A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively, compared with no use of tobacco.

The main objective of this systematic review was to assess cancer risk, and mortality after cancer diagnosis, for exclusive users of Swedish snus, compared with non-users of tobacco. We followed international standards for systematic reviews and graded our confidence in the risk estimates using the GRADE approach. Our search gave 2450 articles, of which 67 were assessed in full text against our inclusion criteria. Of these, 14 cohort-studies and one case-control study were included in the review. The studies investigated risk of cancer in the oral cavity or oropharynx (3 studies), esophagus (1 study), stomach (1 study), pancreas (2 studies), colorectum (2 studies), anus (1 study) and lung (1 study), as well as malignant lymphoma (1 study), leukemia and multiple myeloma (1 study), melanoma (1 study), any cancer (1 study) and mortality after cancer diagnosis (4 studies). Cancer risk could only be evaluated in men as there was a general lack of data for women. All included studies were evaluated to have a moderate risk of bias, mostly related to validity of exposure information. An increased risk of cancer of the esophagus, pancreas, stomach and rectum as well as an association between use of snus and increased mortality after a cancer diagnosis was reported. Our confidence in the various risk estimates varied from moderate through low to very low.

An evaluation of the COVID-19 recommendation map identified diverging clinical and public health guidance.

OBJECTIVES: To describe divergence between actionable statements issued by coronavirus disease 2019 (COVID-19) guideline developers cataloged on the "COVID-19 Recommendations and Gateway to Contextualization" platform. STUDY DESIGN AND SETTING: We defined divergence as at least two comparable actionable statements with different explicit judgments of strength, direction, or subgroup consideration of the population or intervention. We applied a content analysis to compare guideline development methods for a sample of diverging statements and to evaluate factors associated with divergence. RESULTS: Of the 138 guidelines evaluated, 85 (62%) contained at least one statement that diverged from another guideline. We identified 223 diverging statements in these 85 guidelines. We grouped statements into 66 clusters. Each cluster addressed the same population, intervention, and comparator group or just similar interventions. Clinical practice statements were more likely to diverge in an explicit judgment of strength or direction compared to public health statements. Statements were more likely to diverge in strength than direction. The date of publication, used evidence, interpretation of evidence, and contextualization considerations were associated with divergence. CONCLUSION: More than half of the assessed guidelines issued at least one diverging statement. This study helps in understanding the types of differences between guidelines issuing comparable statements and factors associated with their divergence.

Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review.

INTRODUCTION: Acute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies. METHODS: The PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method. RESULTS: A total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine. CONCLUSIONS: Available evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.

Ketamine for the treatment of prehospital acute pain: a systematic review of benefit and harm.

BACKGROUND: Few publications have addressed prehospital use of ketamine in analgesic doses. We aimed to assess the effect and safety profile of ketamine compared with other analgesic drugs (or no drug) in adult prehospital patients with acute pain. METHODS: A systematic review of clinical trials assessing prehospital administration of ketamine in analgesic doses compared with other analgesic drugs or no analgesic treatment in adults. We searched PubMed, EMBASE, Cochrane Library and Epistemonikos from inception until 15 February 2020, including relevant articles in English and Nordic languages. We used the Cochrane and Grading of Recommendations Assessment, Development and Evaluation methodologies and exclusively assessed patient-centred outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias. RESULTS: We included eight studies (2760 patients). Ketamine was compared with various opioids given alone, and intranasal ketamine given with nitrous oxide was compared with nitrous oxide given alone. Four randomised controlled trials (RCTs) and one cluster randomised trial included 699 patients. One prospective cohort included 27 patients and two retrospective cohorts included 2034 patients. Five of the eight studies had high risks of bias. Pain score with ketamine is probably lower than after opioids as demonstrated in a cluster-RCT (308 patients) and a retrospective cohort (158 patients) study, Δvisual analogue scale -0.4 (-0.8 to 0.0) and Δnumeric pain rating scale -3.0 (-3.86 to -2.14), respectively. Ketamine probably leads to less nausea and vomiting (risk ratio (RR) 0.24 (0.11 to 0.52)) but more agitation (RR 7.81 (1.85 to 33)) than opioids. CONCLUSIONS: This systematic literature review finds that ketamine probably reduces pain more than opioids and with less nausea and vomiting but higher risk of agitation. Risk of bias in included studies is high. OTHER: Scandinavian society of anaesthesiology and intensive care medicine funded meetings and software. The Norwegian Air Ambulance Foundation funded publication. Otherwise this research received no grant from any agency in the public, commercial or not-for-profit sectors. PROSPERO REGISTRATION NUMBER: CRD42018114399.

The mental health impact of the covid-19 pandemic on healthcare workers, and interventions to help them: A rapid systematic review.

The covid-19 pandemic has heavily burdened healthcare systems throughout the world. We performed a rapid systematic review to identify, assess and summarize research on the mental health impact of the covid-19 pandemic on HCWs (healthcare workers). We utilized the Norwegian Institute of Public Health's Live map of covid-19 evidence on 11 May and included 59 studies. Six reported on implementing interventions, but none reported on effects of the interventions. HCWs reported low interest in professional help, and greater reliance on social support and contact. Exposure to covid-19 was the most commonly reported correlate of mental health problems, followed by female gender, and worry about infection or about infecting others. Social support correlated with less mental health problems. HCWs reported anxiety, depression, sleep problems, and distress during the covid-19 pandemic. We assessed the certainty of the estimates of prevalence of these symptoms as very low using GRADE. Most studies did not report comparative data on mental health symptoms before the pandemic or in the general population. There seems to be a mismatch between risk factors for adverse mental health outcomes among HCWs in the current pandemic, their needs and preferences, and the individual psychopathology focus of current interventions.

Are the health risks of moist oral snuff (snus) underestimated? / Er helserisikoen ved snus undervurdert?

The use of moist oral snuff (snus) has increased significantly, particularly among young adults who have not previously smoked. Snus increases the risk of cancer, cardiovascular disease, type-2 diabetes and birth defects.

Age assessment by Demirjian's development stages of the third molar: a systematic review.

OBJECTIVES: Radiographic evaluation of the wisdom teeth (third molar) formation is a widely used age assessment method for adolescents and young adults. This systematic review examines evidence on the agreement between Demirjian's development stages of the third molar and chronological age. METHODS: We searched four databases up until May 2016 for studies reporting Demirjian's stages of third molar and confirmed chronological age of healthy individuals aged 10-25 years. Heterogeneity test of the included studies was performed. RESULTS: We included 21 studies from all continents except Australia, all published after 2005. The mean chronological age for Demirjian's stages varied considerably between studies. The results from most studies were affected by age mimicry bias. Only a few of the studies based their results on an unbiased age structure, which we argue as important to provide an adequate description of the method's ability to estimate age. CONCLUSION: Observed study variation in the timing of Demirjian's development stages for third molars has often been interpreted as differences between populations and ethnicities. However, we consider age mimicry to be a dominant bias in these studies. Hence, the scientific evidence is insufficient to conclude whether such differences exist. KEY POINTS: • There is significant heterogeneity between studies evaluating age assessment by Demirjian's third molar development. • Most of the studies were subject to the selection bias age mimicry which can be a source of heterogeneity. • Presence of age mimicry bias makes it impossible to compare and combine results. These biased studies should not be applied as reference studies for age assessment.

A systematic review of the agreement between chronological age and skeletal age based on the Greulich and Pyle atlas.

OBJECTIVES: This systematic review examines the agreement between assessed skeletal age by the Greulich and Pyle atlas (GP skeletal age) and chronological age. METHODS: We searched electronic databases until January 2017 for studies reporting GP skeletal age and confirmed chronological age in healthy individuals aged 10-25 years. Results are presented as forest plots and meta-analyses (random-effects models). RESULTS: In separate meta-analyses for each age group and sex (14-18 years for girls, 14-19 years for boys), the pooled mean differences between GP skeletal age and chronological age varied from -0.52 years to 0.47 years. In individual studies, age group and sex-specific mean differences between GP skeletal age and chronological age rarely exceeded 1 year, but between-study heterogeneities were large in most age groups. Few studies examined mean chronological age and distribution for each GP skeletal age. One study of good methodological quality indicates that 95% prediction intervals for chronological age from given GP skeletal ages are typically around 4 years. CONCLUSIONS: There is still good correlation between GP skeletal age and mean chronological age in modern populations. However, the individual variation of development within a population and heterogeneities between studies are substantial. KEY POINTS: • The GP atlas still corresponds well with mean chronological age in modern populations. • The substantial variation within a population must be considered. • The heterogeneity between studies is relatively large and of unknown origin.

Very early mobilisation in cases of acute stroke. / Veldig tidlig mobilisering ved akutt hjerneslag.

BACKGROUND: Since the first stroke units were established in the 1990s, early mobilisation has formed a key part of the acute treatment. In the context of an updating of national clinical guidelines for stroke, the Norwegian Directorate of Health commissioned the Institute of Public Health to prepare a systematic review of the efficacy and safety of very early mobilisation (within 24 hours) after stroke, compared with current practice, which is early mobilisation (within 48 hours). MATERIAL AND METHOD: We have written a systematic review based on a previous review from the Cochrane Collaboration published in 2009. We performed literature searches for randomised controlled studies in MEDLINE, EMBASE and CENTRAL. RESULTS: Three randomised controlled studies were included. Very early mobilisation showed no statistically significant difference in mortality or functional level compared with early mobilisation. We have very little confidence in the results and are therefore uncertain of the efficacy of the intervention. Very early mobilisation, when prolonged and given regularly, can most likely result in increased mortality and poorer functional level. INTERPRETATION: Early mobilisation is useful for many patients, but very early mobilisation, when frequent and prolonged, may also cause injury. Based on current research, we are uncertain of the optimal time to initiate mobilisation after stroke.

Hypotheses and evidence related to intense sweeteners and effects on appetite and body weight changes: A scoping review of reviews.

Observed associations between consumption of diet foods and obesity have sparked controversy over whether intense sweeteners may promote weight gain, despite their negligible energy contribution. We conducted a scoping review of reviews, to obtain an overview of hypotheses, research approaches and features of the evidence on intense sweeteners' potential relationships to appetite and weight changes. We searched for reviews of the scientific literature published from 2006 to May 2017. Two reviewers independently assessed title and abstracts, and full text publications. Arksey and O'Malley's framework for scoping reviews guided the process. We extracted and charted data on characteristics of the reviews and the evidence presented. The 40 included reviews present hypotheses both on how intense sweeteners can reduce or maintain body weight and on how these can promote weight gain. We classified only five publications as systematic reviews; another nine presented some systematic approaches, while 26 reviews did not describe criteria for selecting or assessing the primary studies. Evidence was often presented for intense sweeteners as a group or unspecified, and against several comparators (e.g. sugar, water, placebo, intake levels) with limited discussion on the interpretation of different combinations. Apart from the observational studies, the presented primary evidence in humans is dominated by small studies with short follow-up-considered insufficient to assess weight change. Systematic reviews of animal studies are lacking in this topic area. The systematic evidence only partly explore forwarded hypotheses found in the literature. Primary studies in humans seem to be available for systematic exploration of some hypotheses, but long-term experimental studies in humans appear sparse. With few exceptions, the reviews on intense sweeteners and weight change underuse systematic methodology, and thus, the available evidence. Further studies and systematic reviews should be explicit about the hypothesis explored and elucidate possible underlying mechanisms.

Emergency cricothyrotomy--a systematic review.

BACKGROUND: An emergency cricothyrotomy is the last-resort in most airway management protocols and is performed when it is not possible to intubate or ventilate a patient. This situation can rapidly prove fatal, making it important to identify the best method to establish a secure airway. We conducted a systematic review to identify whether there exists superiority between available commercial kits versus traditional surgical and needle techniques. METHODS: Medline, EMBASE and other databases were searched for pertinent studies. The inclusion criteria included manikin, animal and human studies and there were no restrictions regarding the professional background of the person performing the procedure. RESULTS: In total, 1,405 unique references were identified; 108 full text articles were retrieved; and 24 studies were included in the review. Studies comparing kits with one another or with various surgical and needle techniques were identified. The outcome measures included in this systematic review were success rate and time consumption. The investigators performing the studies had chosen unique combinations of starting and stopping points for time measurements, making comparisons between studies difficult and leading to many conflicting results. No single method was shown to be better than the others, but the size of the studies makes it impossible to draw firm conclusions. CONCLUSIONS: The large majority of the studies were too small to demonstrate statistically significant differences, and the limited available evidence was of low or very low quality. That none of the techniques in these studies demonstrated better results than the others does not necessarily indicate that each is equally good, and these conclusions will likely change as new evidence becomes available.

Triage systems for pre-hospital emergency medical services - a systematic review.

The emergency medical services (EMS) cover initiatives and services established to provide essential medical assistance in situations of acute illness. Triage-methods for systematic prioritizing of patients according to how urgent patients need care, including triage of requests of acute medical treatment, are adopted in hospitals as well as in the pre-hospital settings. This systematic review searched to identify available research on the effects of validated triage systems for use in the pre-hospital EMS on health outcomes, patient safety, patient satisfaction, user-friendliness, resource use, goal achievement, and the quality on the information exchange between the different settings of the EMS (for example the quality of documentation). The specific research questions were: 1) are pre-hospital triage systems effective, 2) is one triage system more effective than others, and 3) is it effective to use the same triage system in two or more settings of the EMS-chain? We conducted a systematic literature search in nine databases up to June 2012. We searched for systematic reviews (SRs), randomized controlled trials (RCTs), non-randomized controlled trials (non-RCTs), controlled before and after studies (CBAs) and interrupted time series analyses (ITSs). Two persons independently reviewed titles and abstracts, and the same persons read all possibly relevant full text articles and rated the methodological quality where relevant. The literature search identified 11011 unique references. A total of 120 publications were read in full text. None of the identified articles fulfilled our inclusion criteria, thus our question on the effects of pre-hospital triage systems, if one system is better than other systems, and the question on effects of using the same triage system in two or more settings of the EMS, remain unanswered. We conclude that there is an evidence gap regarding the effects of pre-hospital triage systems and the effects of using the same triage system in two or more settings of the EMS. The finding does not mean that pre-hospital triage systems are ineffective, but that we lack knowledge about potential effects. When introducing a new assessment tool in the EMS, it is timely to conduct well-planned studies aimed to assess the effect.

Outcomes of patients who participate in randomized controlled trials compared to similar patients receiving similar interventions who do not participate.

BACKGROUND: Some people believe that patients who take part in randomised controlled trials (RCTs) face risks that they would not face if they opted for non-trial treatment. Others think that trial participation is beneficial and the best way to ensure access to the most up-to-date physicians and treatments. This is an updated version of the original Cochrane review published in Issue 1, 2005. OBJECTIVES: To assess the effects of patient participation in RCTs ('trial effects') independent both of the effects of the clinical treatments being compared ('treatment effects') and any differences between patients who participated in RCTs and those who did not. We aimed to compare similar patients receiving similar treatment inside and outside of RCTs. SEARCH STRATEGY: In March 2007, we searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, The Cochrane Methodology Register, SciSearch and PsycINFO for potentially relevant studies. Our search yielded 7586 new references. In addition, we reviewed the reference lists of relevant articles. SELECTION CRITERIA: Randomized studies and cohort studies with data on clinical outcomes of RCT participants and similar patients who received similar treatment outside of RCTs. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed studies for inclusion, assessed study quality and extracted data. MAIN RESULTS: We identified 30 new non-randomized cohort studies (45 comparisons): no new RCTs were found. This update now includes five RCTs (yielding 6 comparisons) and 80 non-randomized cohort studies (130 comparisons), with 86,640 patients treated in RCTs and 57,205 patients treated outside RCTs. In the randomised studies, patients were invited to participate in an RCT or not; these comparisons provided limited information because of small sample sizes (a total of 412 patients) and the nature of the questions they addressed. When the results of RCTs and non-randomized cohorts that reported dichotomous outcomes were combined, there were 98 comparisons; there was also heterogeneity (P < 0.00001, I(2) = 42.2%) between studies. No statistical significant differences were found for 85 of the 98 comparisons. Eight comparisons reported statistically significant better outcomes for patients treated within RCTs, and five comparisons reported statistically significant worse outcomes for patients treated within RCTs. There was significant heterogeneity (P < 0.00001, I(2) = 58.2%) among the 38 continuous outcome comparisons. No statistically significant differences were found for 30 of the 38 comparisons. Three comparisons reported statistically significant better outcomes for patients treated within RCTs, and five comparisons reported statistically significant worse outcomes for patients treated within RCTs. AUTHORS' CONCLUSIONS: This review indicates that participation in RCTs is associated with similar outcomes to receiving the same treatment outside RCTs. These results challenge the assertion that the results of RCTs are not applicable to usual practice.

Systematic review to determine whether participation in a trial influences outcome.

OBJECTIVE: To systematically compare the outcomes of participants in randomised controlled trials (RCTs) with those in comparable non-participants who received the same or similar treatment. DATA SOURCES: Bibliographic databases, reference lists from eligible articles, medical journals, and study authors. REVIEW METHODS: RCTs and cohort studies that evaluated the clinical outcomes of participants in RCTs and comparable non-participants who received the same or similar treatment. RESULTS: Five RCTs (six comparisons) and 50 cohort studies (85 comparisons) provided data on 31,140 patients treated in RCTs and 20,380 comparable patients treated outside RCTs. In the five RCTs, in which patients were given the option of participating or not, the comparisons provided limited information because of small sample sizes (a total of 412 patients) and the nature of the questions considered. 73 dichotomous outcomes were compared, of which 59 reported no statistically significant differences. For patients treated within RCTs, 10 comparisons reported significantly better outcomes and four reported significantly worse outcomes. Significantly heterogeneity was found (I2 = 89%) among the comparisons of 73 dichotomous outcomes; none of our a priori explanatory factors helped explain this heterogeneity. The 18 comparisons of continuous outcomes showed no significant differences in heterogeneity (I2 = 0%). The overall pooled estimate for continuous outcomes of the effect of participating in an RCT was not significant (standardised mean difference 0.01, 95% confidence interval -0.10 to 0.12). CONCLUSION: No strong evidence was found of a harmful or beneficial effect of participating in RCTs compared with receiving the same or similar treatment outside such trials.