SAT0173 A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2019 UPDATE OF THE JOINT EUROPEAN LEAGUE AGAINST RHEUMATISM AND EUROPEAN RENAL ASSOCIATION–EUROPEAN DIALYSIS AND TRANSPLANT ASSOCIATION (EULAR/ERA-EDTA) RECOMMENDATIONS FOR THE MANAGEMENT OF LUPUS NEPHRITIS

Background:Lupus nephritis (LN) affects ~ 40% of patients with systemic lupus erythematosus (SLE) and is associated with significant morbidity. New data has emerged since the publication of the EULAR/ERA-EDTA recommendations for the management of LN, involving a multidisciplinary panel of experts.Objectives:To analyze the current evidence, in order to inform the 2019 update of the EULAR/ERA-EDTA recommendations for the management of LN.Methods:According to the EULAR standardised operating procedures, a Medline systematic literature review (SLR) was performed, from January 2012 until 31 December 2018. The final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including the LoE of the 2012 recommendations.Results:We identified 542 relevant articles. High-quality evidence supports the use of immunosuppressive treatment for class III and IV LN (LoE 1a) there is moderate quality evidence for immunosuppression in pure class V LN, with nephrotic-range proteinuria (LoE 2b). Treatment should aim for a 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (< 500-700 mg/day) at 12 months (LoE 2a-2b). Strong evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) for the initial treatment of class III/IV LN (LoE 1a,Table); Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a,Table). There is little evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease due to LN, all methods of kidney replacement treatment have been used, but transplantation is accompanied by the most favourable outcomes (LoE 2b).Table.Randomized trials for induction therapy in LNConclusion:There is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment. There is low quality evidence to guide treatment of class V, monitoring and optimal duration of immunosuppression.Disclosure of Interests: :Antonis Fanouriakis Paid instructor for: Paid instructor for Enorasis, Amgen, Speakers bureau: Paid speaker for Roche, Genesis Pharma, Mylan, Myrto Kostopoulou: None declared, Kim Cheema: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, Dimitrios Boumpas: None declared

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Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations

RMD Open ◽

10.1136/rmdopen-2020-001263 ◽

2020 ◽

Vol 6 (2) ◽

pp. e001263 ◽

Cited By ~ 1

Author(s):

Myrto Kostopoulou ◽

Antonis Fanouriakis ◽

Kim Cheema ◽

John Boletis ◽

George Bertsias ◽

...

Keyword(s):

Lupus Nephritis ◽

Literature Review ◽

Systematic Literature Review ◽

Immunosuppressive Treatment ◽

Class Iii ◽

High Quality ◽

Class V ◽

High Quality Evidence ◽

Optimal Duration ◽

Quality Evidence

ObjectivesTo analyse the current evidence for the management of lupus nephritis (LN) informing the 2019 update of the EULAR/European Renal Association-European Dialysis and Transplant Association recommendations.MethodsAccording to the EULAR standardised operating procedures, a PubMed systematic literature review was performed, from January 1, 2012 to December 31, 2018. Since this was an update of the 2012 recommendations, the final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including literature prior to 2012.ResultsWe identified 387 relevant articles. High-quality randomised evidence supports the use of immunosuppressive treatment for class III and class IV LN (LoE 1a), and moderate-level evidence supports the use of immunosuppressive treatment for pure class V LN with nephrotic-range proteinuria (LoE 2b). Treatment should aim for at least 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (<500–700 mg/day) at 12 months (LoE 2a-2b). High-quality evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) as initial treatment of active class III/IV LN (LoE 1a). Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a). There is low-quality level evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease, all methods of kidney replacement treatment can be used, with transplantation having the most favourable outcomes (LoE 2b).ConclusionsThere is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment, but low-to-moderate quality evidence to guide treatment of class V LN, monitoring and optimal duration of immunosuppression.

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Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2021

Endoscopy ◽

10.1055/a-1369-5274 ◽

2021 ◽

Vol 53 (03) ◽

pp. 300-332

Author(s):

Ian M. Gralnek ◽

Adrian J. Stanley ◽

A. John Morris ◽

Marine Camus ◽

James Lau ◽

...

Keyword(s):

High Dose ◽

High Quality ◽

Peptic Ulcer Hemorrhage ◽

Strong Recommendation ◽

Epinephrine Injection ◽

Moderate Quality ◽

High Quality Evidence ◽

Mechanical Therapy ◽

Upper Gastrointestinal ◽

Quality Evidence

MAIN RECOMMENDATIONS 1 ESGE recommends in patients with acute upper gastrointestinal hemorrhage (UGIH) the use of the Glasgow–Blatchford Score (GBS) for pre-endoscopy risk stratification. Patients with GBS ≤ 1 are at very low risk of rebleeding, mortality within 30 days, or needing hospital-based intervention and can be safely managed as outpatients with outpatient endoscopy.Strong recommendation, moderate quality evidence. 2 ESGE recommends that in patients with acute UGIH who are taking low-dose aspirin as monotherapy for secondary cardiovascular prophylaxis, aspirin should not be interrupted. If for any reason it is interrupted, aspirin should be re-started as soon as possible, preferably within 3–5 days.Strong recommendation, moderate quality evidence. 3 ESGE recommends that following hemodynamic resuscitation, early (≤ 24 hours) upper gastrointestinal (GI) endoscopy should be performed. Strong recommendation, high quality evidence. 4 ESGE does not recommend urgent (≤ 12 hours) upper GI endoscopy since as compared to early endoscopy, patient outcomes are not improved. Strong recommendation, high quality evidence. 5 ESGE recommends for patients with actively bleeding ulcers (FIa, FIb), combination therapy using epinephrine injection plus a second hemostasis modality (contact thermal or mechanical therapy). Strong recommendation, high quality evidence. 6 ESGE recommends for patients with an ulcer with a nonbleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy, or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, high quality evidence. 7 ESGE suggests that in patients with persistent bleeding refractory to standard hemostasis modalities, the use of a topical hemostatic spray/powder or cap-mounted clip should be considered. Weak recommendation, low quality evidence. 8 ESGE recommends that for patients with clinical evidence of recurrent peptic ulcer hemorrhage, use of a cap-mounted clip should be considered. In the case of failure of this second attempt at endoscopic hemostasis, transcatheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is not locally available or after failed TAE. Strong recommendation, moderate quality evidence. 9 ESGE recommends high dose proton pump inhibitor (PPI) therapy for patients who receive endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endoscopically. (a) PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g., 80 mg then 8 mg/hour) for 72 hours post endoscopy. (b) High dose PPI therapies given as intravenous bolus dosing (twice-daily) or in oral formulation (twice-daily) can be considered as alternative regimens.Strong recommendation, high quality evidence. 10 ESGE recommends that in patients who require ongoing anticoagulation therapy following acute NVUGIH (e. g., peptic ulcer hemorrhage), anticoagulation should be resumed as soon as the bleeding has been controlled, preferably within or soon after 7 days of the bleeding event, based on thromboembolic risk. The rapid onset of action of direct oral anticoagulants (DOACS), as compared to vitamin K antagonists (VKAs), must be considered in this context.Strong recommendation, low quality evidence.

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Working towards evidence-informed policy: Public health report Stockholm

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1224 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

V Bartelink ◽

D Yacaman Mendez ◽

A Lager

Keyword(s):

Public Health ◽

Resource Allocation ◽

Scientific Literature ◽

Decision Makers ◽

High Quality ◽

Public Health Report ◽

The Public ◽

Health Report ◽

High Quality Evidence ◽

Quality Evidence

Abstract Issue Public health problems and interventions are often addressed in sub-optimal ways by not prioritizing them based on the best available evidence. Description of the Problem The public health report 2019 for the Stockholm region aims to inform decision makers, politicians, and public health workers about the risk factors and diseases that account for the biggest part of the burden of disease with a clear focus on high quality evidence and communication of main messages. How did the public health report 2019 affect public health policy in the Stockholm region? Results The public health report 2019 influenced agenda setting, resource allocation and priority setting in the Stockholm region. Lessons We identified the following facilitating factors in the process, of which most also are supported in scientific literature, in chronological order: 1) understanding the policymaking context to be aware of windows of opportunity, 2) establishing relationships with relevant policymakers, engage with them routinely in the decision-making process, and being accessible for questions, 3) doing high-quality research by considering the latest scientific literature, multiple data sources and involving academic experts in the field, 4) communicating clear and relevant messages for generalists by translating research into easy-understandable texts and attractive figures, and 5) active dissemination of the report through multiple channels. In addition, the following barriers were identified: 1) the timeframe of the policymaking process was not in line with the research process, and 2) involving politicians in an early stage can potentially harm the objectivity of research in media messages. Key messages By focussing on major problems, high quality evidence and clear messages a public health report can contribute to more evidence-informed policy making. Engaging decision makers in the process of public health reporting is critical for the impact on agenda setting, resource allocation, and priority setting.

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Measurement properties of patient-reported outcome measures (PROMs) in hyperhidrosis: a systematic review

Quality of Life Research ◽

10.1007/s11136-021-02958-3 ◽

2021 ◽

Author(s):

Michaela Gabes ◽

Helge Knüttel ◽

Gesina Kann ◽

Christina Tischer ◽

Christian J. Apfelbacher

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Measurement Properties ◽

High Quality ◽

High Quality Evidence ◽

Patient Reported ◽

Quality Evidence

Abstract Purpose To critically appraise, compare and summarize the quality of all existing PROMs that have been validated in hyperhidrosis to at least some extend by applying the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Thereby, we aim to give a recommendation for the use of PROMs in future clinical trials in hyperhidrosis. Methods We considered studies evaluating, describing or comparing measurement properties of PROMs as eligible. A systematic literature search in three big databases (MEDLINE, EMBASE and Web of Science) was performed. We assessed the methodological quality of each included study using the COSMIN Risk of Bias checklist. Furthermore, we applied predefined quality criteria for good measurement properties and finally, graded the quality of the evidence. Results Twenty-four articles reporting on 13 patient-reported outcome measures were included. Three instruments can be further recommended for use. They showed evidence for sufficient content validity and moderate- to high-quality evidence for sufficient internal consistency. The methodological assessment showed existing evidence gaps for eight other PROMs, which therefore require further validation studies to make an adequate decision on their recommendation. The Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) and the short-form health survey with 36 items (SF-36) were the only questionnaires not recommended for use in patients with hyperhidrosis due to moderate- to high-quality evidence for insufficient measurement properties. Conclusion Three PROMs, the Hyperhidrosis Quality of Life Index (HidroQoL), the Hyperhidrosis Questionnaire (HQ) and the Sweating Cognitions Inventory (SCI), can be recommended for use in future clinical trials in hyperhidrosis. Results obtained with these three instruments can be seen as trustworthy. Nevertheless, further validation of all three PROMs is desirable. Systematic review registration PROSPERO CRD42020170247

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Limited not lazy: a quasi-experimental secondary analysis of evidence quality evaluations by those who hold implausible beliefs

Cognitive Research Principles and Implications ◽

10.1186/s41235-020-00264-z ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Kristy A. Martire ◽

Bethany Growns ◽

Agnes S. Bali ◽

Bronte Montgomery-Farrer ◽

Stephanie Summersby ◽

...

Keyword(s):

Secondary Analysis ◽

Past Research ◽

Linear Mixed Effect Model ◽

High Quality ◽

Mixed Effect ◽

High Quality Evidence ◽

Effect Model ◽

Evidence Quality ◽

Quasi Experimental ◽

Quality Evidence

AbstractPast research suggests that an uncritical or ‘lazy’ style of evaluating evidence may play a role in the development and maintenance of implausible beliefs. We examine this possibility by using a quasi-experimental design to compare how low- and high-quality evidence is evaluated by those who do and do not endorse implausible claims. Seven studies conducted during 2019–2020 provided the data for this analysis (N = 746). Each of the seven primary studies presented participants with high- and/or low-quality evidence and measured implausible claim endorsement and evaluations of evidence persuasiveness (via credibility, value, and/or weight). A linear mixed-effect model was used to predict persuasiveness from the interaction between implausible claim endorsement and evidence quality. Our results showed that endorsers were significantly more persuaded by the evidence than non-endorsers, but both groups were significantly more persuaded by high-quality than low-quality evidence. The interaction between endorsement and evidence quality was not significant. These results suggest that the formation and maintenance of implausible beliefs by endorsers may result from less critical evidence evaluations rather than a failure to analyse. This is consistent with a limited rather than a lazy approach and suggests that interventions to develop analytical skill may be useful for minimising the effects of implausible claims.

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1468. Culture Conversion and Mortality in Patients With Mycobacterium abscessus (MAB) Lung Disease: A Systematic Literature Review

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1649 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S736-S736

Author(s):

Kevin L Winthrop ◽

Kevin C Mange ◽

Zhanna Jumadilova ◽

Kristan B Cline ◽

Patrick A Flume

Keyword(s):

Literature Review ◽

Lung Disease ◽

Systematic Literature Review ◽

Panel Member ◽

Cochrane Library ◽

Attributable Mortality ◽

Research Support ◽

Persistent Symptoms ◽

Conversion Rates ◽

Culture Conversion

Abstract Background Prognosis for patients with MAB lung disease is poor. We sought to examine the potential association between culture conversion and outcomes (progression, mortality) in patients with MAB lung disease. Methods English-language MAB lung disease studies with ≥ 10 patients and reporting mortality and/or microbiological outcomes were identified from Embase, PubMed, relevant congress abstracts, and the Cochrane Library (data cutoff, September 24, 2019) using the National Institute for Health and Clinical Excellence guidance for systematic literature reviews. Two independent reviewers screened 1,551 indexed records; relevant extracted data are expressed as population-weighted means. Results Mean all-cause mortality across 17 studies (N=1,291) was 12.1% (range, 3%–33%); mortality attributable to MAB lung disease was 7.6% (range, 0%–27%; N=526, 9 studies). Culture conversion across 44 studies (N=2,237) was 46.7% (range, 0%–98.6%), with higher rates reported for M. massiliense subspecies (76.9%; N=507,15 studies) than M. abscessus subspecies (35.8%; N=834,18 studies). No direct comparisons were made between mortality and culture conversion; in the 13 studies (N=1,202) that reported both outcomes there was a moderate correlation between increased rate of culture conversion and decreased MAB-attributable mortality (R2=0.60). The most common definition of progression (21 studies) was radiographic worsening supported by persistent symptoms and/or positive cultures. Across 8 studies (N=415) 57.8% patients had improvement while 35.2% progressed with treatment. A broad variance in treatment regimen and duration (range, 32 days to > 3 years) was observed. Limitations include a small number of studies, and inconsistency in methods and outcomes definitions. Conclusion In this systematic literature review, available data suggest that culture conversion was achieved in less than half of patients and was lower in patients with M. abscessus compared with M. massiliense. One third of patients had disease progression despite treatment. Some data suggest lower MAB-attributed mortality outcomes in studies with higher culture conversion rates, more evidence is needed to demonstrate a survival benefit associated with culture conversion. Disclosures Kevin L Winthrop, MD, MPH, Insmed Incorporated (Consultant, Grant/Research Support) Kevin C Mange, MD, MSCE, Insmed Incorporated (Employee) Zhanna Jumadilova, MD, Insmed Incorporated (Employee) Kristan B Cline, PhD, Insmed Incorporated (Employee) Patrick A Flume, MD, Insmed Incorporated (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)

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Surgery for Good Prognosis Breast Cancers

Current Breast Cancer Reports ◽

10.1007/s12609-021-00414-2 ◽

2021 ◽

Author(s):

Stuart A. McIntosh

Keyword(s):

Surgical Treatment ◽

Minimally Invasive ◽

Good Prognosis ◽

Surgical Approaches ◽

Breast Cancers ◽

Randomised Trials ◽

High Quality ◽

High Quality Evidence ◽

Small Breast ◽

Quality Evidence

Abstract Purpose of Review The introduction of mammographic screening programmes has resulted increasing numbers of women with small breast cancers with biologically favourable characteristics. Many of these cancers may represent overdiagnosis, with a resulting treatment burden for women and healthcare costs for providers. Here, current surgical approaches to the treatment of such tumours are reviewed, together with alternative approaches to their management. Recent Findings The surgical treatment of small, screen-detected breast cancers with biologically favourable characteristics has been extrapolated from the management of symptomatic breast cancers. There is no prospective randomised evidence for conventional open surgery compared with other approaches in this setting. A number of minimally invasive techniques, most notable vacuum-assisted excision, have been described for the management of these tumours, but at present, there is a lack of high-quality evidence to support their routine use. There are currently ongoing randomised trials evaluating risk-adapted surgical and minimally invasive approaches to the management of good prognosis disease. Summary It is possible that the surgical treatment of good prognosis screen-detected breast cancers may be de-escalated. However, high-quality evidence from ongoing prospective randomised trials will be required in order to change clinical practice.

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European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke

European Stroke Journal ◽

10.1177/2396987321989865 ◽

2021 ◽

pp. 239698732198986

Author(s):

Eivind Berge ◽

William Whiteley ◽

Heinrich Audebert ◽

Gian Marco De Marchis ◽

Ana Catarina Fonseca ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Clinical Decision Making ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis ◽

Late Time ◽

High Quality ◽

High Quality Evidence ◽

Consensus Statements ◽

Quality Evidence

Intravenous thrombolysis is the only approved systemic reperfusion treatment for patients with acute ischaemic stroke. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions with regard to intravenous thrombolysis for acute ischaemic stroke. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Expert consensus statements were provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high quality evidence to recommend intravenous thrombolysis with alteplase to improve functional outcome in patients with acute ischemic stroke within 4.5 h after symptom onset. We also found high quality evidence to recommend intravenous thrombolysis with alteplase in patients with acute ischaemic stroke on awakening from sleep, who were last seen well more than 4.5 h earlier, who have MRI DWI-FLAIR mismatch, and for whom mechanical thrombectomy is not planned. These guidelines provide further recommendations regarding patient subgroups, late time windows, imaging selection strategies, relative and absolute contraindications to alteplase, and tenecteplase. Intravenous thrombolysis remains a cornerstone of acute stroke management. Appropriate patient selection and timely treatment are crucial. Further randomized controlled clinical trials are needed to inform clinical decision-making with regard to tenecteplase and the use of intravenous thrombolysis before mechanical thrombectomy in patients with large vessel occlusion.

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Analysis Of Factors Influencing Acupuncture Clinical Effects: A Systematic Review

Acupuncture & Electro-Therapeutics Research ◽

10.3727/036012921x16321477053935 ◽

2021 ◽

Author(s):

Yali Liu ◽

Honglin Jiang ◽

Xiaotong Li ◽

Xingyue Yang

Keyword(s):

Systematic Review ◽

Individual Difference ◽

Current Status ◽

Clinical Effects ◽

High Quality ◽

Psychological States ◽

Factors Influencing ◽

High Quality Evidence ◽

Stimulus Parameters ◽

Quality Evidence

Background: Acupuncture therapy has been widely applied all around the world. But there still lacks high-quality evidence to evaluate its clinical effects, safety and cost-effectiveness, which seriously restricts its further promotion and development. Acupuncture, as an operational intervention, is more complex than drug therapy. Factors involved in the acupuncture operation process, such as individual and interventional factors, may affect clinical effects. Purpose:s Through this systematic review, we attempt to analyze the current status of studies about the key factors influencing clinical effects, so as to provide evidence for the design of acupuncture studies. Methods: A literature research was conducted in six databases until May, 2020. Studies were screened and assessed by two authors independently. Data extraction was made after screening. We extracted the basic information of these studies, including publishing years and countries, population and factors influencing clinical effects.Results: Through the initial search in these six database, 6404 records were retrieved. After duplication and screening, a total of 355 studies were finally included in the qualitative analysis. About 88.5% of these studies were conducted in China with increasing number in the past decades, covering neurological disorders, orthopedic disorders, obstetrical and gynecological diseases, digestive diseases and so on; 239 studies focused on stimulus parameters which may influence effects, accounting for 67.3%, and 128, 44, 39, 32, 15, 11 studies discussed acupoints, patients’ pathological states, individual difference, psychological states, deqi, and other factors separately. Conclusion: There are more and more studies focusing on factors influencing acupuncture clinical effects, including stimulus parameters, acupoints, individual difference, patient pathological and psychological states. Based on this systematic review, several ignored factors should be considered for future researches, and more scientifically and objectively high quality evidence should also be proved.

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Cannabis and breastfeeding

Paediatrics & Child Health ◽

10.1093/pch/pxaa037 ◽

2020 ◽

Vol 25 (Supplement_1) ◽

pp. S26-S28 ◽

Cited By ~ 1

Author(s):

Lisa Graves

Keyword(s):

Health Care Providers ◽

Small Sample ◽

Adverse Outcomes ◽

Care Providers ◽

High Quality ◽

High Quality Evidence ◽

Small Sample Sizes ◽

The Impact ◽

Quality Evidence

Abstract Cannabis is one of the most commonly used substances in Canada with 15% of Canadians reporting use in 2019. There is emerging evidence that cannabis is linked to an impact on the developing brain in utero and adverse outcomes in infants, children, and adolescents. The impact of cannabis during breastfeeding has been limited by studies with small sample sizes, follow-up limited to 1 year and the challenge of separating prenatal exposure from that during breastfeeding. In the absence of high-quality evidence, health care providers need to continue to engage women in conversation about the potential concerns related to breastfeeding and cannabis use.

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