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1.
J Peripher Nerv Syst ; 28(4): 535-563, 2023 12.
Article in English | MEDLINE | ID: mdl-37814551

ABSTRACT

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.


Subject(s)
Guillain-Barre Syndrome , Respiratory Insufficiency , Humans , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/therapy , Immunoglobulins, Intravenous/therapeutic use , Peripheral Nerves , Pain , Respiratory Insufficiency/drug therapy , Adrenal Cortex Hormones
2.
Eur J Neurol ; 30(12): 3646-3674, 2023 12.
Article in English | MEDLINE | ID: mdl-37814552

ABSTRACT

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.


Subject(s)
Guillain-Barre Syndrome , Respiratory Insufficiency , Humans , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/therapy , Immunoglobulins, Intravenous/therapeutic use , Peripheral Nerves , Pain/drug therapy , Adrenal Cortex Hormones
3.
Pharmacoecon Open ; 7(5): 679-708, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37365482

ABSTRACT

BACKGROUND AND OBJECTIVE: Evidence-based guidelines on platelet transfusion therapy assist clinicians to optimize patient care, but currently do not take into account costs associated with different methods used during the preparation, storage, selection and dosing of platelets for transfusion. This systematic review aimed to summarize the available literature regarding the cost effectiveness (CE) of these methods. METHODS: Eight databases and registries, as well as 58 grey literature sources, were searched up to 29 October 2021 for full economic evaluations comparing the CE of methods for preparation, storage, selection and dosing of allogeneic platelets intended for transfusion in adults. Incremental CE ratios, expressed as standardized cost (in 2022 EUR) per quality-adjusted life-year (QALY) or per health outcome, were synthesized narratively. Studies were critically appraised using the Philips checklist. RESULTS: Fifteen full economic evaluations were identified. Eight investigated the costs and health consequences (transfusion-related events, bacterial and viral infections or illnesses) of pathogen reduction. The estimated incremental cost per QALY varied widely from EUR 259,614 to EUR 36,688,323. For other methods, such as pathogen testing/culturing, use of apheresis instead of whole blood-derived platelets, and storage in platelet additive solution, evidence was sparse. Overall, the quality and applicability of the included studies was limited. CONCLUSIONS: Our findings are of interest to decision makers who consider implementing pathogen reduction. For other preparation, storage, selection and dosing methods in platelet transfusion, CE remains unclear due to insufficient and outdated evaluations. Future high-quality research is needed to expand the evidence base and increase our confidence in the findings.

4.
Pharmacoeconomics ; 41(8): 869-911, 2023 08.
Article in English | MEDLINE | ID: mdl-37145291

ABSTRACT

OBJECTIVES: Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. METHODS: Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. RESULTS: Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). CONCLUSIONS: Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.


Subject(s)
Thrombocytopenia , Thrombopoietin , Adult , Humans , Thrombopoietin/therapeutic use , Cost-Benefit Analysis , Thrombocytopenia/drug therapy , Hemorrhage , Quality-Adjusted Life Years
5.
Vox Sang ; 118(1): 16-23, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36454598

ABSTRACT

BACKGROUND AND OBJECTIVES: Platelet transfusions are used across multiple patient populations to prevent and correct bleeding. This scoping review aimed to map the currently available systematic reviews (SRs) and evidence-based guidelines in the field of platelet transfusion. MATERIALS AND METHODS: A systematic literature search was conducted in seven databases for SRs on effectiveness (including dose and timing, transfusion trigger and ratio to other blood products), production modalities and decision support related to platelet transfusion. The following data were charted: methodological features of the SR, population, concept and context features, outcomes reported, study design and number of studies included. Results were synthesized in interactive evidence maps. RESULTS: We identified 110 SRs. The majority focused on clinical effectiveness, including prophylactic or therapeutic transfusions compared to no platelet transfusion (34 SRs), prophylactic compared to therapeutic-only transfusion (8 SRs), dose, timing (11 SRs) and threshold for platelet transfusion (15 SRs) and the ratio of platelet transfusion to other blood products in massive transfusion (14 SRs). Furthermore, we included 34 SRs on decision support, of which 26 evaluated viscoelastic testing. Finally, we identified 22 SRs on platelet production modalities, including derivation (4 SRs), pathogen inactivation (6 SRs), leucodepletion (4 SRs) and ABO/human leucocyte antigen matching (5 SRs). The SRs were mapped according to concept and clinical context. CONCLUSION: An interactive evidence map of SRs and evidence-based guidelines in the field of platelet transfusion has been developed and identified multiple reviews. This work serves as a tool for researchers looking for evidence gaps, thereby both supporting research and avoiding unnecessary duplication.


Subject(s)
Platelet Transfusion , Thrombocytopenia , Humans , Hemorrhage/therapy , Platelet Transfusion/methods , Thrombocytopenia/therapy
6.
Syst Rev ; 11(1): 224, 2022 10 17.
Article in English | MEDLINE | ID: mdl-36253838

ABSTRACT

BACKGROUND: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. RESULTS: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. CONCLUSIONS: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.


Subject(s)
Anemia , Hematinics , Adult , Anemia/drug therapy , Anemia/etiology , Elective Surgical Procedures/adverse effects , Erythropoiesis , Ferric Oxide, Saccharated/therapeutic use , Hematinics/adverse effects , Humans
7.
Simul Healthc ; 17(4): 213-219, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35921627

ABSTRACT

BACKGROUND: First aid training is a cost-effective way to improve public health, but the most effective methods to teach first aid are currently unclear. The aim of this research was to investigate the added value of simulated patients during first aid certification trainings. METHODS: Occupational first aid trainings organized by the Belgian Red Cross between September 2018 and August 2019 were allocated to either training with a simulated patient or regular training, for the topics "stroke" and "burns." Participants' knowledge and self-efficacy related to these topics were assessed at baseline, directly after training and after 1 year. First aid skills for "stroke" and "burns" and participant satisfaction were assessed after training. Knowledge and self-efficacy were measured via a questionnaire, and skills were assessed during a practical skills test. Data were analyzed using generalized linear mixed model analyses. RESULTS: A total of 1113 participants were enrolled, 403 in the simulated patient group and 710 in the control group. First aid knowledge and self-efficacy increased strongly immediately after training. These increases did not differ between groups, nor did the level of practical skills. The simulated patient group had a significantly increased retention in first aid knowledge after 1 year, compared with control, while retention in self-efficacy did not differ. Participant satisfaction with training was similar between groups. CONCLUSIONS: Using simulated patients during occupational first aid trainings for laypeople did not improve outcomes immediately after training but did improve retention of first aid knowledge after 1 year. These results support the use of simulated patients during first aid training.


Subject(s)
First Aid , Health Knowledge, Attitudes, Practice , Patient Simulation , Educational Measurement/statistics & numerical data , First Aid/methods , Humans , Self Efficacy , Surveys and Questionnaires
9.
J Med Libr Assoc ; 109(4): 599-608, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34858089

ABSTRACT

OBJECTIVE: The aim of this project was to validate search filters for systematic reviews, intervention studies, and observational studies translated from Ovid MEDLINE and Embase syntax and used for searches in PubMed and Embase.com during the development of evidence summaries supporting first aid guidelines. We aimed to achieve a balance among recall, specificity, precision, and number needed to read (NNR). METHODS: Reference gold standards were constructed per study type derived from existing evidence summaries. Search filter performance was assessed through retrospective searches and measurement of relative recall, specificity, precision, and NNR when using the translated search filters. Where necessary, search filters were optimized. Adapted filters were validated in separate validation gold standards. RESULTS: Search filters for systematic reviews and observational studies reached recall of ≥85% in both PubMed and Embase. Corresponding specificities for systematic review filters were ≥96% in both databases, with a precision of 9.7% (NNR 10) in PubMed and 5.4% (NNR 19) in Embase. For observational study filters, specificity, precision, and NNR were 68%, 2%, and 51 in PubMed and 47%, 0.8%, and 123 in Embase, respectively. These filters were considered sufficiently effective. Search filters for intervention studies reached a recall of 85% and 83% in PubMed and Embase, respectively. Optimization led to recall of ≥95% with specificity, precision, and NNR of 49%, 1.3%, and 79 in PubMed and 56%, 0.74%, and 136 in Embase, respectively. CONCLUSIONS: We report validated filters to search for systematic reviews, observational studies, and intervention studies in guideline projects in PubMed and Embase.com.


Subject(s)
First Aid , Databases, Bibliographic , MEDLINE , PubMed , Retrospective Studies , Systematic Reviews as Topic
10.
Pharmacoeconomics ; 39(10): 1123-1139, 2021 10.
Article in English | MEDLINE | ID: mdl-34235646

ABSTRACT

OBJECTIVES: For anaemic elective surgery patients, current clinical practice guidelines weakly recommend the routine use of iron, but not erythrocyte-stimulating agents (ESAs), except for short-acting ESAs in major orthopaedic surgery. This recommendation is, however, not based on any cost-effectiveness studies. The aim of this research was to (1) systematically review the literature regarding cost effectiveness of preoperative iron and/or ESAs in anaemic, elective surgery patients and (2) update existing economic evaluations (EEs) with recent data. METHODS: Eight databases and registries were searched for EEs and randomized controlled trials (RCTs) reporting cost-effectiveness data on November 11, 2020. Data were extracted, narratively synthesized and critically appraised using the Philips reporting checklist. Pre-existing full EEs were updated with effectiveness data from a recent systematic review and current cost data. Incremental cost-effectiveness ratios were expressed as cost per (quality-adjusted) life-year [(QA)LY] gained. RESULTS: Only five studies (4 EEs and 1 RCT) were included, one on intravenous iron and four on ESAs + oral iron. The EE on intravenous iron only had an in-hospital time horizon. Therefore, cost effectiveness of preoperative iron remains uncertain. The three EEs on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD). CONCLUSIONS: Cost effectiveness of preoperative iron is unproven, whereas routine preoperative ESA therapy cannot be considered cost effective in elective surgery, based on the limited available data. Future guidelines should reflect these findings.


Subject(s)
Hematinics , Cost-Benefit Analysis , Erythropoiesis , Hematinics/therapeutic use , Humans , Iron , Quality-Adjusted Life Years
11.
Eur J Neurol ; 28(11): 3556-3583, 2021 11.
Article in English | MEDLINE | ID: mdl-34327760

ABSTRACT

OBJECTIVE: To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). RESULTS: Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).


Subject(s)
Neurology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Humans , Immunoglobulins, Intravenous/therapeutic use , Peripheral Nerves , Plasma Exchange , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy
12.
J Peripher Nerv Syst ; 26(3): 242-268, 2021 09.
Article in English | MEDLINE | ID: mdl-34085743

ABSTRACT

To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).


Subject(s)
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Adrenal Cortex Hormones , Humans , Immunoglobulins, Intravenous/therapeutic use , Neurology , Peripheral Nerves , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy
13.
Transfus Med Rev ; 35(2): 103-124, 2021 04.
Article in English | MEDLINE | ID: mdl-33965294

ABSTRACT

Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).


Subject(s)
Anemia , Hematinics , Anemia/drug therapy , Dietary Supplements , Erythrocytes , Erythropoiesis , Hematinics/therapeutic use , Humans , Iron
14.
Cureus ; 12(11): e11386, 2020 Nov 08.
Article in English | MEDLINE | ID: mdl-33312787

ABSTRACT

Aim To perform a systematic review of the literature on the effectiveness of existing stroke recognition scales used in a prehospital setting and suitable for use by first aid providers. The systematic review will be used to inform an update of international first aid guidelines. Methods We followed the Cochrane Handbook for Systematic Reviews of Interventions methodology and report results according to PRISMA guidelines. We searched Medline, Embase and CENTRAL on May 25, 2020 for studies of stroke recognition scales used by first aid providers, paramedics and nurses for adults with suspected acute stroke in a prehospital setting. Outcomes included change in time to treatment, initial recognition of stroke, survival and discharge with favorable neurologic status, and increased layperson recognition of the signs of stroke. Two investigators reviewed abstracts, extracted and assessed the data for risk of bias. The certainty of evidence was evaluated using GRADE methodology. Results We included 24 observational studies with 10,446 patients evaluating 10 stroke scales (SS). All evidence was of moderate to very low certainty. Use of the Kurashiki Prehospital SS (KPSS), Ontario Prehospital SS (OPSS) and Face Arm Speech Time SS (FAST) was associated with an increased number of suspected stroke patients arriving to a hospital within three hours and, for OPSS, a higher rate of thrombolytic therapy. The KPSS was associated with a decreased time from symptom onset to hospital arrival. Use of FAST Emergency Response (FASTER) was associated with decreased time from door to tomography and from symptom onset to treatment. The Los Angeles Prehospital Stroke Scale (LAPSS) was associated with an increased number of correct initial diagnoses. Meta-analysis found the summary estimate sensitivity of four scales ranged from 0.78 to 0.86. The FAST and Cincinnati Prehospital Stroke Scale (CPSS) were found to have a summary estimated sensitivity of 0.86, 95% CI [0.69-0.94] and 0.81, 95% CI [0.70-0.89], respectively. Conclusion Stroke recognition scales used in the prehospital first aid setting improves the recognition and diagnosis of stroke, thereby aiding the emergency services to triage stroke victims directly down an appropriate stroke care pathway. Of those prehospital scales evaluated by more than a single study, FAST and Melbourne Ambulance Stroke Screen (MASS) were found to be the most sensitive for stroke recognition, while the CPSS had higher specificity. When blood glucose cannot be measured, the simplicity of FAST and CPSS makes these particular stroke scales appropriate for non-medical first aid providers.

15.
Vox Sang ; 115(2): 107-123, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31823386

ABSTRACT

BACKGROUND AND OBJECTIVES: The donor medical questionnaire is designed to aid blood establishments in supporting a safe blood supply. According to blood donor deferral policies, sexual risk behaviour (SRB) leads to a (temporary) deferral from blood donation. This systematic review aimed to scientifically underpin these policies by identifying the best available evidence on the association between SRB and the risk of transfusion transmissible infections (TTIs). MATERIALS & METHODS: Studies from three databases investigating the link between SRB (excluding men who have sex with men (MSM)) and TTIs (HBV, HCV, HIV, Treponema pallidum) in donors from Western and Pacific countries were obtained and assessed on eligibility by two reviewers independently. The association between SRB and TTIs was expressed by calculating pooled effect measures via meta-analyses. The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 3750 references and finally included 15 observational studies. Meta-analyses showed that there is a significant (P < 0·05) positive association between the following SRB and HBV and/or HCV infection: having sex with an intravenous drug user (high-certainty evidence), receiving money or goods for sex (moderate-high certainty evidence), having a sex partner with hepatitis/HIV (moderate-certainty evidence) and paid for sex or anal sex (low-certainty evidence). CONCLUSION: Sexual risk behaviour (including having sex with an intravenous drug user, receiving money or goods for sex or having a sex partner with hepatitis/HIV) is probably associated with an increased risk of HBV/HCV infection in blood donors from Western and Pacific countries.


Subject(s)
Blood Donors/statistics & numerical data , HIV Infections/epidemiology , Hepatitis C/epidemiology , Substance Abuse, Intravenous/epidemiology , Transfusion Reaction/epidemiology , Unsafe Sex/statistics & numerical data , Adult , Humans , Male , Sexual and Gender Minorities/statistics & numerical data
16.
Vox Sang ; 114(4): 297-309, 2019 May.
Article in English | MEDLINE | ID: mdl-30972765

ABSTRACT

BACKGROUND AND OBJECTIVES: The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs). MATERIALS AND METHODS: Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5·28, 95% CI [4·33, 6·44], P < 0·00001 (low-quality evidence); acupuncture: pooled OR 1·56, 95% CI [1·17, 2·08], P = 0·03 (very low-quality evidence); and piercing: pooled OR 3·25, 95% CI [1·68, 6·30], P = 0·0005 (low-quality evidence)). CONCLUSION: Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion.


Subject(s)
Acupuncture Therapy/adverse effects , Blood Donors , Blood Safety/methods , Body Piercing/adverse effects , Donor Selection , Tattooing/adverse effects , Transfusion Reaction/prevention & control , Virus Diseases/transmission , Adolescent , Adult , Australia , Blood Banks , Blood Safety/adverse effects , Canada , Databases, Factual , Europe , Female , HIV Infections/etiology , HIV Infections/transmission , Humans , Male , Middle Aged , Observational Studies as Topic , Odds Ratio , Surveys and Questionnaires , Transfusion Reaction/diagnosis , Transfusion Reaction/etiology , United States , Young Adult
17.
Cochrane Database Syst Rev ; 3: CD012387, 2019 Mar 26.
Article in English | MEDLINE | ID: mdl-30909317

ABSTRACT

BACKGROUND: Receiving a diagnosis of cancer and the subsequent related treatments can have a significant impact on an individual's physical and psychosocial well-being. To ensure that cancer care addresses all aspects of well-being, systematic screening for distress and supportive care needs is recommended. Appropriate screening could help support the integration of psychosocial approaches in daily routines in order to achieve holistic cancer care and ensure that the specific care needs of people with cancer are met and that the organisation of such care is optimised. OBJECTIVES: To examine the effectiveness and safety of screening of psychosocial well-being and care needs of people with cancer. To explore the intervention characteristics that contribute to the effectiveness of these screening interventions. SEARCH METHODS: We searched five electronic databases in January 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL. We also searched five trial registers and screened the contents of relevant journals, citations, and references to find published and unpublished trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised controlled trials (NRCTs) that studied the effect of screening interventions addressing the psychosocial well-being and care needs of people with cancer compared to usual care. These screening interventions could involve self-reporting of people with a patient-reported outcome measures (PROMs) or a semi-structured interview with a screening interventionist, and comprise a solitary screening intervention or screening with guided actions. We excluded studies that evaluated screening integrated as an element in more complex interventions (e.g. therapy, coaching, full care pathways, or care programmes). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed methodological quality for each included study using the Cochrane tool for RCTs and the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool for NRCTs. Due to the high level of heterogeneity in the included studies, only three were included in meta-analysis. Results of the remaining 23 studies were analysed narratively. MAIN RESULTS: We included 26 studies (18 RCTs and 8 NRCTs) with sample sizes of 41 to 1012 participants, involving a total of 7654 adults with cancer. Two studies included only men or women; all other studies included both sexes. For most studies people with breast, lung, head and neck, colorectal, prostate cancer, or several of these diagnoses were included; some studies included people with a broader range of cancer diagnosis. Ten studies focused on a solitary screening intervention, while the remaining 16 studies evaluated a screening intervention combined with guided actions. A broad range of intervention instruments was used, and were described by study authors as a screening of health-related quality of life (HRQoL), distress screening, needs assessment, or assessment of biopsychosocial symptoms or overall well-being. In 13 studies, the screening was a self-reported questionnaire, while in the remaining 13 studies an interventionist conducted the screening by interview or paper-pencil assessment. The interventional screenings in the studies were applied 1 to 12 times, without follow-up or from 4 weeks to 18 months after the first interventional screening. We assessed risk of bias as high for eight RCTs, low for five RCTs, and unclear for the five remaining RCTs. There were further concerns about the NRCTs (1 = critical risk study; 6 = serious risk studies; 1 = risk unclear).Due to considerable heterogeneity in several intervention and study characteristics, we have reported the results narratively for the majority of the evidence.In the narrative synthesis of all included studies, we found very low-certainty evidence for the effect of screening on HRQoL (20 studies). Of these studies, eight found beneficial effects of screening for several subdomains of HRQoL, and 10 found no effects of screening. One study found adverse effects, and the last study did not report quantitative results. We found very low-certainty evidence for the effect of screening on distress (16 studies). Of these studies, two found beneficial effects of screening, and 14 found no effects of screening. We judged the overall certainty of the evidence for the effect of screening on HRQoL to be very low. We found very low-certainty evidence for the effect of screening on care needs (seven studies). Of these studies, three found beneficial effects of screening for several subdomains of care needs, and two found no effects of screening. One study found adverse effects, and the last study did not report quantitative results. We judged the overall level of evidence for the effect of screening on HRQoL to be very low. None of the studies specifically evaluated or reported adverse effects of screening. However, three studies reported unfavourable effects of screening, including lower QoL, more unmet needs, and lower satisfaction.Three studies could be included in a meta-analysis. The meta-analysis revealed no beneficial effect of the screening intervention on people with cancer HRQoL (mean difference (MD) 1.65, 95% confidence interval (CI) -4.83 to 8.12, 2 RCTs, 6 months follow-up); distress (MD 0.0, 95% CI -0.36 to 0.36, 1 RCT, 3 months follow-up); or care needs (MD 2.32, 95% CI -7.49 to 12.14, 2 RCTs, 3 months follow-up). However, these studies all evaluated one specific screening intervention (CONNECT) in people with colorectal cancer.In the studies where some effects could be identified, no recurring relationships were found between intervention characteristics and the effectiveness of screening interventions. AUTHORS' CONCLUSIONS: We found low-certainty evidence that does not support the effectiveness of screening of psychosocial well-being and care needs in people with cancer. Studies were heterogeneous in population, intervention, and outcome assessment.The results of this review suggest a need for more uniformity in outcomes and reporting; for the use of intervention description guidelines; for further improvement of methodological certainty in studies and for combining subjective patient-reported outcomes with objective outcomes.


Subject(s)
Mental Health , Needs Assessment , Neoplasms/psychology , Quality of Life , Female , Humans , Male , Neoplasms/diagnosis , Non-Randomized Controlled Trials as Topic , Randomized Controlled Trials as Topic , Stress, Psychological/diagnosis
18.
PLoS One ; 14(2): e0212012, 2019.
Article in English | MEDLINE | ID: mdl-30818337

ABSTRACT

AIMS: To summarize the best available evidence on the effectiveness of physical counterpressure manoeuvers (PCM) for vasovagal syncope management compared to a control intervention. Control interventions included either a PCM, no intervention, or other interventions feasible in a lay setting. METHODS: A systematic literature search (March 21st 2018) was performed in the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. PCM were subdivided into 1) PCM decreasing orthostatic load (PCMOL), 2) PCM shortening the hydrostatic column between heart and brain (PCMHC), 3) PCM using mechanical compression of the veins (PCMMC). The primary outcome was syncope, secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR). When possible, a random effects meta-analysis was performed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes, and mean differences (MD) or standardized mean differences (SMD) were calculated for continuous outcomes. Heterogeneity was assessed by means of the I2 statistic. The total body of evidence was evaluated by means of the GRADE methodology. RESULTS: Eleven trials involving 688 people with vasovagal syncope were included. Risk of bias was high in all included studies. The total body of evidence (GRADE) was considered to be low or very low. PCM were found to improve syncope as compared to control (OR: 0.52, 95% CI [0.33;0.81], p = 0.004). Similarly, before-and-after studies without a control group showed a significant reduction in syncope following PCM (OR: 0.01, 95%CI [0.00;0.01], p<0.001). No studies investigated PCMOL. PCMHC increased SBP, DBP, MAP, SV, and CO, and decreased HR. PCMMC increased SBP, DBP, and MAP. CONCLUSION: PCM may reduce syncope and increase SBP, DBP, and MAP. The effects on other outcomes are less clear. Additional high-quality studies are needed.


Subject(s)
Motor Activity/physiology , Syncope, Vasovagal/prevention & control , Bias , Blood Pressure , Female , Humans , Male , Non-Randomized Controlled Trials as Topic , Randomized Controlled Trials as Topic , Syncope, Vasovagal/physiopathology , Treatment Outcome
19.
Clin Toxicol (Phila) ; 57(7): 603-616, 2019 07.
Article in English | MEDLINE | ID: mdl-30784327

ABSTRACT

Introduction: In acute oral poisoning, any first aid intervention that limits or delays the uptake of the ingested substance, and which can be performed by bystanders as first responders, might assist in reducing morbidity if a toxic substance has been ingested. The current recommendation by the International Federation of Red Cross/Red Crescent Societies is to place a victim in the left lateral decubitus position. Objective: The aim of this PRISMA compliant systematic review is to assess whether the current recommendation by the International Federation of Red Cross/Red Crescent Societies decreases or delays the absorption of an orally ingested poison. Methods: The Cochrane Library, MEDLINE, Embase, CINAHL and ISI Web of Science were searched in April 2018 for (quasi) randomized controlled trials investigating different body positions that are feasible in a pre-hospital setting by non-healthcare professionals. Data concerning study identification, study design, population, intervention and comparison, outcome measures and study quality were independently extracted and tabulated from the included studies by two reviewers, using a standardized and piloted data extraction form. The same two authors assessed the risk of bias in the included studies independently, using Cochrane's tool for assessing risk of bias. The GRADE approach was used to judge the certainty of evidence. Results: A total of 4991 citations were identified. After removal of 1313 duplicates, the titles and abstracts of 3678 references were screened using the predefined selection criteria. This screening yielded 35 potentially relevant articles which were assessed for eligibility using their full text. Twenty-four papers were excluded as they did not meet the selection criteria; nine studies reported in 10 papers were included with a total of 72 participants. All selected studies were performed in a controlled setting using healthy volunteers in a cross-over design. No studies involved poisoned patients. In four studies, the participants ingested paracetamol as a test drug. In five other studies, the following pharmaceuticals were ingested: sodium salicylate, midazolam, nifedipine combined with paracetamol, amoxicillin or slow release theophylline. Drugs were ingested after a period of fasting which varied between 2 h and 9 h. Different body positions were tested: left lateral position, right lateral position, bed rest during the day, supine position, prone position or upright position, standing or remaining ambulatory. In two studies, it was shown that the left lateral position (with or without 20% head down tilt) resulted in a statistically significant decrease of paracetamol AUC and Cmax compared to the right lateral position (with or without 20% head up tilt), sitting and prone position. In two further studies, a statistically significant difference in paracetamol AUC and Cmax between bed rest or the left lateral position and ambulation could not be demonstrated. In another study, it was shown that lying on the left side resulted in a statistically significant decrease of nifedipine and its nitropyridine metabolite AUC and Cmax, and a statistically significant increase of paracetamol, nifedipine and nitropyridine metabolite Tmax compared to lying on the right side or standing. One study looked at the effect of remaining strictly supine compared to remaining ambulant on the uptake of oral midazolam 15 mg. It was shown that remaining strictly supine resulted in a statistically significant decrease of Cmax compared to remaining ambulant. Overall, evidence was of very low certainty due to limitations in study design, imprecision due to limited sample size and lack of data and indirectness. Conclusions: The identified studies provide evidence of very low certainty. However, based on the evidence that the left lateral decubitus position may be effective in decreasing the absorption of several drugs, the simplicity of the intervention and the generally low perceived risk of this intervention, the recommendation of the first aid guidelines of the International Federation of Red Cross and Red Crescent Societies can remain unchanged.


Subject(s)
First Aid/methods , Patient Positioning , Poisoning/therapy , Humans , Randomized Controlled Trials as Topic
20.
Cochrane Database Syst Rev ; 12: CD013230, 2018 12 19.
Article in English | MEDLINE | ID: mdl-30565220

ABSTRACT

BACKGROUND: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives. OBJECTIVES: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 11 May 2017, and we also carried out reference checking and citation searching. SELECTION CRITERIA: We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre-hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission. MAIN RESULTS: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Eighteen trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.First aid interventions that limit or delay the absorption of the poison in the bodyWe are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) -0.15, 95% CI -0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.First aid interventions that evacuate the poison from the gastrointestinal tractWe found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.No studies used cathartics as an individual intervention.First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.The review also considered combinations of different first aid interventions. AUTHORS' CONCLUSIONS: The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.


Subject(s)
First Aid/methods , Poisoning/therapy , Acetaminophen/poisoning , Analgesics, Non-Narcotic/poisoning , Antidepressive Agents/poisoning , Antidotes/therapeutic use , Benzodiazepines/poisoning , Carbamazepine/poisoning , Cathartics/therapeutic use , Charcoal/therapeutic use , Fruit/poisoning , Humans , Ipecac/therapeutic use , Poisoning/etiology , Publication Bias , Randomized Controlled Trials as Topic , Thevetia/poisoning
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