with potentially undesirable health effects. Primary Funding Source: None. (PROSPERO: CRD42018088854).

Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. Purpose: To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. Data Sources: Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. Study Selection: Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. Data Synthesis: Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer. Limitation: Limited causal inferences due to residual confounding in observational studies, risk of bias due to limitations in diet assessment and adjustment for confounders, recall bias in dietary assessment, and insufficient data for planned subgroup analyses. Conclusion: The possible absolute effects of red and processed meat consumption on cancer mortality and incidence are very small, and the certainty of evidence is low to very low. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Support for Metastatic Breast Cancer Patients-a Systematic Review.

Our study objective was to evaluate existing evidence on different types of support received by metastatic breast cancer patients as well as the need for support expressed by such patients. We searched Medline and EMBASE up to January 2019 for survey studies that aimed to assess any type of support among women of any age, with metastatic breast cancer diagnosis. Two reviewers independently screened titles and abstracts, then full texts of retrieved records against inclusion/exclusion criteria, and extracted the data and assessed the quality of included studies with AXIS tool. From a total of 2876 abstracts, we selected 100 potentially eligible full-text articles, and finally, we included 12 records reporting on 11 studies. Due to the variability of methods used to measure and define support, it was not possible to quantitatively synthesize data; therefore, we synthesized them narratively. The quality of the included studies was moderate. We found that most patients are satisfied with the received psychosocial, emotional, informational, and medical support. In the analysis of any support received from a certain type of group of people, we found that the majority of patients reported receiving sufficient support from their family, friends, and healthcare providers. Ten studies showed a high need for informational support. If asked about the need for psychosocial, medical, and sexual support, women also declared the need for such support. Our review revealed that the patients generally receive support from their community but they express high need for information and treatment choice. PROSPERO CRD42019127496.

Cryotherapy for liver metastases.

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma. Liver metastases are significantly more common than primary liver cancer and long-term survival rates reported for patients after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients. Cryotherapy is performed with the use of an image-guided cryoprobe which delivers liquid nitrogen or argon gas to the tumour tissue. The subsequent process of freezing is associated with formation of ice crystals, which directly damage exposed tissue, including cancer cells. OBJECTIVES: To assess the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and six other databases up to June 2018. SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of cryotherapy and its comparators for liver metastases, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, and data on the outcomes important for our review, as well as information on the design and methodology of the trials. Two review authors independently assessed risk of bias in each study. One review author performed data extraction and a second review author checked entries. MAIN RESULTS: We found no randomised clinical trials comparing cryotherapy versus no intervention or versus systemic treatments; however, we identified one randomised clinical trial comparing cryotherapy with conventional surgery. The trial was conducted in Ukraine. The trial included 123 participants with solitary, or multiple unilobar or bilobar liver metastases; 63 participants received cryotherapy and 60 received conventional surgery. There were 36 women and 87 men. The primary sites for the metastases were colon and rectum (66.6%), stomach (7.3%), breast (6.5%), skin (4.9%), ovaries (4.1%), uterus (3.3%), kidney (3.3%), intestines (1.6%), pancreas (1.6%), and unknown (0.8%). The trial was not reported sufficiently enough to assess the risk of bias of the randomisation process, allocation concealment, or presence of blinding. It was also not possible to assess incomplete outcome data and selective outcome reporting bias. The certainty of evidence was low because of risk of bias and imprecision.The participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group. The calculated by us relative risk (RR) with 95% Confidence Interval (CI) was: RR 0.88, 95% CI 0.77 to 1.02. We judged the evidence as low-certainty evidence. Regarding adverse events and complications, separately and in total, our calculation showed no evidence of a difference in recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (RR 0.90, 95% CI 0.80 to 1.01; low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, the authors did not report whether there was any evidence of a difference. There were no intervention-related mortality or bile leakages.We identified no evidence for health-related quality of life, cancer mortality, or time to progression of liver metastases. The study reported tumour response in terms of the carcinoembryonic antigen level in 69% of participants, and reported results in the form of a graph for 30% of participants. The carcinoembryonic antigen level was lower in the cryotherapy group, and decreased to normal values faster in comparison with the control group (P < 0.05). FUNDING: the trial did not provide information on funding. AUTHORS' CONCLUSIONS: The evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.

Satisfaction of physicians working in hospitals within the European Union: state of the evidence based on systematic review.

BACKGROUND: Despite the wide range of studies concerning physician satisfaction in different European countries, there is a lack of literature reviews synthesizing and analyzing current evidence evaluating satisfaction of physicians working in European hospitals. The goal of our research was to provide a general overview of the studies in this area and their results. METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL and the Cochrane Library from January 2000 to January 2017 including both MESH/Emtree terms and free text words related to the subject with no language restrictions. The eligibility criteria included: (i) target population: physicians working in European hospitals, (ii) quantitative research aimed at assessing physician satisfaction and (iii) validated tools. We performed a narrative synthesis and meta-analysis. RESULTS: A total of 8585 abstracts and 368 full text articles were independently screened by 2 reviewers against inclusion/exclusion criteria. Finally 61 studies were eligible for qualitative analysis. Included studies enrolled a total of 50 001 physicians from 17 countries. Sample sizes varied between 54 and 7090 participants (median: 336). According to our review ∼59% of physicians working in European hospitals are overall satisfied, 3.54 was the mean satisfaction among studies reporting data on a scale from 1 to 5, 4.81 for studies with a scale from 1 to 7, 6.12 among studies reporting data on a scale from 1 to 10, and 59.65 among studies with a scale from 0 to 100. CONCLUSIONS: The level of physician satisfaction in Europe is moderate. There is a large variety of tools and scales used to assess it.

Nasal Septal Deviation and Concha Bullosa - Do They Have an Impact on Maxillary Sinus Volumes and Prevalence of Maxillary Sinusitis?

BACKGROUND: The aim of the study was to assess if the presence of nasal septal deviation and concha bullosa is connected with the development of sinuses and the incidence of inflammation within them. MATERIAL/METHODS: We retrospectively analysed 214 patients who underwent paranasal sinus computed tomography. There were 125 females and 89 males, the mean age being 47.67±16.74 years (range 18-97). Exclusion criteria included: age under 18 years, prior sinonasal surgery and S-shaped septum. RESULTS: Mean volume of the right maxillary sinus was 17.794 cm3, while for the left one it was 17.713 cm3. Nasal septal deviation was found in 79.9% of computed tomography examinations and concha bullosa was observed in 42.1% of the patients' examinations. There was an association between the presence of unilateral or dominant concha bullosa and contralateral direction of septal deviation [right-sided (p=0.039), left-sided (p=0.003)]. There was higher incidence of bilateral maxillary sinusitis in patients with septal deviation (p=0.007). Bilateral concha bullosa did not influence the incidence of bilateral maxillary sinusitis (p=0.495). Neither septal deviation (right sided: p=0.962; left-sided: p=0.731), nor unilateral/dominant concha bullosa (right: p=0.512; left: p=0,430) affected the asymmetry in volumes of maxillary sinuses. Bilateral concha bullosa was connected with larger volume of maxillary sinuses (right sinus: p=0.005; left sinus: p=0.048). CONCLUSIONS: Nasal septal deviation, contrary to concha bullosa, has influence on the development of maxillary sinusitis. There is a connection between the presence of concha bullosa and direction of septal deviation. Only bilateral concha bullosa affects maxillary sinus volumes.

Attitudes of European psychiatrists on psychedelics: a cross-sectional survey study.

Research and public interest in psychedelic-assisted psychotherapy (PAP) are growing. This study investigated attitudes toward psychedelics among a diverse and multinational sample of psychiatrists currently working in Europe. We conducted an anonymous, web-based survey consisting of demographic information, a test of basic knowledge on psychedelics, and the previously validated 20-item Attitudes on Psychedelics Questionnaire (APQ), which was validated for the first time in English within this sample. We included N = 419 participants from 33 countries in the study. One-third of participants (34%) reported past use of psychedelics. The APQ sub-scale with the highest score was Openness to Psychedelics, while Risk Assessment of Psychedelics was rated lowest. Regression modelling, explaining 31.3% of variance in APQ scores, showed that younger male psychiatrists who identified as spiritual, were better at recognizing and classifying substances as psychedelics and had previously used psychedelics had more positive attitudes on psychedelics. No professional variables besides self-reported previous experience with PAP or psychedelic research predicted APQ scores. European psychiatrists, therefore, show a general openness to psychedelics and PAP, but are concerned by the potential risks associated with them. Our findings overall suggest that psychedelics are a subject where it is difficult to remain impartial. Protocol registration: The study was pre-registered at the Open Science Framework (available online at https://osf.io/upkv3 ).

Diabetes distress and diabetes burnout explored in various areas of life in patients with type 1 diabetes: effect of short-term psychological intervention.

INTRODUCTION: Diabetes distress (DD) and diabetes burnout (DB) are recognized psychological phenomena in patients with T1DM (type 1 diabetes mellitus). Still, there is an urgent need to create professional psychological intervention procedures to provide patients with adequate care. AIM: The aim of the study was to assess the level of DD and DB in T1DM patients at baseline and after 5 of sessions psychological intervention in the group of participants who applied for help. METHODS: 34 T1DM patients who requested psychological support (22 females, 12 males) and 30 patients in a control group (14 females, 16 males) participated in the study. At baseline clinical test results between groups were compared. Next, in the studied group measurements were repeated after a set of five psychological face-to-face individual interventions which lasted 30-60 min each. They were support sessions with elements of cognitive-behavioral interventions done by clinical psychologists. Session 1: introduction, interview and collection of test results; session 2-4: work on the indicated by the patient and test results most problematic aspect of diabetes, session 5: a summary and plan for further treatment if needed. The control group results were obtained only at baseline. Research tools: DDS; PAID, Diabetes Burnout test by Polonsky. RESULTS: At the baseline, significant differences were observed between the studied group and control group: in DB/DD levels: DB (3.9 ± 1.7 vs 2.4 ± 1.6; p < 0.001); DDS (3.2 ± 1.0 vs 2.7 ± 1.0; p = 0.064); PAID (62.3 ± 14.1vs 34.4 ± 21.0; p < 0.001). There were also group differences in HbA1c levels (8.7 ± 2.4 vs 7.3 ± 1.5; p = 0.028). After psychological interventions, there was a significant improvement in DB (3.9 ± 1.7vs 2.9 ± 1.2; p < 0.001; DDS (3.2 ± 1 vs 3.0 ± 0.7; p = 0.03); PAID (62.3 ± 14.1 vs 51.8 ± 12.5; p < 0.001). CONCLUSIONS: DD and DB constitute a significant problem in the group of T1DM patients, but providing appropriate specialist care may help them accept diabetes and improve life satisfaction, as well as regain control over their diabetes management.

Teaching methods for critical thinking in health education of children up to high school: A scoping review.

According to the World Health Organization, the improvement of people's health literacy is one of the fundamental public health challenges in the 21st century. The key issue in teaching health literacy is to develop critical thinking skills. As health literacy and critical thinking should be developed at school age, we reviewed teaching methods or educational interventions used in empirical studies focused on the development of critical thinking regarding health and implemented by teachers in preschools, primary schools, or secondary schools. We searched seven databases (Medline, Embase, Web of Science, ERIC, ProqQuest, PsycArticles, and CINAHL) from inception to 20 September 2023 for any type of empirical studies. Due to the heterogeneity in interventions and inadequate reporting of results, a descriptive synthesis of studies was performed in addition to quantitative analysis. Of the 15919 initial records, 115 studies were included in the review. Most of the educational interventions focused on lifestyle-related health issues such as substance use, sexual and reproductive health, and nutrition. The popularity of health issues changed over time and depended on the geographical context. Six dimensions that differentiated the teaching methods were identified: central teaching component, central educator, pupils' activity level, teaching context, educational materials, and significance of critical thinking. Many educational interventions did not address the development of critical thinking skills in a comprehensive manner, and the significance of critical thinking varied greatly. Interventions in which critical thinking had high and very high significance applied mainly problem-solving methods and involved pupils' activity. The evidence on the effectiveness of the teaching methods that develop critical thinking is limited because most articles failed to provide detailed information on the teaching methods or did not examine their effects. We recommend that a checklist is developed to facilitate a detailed description of health educational interventions and thus promoting their replicability. Study registration: The protocol of the review was registered in the OSF Registries on 13 January 2022 (doi: https://doi.org/10.17605/OSF.IO/46TEZ).

AMSTAR 2 is only partially applicable to systematic reviews of non-intervention studies: a meta-research study.

OBJECTIVES: A measurement tool to assess systematic reviews 2 (AMSTAR 2) was originally developed for systematic reviews (SRs) of health-care interventions. The aim of this study was to assess the applicability of AMSTAR 2 to SRs of non-intervention studies. STUDY DESIGN AND SETTING: This was a meta-research study. We used 20 SRs for each of the following four types of SRs: Diagnostic Test Accuracy reviews, Etiology and/or Risk reviews, Prevalence and/or Incidence reviews, and Prognostic reviews (80 in total). Three authors applied AMSTAR 2 independently to each included SRs. Then, the authors assessed the applicability of each item to that SR type and any SR type. RESULTS: Researchers unanimously indicated that 7 of 16 AMSTAR 2 items were applicable for all four specific SR types and any SR type (items 2, 5, 6, 7, 10, 14 and 16), but 8 of 16 items for any SR type. These items could cover generic SR methods that do not depend on a specific SR type. CONCLUSION: AMSTAR 2 is only partially applicable for non-intervention SRs. There is a need to adapt/extend AMSTAR 2 for SRs of non-intervention studies. Our study can help to further define generic methodological aspects shared across SR types and methodological expectations for non-intervention SRs.

Using evidence to decision frameworks led to guidelines of better quality and more credible and transparent recommendations.

BACKGROUND AND OBJECTIVES: To determine whether the use of Evidence to Decision (EtD) frameworks is associated to higher quality of both guidelines and individual recommendations. METHODS: We identified guidelines recently published by international organizations that have methodological guidance documents for their development. Pairs of researchers independently extracted information on the use of these frameworks, appraised the quality of the guidelines using the Appraisal of Guidelines, Research and Evaluation II Instrument (AGREE-II), and assessed the clinical credibility and implementability of the recommendations with the Appraisal of Guidelines for REsearch & Evaluation Recommendations Excellence (AGREE-REX) tool. We conducted both descriptive and inferential analyses. RESULTS: We included 66 guidelines from 17 different countries, published in the last 5 years. Thirty guidelines (45%) used an EtD framework to formulate their recommendations. Compared to those that did not use a framework, those using an EtD framework scored higher in all domains of both AGREE-II and AGREE-REX (P < 0.05). Quality scores did not differ between the use of the The Grading of Recommendations Assessment, Development and Evaluation-EtD framework (17 guidelines) or another EtD framework (13 guidelines) (P > 0.05). CONCLUSION: The use of EtD frameworks is associated with guidelines of better quality, and more credible and transparent recommendations. Endorsement of EtD frameworks by guideline developing organizations will likely increase the quality of their guidelines.

Saturated fat and human health: a protocol for a methodologically innovative systematic review and meta-analysis to inform public health nutrition guidelines.

BACKGROUND: The health effects of dietary fats are a controversial issue on which experts and authoritative organizations have often disagreed. Care providers, guideline developers, policy-makers, and researchers use systematic reviews to advise patients and members of the public on optimal dietary habits, and to formulate public health recommendations and policies. Existing reviews, however, have serious limitations that impede optimal dietary fat recommendations, such as a lack of focus on outcomes important to people, substantial risk of bias (RoB) issues, ignoring absolute estimates of effects together with comprehensive assessments of the certainty of the estimates for all outcomes. OBJECTIVE: We therefore propose a methodologically innovative systematic review using direct and indirect evidence on diet and food-based fats (i.e., reduction or replacement of saturated fat with monounsaturated or polyunsaturated fat, or carbohydrates or protein) and the risk of important health outcomes. METHODS: We will collaborate with an experienced research librarian to search MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR) for randomized clinical trials (RCTs) addressing saturated fat and our health outcomes of interest. In duplicate, we will screen, extract results from primary studies, assess their RoB, conduct de novo meta-analyses and/or network meta-analysis, assess the impact of missing outcome data on meta-analyses, present absolute effect estimates, and assess the certainty of evidence for each outcome using the GRADE contextualized approach. Our work will inform recommendations on saturated fat based on international standards for reporting systematic reviews and guidelines. CONCLUSION: Our systematic review and meta-analysis will provide the most comprehensive and rigorous summary of the evidence addressing the relationship between saturated fat modification for people-important health outcomes. The evidence from this review will be used to inform public health nutrition guidelines. TRIAL REGISTRATION: PROSPERO Registration: CRD42023387377 .