scholarly journals Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: May 2021 Update

2021 ◽  
Author(s):  
Marian S. McDonagh ◽  
Jesse Wagner ◽  
Azrah Y. Ahmed ◽  
Benjamin Morasco ◽  
Devan Kansagara ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Pain ◽  
Adverse Events ◽  
Progress Report ◽  
Pain Severity ◽  
Short Term Treatment ◽  
Serious Adverse Events ◽  
Whole Plant ◽  
Increased Risk ◽  
The Impact

Overview This is the third quarterly progress report for an ongoing living systematic review on cannabis and other plant-based treatments for chronic pain. The first progress report was published in January 2021 and the second in March 2021. The draft systematic review was available for public comment from May 19 through June 15, 2021, on the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care website. The systematic review synthesizes evidence on the benefits and harms of plant-based compounds (PBCs), such as cannabinoids and kratom, used to treat chronic pain, addressing concerns about severe adverse effects, abuse, misuse, dependence, and addiction. The purpose of this progress report is to describe the cumulative literature identified thus far. This report will be periodically updated with new studies as they are published and identified, culminating in an annual systematic review that provides a synthesis of the accumulated evidence. Main Points In patients with chronic (mainly neuropathic) pain with short-term treatment (4 weeks to <6 months): • Studies of cannabis-related products were grouped based on their tetrahydrocannabinol (THC) to cannabidiol (CBD) ratio using the following categories: high THC to CBD, comparable THC to CBD, and low THC to CBD. • Comparable THC to CBD ratio oral spray is probably associated with small improvements in pain severity and may be associated with small improvements in function. There was no effect in pain interference or serious adverse events. There may be a large increased risk of dizziness and sedation, and a moderate increased risk of nausea. • Synthetic THC (high THC to CBD) may be associated with moderate improvement in pain severity and increased risk of sedation, and large increased risk of nausea. Synthetic THC is probably associated with a large increased risk of dizziness. • Extracted whole-plant high THC to CBD ratio products may be associated with large increases in risk of withdrawal due to adverse events and dizziness. • Evidence on whole-plant cannabis, low THC to CBD ratio products (topical CBD), other cannabinoids (cannabidivarin), and comparisons with other active interventions was insufficient to draw conclusions. • Other key adverse event outcomes (psychosis, cannabis use disorder, cognitive deficits) and outcomes on the impact on opioid use were not reported. • No evidence on other plant-based compounds, such as kratom, met criteria for this review.

scholarly journals Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

2021 ◽  
Author(s):  
Marian S. McDonagh ◽  
Jesse Wagner ◽  
Azrah Y. Ahmed ◽  
Rongwei Fu ◽  
Benjamin Morasco ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Adverse Events ◽  
Observational Studies ◽  
Pain Severity ◽  
Cochrane Library ◽  
Short Term ◽  
Strength Of Evidence ◽  
Moderate Improvement ◽  
Whole Plant ◽  
Increased Risk

Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain. Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021. Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects. Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported. Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.

scholarly journals Prone Positioning of Non-intubated Patients with COVID-19 - A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Mallikarjuna Reddy PONNAPA REDDY ◽  
Ashwin SUBRAMANIAM ◽  
Zheng Jie LIM ◽  
Alexandr ZUBAREV ◽  
Afsana AFROZ ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Prone Positioning ◽  
Serious Adverse Events ◽  
Lack Of Control ◽  
The Impact ◽  
Substantial Heterogeneity ◽  
Major Adverse Events

Abstract Purpose: Several studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes.Methods: We searched PubMed, Embase and the COVID-19 living systematic review from December 1, 2019 to July 23, 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult patients with COVID-19. Primary outcome measureed was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. Results: Fifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports during PP, and frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2 (MD 37.6, 95% CI 18.8-56.5); PaO2 (MD 30.4 mmHg, 95% CI 10.9 to 49.9); and SpO2 (MD 5.8%, 95% CI 3.7 to 7.9). Patients with a pre-PP PaO2/FiO2 ≤150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95% CI -3.5 to 84.6) vs. 37, 95% CI 17.1 to 56.9). Respiratory rate decreased post-PP (MD -2.9, 95% CI -5.4 to -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. There were no major adverse events reported. Conclusions: Despite the significant variability in frequency and duration of PP and respiratory supports applied, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. The results are limited by lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.Systematic review registration: Registration/protocol in PROSPERO (CRD42020194080).

scholarly journals Safety of Influenza A H1N1pdm09 Vaccines: An Overview of Systematic Reviews

2021 ◽  
Vol 12 ◽  
Author(s):  
Lene Kristine Juvet ◽  
Anna Hayman Robertson ◽  
Ida Laake ◽  
Siri Mjaaland ◽  
Lill Trogstad
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Systematic Reviews ◽  
Pregnancy Outcomes ◽  
Influenza A ◽  
Demyelinating Diseases ◽  
Short Term ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Influenza A H1n1

BackgroundIn 2009, a new influenza A H1N1 virus emerged causing a global pandemic. A range of monovalent influenza A H1N1pdm09 vaccines with or without adjuvants were developed. After the mass vaccination campaigns safety concerns related to H1N1pdm09 vaccines were reported. More than a decade later, reported AEFIs are still under scrutiny. We performed a systematic review aiming to synthesize the evidence on the safety of the H1N1pdm09 vaccines on reported outcomes from existing systematic reviews.MethodsFour electronic databases, PubMed, EMBASE, Epistimonikos and the Cochrane Database of Systematic Reviews were searched for articles on H1N1pdm09 vaccination published from 2009 to January 2021. Systematic reviews assessing short- or long-term adverse events after H1N1pdm09 vaccination were considered for inclusion. Data was extracted from all selected reviews. Outcomes were grouped and results from each included review were presented narratively and in tables.Results16 systematic reviews met the inclusion criteria. Reported outcomes were short-term events (3 reviews), fetal/pregnancy outcomes (8 reviews), Guillain-Barré syndrome (GBS) (4 reviews), narcolepsy (2 reviews) demyelinating diseases (1 review based on one study only) and inflammatory bowel disease (IBD) (1 review). Short-term serious adverse events were rare, 3 cases amongst 16725 subjects in 18 randomized controlled trials (0.018%). No deaths were reported. The risks of local events were generally higher for adjuvanted vaccines as compared to unadjuvanted vaccines. Maternal H1N1pdm09 vaccination in any trimester was not associated with an increase in preterm birth, small for gestational age, congenital malformations or fetal death. For GBS, results were conflicting. The main systematic review on narcolepsy found a 5-14-fold increased risk in children, and a 2-7- fold increased risk in adults after vaccination with Pandemrix. The attributable risk of narcolepsy one year after vaccination was 1 case per 18 400 vaccine doses in children/adolescents, and 1 case per 181 000 vaccine doses in adults.ConclusionAdjuvanted vaccines had more local but not serious adverse events compared to unadjuvanted vaccines. Vaccination with Pandemrix was strongly associated with narcolepsy, particularly in children. No increased risks of pregnancy outcomes were seen after pandemic vaccination. The findings on GBS were inconclusive.

scholarly journals Prone positioning of non-intubated patients with COVID-19 - A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Mallikarjuna Ponnapa Reddy ◽  
Ashwin Subramaniam ◽  
Zheng Jie Lim ◽  
Alexandr Zubarev ◽  
Afsana Afroz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Prone Position ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Primary Outcome Measure ◽  
Prone Positioning ◽  
Bottom Line ◽  
Serious Adverse Events ◽  
The Impact

ABSTRACTPurposeSeveral studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes.MethodsWe searched PubMed, Embase and COVID-19 living systematic review from December1st 2019 to July23rd 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult COVID-19 patients. Primary outcome measure was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP.ResultsFifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports, frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2, (MD 37.6, 95%CI 18.8, 56.5); PaO2, (MD 30.4 mmHg, 95%CI 10.9, 49.9); and SpO2, (MD 5.8%, 95%CI 3.7, 7.9). Patients with a pre-PP PaO2/FiO2 ≤150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95%CI −3.5, 84.6) vs. 37, 95%CI 17.1, 56.9). Respiratory rate decreased post-PP (MD −2.9, 95%CI −5.4, −0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. No major adverse events were reported.ConclusionsDespite significant variability in frequency and duration of PP and respiratory supports, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. Major limitation being lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.Systematic review registrationRegistration/protocol in PROSPERO (CRD42020194080).What is the key question?Is the novel approach of prone positioning in non-intubated patients associated with improvement in oxygenation?What is the bottom line?Prone position in non-intubated severe COIVD 19 suffers is associated with improvement of oxygenation while the short- and long-term patient centred out comes in this awake prone patient need more investigation.Why read on?Our study is first of its kind (Systematic review and Meta-analysis) summarising the evidence surrounding the less invasive innovate technique of prone position in non-intubated COVID-19 patients.

scholarly journals P01.06 Overweight and obesity as biomarkers for survival outcomes and immune related adverse events undergoing immunotherapy – a systematic review and meta-analysis

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A5.2-A6
Author(s):  
P Trinkner ◽  
S Günther ◽  
M von Bergwelt ◽  
D Cordas dos Santos ◽  
S Theurich
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Obese Patients ◽  
Increased Risk ◽  
Underweight Patients ◽  
The Impact

BackgroundThe impact of overweight/obesity in cancer patients treated with immune checkpoint inhibitors (ICIs) is controversial. To further contribute to this debate, we performed a systematic review and meta-analysis of published articles evaluating the effects of overweight/obesity on survival and immune-related adverse events (irAEs).Materials and MethodsIn analogy to Cochrane recommendations, systematic literature searches included all published articles in PubMed until February 2021 with key terms ‘obesity’ and ‘overweight’ and ICI treatment irrespective of cancer entity and ICI used. Further selection criteria for meta-analysis included WHO cut-offs for overweight/obesity. For the random effects meta-analysis, we used Hazard Ratios (HR) for overall and progression-free survival (OS, PFS) and Odds Ratios (OR) for occurrence of irAEs with corresponding 95% confidence intervals (95%CI), respectively.ResultsA total of 30 studies (12,895 patients, 38% female) selected for meta-analysis revealed a superior survival of overweight/obese patients (PFS: HR 0.9, 95%CI 0.77-1.04, p = 0.11; OS: 0.74, 95%CI 0.63-0.92, p = 0.0005) compared to normal weight patients. In subgroup analyses based on sex, overweight/obese male patients showed increased survival (PFS: HR 0.79, 95%CI 0.63-1.00, p = 0.05; OS: 0.71, 95%CI 0.58-0.86, p = 0.0005), whereas overweight/obese female patients had similar survival probabilities compared to their normal weight counterparts (PFS: HR 1.01, 95%CI 0.69-1.47, p = 0.96; OS: HR 0.73, 95%CI 0.48-1.10, p = 0.13). Underweight patients showed inferior survival (PFS: HR 1.48, 95%CI 1.07-2.04, p = 0.02; OS: HR 1.86, 95%CI 1.13-3.04, p = 0.01). In addition, overweight/obese patients had a higher risk of developing irAEs with grade ≥ 3 (OR 1.91, 95%CI 1.18-3.10, p = 0.008).ConclusionsOur meta-analysis revealed that overweight/obesity is a beneficial factor for PFS and OS in a mixed cohort of cancer patients undergoing ICI treatment accompanied by an increased risk of severe irAEs. The differences between overweight/obese males and overweight/obese females might point to sex specific adipose distribution patterns and interactions of sex steroids on a molecular level. A significant number of studies included underweight patients into normal weight control groups which led to a compromised interpretation of the data and should be addressed in future studies.Disclosure InformationP. Trinkner: None. S. Günther: None. M. von Bergwelt: None. D. Cordas dos Santos: None. S. Theurich: None.

scholarly journals Enough with the madness: a systematic review and meta-analysis of hydroxychloroquine for COVID-19

2021 ◽  
Vol 13 (2) ◽  
pp. 186-220
Author(s):  
André Santos ◽  
◽  
Érica Gonçalves ◽  
Ananda Oliveira ◽  
Douglas Lima ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Standard Of Care ◽  
P Value ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Objective: Because of preliminary results from in vitro studies, hydroxychloroquine (HCQ) and chloroquine (CQ) have been proposed as possible treatments for COVID-19, but the clinical evidence is discordant. This study aims to evaluate the safety and efficacy of CQ and HCQ for the treatment of COVID-19. Methods: A systematic review with meta-analysis was performed. An electronic search was conducted in four databases for randomized controlled trials that compared HCQ or CQ with standard-of-care. A complementary search was performed. A quantitative synthesis of clinical outcomes was performed using the inverse variance method adjusting for a random-effects model. Results: In total, 16 studies were included. The meta-analysis found no significant difference between intervention and control groups in terms of mortality at the most extended follow-up (RR = 1.09, CI95% = 0.99-1.19, p-value = 0.08), patients with negative PCR results (RR = 0.99, CI95% = 0.89-1.10, p-value = 0.86), or serious adverse events (RR = 2.21, CI95% = 0.89-5.47, p-value = 0.09). HCQ was associated with an increased risk of adverse events (RR = 2.28, CI95% = 1.36-2.83, p-value < 0.01). The quality of evidence varied from very low to high. Conclusion: There is no evidence that HCQ reduces the risk of death or improves cure rates in patients with COVID-19, but it might be associated with an increased risk of adverse events

scholarly journals Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: A systematic review of non-randomized studies

2021 ◽  
Author(s):  
Dena Zeraatkar ◽  
Matthew Cooper ◽  
Arnav Agarwal ◽  
Robin Vernooij ◽  
Gareth Leung ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Pain ◽  
Adverse Events ◽  
Cochrane Central Register ◽  
Medical Cannabis ◽  
Management Options ◽  
Serious Adverse Events ◽  
Randomized Studies

Objective: To establish the risk and prevalence of long-term and serious harms of medical cannabis and cannabinoids for chronic pain. Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE, PsycInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 1, 2020. Study selection: Non-randomized studies reporting on harms of medical cannabis or cannabinoids in people living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis: A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data, and assessed risk of bias. We used random-effects models for all meta-analyses and the GRADE approach to evaluate the certainty of evidence. Results: We identified 39 eligible studies that enrolled 12,143 patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2 to 41.2) among users of medical cannabis or cannabinoids for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6 to 30.6). However, very low certainty evidence indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are uncommon and typically occur in fewer than one in 20 patients. We compared studies with <24 weeks and ≥ 24 weeks cannabis use and found more adverse events reported among studies with longer follow-up (test of interaction p < 0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared to other pain management options, such as opioids. Conclusions: There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events. Future research should compare long-term and serious harms of medical cannabis with other management options for chronic pain, including opioids.

scholarly journals Serious adverse events and the risk of stroke in patients with rheumatoid arthritis: results from the German RABBIT cohort

2017 ◽  
Vol 76 (9) ◽  
pp. 1583-1590 ◽  
Author(s):  
Y Meissner ◽  
A Richter ◽  
B Manger ◽  
HP Tony ◽  
E Wilden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Adverse Events ◽  
Case Control Study ◽  
Case Control ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Serious Infections ◽  
The Impact ◽  
Control Study

ObjectiveIn the general population, the incidence of stroke is increased following other serious events and hospitalisation. We investigated the impact of serious adverse events on the risk of stroke in patients with rheumatoid arthritis (RA), taking risk factors and treatment into account.MethodsUsing data of the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) with 12354 patients with RA, incidence rates (IRs) and risk factors for stroke were investigated using multi-state and Cox proportional hazard models. In addition, in a nested case–control study, all patients with stroke were matched 1:2 to patients with identical baseline risk profile and analysed using a shared frailty model.ResultsDuring follow-up, 166 strokes were reported. The overall IR was 3.2/1000 patient-years (PY) (95% CI 2.7 to 3.7). It was higher after a serious adverse event (IR: 9.0 (7.3 to 11.0)), particularly within 30 days after the event (IR: 94.9 (72.6 to 121.9)). The adjusted Cox model showed increased risks of age per 5 years (HR: 1.4 (1.3 to 1.5)), hyperlipoproteinaemia (HR: 1.6 (1.0 to 2.5)) and smoking (HR: 1.9 (1.3 to 2.6)). The risk decreased with better physical function (HR: 0.9 (0.8 to 0.96)). In the case–control study, 163 patients were matched to 326 controls. Major risk factors for stroke were untreated cardiovascular disease (HR: 3.3 (1.5 to 7.2)) and serious infections (HR:4.4 (1.6 to 12.5)) or other serious adverse events (HR: 2.6 (1.4 to 4.8)).ConclusionsIncident adverse events, in particular serious infections, and insufficient treatment of cardiovascular diseases are independent drivers of the risk of stroke. Physicians should be aware that patients who experience a serious event are at increased risk of subsequent stroke.

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