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Registrational Study With Omecamtiv Mecarbil (AMG 423) to Treat Chronic Heart Failure With Reduced Ejection Fraction (GALACTIC-HF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02929329
Recruitment Status : Completed
First Posted : October 11, 2016
Results First Posted : July 20, 2021
Last Update Posted : November 5, 2021
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Omecamtiv Mecarbil
Drug: Placebo
Drug: Standard of Care
Enrollment 8256
Recruitment Details A total of 11,121 patients underwent screening at 944 sites in 35 countries. Of these patients, 8,256 were randomized, but 24 patients from one site were excluded because of Good Clinical Practice violations and are not included in the data reported below.
Pre-assignment Details

Participants were randomly assigned in a 1:1 ratio to receive either oral omecamtiv mecarbil (OM) or placebo.

Randomization was stratified by randomization setting (currently hospitalized for heart failure [HF] or recently and not currently hospitalized for HF) and region (United States and Canada; Latin America; Western Europe, South Africa, and Australasia; Eastern Europe including Russia; Asia).

Arm/Group Title Placebo Omecamtiv Mecarbil
Hide Arm/Group Description Participants received matching placebo tablets twice a day (BID). Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Period Title: Overall Study
Started 4112 4120
Received Treatment 4101 4110
Completed 3008 [1] 3028 [2]
Not Completed 1104 1092
Reason Not Completed
Withdrawal by Subject             24             21
Lost to Follow-up             26             20
Death             1054             1051
[1]
7 participants in this group who discontinued the study had unknown vital status at the end of study
[2]
9 participants in this group who discontinued the study had unknown vital status at the end of study
Arm/Group Title Placebo Omecamtiv Mecarbil Total
Hide Arm/Group Description Participants received matching placebo tablets (BID). Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2. Total of all reporting groups
Overall Number of Baseline Participants 4112 4120 8232
Hide Baseline Analysis Population Description
The full analysis set included all the randomized participants except for 24 patients from a single site who were excluded on the basis of Good Clinical Practice violations.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4112 participants 4120 participants 8232 participants
64.5  (11.4) 64.5  (11.3) 64.5  (11.4)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4112 participants 4120 participants 8232 participants
18 to 64 years
1873
  45.5%
1874
  45.5%
3747
  45.5%
65 to 84 years
2211
  53.8%
2220
  53.9%
4431
  53.8%
85 years and over
28
   0.7%
26
   0.6%
54
   0.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4112 participants 4120 participants 8232 participants
Female
874
  21.3%
875
  21.2%
1749
  21.2%
Male
3238
  78.7%
3245
  78.8%
6483
  78.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4112 participants 4120 participants 8232 participants
Hispanic or Latino
885
  21.5%
886
  21.5%
1771
  21.5%
Not Hispanic or Latino
3227
  78.5%
3234
  78.5%
6461
  78.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4112 participants 4120 participants 8232 participants
American Indian or Alaska Native
38
   0.9%
35
   0.8%
73
   0.9%
Asian
355
   8.6%
355
   8.6%
710
   8.6%
Black or African American
277
   6.7%
285
   6.9%
562
   6.8%
Multiple
96
   2.3%
99
   2.4%
195
   2.4%
Native Hawaiian or Other Pacific Islander
6
   0.1%
7
   0.2%
13
   0.2%
White
3201
  77.8%
3196
  77.6%
6397
  77.7%
Other
139
   3.4%
143
   3.5%
282
   3.4%
Randomization Setting  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4112 participants 4120 participants 8232 participants
Currently hospitalized for heart failure
1050
  25.5%
1051
  25.5%
2101
  25.5%
Recently and not currently hospitalized for heart failure
3062
  74.5%
3069
  74.5%
6131
  74.5%
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4112 participants 4120 participants 8232 participants
United States and Canada
693
  16.9%
693
  16.8%
1386
  16.8%
Latin America
787
  19.1%
787
  19.1%
1574
  19.1%
Western Europe, South Africa, and Australasia
960
  23.3%
961
  23.3%
1921
  23.3%
Eastern Europe including Russia
1337
  32.5%
1344
  32.6%
2681
  32.6%
Asia
335
   8.1%
335
   8.1%
670
   8.1%
1.Primary Outcome
Title Time to Cardiovascular Death or First Heart Failure Event
Hide Description

The primary outcome was a composite of a heart-failure (HF) event or cardiovascular (CV) death, whichever occurred first, in a time-to-event analysis.

A heart-failure event was defined as an urgent clinic visit, emergency department visit, or hospitalization for subjectively and objectively worsening heart failure leading to treatment intensification beyond a change in oral diuretic therapy.

All deaths and HF events were adjudicated by an independent external clinical events committee (CEC) at the Duke Clinical Research Institute, using standardized definitions based on the recent American College of Cardiology/American Heart Association (ACC/AHA) standards for endpoint definitions in cardiovascular clinical trials.

Time to cardiovascular death or first HF event was analyzed using Kaplan-Meier (KM) methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.

Time Frame From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Omecamtiv Mecarbil
Hide Arm/Group Description:
Participants received matching placebo tablets (BID).
Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Overall Number of Participants Analyzed 4112 4120
Measure Type: Number
Unit of Measure: percentage of participants
39.1 37.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments

The overall type I error was 0.05 for 2-sided testing across primary and secondary outcomes.

Control for multiple comparisons was achieved using the following testing algorithm: if the primary outcome met the P-value threshold of 0.05, the alpha error would be divided unequally between cardiovascular death (96% of the overall alpha error, or 0.048) and change from baseline to week 24 in the Kansas City Cardiomyopathy Questionnaire total symptom score (4% of the overall alpha error, or 0.002).

Statistical Test of Hypothesis P-Value 0.0252
Comments [Not Specified]
Method Regression, Cox
Comments Stratified by randomization setting and region, including terms for baseline estimated glomerular filtration rate (eGFR) and treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.86 to 0.99
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0211
Comments [Not Specified]
Method Stratified log-rank test
Comments Log-rank test stratified by randomization setting and region.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments Competing risk subdistribution hazard ratio and associated 95% confidence intervals for treatment were computed. Deaths not included in the endpoint were considered as the competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.86 to 0.99
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.
2.Secondary Outcome
Title Time to Cardiovascular Death
Hide Description

Cardiovascular death includes acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes.

All deaths were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials.

Time to cardiovascular death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.

Time Frame From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Omecamtiv Mecarbil
Hide Arm/Group Description:
Participants received matching placebo tablets (BID).
Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Overall Number of Participants Analyzed 4112 4120
Measure Type: Number
Unit of Measure: percentage of participants
19.4 19.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8555
Comments If significance for the primary outcome was determined, cardiovascular death was tested against an alpha of 0.048.
Method Regression, Cox
Comments Stratified by randomization setting and region, including terms for baseline eGFR and treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.92 to 1.11
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments Competing risk subdistribution hazard ratio and associated 95% confidence intervals for treatment were computed. Deaths not included in the endpoint were considered as the competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.92 to 1.11
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the treatment group and baseline eGFR as covariates.
3.Secondary Outcome
Title Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at Week 24
Hide Description

The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire with a 2-week recall period that includes 23 items that map to 7 domains: symptom frequency; symptom burden; symptom stability; physical limitations; social limitations; quality of life; and self-efficacy (the patient's understanding of how to manage their heart failure). The symptom frequency and symptom burden domains are merged into a total symptom score. Scores are represented on a 0-to-100-point scale, where lower scores represent more frequent and severe symptoms and scores of 100 indicate no symptoms.

The change from baseline in KCCQ TSS was analyzed separately for each randomization setting (inpatient and outpatient).

Least squares means are from the mixed model which includes baseline total symptom score value, region, baseline eGFR, scheduled visit, treatment group and interaction of treatment with scheduled visit as covariates.

Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available data
Arm/Group Title Placebo: Oupatients Omecamtiv Mecarbil: Outpatients Placebo: Inpatients Omecamtiv Mecarbil: Inpatients
Hide Arm/Group Description:
Participants who had either made an urgent visit to the emergency department or been hospitalized for heart failure within 1 year before screening received placebo tablets twice a day.
Participants who had either made an urgent visit to the emergency department or been hospitalized for heart failure within 1 year before screening received oral omecamtiv mecarbil twice daily. The starting dose was 25 mg; the dose could be adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Participants who were currently hospitalized for heart failure received placebo tablets twice a day.
Participants who were currently hospitalized for heart failure received oral omecamtiv mecarbil twice daily. The starting dose was 25 mg; the dose could be adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Overall Number of Participants Analyzed 2704 2715 835 868
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
6.29  (0.34) 5.83  (0.34) 21.15  (0.71) 23.65  (0.70)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: Oupatients, Omecamtiv Mecarbil: Outpatients
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-1.40 to 0.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48
Estimation Comments Treatment difference = Omecamtiv mecarbil - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.50
Confidence Interval (2-Sided) 95%
0.54 to 4.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.00
Estimation Comments Treatment difference = Omecamtiv mecarbil - Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo: Oupatients, Omecamtiv Mecarbil: Outpatients, Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
Comments [Not Specified]
Type of Statistical Test Superiority
Comments If significance for the primary outcome was determined, change from baseline in the KCCQ total symptom score was tested against an alpha of 0.002.
Statistical Test of Hypothesis P-Value 0.0278
Comments [Not Specified]
Method Omnibus F-test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo: Oupatients, Omecamtiv Mecarbil: Outpatients, Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Pooled treatment difference
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
-2.55 to 4.51
Estimation Comments Overall pooled estimate of treatment difference (Omecamtiv mecarbil - Placebo) using random effects meta-analysis approach.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo: Oupatients, Omecamtiv Mecarbil: Outpatients
Comments As a sensitivity for missing data due to death, joint longitudinal and survival models were fit using KCCQ TSS observed values with random subject slopes and intercepts for the longitudinal models with terms for baseline eGFR, region, and treatment by slope. The survival models were fit for all-cause death with baseline eGFR and treatment in the proportional hazard part of the models, KCCQ TSS modeled values as the shared parameterization, stratified by region with Weibull baseline functions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.71
Confidence Interval (2-Sided) 95%
-1.62 to 0.20
Estimation Comments Treatment difference = Omecamtiv mecarbil - Placebo
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo: Inpatients, Omecamtiv Mecarbil: Inpatients
Comments As a sensitivity for missing data due to death, joint longitudinal and survival models were fit using KCCQ TSS observed values with random subject slopes and intercepts for the longitudinal models with terms for baseline eGFR, region, and treatment by slope. The survival models were fit for all-cause death with baseline eGFR and treatment in the proportional hazard part of the models, KCCQ TSS modeled values as the shared parameterization, stratified by region with Weibull baseline functions.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.31
Confidence Interval (2-Sided) 95%
0.80 to 3.82
Estimation Comments Treatment difference = Omecamtiv mecarbil - Placebo
4.Secondary Outcome
Title Time to First Heart Failure Hospitalization
Hide Description

A HF hospitalization is defined as an event that met all of the following criteria:

  1. The participant was admitted to the hospital with a primary diagnosis of HF;
  2. The length of stay in the hospital extended for at least 24 hours;
  3. The participant exhibited documented new or worsening symptoms due to HF on presentation;
  4. The participant had objective evidence of new or worsening HF;
  5. The participant received initiation or intensification of treatment specifically for HF, including an intravenous diuretic or vasoactive agent, mechanical or surgical intervention, or mechanical fluid removal.

Events were adjudicated by an independent external CEC at the Duke Clinical Research Institute using standardized definitions based on the ACC/AHA standards for endpoint definitions in CV clinical trials.

Time to first HF hospitalization was analyzed using KM methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event is reported.

Time Frame From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Omecamtiv Mecarbil
Hide Arm/Group Description:
Participants received matching placebo tablets (BID).
Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Overall Number of Participants Analyzed 4112 4120
Measure Type: Number
Unit of Measure: percentage of participants
28.7 27.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1902
Comments If statistical significance was achieved for both the time to CV death and change from baseline in the KCCQ TSS, time to first heart failure hospitalization was to be tested at the full alpha.
Method Regression, Cox
Comments Stratified by randomization setting and region, including terms for baseline eGFR and treatment group.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.87 to 1.03
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the trial group and the baseline eGFR as covariates.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments Competing risk subdistribution hazard ratio and associated 95% confidence intervals for treatment were computed. Deaths not included in the endpoint are considered as the competing risk.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.88 to 1.04
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the trial group and the baseline eGFR as covariates.
5.Secondary Outcome
Title Time to All-cause Death
Hide Description

All events were adjudicated by an independent external clinical-events committee at the Duke Clinical Research Institute, using standardized definitions based on the recent ACC/AHA standards for endpoint definitions in cardiovascular clinical trials.

Time to all-cause death was analyzed using Kaplan-Meier methods. Since the median was not calculated, the percentage of participants with an event are reported. Events that occurred up to the earliest of last confirmed survival status date or analysis cut-off date (07 August 2020) are included.

Time Frame From randomization up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Omecamtiv Mecarbil
Hide Arm/Group Description:
Participants received matching placebo tablets (BID).
Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
Overall Number of Participants Analyzed 4112 4120
Measure Type: Number
Unit of Measure: percentage of participants
25.9 25.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Omecamtiv Mecarbil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9633
Comments If time to first heart failure hospitalization was statistically significant, time to all-cause death was to be tested with the same alpha as time to first heart failure hospitalization.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.92 to 1.09
Estimation Comments Cox proportional-hazards model with baseline hazards stratified according to the randomization setting and geographic region and with the trial group and the baseline eGFR as covariates.
Time Frame All-cause mortality is reported from randomization until end of study (27 August 2020); median (min, max) time on study was 21.8 (0, 42) months. Adverse events are reported from first dose of study drug until 30 days after last dose; median (min, max) treatment duration was 19.5 (0, 42) months.
Adverse Event Reporting Description

All-cause mortality is reported for all participants randomized in the study, excluding 24 participants due to GCP violations. All-cause mortality includes all deaths that occurred during the study including any that occurred after the efficacy analysis cut-off date.

Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

 
Arm/Group Title Placebo Omecamtiv Mecarbil
Hide Arm/Group Description Participants received matching placebo tablets (BID). Participants received oral omecamtiv mecarbil BID. The starting dose was 25 mg; the dose may have been adjusted at week 4 to 37.5 or 50 mg based on the predose plasma concentration measured at week 2.
All-Cause Mortality
Placebo Omecamtiv Mecarbil
Affected / at Risk (%) Affected / at Risk (%)
Total   1078/4112 (26.22%)   1078/4120 (26.17%) 
Hide Serious Adverse Events
Placebo Omecamtiv Mecarbil
Affected / at Risk (%) Affected / at Risk (%)
Total   2435/4101 (59.38%)   2373/4110 (57.74%) 
Blood and lymphatic system disorders     
Anaemia  1  28/4101 (0.68%)  34/4110 (0.83%) 
Anaemia of chronic disease  1  2/4101 (0.05%)  0/4110 (0.00%) 
Anaemia vitamin B12 deficiency  1  1/4101 (0.02%)  1/4110 (0.02%) 
Blood loss anaemia  1  2/4101 (0.05%)  2/4110 (0.05%) 
Coagulopathy  1  0/4101 (0.00%)  3/4110 (0.07%) 
Cold type haemolytic anaemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hypercoagulation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypochromic anaemia  1  1/4101 (0.02%)  2/4110 (0.05%) 
Immune thrombocytopenia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Iron deficiency anaemia  1  3/4101 (0.07%)  3/4110 (0.07%) 
Leukopenia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Lymphadenopathy  1  0/4101 (0.00%)  2/4110 (0.05%) 
Microcytic anaemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Neutropenia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Normochromic anaemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Normochromic normocytic anaemia  1  2/4101 (0.05%)  0/4110 (0.00%) 
Normocytic anaemia  1  2/4101 (0.05%)  0/4110 (0.00%) 
Pancytopenia  1  1/4101 (0.02%)  1/4110 (0.02%) 
Splenic infarction  1  2/4101 (0.05%)  0/4110 (0.00%) 
Spontaneous haematoma  1  1/4101 (0.02%)  2/4110 (0.05%) 
Thrombocytopenia  1  5/4101 (0.12%)  1/4110 (0.02%) 
Cardiac disorders     
Acute coronary syndrome  1  12/4101 (0.29%)  11/4110 (0.27%) 
Acute left ventricular failure  1  16/4101 (0.39%)  9/4110 (0.22%) 
Acute myocardial infarction  1  64/4101 (1.56%)  71/4110 (1.73%) 
Acute right ventricular failure  1  0/4101 (0.00%)  2/4110 (0.05%) 
Angina pectoris  1  40/4101 (0.98%)  41/4110 (1.00%) 
Angina unstable  1  49/4101 (1.19%)  63/4110 (1.53%) 
Aortic valve disease  1  1/4101 (0.02%)  0/4110 (0.00%) 
Aortic valve disease mixed  1  1/4101 (0.02%)  1/4110 (0.02%) 
Aortic valve incompetence  1  1/4101 (0.02%)  1/4110 (0.02%) 
Aortic valve stenosis  1  3/4101 (0.07%)  3/4110 (0.07%) 
Arrhythmia  1  6/4101 (0.15%)  4/4110 (0.10%) 
Arrhythmia supraventricular  1  3/4101 (0.07%)  4/4110 (0.10%) 
Arteriosclerosis coronary artery  1  7/4101 (0.17%)  2/4110 (0.05%) 
Atrial fibrillation  1  113/4101 (2.76%)  94/4110 (2.29%) 
Atrial flutter  1  25/4101 (0.61%)  23/4110 (0.56%) 
Atrial tachycardia  1  9/4101 (0.22%)  9/4110 (0.22%) 
Atrial thrombosis  1  2/4101 (0.05%)  1/4110 (0.02%) 
Atrioventricular block  1  1/4101 (0.02%)  0/4110 (0.00%) 
Atrioventricular block complete  1  12/4101 (0.29%)  14/4110 (0.34%) 
Atrioventricular block second degree  1  0/4101 (0.00%)  3/4110 (0.07%) 
Bradyarrhythmia  1  5/4101 (0.12%)  1/4110 (0.02%) 
Bradycardia  1  3/4101 (0.07%)  8/4110 (0.19%) 
Bundle branch block left  1  5/4101 (0.12%)  1/4110 (0.02%) 
Cardiac amyloidosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cardiac aneurysm  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cardiac arrest  1  64/4101 (1.56%)  50/4110 (1.22%) 
Cardiac asthma  1  1/4101 (0.02%)  2/4110 (0.05%) 
Cardiac disorder  1  3/4101 (0.07%)  0/4110 (0.00%) 
Cardiac failure  1  1045/4101 (25.48%)  988/4110 (24.04%) 
Cardiac failure acute  1  251/4101 (6.12%)  212/4110 (5.16%) 
Cardiac failure chronic  1  170/4101 (4.15%)  156/4110 (3.80%) 
Cardiac failure congestive  1  154/4101 (3.76%)  147/4110 (3.58%) 
Cardiac flutter  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cardiac tamponade  1  2/4101 (0.05%)  1/4110 (0.02%) 
Cardiac valve disease  1  1/4101 (0.02%)  1/4110 (0.02%) 
Cardiac ventricular thrombosis  1  2/4101 (0.05%)  1/4110 (0.02%) 
Cardio-respiratory arrest  1  14/4101 (0.34%)  9/4110 (0.22%) 
Cardiogenic shock  1  68/4101 (1.66%)  75/4110 (1.82%) 
Cardiomyopathy  1  8/4101 (0.20%)  12/4110 (0.29%) 
Cardiopulmonary failure  1  6/4101 (0.15%)  3/4110 (0.07%) 
Cardiorenal syndrome  1  10/4101 (0.24%)  14/4110 (0.34%) 
Cardiovascular insufficiency  1  2/4101 (0.05%)  1/4110 (0.02%) 
Chordae tendinae rupture  1  0/4101 (0.00%)  1/4110 (0.02%) 
Chronic left ventricular failure  1  8/4101 (0.20%)  6/4110 (0.15%) 
Chronotropic incompetence  1  0/4101 (0.00%)  1/4110 (0.02%) 
Conduction disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Congestive cardiomyopathy  1  24/4101 (0.59%)  14/4110 (0.34%) 
Coronary artery disease  1  24/4101 (0.59%)  26/4110 (0.63%) 
Coronary artery insufficiency  1  1/4101 (0.02%)  0/4110 (0.00%) 
Coronary artery occlusion  1  2/4101 (0.05%)  1/4110 (0.02%) 
Coronary artery stenosis  1  10/4101 (0.24%)  6/4110 (0.15%) 
Extrasystoles  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypertensive heart disease  1  3/4101 (0.07%)  0/4110 (0.00%) 
Intracardiac thrombus  1  1/4101 (0.02%)  1/4110 (0.02%) 
Ischaemic cardiomyopathy  1  8/4101 (0.20%)  9/4110 (0.22%) 
Left ventricular dysfunction  1  3/4101 (0.07%)  1/4110 (0.02%) 
Left ventricular failure  1  4/4101 (0.10%)  4/4110 (0.10%) 
Low cardiac output syndrome  1  3/4101 (0.07%)  2/4110 (0.05%) 
Mitral valve incompetence  1  8/4101 (0.20%)  9/4110 (0.22%) 
Myocardial fibrosis  1  3/4101 (0.07%)  2/4110 (0.05%) 
Myocardial infarction  1  54/4101 (1.32%)  36/4110 (0.88%) 
Myocardial ischaemia  1  10/4101 (0.24%)  12/4110 (0.29%) 
Myocarditis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Palpitations  1  3/4101 (0.07%)  2/4110 (0.05%) 
Paroxysmal arrhythmia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pericardial effusion  1  1/4101 (0.02%)  2/4110 (0.05%) 
Pericardial haemorrhage  1  1/4101 (0.02%)  1/4110 (0.02%) 
Pericarditis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Pericarditis constrictive  1  0/4101 (0.00%)  1/4110 (0.02%) 
Postinfarction angina  1  0/4101 (0.00%)  1/4110 (0.02%) 
Prinzmetal angina  1  1/4101 (0.02%)  1/4110 (0.02%) 
Prosthetic cardiac valve thrombosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pulseless electrical activity  1  2/4101 (0.05%)  1/4110 (0.02%) 
Right ventricular dysfunction  1  0/4101 (0.00%)  1/4110 (0.02%) 
Right ventricular failure  1  1/4101 (0.02%)  1/4110 (0.02%) 
Sinus arrest  1  1/4101 (0.02%)  0/4110 (0.00%) 
Sinus bradycardia  1  1/4101 (0.02%)  2/4110 (0.05%) 
Sinus node dysfunction  1  2/4101 (0.05%)  5/4110 (0.12%) 
Sinus tachycardia  1  2/4101 (0.05%)  2/4110 (0.05%) 
Supraventricular extrasystoles  1  2/4101 (0.05%)  1/4110 (0.02%) 
Supraventricular tachyarrhythmia  1  1/4101 (0.02%)  2/4110 (0.05%) 
Supraventricular tachycardia  1  11/4101 (0.27%)  8/4110 (0.19%) 
Tachyarrhythmia  1  2/4101 (0.05%)  1/4110 (0.02%) 
Tachycardia  1  5/4101 (0.12%)  2/4110 (0.05%) 
Tricuspid valve incompetence  1  1/4101 (0.02%)  1/4110 (0.02%) 
Trifascicular block  1  0/4101 (0.00%)  1/4110 (0.02%) 
Ventricular arrhythmia  1  18/4101 (0.44%)  24/4110 (0.58%) 
Ventricular extrasystoles  1  9/4101 (0.22%)  8/4110 (0.19%) 
Ventricular fibrillation  1  49/4101 (1.19%)  30/4110 (0.73%) 
Ventricular flutter  1  1/4101 (0.02%)  2/4110 (0.05%) 
Ventricular tachyarrhythmia  1  7/4101 (0.17%)  7/4110 (0.17%) 
Ventricular tachycardia  1  129/4101 (3.15%)  106/4110 (2.58%) 
Congenital, familial and genetic disorders     
Congenital megaureter  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hydrocele  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypertrophic cardiomyopathy  1  0/4101 (0.00%)  1/4110 (0.02%) 
Myocardial bridging  1  1/4101 (0.02%)  0/4110 (0.00%) 
Non-compaction cardiomyopathy  1  1/4101 (0.02%)  1/4110 (0.02%) 
Ear and labyrinth disorders     
Deafness unilateral  1  0/4101 (0.00%)  1/4110 (0.02%) 
Sudden hearing loss  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vertigo  1  3/4101 (0.07%)  3/4110 (0.07%) 
Vertigo positional  1  1/4101 (0.02%)  1/4110 (0.02%) 
Vestibular disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Endocrine disorders     
Basedow's disease  1  1/4101 (0.02%)  0/4110 (0.00%) 
Goitre  1  3/4101 (0.07%)  0/4110 (0.00%) 
Hypercalcaemia of malignancy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hyperthyroidism  1  2/4101 (0.05%)  4/4110 (0.10%) 
Hypothyroidism  1  3/4101 (0.07%)  1/4110 (0.02%) 
Thyroiditis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Thyrotoxic crisis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Eye disorders     
Amaurosis fugax  1  1/4101 (0.02%)  1/4110 (0.02%) 
Arteriosclerotic retinopathy  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cataract  1  9/4101 (0.22%)  8/4110 (0.19%) 
Cataract diabetic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Diabetic retinopathy  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diplopia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Eye inflammation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Glaucoma  1  0/4101 (0.00%)  2/4110 (0.05%) 
Iridodialysis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Iris disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Macular fibrosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Ocular hypertension  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pterygium  1  0/4101 (0.00%)  1/4110 (0.02%) 
Retinal detachment  1  0/4101 (0.00%)  1/4110 (0.02%) 
Scleromalacia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Ulcerative keratitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Visual impairment  1  0/4101 (0.00%)  1/4110 (0.02%) 
Vitreous haematoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Vitreous haemorrhage  1  0/4101 (0.00%)  2/4110 (0.05%) 
Gastrointestinal disorders     
Abdominal adhesions  1  1/4101 (0.02%)  1/4110 (0.02%) 
Abdominal discomfort  1  2/4101 (0.05%)  1/4110 (0.02%) 
Abdominal distension  1  3/4101 (0.07%)  3/4110 (0.07%) 
Abdominal hernia  1  3/4101 (0.07%)  0/4110 (0.00%) 
Abdominal incarcerated hernia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Abdominal pain  1  13/4101 (0.32%)  6/4110 (0.15%) 
Abdominal pain upper  1  5/4101 (0.12%)  6/4110 (0.15%) 
Abnormal faeces  1  0/4101 (0.00%)  1/4110 (0.02%) 
Acute abdomen  1  0/4101 (0.00%)  2/4110 (0.05%) 
Anal fistula  1  1/4101 (0.02%)  0/4110 (0.00%) 
Anorectal disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Ascites  1  2/4101 (0.05%)  3/4110 (0.07%) 
Chronic gastritis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Colitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Colitis ischaemic  1  1/4101 (0.02%)  1/4110 (0.02%) 
Colitis microscopic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Colitis ulcerative  1  1/4101 (0.02%)  0/4110 (0.00%) 
Constipation  1  7/4101 (0.17%)  5/4110 (0.12%) 
Crohn's disease  1  0/4101 (0.00%)  1/4110 (0.02%) 
Dental caries  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diabetic gastroparesis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Diarrhoea  1  12/4101 (0.29%)  6/4110 (0.15%) 
Dieulafoy's vascular malformation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diverticular perforation  1  2/4101 (0.05%)  1/4110 (0.02%) 
Diverticulum intestinal  1  1/4101 (0.02%)  2/4110 (0.05%) 
Diverticulum intestinal haemorrhagic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Duodenal ulcer haemorrhage  1  2/4101 (0.05%)  1/4110 (0.02%) 
Duodenitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Dyspepsia  1  1/4101 (0.02%)  1/4110 (0.02%) 
Dysphagia  1  1/4101 (0.02%)  4/4110 (0.10%) 
Enterocolitis  1  3/4101 (0.07%)  1/4110 (0.02%) 
Epiploic appendagitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Erosive oesophagitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Food poisoning  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gastric disorder  1  1/4101 (0.02%)  1/4110 (0.02%) 
Gastric haemorrhage  1  1/4101 (0.02%)  1/4110 (0.02%) 
Gastric polyps  1  2/4101 (0.05%)  1/4110 (0.02%) 
Gastric ulcer  1  1/4101 (0.02%)  5/4110 (0.12%) 
Gastric ulcer haemorrhage  1  2/4101 (0.05%)  2/4110 (0.05%) 
Gastric ulcer perforation  1  1/4101 (0.02%)  1/4110 (0.02%) 
Gastritis  1  7/4101 (0.17%)  4/4110 (0.10%) 
Gastritis erosive  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gastritis haemorrhagic  1  0/4101 (0.00%)  2/4110 (0.05%) 
Gastrointestinal angiodysplasia  1  2/4101 (0.05%)  0/4110 (0.00%) 
Gastrointestinal disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gastrointestinal haemorrhage  1  14/4101 (0.34%)  18/4110 (0.44%) 
Gastrointestinal necrosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gastrointestinal obstruction  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gastrooesophageal reflux disease  1  7/4101 (0.17%)  3/4110 (0.07%) 
Gingival bleeding  1  1/4101 (0.02%)  0/4110 (0.00%) 
Haematemesis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Haematochezia  1  2/4101 (0.05%)  1/4110 (0.02%) 
Haemoperitoneum  1  0/4101 (0.00%)  1/4110 (0.02%) 
Haemorrhagic erosive gastritis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Haemorrhoidal haemorrhage  1  1/4101 (0.02%)  2/4110 (0.05%) 
Haemorrhoids  1  0/4101 (0.00%)  2/4110 (0.05%) 
Hernial eventration  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hiatus hernia  1  1/4101 (0.02%)  3/4110 (0.07%) 
Ileus  1  5/4101 (0.12%)  3/4110 (0.07%) 
Ileus paralytic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Impaired gastric emptying  1  0/4101 (0.00%)  1/4110 (0.02%) 
Incarcerated umbilical hernia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Inguinal hernia  1  9/4101 (0.22%)  10/4110 (0.24%) 
Inguinal hernia strangulated  1  0/4101 (0.00%)  1/4110 (0.02%) 
Intestinal angina  1  0/4101 (0.00%)  1/4110 (0.02%) 
Intestinal haemorrhage  1  2/4101 (0.05%)  1/4110 (0.02%) 
Intestinal infarction  1  1/4101 (0.02%)  0/4110 (0.00%) 
Intestinal ischaemia  1  2/4101 (0.05%)  4/4110 (0.10%) 
Intestinal obstruction  1  6/4101 (0.15%)  4/4110 (0.10%) 
Intestinal perforation  1  1/4101 (0.02%)  1/4110 (0.02%) 
Intra-abdominal haemorrhage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Intussusception  1  0/4101 (0.00%)  1/4110 (0.02%) 
Irritable bowel syndrome  1  0/4101 (0.00%)  2/4110 (0.05%) 
Ischaemic enteritis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Large intestine perforation  1  1/4101 (0.02%)  1/4110 (0.02%) 
Large intestine polyp  1  3/4101 (0.07%)  4/4110 (0.10%) 
Lower gastrointestinal haemorrhage  1  2/4101 (0.05%)  3/4110 (0.07%) 
Lower gastrointestinal perforation  1  1/4101 (0.02%)  0/4110 (0.00%) 
Mechanical ileus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Melaena  1  1/4101 (0.02%)  1/4110 (0.02%) 
Mesenteric arterial occlusion  1  0/4101 (0.00%)  2/4110 (0.05%) 
Mesenteric artery embolism  1  2/4101 (0.05%)  0/4110 (0.00%) 
Mesenteric vascular insufficiency  1  1/4101 (0.02%)  0/4110 (0.00%) 
Nausea  1  1/4101 (0.02%)  1/4110 (0.02%) 
Necrotising oesophagitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Obstructive pancreatitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Oesophageal motility disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Oesophageal spasm  1  0/4101 (0.00%)  1/4110 (0.02%) 
Oesophageal ulcer haemorrhage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Oesophageal varices haemorrhage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Oesophagitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pancreatitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pancreatitis acute  1  2/4101 (0.05%)  9/4110 (0.22%) 
Pancreatitis haemorrhagic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pancreatolithiasis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Peptic ulcer haemorrhage  1  2/4101 (0.05%)  0/4110 (0.00%) 
Rectal fissure  1  1/4101 (0.02%)  0/4110 (0.00%) 
Rectal haemorrhage  1  2/4101 (0.05%)  3/4110 (0.07%) 
Rectal polyp  1  1/4101 (0.02%)  0/4110 (0.00%) 
Rectal prolapse  1  0/4101 (0.00%)  1/4110 (0.02%) 
Small intestinal haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Small intestinal obstruction  1  5/4101 (0.12%)  1/4110 (0.02%) 
Subileus  1  1/4101 (0.02%)  0/4110 (0.00%) 
Thrombosis mesenteric vessel  1  1/4101 (0.02%)  0/4110 (0.00%) 
Tooth disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Umbilical hernia  1  0/4101 (0.00%)  4/4110 (0.10%) 
Upper gastrointestinal haemorrhage  1  9/4101 (0.22%)  10/4110 (0.24%) 
Volvulus  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vomiting  1  4/4101 (0.10%)  6/4110 (0.15%) 
General disorders     
Asthenia  1  7/4101 (0.17%)  5/4110 (0.12%) 
Cardiac death  1  4/4101 (0.10%)  2/4110 (0.05%) 
Catheter site haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Chest discomfort  1  2/4101 (0.05%)  1/4110 (0.02%) 
Chest pain  1  22/4101 (0.54%)  15/4110 (0.36%) 
Complication associated with device  1  0/4101 (0.00%)  3/4110 (0.07%) 
Death  1  49/4101 (1.19%)  65/4110 (1.58%) 
Discomfort  1  1/4101 (0.02%)  0/4110 (0.00%) 
Drug withdrawal syndrome  1  0/4101 (0.00%)  1/4110 (0.02%) 
Fatigue  1  2/4101 (0.05%)  2/4110 (0.05%) 
Gait disturbance  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gait inability  1  1/4101 (0.02%)  0/4110 (0.00%) 
General physical health deterioration  1  2/4101 (0.05%)  3/4110 (0.07%) 
Generalised oedema  1  2/4101 (0.05%)  1/4110 (0.02%) 
Hypothermia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Impaired healing  1  1/4101 (0.02%)  0/4110 (0.00%) 
Incarcerated hernia  1  1/4101 (0.02%)  1/4110 (0.02%) 
Inflammation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Influenza like illness  1  1/4101 (0.02%)  1/4110 (0.02%) 
Infusion site extravasation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Localised oedema  1  2/4101 (0.05%)  0/4110 (0.00%) 
Malaise  1  1/4101 (0.02%)  0/4110 (0.00%) 
Medical device site haematoma  1  1/4101 (0.02%)  1/4110 (0.02%) 
Medical device site haemorrhage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Medical device site thrombosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Multiple organ dysfunction syndrome  1  14/4101 (0.34%)  17/4110 (0.41%) 
Nodule  1  1/4101 (0.02%)  0/4110 (0.00%) 
Non-cardiac chest pain  1  27/4101 (0.66%)  33/4110 (0.80%) 
Oedema  1  2/4101 (0.05%)  2/4110 (0.05%) 
Oedema peripheral  1  7/4101 (0.17%)  8/4110 (0.19%) 
Pacemaker generated arrhythmia  1  0/4101 (0.00%)  2/4110 (0.05%) 
Pain  1  0/4101 (0.00%)  1/4110 (0.02%) 
Performance status decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Peripheral swelling  1  0/4101 (0.00%)  1/4110 (0.02%) 
Physical deconditioning  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumatosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pyrexia  1  6/4101 (0.15%)  3/4110 (0.07%) 
Sudden cardiac death  1  37/4101 (0.90%)  27/4110 (0.66%) 
Sudden death  1  58/4101 (1.41%)  52/4110 (1.27%) 
Swelling face  1  1/4101 (0.02%)  0/4110 (0.00%) 
Systemic inflammatory response syndrome  1  0/4101 (0.00%)  3/4110 (0.07%) 
Ulcer haemorrhage  1  1/4101 (0.02%)  1/4110 (0.02%) 
Vascular stent occlusion  1  0/4101 (0.00%)  1/4110 (0.02%) 
Vascular stent stenosis  1  0/4101 (0.00%)  2/4110 (0.05%) 
Vessel puncture site haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hepatobiliary disorders     
Acute hepatic failure  1  2/4101 (0.05%)  1/4110 (0.02%) 
Alcoholic liver disease  1  1/4101 (0.02%)  0/4110 (0.00%) 
Autoimmune hepatitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Bile duct obstruction  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bile duct stone  1  6/4101 (0.15%)  2/4110 (0.05%) 
Biliary colic  1  1/4101 (0.02%)  1/4110 (0.02%) 
Cardiac cirrhosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cholangitis  1  1/4101 (0.02%)  6/4110 (0.15%) 
Cholangitis acute  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cholecystitis  1  9/4101 (0.22%)  11/4110 (0.27%) 
Cholecystitis acute  1  18/4101 (0.44%)  11/4110 (0.27%) 
Cholecystitis chronic  1  0/4101 (0.00%)  3/4110 (0.07%) 
Cholelithiasis  1  11/4101 (0.27%)  9/4110 (0.22%) 
Cholelithiasis obstructive  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cholestasis  1  1/4101 (0.02%)  2/4110 (0.05%) 
Cirrhosis alcoholic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Congestive hepatopathy  1  3/4101 (0.07%)  3/4110 (0.07%) 
Drug-induced liver injury  1  2/4101 (0.05%)  5/4110 (0.12%) 
Hepatic cirrhosis  1  2/4101 (0.05%)  5/4110 (0.12%) 
Hepatic failure  1  4/4101 (0.10%)  5/4110 (0.12%) 
Hepatic function abnormal  1  3/4101 (0.07%)  3/4110 (0.07%) 
Hepatic haematoma  1  2/4101 (0.05%)  0/4110 (0.00%) 
Hepatic ischaemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hepatitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Hepatitis acute  1  0/4101 (0.00%)  3/4110 (0.07%) 
Hepatocellular injury  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hepatorenal failure  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hepatorenal syndrome  1  3/4101 (0.07%)  3/4110 (0.07%) 
Hepatotoxicity  1  3/4101 (0.07%)  0/4110 (0.00%) 
Ischaemic hepatitis  1  5/4101 (0.12%)  5/4110 (0.12%) 
Jaundice  1  1/4101 (0.02%)  1/4110 (0.02%) 
Jaundice cholestatic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Liver disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Liver injury  1  8/4101 (0.20%)  3/4110 (0.07%) 
Portal hypertension  1  1/4101 (0.02%)  0/4110 (0.00%) 
Portal vein thrombosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Primary biliary cholangitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Venoocclusive liver disease  1  0/4101 (0.00%)  1/4110 (0.02%) 
Immune system disorders     
Anaphylactic shock  1  1/4101 (0.02%)  0/4110 (0.00%) 
Drug hypersensitivity  1  1/4101 (0.02%)  2/4110 (0.05%) 
Heart transplant rejection  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hypersensitivity  1  1/4101 (0.02%)  0/4110 (0.00%) 
Infections and infestations     
Abdominal sepsis  1  1/4101 (0.02%)  2/4110 (0.05%) 
Abscess jaw  1  0/4101 (0.00%)  1/4110 (0.02%) 
Abscess limb  1  4/4101 (0.10%)  2/4110 (0.05%) 
Acute endocarditis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Acute hepatitis B  1  1/4101 (0.02%)  0/4110 (0.00%) 
Anal abscess  1  3/4101 (0.07%)  3/4110 (0.07%) 
Appendiceal abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Appendicitis  1  3/4101 (0.07%)  4/4110 (0.10%) 
Appendicitis perforated  1  3/4101 (0.07%)  1/4110 (0.02%) 
Arteriosclerotic gangrene  1  1/4101 (0.02%)  0/4110 (0.00%) 
Arthritis bacterial  1  2/4101 (0.05%)  2/4110 (0.05%) 
Atypical pneumonia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bacteraemia  1  6/4101 (0.15%)  4/4110 (0.10%) 
Bacterial infection  1  2/4101 (0.05%)  0/4110 (0.00%) 
Bacterial sepsis  1  3/4101 (0.07%)  3/4110 (0.07%) 
Bacterial tracheitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Biliary sepsis  1  0/4101 (0.00%)  3/4110 (0.07%) 
Bronchitis  1  24/4101 (0.59%)  25/4110 (0.61%) 
Bronchitis bacterial  1  1/4101 (0.02%)  3/4110 (0.07%) 
Bronchitis viral  1  1/4101 (0.02%)  1/4110 (0.02%) 
Bronchopulmonary aspergillosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Burn infection  1  2/4101 (0.05%)  0/4110 (0.00%) 
Bursitis infective staphylococcal  1  1/4101 (0.02%)  0/4110 (0.00%) 
COVID-19  1  3/4101 (0.07%)  8/4110 (0.19%) 
COVID-19 pneumonia  1  3/4101 (0.07%)  7/4110 (0.17%) 
Catheter bacteraemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Catheter site infection  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cellulitis  1  24/4101 (0.59%)  34/4110 (0.83%) 
Chagas' cardiomyopathy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cholecystitis infective  1  1/4101 (0.02%)  1/4110 (0.02%) 
Chronic sinusitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Citrobacter sepsis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Clostridial infection  1  1/4101 (0.02%)  0/4110 (0.00%) 
Clostridial sepsis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Clostridium difficile colitis  1  1/4101 (0.02%)  2/4110 (0.05%) 
Clostridium difficile infection  1  2/4101 (0.05%)  3/4110 (0.07%) 
Complicated appendicitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Conjunctivitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cystitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Dengue fever  1  0/4101 (0.00%)  1/4110 (0.02%) 
Device related infection  1  5/4101 (0.12%)  3/4110 (0.07%) 
Device related sepsis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diabetic foot infection  1  2/4101 (0.05%)  6/4110 (0.15%) 
Diabetic gangrene  1  1/4101 (0.02%)  1/4110 (0.02%) 
Diarrhoea infectious  1  1/4101 (0.02%)  0/4110 (0.00%) 
Diverticulitis  1  2/4101 (0.05%)  4/4110 (0.10%) 
Eczema infected  1  1/4101 (0.02%)  0/4110 (0.00%) 
Embolic pneumonia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Empyema  1  0/4101 (0.00%)  1/4110 (0.02%) 
Encephalitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Endocarditis  1  7/4101 (0.17%)  3/4110 (0.07%) 
Endocarditis bacterial  1  1/4101 (0.02%)  2/4110 (0.05%) 
Endocarditis enterococcal  1  0/4101 (0.00%)  2/4110 (0.05%) 
Enterobacter bacteraemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Enterococcal bacteraemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Enterococcal infection  1  1/4101 (0.02%)  0/4110 (0.00%) 
Enterocolitis bacterial  1  2/4101 (0.05%)  0/4110 (0.00%) 
Enterocolitis viral  1  1/4101 (0.02%)  0/4110 (0.00%) 
Epididymitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Erysipelas  1  9/4101 (0.22%)  10/4110 (0.24%) 
Escherichia infection  1  0/4101 (0.00%)  2/4110 (0.05%) 
Escherichia urinary tract infection  1  2/4101 (0.05%)  0/4110 (0.00%) 
Fournier's gangrene  1  2/4101 (0.05%)  0/4110 (0.00%) 
Fungal infection  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gallbladder abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gangrene  1  8/4101 (0.20%)  5/4110 (0.12%) 
Gas gangrene  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gastroenteritis  1  11/4101 (0.27%)  15/4110 (0.36%) 
Gastroenteritis bacterial  1  1/4101 (0.02%)  2/4110 (0.05%) 
Gastroenteritis norovirus  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gastroenteritis viral  1  2/4101 (0.05%)  1/4110 (0.02%) 
Gastrointestinal viral infection  1  0/4101 (0.00%)  1/4110 (0.02%) 
Graft infection  1  1/4101 (0.02%)  1/4110 (0.02%) 
Groin abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hepatitis A  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hepatitis viral  1  0/4101 (0.00%)  1/4110 (0.02%) 
Herpes dermatitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Herpes virus infection  1  0/4101 (0.00%)  1/4110 (0.02%) 
Herpes zoster  1  1/4101 (0.02%)  1/4110 (0.02%) 
Implant site infection  1  1/4101 (0.02%)  3/4110 (0.07%) 
Incision site abscess  1  1/4101 (0.02%)  0/4110 (0.00%) 
Infected seroma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Infected skin ulcer  1  5/4101 (0.12%)  2/4110 (0.05%) 
Infection  1  6/4101 (0.15%)  2/4110 (0.05%) 
Infectious pleural effusion  1  1/4101 (0.02%)  2/4110 (0.05%) 
Infective exacerbation of chronic obstructive airways disease  1  3/4101 (0.07%)  4/4110 (0.10%) 
Infective myositis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Infective spondylitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Influenza  1  15/4101 (0.37%)  19/4110 (0.46%) 
Intervertebral discitis  1  2/4101 (0.05%)  0/4110 (0.00%) 
Jejunal gangrene  1  0/4101 (0.00%)  1/4110 (0.02%) 
Kidney infection  1  1/4101 (0.02%)  0/4110 (0.00%) 
Klebsiella bacteraemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Klebsiella sepsis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Labyrinthitis  1  1/4101 (0.02%)  2/4110 (0.05%) 
Large intestine infection  1  1/4101 (0.02%)  1/4110 (0.02%) 
Laryngitis  1  0/4101 (0.00%)  2/4110 (0.05%) 
Liver abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Localised infection  1  6/4101 (0.15%)  3/4110 (0.07%) 
Lower respiratory tract infection  1  6/4101 (0.15%)  7/4110 (0.17%) 
Lower respiratory tract infection viral  1  2/4101 (0.05%)  1/4110 (0.02%) 
Lung abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Lymphadenitis bacterial  1  1/4101 (0.02%)  0/4110 (0.00%) 
Mediastinitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Medical device site infection  1  3/4101 (0.07%)  0/4110 (0.00%) 
Meningitis bacterial  1  0/4101 (0.00%)  1/4110 (0.02%) 
Metapneumovirus infection  1  1/4101 (0.02%)  1/4110 (0.02%) 
Myiasis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Nasopharyngitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Necrotising fasciitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Ophthalmic herpes zoster  1  0/4101 (0.00%)  1/4110 (0.02%) 
Orchitis  1  0/4101 (0.00%)  2/4110 (0.05%) 
Osteomyelitis  1  12/4101 (0.29%)  8/4110 (0.19%) 
Osteomyelitis acute  1  0/4101 (0.00%)  1/4110 (0.02%) 
Osteomyelitis bacterial  1  0/4101 (0.00%)  1/4110 (0.02%) 
Osteomyelitis chronic  1  1/4101 (0.02%)  1/4110 (0.02%) 
Otitis media bacterial  1  0/4101 (0.00%)  1/4110 (0.02%) 
Parainfluenzae virus infection  1  1/4101 (0.02%)  0/4110 (0.00%) 
Peritonitis  1  5/4101 (0.12%)  0/4110 (0.00%) 
Peritonitis bacterial  1  0/4101 (0.00%)  1/4110 (0.02%) 
Peritonsillar abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pharyngitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Pilonidal cyst  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumococcal sepsis  1  3/4101 (0.07%)  1/4110 (0.02%) 
Pneumonia  1  179/4101 (4.36%)  171/4110 (4.16%) 
Pneumonia adenoviral  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pneumonia bacterial  1  6/4101 (0.15%)  7/4110 (0.17%) 
Pneumonia escherichia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumonia haemophilus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumonia influenzal  1  2/4101 (0.05%)  0/4110 (0.00%) 
Pneumonia klebsiella  1  2/4101 (0.05%)  1/4110 (0.02%) 
Pneumonia moraxella  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pneumonia mycoplasmal  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pneumonia necrotising  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumonia pneumococcal  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumonia respiratory syncytial viral  1  0/4101 (0.00%)  2/4110 (0.05%) 
Pneumonia staphylococcal  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumonia viral  1  1/4101 (0.02%)  1/4110 (0.02%) 
Postoperative wound infection  1  0/4101 (0.00%)  2/4110 (0.05%) 
Prostatic abscess  1  1/4101 (0.02%)  1/4110 (0.02%) 
Pseudomembranous colitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pulmonary sepsis  1  4/4101 (0.10%)  6/4110 (0.15%) 
Pulmonary tuberculosis  1  4/4101 (0.10%)  2/4110 (0.05%) 
Pyelonephritis  1  5/4101 (0.12%)  2/4110 (0.05%) 
Pyelonephritis acute  1  4/4101 (0.10%)  3/4110 (0.07%) 
Respiratory syncytial virus infection  1  1/4101 (0.02%)  1/4110 (0.02%) 
Respiratory tract infection  1  24/4101 (0.59%)  15/4110 (0.36%) 
Respiratory tract infection bacterial  1  1/4101 (0.02%)  0/4110 (0.00%) 
Respiratory tract infection fungal  1  0/4101 (0.00%)  1/4110 (0.02%) 
Respiratory tract infection viral  1  2/4101 (0.05%)  0/4110 (0.00%) 
Scrotal abscess  1  1/4101 (0.02%)  0/4110 (0.00%) 
Sepsis  1  60/4101 (1.46%)  51/4110 (1.24%) 
Sepsis syndrome  1  2/4101 (0.05%)  0/4110 (0.00%) 
Septic shock  1  32/4101 (0.78%)  37/4110 (0.90%) 
Sinusitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Sinusitis bacterial  1  0/4101 (0.00%)  2/4110 (0.05%) 
Skin graft infection  1  0/4101 (0.00%)  1/4110 (0.02%) 
Skin infection  1  1/4101 (0.02%)  1/4110 (0.02%) 
Soft tissue infection  1  1/4101 (0.02%)  4/4110 (0.10%) 
Staphylococcal bacteraemia  1  2/4101 (0.05%)  3/4110 (0.07%) 
Staphylococcal infection  1  2/4101 (0.05%)  0/4110 (0.00%) 
Staphylococcal sepsis  1  5/4101 (0.12%)  2/4110 (0.05%) 
Sternitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Stitch abscess  1  1/4101 (0.02%)  0/4110 (0.00%) 
Streptococcal bacteraemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Streptococcal endocarditis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tooth abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tooth infection  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tracheitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Tracheobronchitis  1  4/4101 (0.10%)  3/4110 (0.07%) 
Tuberculoma of central nervous system  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tuberculosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Upper respiratory tract infection  1  11/4101 (0.27%)  14/4110 (0.34%) 
Urinary tract infection  1  32/4101 (0.78%)  33/4110 (0.80%) 
Urinary tract infection bacterial  1  6/4101 (0.15%)  3/4110 (0.07%) 
Urinary tract infection enterococcal  1  2/4101 (0.05%)  0/4110 (0.00%) 
Urinary tract infection staphylococcal  1  1/4101 (0.02%)  0/4110 (0.00%) 
Urogenital infection bacterial  1  1/4101 (0.02%)  0/4110 (0.00%) 
Urosepsis  1  15/4101 (0.37%)  7/4110 (0.17%) 
Vascular device infection  1  1/4101 (0.02%)  1/4110 (0.02%) 
Viraemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Viral infection  1  3/4101 (0.07%)  3/4110 (0.07%) 
Viral upper respiratory tract infection  1  2/4101 (0.05%)  0/4110 (0.00%) 
Wound abscess  1  0/4101 (0.00%)  1/4110 (0.02%) 
Wound infection  1  5/4101 (0.12%)  1/4110 (0.02%) 
Wound infection bacterial  1  1/4101 (0.02%)  0/4110 (0.00%) 
Wound infection staphylococcal  1  1/4101 (0.02%)  0/4110 (0.00%) 
Wound sepsis  1  1/4101 (0.02%)  2/4110 (0.05%) 
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  0/4101 (0.00%)  1/4110 (0.02%) 
Accidental exposure to product by child  1  0/4101 (0.00%)  1/4110 (0.02%) 
Accidental overdose  1  2/4101 (0.05%)  1/4110 (0.02%) 
Alcohol poisoning  1  1/4101 (0.02%)  1/4110 (0.02%) 
Ankle fracture  1  5/4101 (0.12%)  4/4110 (0.10%) 
Arterial bypass thrombosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Arteriovenous fistula thrombosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bone contusion  1  1/4101 (0.02%)  0/4110 (0.00%) 
Brain contusion  1  1/4101 (0.02%)  2/4110 (0.05%) 
Burns third degree  1  0/4101 (0.00%)  1/4110 (0.02%) 
Carbon monoxide poisoning  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cardiac procedure complication  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cardiac vein perforation  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cataract traumatic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Clavicle fracture  1  0/4101 (0.00%)  1/4110 (0.02%) 
Concussion  1  1/4101 (0.02%)  1/4110 (0.02%) 
Contusion  1  3/4101 (0.07%)  3/4110 (0.07%) 
Craniocerebral injury  1  0/4101 (0.00%)  2/4110 (0.05%) 
Dialysis disequilibrium syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Epidural haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Eschar  1  1/4101 (0.02%)  0/4110 (0.00%) 
Facial bones fracture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Fall  1  7/4101 (0.17%)  10/4110 (0.24%) 
Femoral neck fracture  1  8/4101 (0.20%)  8/4110 (0.19%) 
Femur fracture  1  14/4101 (0.34%)  11/4110 (0.27%) 
Foot fracture  1  1/4101 (0.02%)  1/4110 (0.02%) 
Foreign body in eye  1  0/4101 (0.00%)  1/4110 (0.02%) 
Foreign body in gastrointestinal tract  1  0/4101 (0.00%)  1/4110 (0.02%) 
Fracture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Fracture displacement  1  1/4101 (0.02%)  0/4110 (0.00%) 
Fractured coccyx  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gastrostomy tube site complication  1  0/4101 (0.00%)  1/4110 (0.02%) 
Graft thrombosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Haematuria traumatic  1  1/4101 (0.02%)  1/4110 (0.02%) 
Hand fracture  1  1/4101 (0.02%)  1/4110 (0.02%) 
Head injury  1  3/4101 (0.07%)  1/4110 (0.02%) 
Hip fracture  1  5/4101 (0.12%)  7/4110 (0.17%) 
Humerus fracture  1  4/4101 (0.10%)  6/4110 (0.15%) 
Hyphaema  1  0/4101 (0.00%)  1/4110 (0.02%) 
Incisional hernia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Injury  1  2/4101 (0.05%)  3/4110 (0.07%) 
Injury corneal  1  0/4101 (0.00%)  1/4110 (0.02%) 
Intentional overdose  1  0/4101 (0.00%)  1/4110 (0.02%) 
Intestinal anastomosis complication  1  1/4101 (0.02%)  0/4110 (0.00%) 
Joint dislocation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Joint injury  1  1/4101 (0.02%)  0/4110 (0.00%) 
Limb crushing injury  1  0/4101 (0.00%)  1/4110 (0.02%) 
Limb injury  1  1/4101 (0.02%)  1/4110 (0.02%) 
Limb traumatic amputation  1  1/4101 (0.02%)  0/4110 (0.00%) 
Lower limb fracture  1  1/4101 (0.02%)  1/4110 (0.02%) 
Lumbar vertebral fracture  1  1/4101 (0.02%)  3/4110 (0.07%) 
Meniscus injury  1  0/4101 (0.00%)  2/4110 (0.05%) 
Multiple fractures  1  0/4101 (0.00%)  1/4110 (0.02%) 
Multiple injuries  1  0/4101 (0.00%)  3/4110 (0.07%) 
Osteophyte fracture  1  0/4101 (0.00%)  1/4110 (0.02%) 
Overdose  1  1/4101 (0.02%)  1/4110 (0.02%) 
Patella fracture  1  0/4101 (0.00%)  2/4110 (0.05%) 
Pelvic fracture  1  1/4101 (0.02%)  1/4110 (0.02%) 
Periorbital haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumocephalus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pneumothorax traumatic  1  1/4101 (0.02%)  1/4110 (0.02%) 
Post procedural bile leak  1  0/4101 (0.00%)  1/4110 (0.02%) 
Post procedural complication  1  0/4101 (0.00%)  3/4110 (0.07%) 
Post procedural fever  1  1/4101 (0.02%)  0/4110 (0.00%) 
Post procedural haematoma  1  1/4101 (0.02%)  1/4110 (0.02%) 
Post procedural haematuria  1  1/4101 (0.02%)  1/4110 (0.02%) 
Post procedural haemorrhage  1  1/4101 (0.02%)  5/4110 (0.12%) 
Post procedural hypotension  1  0/4101 (0.00%)  1/4110 (0.02%) 
Postpericardiotomy syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Procedural pneumothorax  1  2/4101 (0.05%)  1/4110 (0.02%) 
Pulmonary contusion  1  0/4101 (0.00%)  1/4110 (0.02%) 
Radius fracture  1  2/4101 (0.05%)  2/4110 (0.05%) 
Rib fracture  1  7/4101 (0.17%)  6/4110 (0.15%) 
Road traffic accident  1  1/4101 (0.02%)  2/4110 (0.05%) 
Scrotal haematoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Skin laceration  1  1/4101 (0.02%)  1/4110 (0.02%) 
Skull fracture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Skull fractured base  1  0/4101 (0.00%)  1/4110 (0.02%) 
Spinal compression fracture  1  3/4101 (0.07%)  4/4110 (0.10%) 
Spinal fracture  1  0/4101 (0.00%)  3/4110 (0.07%) 
Subdural haematoma  1  9/4101 (0.22%)  8/4110 (0.19%) 
Subdural haemorrhage  1  1/4101 (0.02%)  2/4110 (0.05%) 
Synovial rupture  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tendon injury  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tendon rupture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Thermal burn  1  2/4101 (0.05%)  1/4110 (0.02%) 
Thoracic vertebral fracture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Tibia fracture  1  1/4101 (0.02%)  2/4110 (0.05%) 
Toxicity to various agents  1  3/4101 (0.07%)  5/4110 (0.12%) 
Traumatic haematoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Traumatic intracranial haemorrhage  1  0/4101 (0.00%)  2/4110 (0.05%) 
Upper limb fracture  1  0/4101 (0.00%)  1/4110 (0.02%) 
Urethral injury  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vascular graft complication  1  0/4101 (0.00%)  1/4110 (0.02%) 
Vascular graft occlusion  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vascular procedure complication  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vascular pseudoaneurysm  1  0/4101 (0.00%)  2/4110 (0.05%) 
Vasoplegia syndrome  1  0/4101 (0.00%)  1/4110 (0.02%) 
Vena cava injury  1  0/4101 (0.00%)  1/4110 (0.02%) 
Wound  1  0/4101 (0.00%)  2/4110 (0.05%) 
Wound complication  1  1/4101 (0.02%)  0/4110 (0.00%) 
Wrist fracture  1  1/4101 (0.02%)  1/4110 (0.02%) 
Investigations     
Alanine aminotransferase increased  1  3/4101 (0.07%)  2/4110 (0.05%) 
Anticoagulation drug level above therapeutic  1  1/4101 (0.02%)  5/4110 (0.12%) 
Anticoagulation drug level below therapeutic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Aspartate aminotransferase increased  1  1/4101 (0.02%)  1/4110 (0.02%) 
Blood alkaline phosphatase increased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Blood calcium decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Blood creatine phosphokinase increased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Blood creatinine increased  1  1/4101 (0.02%)  1/4110 (0.02%) 
Blood glucose decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Blood lactate dehydrogenase increased  1  0/4101 (0.00%)  1/4110 (0.02%) 
Blood magnesium decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Blood potassium decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cardiac output decreased  1  1/4101 (0.02%)  2/4110 (0.05%) 
Catheterisation cardiac  1  0/4101 (0.00%)  1/4110 (0.02%) 
Coagulation time prolonged  1  1/4101 (0.02%)  0/4110 (0.00%) 
Ejection fraction decreased  1  1/4101 (0.02%)  1/4110 (0.02%) 
Electrocardiogram QT prolonged  1  1/4101 (0.02%)  0/4110 (0.00%) 
Electrocardiogram ST segment elevation  1  0/4101 (0.00%)  1/4110 (0.02%) 
HIV antibody positive  1  1/4101 (0.02%)  0/4110 (0.00%) 
Haemoglobin decreased  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hepatic enzyme abnormal  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hepatic enzyme increased  1  6/4101 (0.15%)  4/4110 (0.10%) 
Influenza A virus test positive  1  1/4101 (0.02%)  1/4110 (0.02%) 
International normalised ratio abnormal  1  1/4101 (0.02%)  0/4110 (0.00%) 
International normalised ratio decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
International normalised ratio increased  1  2/4101 (0.05%)  3/4110 (0.07%) 
Liver function test abnormal  1  0/4101 (0.00%)  4/4110 (0.10%) 
Liver function test increased  1  2/4101 (0.05%)  2/4110 (0.05%) 
Oxygen consumption increased  1  0/4101 (0.00%)  1/4110 (0.02%) 
SARS-CoV-2 test positive  1  1/4101 (0.02%)  3/4110 (0.07%) 
Staphylococcus test positive  1  1/4101 (0.02%)  0/4110 (0.00%) 
Transaminases increased  1  2/4101 (0.05%)  3/4110 (0.07%) 
Transplant evaluation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Troponin increased  1  1/4101 (0.02%)  3/4110 (0.07%) 
Weight decreased  1  2/4101 (0.05%)  1/4110 (0.02%) 
Metabolism and nutrition disorders     
Abnormal loss of weight  1  1/4101 (0.02%)  0/4110 (0.00%) 
Acidosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cachexia  1  1/4101 (0.02%)  2/4110 (0.05%) 
Decreased appetite  1  0/4101 (0.00%)  1/4110 (0.02%) 
Dehydration  1  15/4101 (0.37%)  19/4110 (0.46%) 
Diabetes mellitus  1  8/4101 (0.20%)  15/4110 (0.36%) 
Diabetes mellitus inadequate control  1  5/4101 (0.12%)  6/4110 (0.15%) 
Diabetic ketoacidosis  1  5/4101 (0.12%)  3/4110 (0.07%) 
Diabetic ketosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diabetic metabolic decompensation  1  8/4101 (0.20%)  1/4110 (0.02%) 
Electrolyte imbalance  1  1/4101 (0.02%)  0/4110 (0.00%) 
Failure to thrive  1  1/4101 (0.02%)  0/4110 (0.00%) 
Fluid overload  1  7/4101 (0.17%)  3/4110 (0.07%) 
Fluid retention  1  0/4101 (0.00%)  1/4110 (0.02%) 
Folate deficiency  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gout  1  7/4101 (0.17%)  14/4110 (0.34%) 
Hypercalcaemia  1  0/4101 (0.00%)  2/4110 (0.05%) 
Hyperglycaemia  1  11/4101 (0.27%)  9/4110 (0.22%) 
Hyperglycaemic hyperosmolar nonketotic syndrome  1  2/4101 (0.05%)  2/4110 (0.05%) 
Hyperkalaemia  1  21/4101 (0.51%)  20/4110 (0.49%) 
Hyperosmolar state  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hyperphosphataemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypervolaemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hypoalbuminaemia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hypocalcaemia  1  1/4101 (0.02%)  2/4110 (0.05%) 
Hypoglycaemia  1  13/4101 (0.32%)  7/4110 (0.17%) 
Hypokalaemia  1  13/4101 (0.32%)  7/4110 (0.17%) 
Hypokalaemic syndrome  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypomagnesaemia  1  1/4101 (0.02%)  1/4110 (0.02%) 
Hyponatraemia  1  19/4101 (0.46%)  14/4110 (0.34%) 
Hypophagia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hypovolaemia  1  1/4101 (0.02%)  3/4110 (0.07%) 
Lactic acidosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Latent autoimmune diabetes in adults  1  1/4101 (0.02%)  0/4110 (0.00%) 
Malnutrition  1  1/4101 (0.02%)  1/4110 (0.02%) 
Metabolic acidosis  1  6/4101 (0.15%)  2/4110 (0.05%) 
Metabolic alkalosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Obesity  1  2/4101 (0.05%)  0/4110 (0.00%) 
Type 2 diabetes mellitus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/4101 (0.10%)  1/4110 (0.02%) 
Arthritis  1  3/4101 (0.07%)  2/4110 (0.05%) 
Arthritis reactive  1  0/4101 (0.00%)  1/4110 (0.02%) 
Arthropathy  1  2/4101 (0.05%)  0/4110 (0.00%) 
Back pain  1  6/4101 (0.15%)  7/4110 (0.17%) 
Bursitis  1  3/4101 (0.07%)  1/4110 (0.02%) 
Compartment syndrome  1  0/4101 (0.00%)  1/4110 (0.02%) 
Costochondritis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Dupuytren's contracture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Elbow deformity  1  1/4101 (0.02%)  0/4110 (0.00%) 
Facial asymmetry  1  1/4101 (0.02%)  0/4110 (0.00%) 
Fasciitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Flank pain  1  1/4101 (0.02%)  0/4110 (0.00%) 
Gouty arthritis  1  1/4101 (0.02%)  2/4110 (0.05%) 
Haemarthrosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Haematoma muscle  1  0/4101 (0.00%)  2/4110 (0.05%) 
Intervertebral disc compression  1  0/4101 (0.00%)  1/4110 (0.02%) 
Intervertebral disc protrusion  1  4/4101 (0.10%)  1/4110 (0.02%) 
Joint effusion  1  0/4101 (0.00%)  1/4110 (0.02%) 
Limb discomfort  1  1/4101 (0.02%)  0/4110 (0.00%) 
Lumbar spinal stenosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Mobility decreased  1  1/4101 (0.02%)  0/4110 (0.00%) 
Muscle spasms  1  1/4101 (0.02%)  0/4110 (0.00%) 
Muscular weakness  1  0/4101 (0.00%)  2/4110 (0.05%) 
Musculoskeletal chest pain  1  4/4101 (0.10%)  10/4110 (0.24%) 
Musculoskeletal disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Musculoskeletal pain  1  1/4101 (0.02%)  0/4110 (0.00%) 
Myalgia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Myofascial pain syndrome  1  0/4101 (0.00%)  1/4110 (0.02%) 
Osteitis  1  0/4101 (0.00%)  2/4110 (0.05%) 
Osteoarthritis  1  9/4101 (0.22%)  12/4110 (0.29%) 
Osteochondritis  1  0/4101 (0.00%)  2/4110 (0.05%) 
Osteochondrosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Osteolysis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Osteonecrosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Osteoporotic fracture  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pain in extremity  1  1/4101 (0.02%)  2/4110 (0.05%) 
Polyarthritis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Polymyalgia rheumatica  1  1/4101 (0.02%)  1/4110 (0.02%) 
Pseudarthrosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Rhabdomyolysis  1  4/4101 (0.10%)  1/4110 (0.02%) 
Rheumatoid arthritis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Rotator cuff syndrome  1  2/4101 (0.05%)  0/4110 (0.00%) 
Spinal osteoarthritis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Spinal pain  1  4/4101 (0.10%)  0/4110 (0.00%) 
Spondylitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Synovitis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Tenosynovitis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vertebral foraminal stenosis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  1/4101 (0.02%)  1/4110 (0.02%) 
Adenocarcinoma gastric  1  2/4101 (0.05%)  1/4110 (0.02%) 
Adenocarcinoma of colon  1  7/4101 (0.17%)  5/4110 (0.12%) 
Adenocarcinoma pancreas  1  1/4101 (0.02%)  1/4110 (0.02%) 
Adenosquamous cell lung cancer stage III  1  1/4101 (0.02%)  0/4110 (0.00%) 
Adrenal adenoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
B-cell lymphoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Basal cell carcinoma  1  1/4101 (0.02%)  3/4110 (0.07%) 
Basosquamous carcinoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Benign neoplasm of testis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Bladder adenocarcinoma stage 0  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bladder cancer  1  1/4101 (0.02%)  2/4110 (0.05%) 
Bladder neoplasm  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bladder transitional cell carcinoma  1  2/4101 (0.05%)  1/4110 (0.02%) 
Bone sarcoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cholangiocarcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Chronic lymphocytic leukaemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Colon adenoma  1  0/4101 (0.00%)  2/4110 (0.05%) 
Colon cancer  1  7/4101 (0.17%)  4/4110 (0.10%) 
Colon cancer metastatic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Colorectal cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Colorectal cancer metastatic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diffuse large B-cell lymphoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Endometrial adenocarcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Essential thrombocythaemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gallbladder cancer metastatic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Gastric cancer  1  1/4101 (0.02%)  2/4110 (0.05%) 
Gastrointestinal stromal tumour  1  0/4101 (0.00%)  1/4110 (0.02%) 
Glioblastoma  1  2/4101 (0.05%)  0/4110 (0.00%) 
Glioblastoma multiforme  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hepatic cancer  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hepatic cancer metastatic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hypopharyngeal cancer  1  0/4101 (0.00%)  1/4110 (0.02%) 
Invasive ductal breast carcinoma  1  1/4101 (0.02%)  1/4110 (0.02%) 
Keratoacanthoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Laryngeal squamous cell carcinoma  1  0/4101 (0.00%)  2/4110 (0.05%) 
Lipoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Liposarcoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Lung adenocarcinoma  1  1/4101 (0.02%)  3/4110 (0.07%) 
Lung adenocarcinoma stage II  1  0/4101 (0.00%)  1/4110 (0.02%) 
Lung cancer metastatic  1  2/4101 (0.05%)  2/4110 (0.05%) 
Lung carcinoma cell type unspecified stage III  1  1/4101 (0.02%)  2/4110 (0.05%) 
Lung carcinoma cell type unspecified stage IV  1  2/4101 (0.05%)  1/4110 (0.02%) 
Lung neoplasm  1  3/4101 (0.07%)  1/4110 (0.02%) 
Lung neoplasm malignant  1  5/4101 (0.12%)  6/4110 (0.15%) 
Lymphangiosis carcinomatosa  1  0/4101 (0.00%)  1/4110 (0.02%) 
Lymphoma  1  2/4101 (0.05%)  0/4110 (0.00%) 
Malignant melanoma  1  1/4101 (0.02%)  2/4110 (0.05%) 
Malignant neoplasm progression  1  1/4101 (0.02%)  0/4110 (0.00%) 
Mediastinum neoplasm  1  1/4101 (0.02%)  0/4110 (0.00%) 
Medullary thyroid cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Melanoma recurrent  1  0/4101 (0.00%)  1/4110 (0.02%) 
Metastases to bone  1  2/4101 (0.05%)  1/4110 (0.02%) 
Metastases to liver  1  2/4101 (0.05%)  1/4110 (0.02%) 
Metastases to lymph nodes  1  1/4101 (0.02%)  0/4110 (0.00%) 
Metastases to peritoneum  1  0/4101 (0.00%)  1/4110 (0.02%) 
Metastasis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Metastatic bronchial carcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Metastatic neoplasm  1  0/4101 (0.00%)  2/4110 (0.05%) 
Myelodysplastic syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Myelofibrosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Nasopharyngeal cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Neoplasm malignant  1  2/4101 (0.05%)  1/4110 (0.02%) 
Neoplasm skin  1  1/4101 (0.02%)  0/4110 (0.00%) 
Neuroendocrine carcinoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Neuroendocrine carcinoma of the skin  1  0/4101 (0.00%)  1/4110 (0.02%) 
Neuroendocrine tumour of the lung metastatic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Non-Hodgkin's lymphoma  1  1/4101 (0.02%)  1/4110 (0.02%) 
Non-small cell lung cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Non-small cell lung cancer stage IV  1  0/4101 (0.00%)  2/4110 (0.05%) 
Oesophageal adenocarcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Oesophageal carcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Oesophageal neoplasm  1  1/4101 (0.02%)  0/4110 (0.00%) 
Oesophageal squamous cell carcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Oesophageal squamous cell carcinoma stage IV  1  0/4101 (0.00%)  1/4110 (0.02%) 
Ovarian cancer  1  0/4101 (0.00%)  1/4110 (0.02%) 
Pancreatic carcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pancreatic carcinoma metastatic  1  2/4101 (0.05%)  1/4110 (0.02%) 
Pancreatic neoplasm  1  0/4101 (0.00%)  1/4110 (0.02%) 
Papillary thyroid cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Penile cancer  1  1/4101 (0.02%)  1/4110 (0.02%) 
Penile squamous cell carcinoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Plasma cell myeloma  1  1/4101 (0.02%)  1/4110 (0.02%) 
Prostate cancer  1  6/4101 (0.15%)  3/4110 (0.07%) 
Prostate cancer metastatic  1  2/4101 (0.05%)  0/4110 (0.00%) 
Prostate cancer recurrent  1  1/4101 (0.02%)  0/4110 (0.00%) 
Prostate cancer stage I  1  1/4101 (0.02%)  0/4110 (0.00%) 
Prostate cancer stage IV  1  0/4101 (0.00%)  1/4110 (0.02%) 
Prostatic adenoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Rectal adenocarcinoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Rectal cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Rectal cancer metastatic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Rectal neoplasm  1  1/4101 (0.02%)  0/4110 (0.00%) 
Renal cancer  1  1/4101 (0.02%)  0/4110 (0.00%) 
Renal cell carcinoma  1  0/4101 (0.00%)  2/4110 (0.05%) 
Renal neoplasm  1  0/4101 (0.00%)  1/4110 (0.02%) 
Small cell lung cancer  1  2/4101 (0.05%)  1/4110 (0.02%) 
Small cell lung cancer metastatic  1  1/4101 (0.02%)  0/4110 (0.00%) 
Squamous cell carcinoma  1  2/4101 (0.05%)  2/4110 (0.05%) 
Squamous cell carcinoma of lung  1  1/4101 (0.02%)  1/4110 (0.02%) 
Squamous cell carcinoma of pharynx  1  1/4101 (0.02%)  0/4110 (0.00%) 
Squamous cell carcinoma of the cervix  1  0/4101 (0.00%)  1/4110 (0.02%) 
Squamous cell carcinoma of the tongue  1  0/4101 (0.00%)  1/4110 (0.02%) 
Thyroid adenoma  1  1/4101 (0.02%)  0/4110 (0.00%) 
Tonsil cancer  1  0/4101 (0.00%)  1/4110 (0.02%) 
Transitional cell carcinoma  1  3/4101 (0.07%)  2/4110 (0.05%) 
Ureteric cancer  1  0/4101 (0.00%)  1/4110 (0.02%) 
Uterine leiomyoma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Nervous system disorders     
Alcohol induced persisting dementia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Altered state of consciousness  1  1/4101 (0.02%)  1/4110 (0.02%) 
Amnesia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Balance disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Brain compression  1  0/4101 (0.00%)  1/4110 (0.02%) 
Brain hypoxia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Brain injury  1  2/4101 (0.05%)  2/4110 (0.05%) 
Brain oedema  1  0/4101 (0.00%)  2/4110 (0.05%) 
Brain stem stroke  1  2/4101 (0.05%)  1/4110 (0.02%) 
Carotid arteriosclerosis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Carotid artery disease  1  0/4101 (0.00%)  1/4110 (0.02%) 
Carotid artery occlusion  1  1/4101 (0.02%)  0/4110 (0.00%) 
Carotid artery stenosis  1  3/4101 (0.07%)  2/4110 (0.05%) 
Carpal tunnel syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cerebellar haemorrhage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cerebral artery embolism  1  1/4101 (0.02%)  0/4110 (0.00%) 
Cerebral circulatory failure  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cerebral haematoma  1  0/4101 (0.00%)  2/4110 (0.05%) 
Cerebral haemorrhage  1  7/4101 (0.17%)  2/4110 (0.05%) 
Cerebral hypoperfusion  1  2/4101 (0.05%)  0/4110 (0.00%) 
Cerebral infarction  1  13/4101 (0.32%)  8/4110 (0.19%) 
Cerebral ischaemia  1  4/4101 (0.10%)  3/4110 (0.07%) 
Cerebrovascular accident  1  29/4101 (0.71%)  25/4110 (0.61%) 
Cerebrovascular disorder  1  0/4101 (0.00%)  2/4110 (0.05%) 
Cerebrovascular insufficiency  1  1/4101 (0.02%)  1/4110 (0.02%) 
Cognitive disorder  1  1/4101 (0.02%)  1/4110 (0.02%) 
Coma  1  0/4101 (0.00%)  1/4110 (0.02%) 
Complex regional pain syndrome  1  0/4101 (0.00%)  1/4110 (0.02%) 
Diabetic neuropathy  1  1/4101 (0.02%)  2/4110 (0.05%) 
Dizziness  1  8/4101 (0.20%)  6/4110 (0.15%) 
Dizziness postural  1  3/4101 (0.07%)  0/4110 (0.00%) 
Dysaesthesia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Dysarthria  1  1/4101 (0.02%)  1/4110 (0.02%) 
Embolic stroke  1  1/4101 (0.02%)  2/4110 (0.05%) 
Encephalopathy  1  2/4101 (0.05%)  2/4110 (0.05%) 
Epilepsy  1  2/4101 (0.05%)  1/4110 (0.02%) 
Generalised tonic-clonic seizure  1  0/4101 (0.00%)  1/4110 (0.02%) 
Haemorrhage intracranial  1  2/4101 (0.05%)  0/4110 (0.00%) 
Haemorrhagic cerebral infarction  1  1/4101 (0.02%)  1/4110 (0.02%) 
Haemorrhagic stroke  1  7/4101 (0.17%)  3/4110 (0.07%) 
Haemorrhagic transformation stroke  1  1/4101 (0.02%)  1/4110 (0.02%) 
Headache  1  4/4101 (0.10%)  1/4110 (0.02%) 
Hemianopia  1  1/4101 (0.02%)  1/4110 (0.02%) 
Hemiparesis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hepatic encephalopathy  1  0/4101 (0.00%)  2/4110 (0.05%) 
Hydrocephalus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hyperglycaemic unconsciousness  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypoaesthesia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hypoglycaemic unconsciousness  1  1/4101 (0.02%)  0/4110 (0.00%) 
Ischaemic cerebral infarction  1  7/4101 (0.17%)  2/4110 (0.05%) 
Ischaemic stroke  1  38/4101 (0.93%)  36/4110 (0.88%) 
Lacunar infarction  1  1/4101 (0.02%)  1/4110 (0.02%) 
Lethargy  1  0/4101 (0.00%)  1/4110 (0.02%) 
Loss of consciousness  1  2/4101 (0.05%)  2/4110 (0.05%) 
Meningism  1  1/4101 (0.02%)  0/4110 (0.00%) 
Metabolic encephalopathy  1  5/4101 (0.12%)  5/4110 (0.12%) 
Mononeuritis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Monoplegia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Muscle contractions involuntary  1  0/4101 (0.00%)  1/4110 (0.02%) 
Myoclonus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Neuralgia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Neuromyopathy  1  1/4101 (0.02%)  1/4110 (0.02%) 
Neuropathy peripheral  1  1/4101 (0.02%)  2/4110 (0.05%) 
Normal pressure hydrocephalus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Orthostatic intolerance  1  2/4101 (0.05%)  0/4110 (0.00%) 
Parkinson's disease  1  1/4101 (0.02%)  0/4110 (0.00%) 
Partial seizures  1  1/4101 (0.02%)  0/4110 (0.00%) 
Peripheral sensorimotor neuropathy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Polyneuropathy  1  0/4101 (0.00%)  1/4110 (0.02%) 
Post-traumatic epilepsy  1  0/4101 (0.00%)  1/4110 (0.02%) 
Presyncope  1  5/4101 (0.12%)  8/4110 (0.19%) 
Psychogenic seizure  1  1/4101 (0.02%)  0/4110 (0.00%) 
Psychomotor disadaptation syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Psychomotor hyperactivity  1  1/4101 (0.02%)  0/4110 (0.00%) 
Radicular pain  1  0/4101 (0.00%)  1/4110 (0.02%) 
Sciatica  1  1/4101 (0.02%)  0/4110 (0.00%) 
Sedation  1  0/4101 (0.00%)  1/4110 (0.02%) 
Seizure  1  1/4101 (0.02%)  2/4110 (0.05%) 
Seizure like phenomena  1  1/4101 (0.02%)  0/4110 (0.00%) 
Status epilepticus  1  0/4101 (0.00%)  1/4110 (0.02%) 
Stroke in evolution  1  0/4101 (0.00%)  1/4110 (0.02%) 
Subarachnoid haemorrhage  1  6/4101 (0.15%)  3/4110 (0.07%) 
Syncope  1  46/4101 (1.12%)  42/4110 (1.02%) 
Thrombotic stroke  1  0/4101 (0.00%)  2/4110 (0.05%) 
Transient ischaemic attack  1  24/4101 (0.59%)  17/4110 (0.41%) 
Trigeminal neuralgia  1  1/4101 (0.02%)  0/4110 (0.00%) 
Vertebrobasilar insufficiency  1  0/4101 (0.00%)  1/4110 (0.02%) 
Vertigo CNS origin  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Ectopic pregnancy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Pregnancy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Product Issues     
Device alarm issue  1  0/4101 (0.00%)  1/4110 (0.02%) 
Device dislocation  1  2/4101 (0.05%)  0/4110 (0.00%) 
Device electrical impedance issue  1  1/4101 (0.02%)  0/4110 (0.00%) 
Device extrusion  1  1/4101 (0.02%)  1/4110 (0.02%) 
Device inappropriate shock delivery  1  1/4101 (0.02%)  1/4110 (0.02%) 
Device lead damage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Device lead issue  1  1/4101 (0.02%)  0/4110 (0.00%) 
Device leakage  1  1/4101 (0.02%)  0/4110 (0.00%) 
Device malfunction  1  6/4101 (0.15%)  6/4110 (0.15%) 
Device occlusion  1  0/4101 (0.00%)  2/4110 (0.05%) 
Device physical property issue  1  1/4101 (0.02%)  0/4110 (0.00%) 
Device power source issue  1  1/4101 (0.02%)  3/4110 (0.07%) 
Device signal detection issue  1  0/4101 (0.00%)  1/4110 (0.02%) 
Device stimulation issue  1  1/4101 (0.02%)  2/4110 (0.05%) 
Lead dislodgement  1  0/4101 (0.00%)  2/4110 (0.05%) 
Oversensing  1  1/4101 (0.02%)  0/4110 (0.00%) 
Undersensing  1  1/4101 (0.02%)  0/4110 (0.00%) 
Psychiatric disorders     
Alcohol abuse  1  1/4101 (0.02%)  1/4110 (0.02%) 
Alcohol withdrawal syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Alcoholism  1  0/4101 (0.00%)  1/4110 (0.02%) 
Anxiety  1  2/4101 (0.05%)  1/4110 (0.02%) 
Anxiety disorder  1  1/4101 (0.02%)  1/4110 (0.02%) 
Behaviour disorder  1  1/4101 (0.02%)  1/4110 (0.02%) 
Bipolar disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Communication disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Completed suicide  1  4/4101 (0.10%)  2/4110 (0.05%) 
Confusional state  1  1/4101 (0.02%)  2/4110 (0.05%) 
Conversion disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Delirium  1  0/4101 (0.00%)  1/4110 (0.02%) 
Delusion  1  1/4101 (0.02%)  1/4110 (0.02%) 
Depression  1  4/4101 (0.10%)  2/4110 (0.05%) 
Disorientation  1  1/4101 (0.02%)  0/4110 (0.00%) 
Hallucination  1  1/4101 (0.02%)  0/4110 (0.00%) 
Major depression  1  2/4101 (0.05%)  0/4110 (0.00%) 
Mental disorder  1  1/4101 (0.02%)  1/4110 (0.02%) 
Mental status changes  1  4/4101 (0.10%)  2/4110 (0.05%) 
Panic attack  1  0/4101 (0.00%)  1/4110 (0.02%) 
Personality disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Psychotic behaviour  1  1/4101 (0.02%)  0/4110 (0.00%) 
Suicidal ideation  1  1/4101 (0.02%)  2/4110 (0.05%) 
Suicide attempt  1  1/4101 (0.02%)  1/4110 (0.02%) 
Renal and urinary disorders     
Acute kidney injury  1  138/4101 (3.37%)  129/4110 (3.14%) 
Anuria  1  1/4101 (0.02%)  1/4110 (0.02%) 
Atonic urinary bladder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Azotaemia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Bladder neck obstruction  1  0/4101 (0.00%)  1/4110 (0.02%) 
Calculus bladder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Calculus urinary  1  0/4101 (0.00%)  1/4110 (0.02%) 
Chronic kidney disease  1  36/4101 (0.88%)  36/4110 (0.88%) 
Diabetic nephropathy  1  1/4101 (0.02%)  0/4110 (0.00%) 
End stage renal disease  1  4/4101 (0.10%)  7/4110 (0.17%) 
Haematinuria  1  1/4101 (0.02%)  0/4110 (0.00%) 
Haematuria  1  7/4101 (0.17%)  3/4110 (0.07%) 
Haemorrhage urinary tract  1  0/4101 (0.00%)  1/4110 (0.02%) 
Hydronephrosis  1  2/4101 (0.05%)  2/4110 (0.05%) 
Hypertensive nephropathy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Micturition disorder  1  1/4101 (0.02%)  0/4110 (0.00%) 
Nephrolithiasis  1  5/4101 (0.12%)  1/4110 (0.02%) 
Nephropathy  1  1/4101 (0.02%)  2/4110 (0.05%) 
Oliguria  1  0/4101 (0.00%)  1/4110 (0.02%) 
Postrenal failure  1  1/4101 (0.02%)  3/4110 (0.07%) 
Renal arteriosclerosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Renal artery stenosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Renal artery thrombosis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Renal colic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Renal cyst haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Renal failure  1  31/4101 (0.76%)  25/4110 (0.61%) 
Renal haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Renal impairment  1  29/4101 (0.71%)  25/4110 (0.61%) 
Renal infarct  1  1/4101 (0.02%)  0/4110 (0.00%) 
Ureterolithiasis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Urethral haemorrhage  1  0/4101 (0.00%)  1/4110 (0.02%) 
Urethral stenosis  1  0/4101 (0.00%)  1/4110 (0.02%) 
Urinary retention  1  2/4101 (0.05%)  4/4110 (0.10%) 
Urinary tract obstruction  1  1/4101 (0.02%)  0/4110 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  5/4101 (0.12%)  5/4110 (0.12%) 
Epididymal cyst  1  1/4101 (0.02%)  1/4110 (0.02%) 
Metrorrhagia  1  0/4101 (0.00%)  1/4110 (0.02%) 
Prostatitis  1  1/4101 (0.02%)  1/4110 (0.02%) 
Prostatomegaly  1  0/4101 (0.00%)  1/4110 (0.02%) 
Scrotal oedema  1  2/4101 (0.05%)  0/4110 (0.00%) 
Spermatocele  1  1/4101 (0.02%)  0/4110 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  10/4101 (0.24%)  10/4110 (0.24%) 
Acute respiratory distress syndrome  1  2/4101 (0.05%)  2/4110 (0.05%) 
Acute respiratory failure  1  18/4101 (0.44%)  20/4110 (0.49%) 
Aspiration  1  3/4101 (0.07%)  1/4110 (0.02%) 
Asthma  1  6/4101 (0.15%)  2/4110 (0.05%) 
Asthma-chronic obstructive pulmonary disease overlap syndrome  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bronchial disorder  1  0/4101 (0.00%)  1/4110 (0.02%) 
Bronchiectasis  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bronchitis chronic  1  0/4101 (0.00%)  1/4110 (0.02%) 
Bronchopneumopathy  1  1/4101 (0.02%)  0/4110 (0.00%) 
Bronchospasm  1  2/4101 (0.05%)  1/4110 (0.02%) 
Chronic obstructive pulmonary disease  1  38/4101 (0.93%)  63/4110 (1.53%) 
Chronic respiratory disease  1  0/4101 (0.00%)  1/4110 (0.02%) 
Cystic lung disease  1  0/4101 (0.00%)  1/4110 (0.02%) 
Dyspnoea  1  31/4101 (0.76%)  28/4110 (0.68%) 
Dyspnoea at rest  1  2/4101 (0.05%)  1/4110 (0.02%) 
Dyspnoea exertional  1  1/4101 (0.02%)  2/4110 (0.05%) 
Epistaxis  1  5/4101 (0.12%)  5/4110 (0.12%) 
Haemoptysis  1  4/4101 (0.10%)  3/4110 (0.07%) 
Haemothorax  1