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A Study Comparing the Efficacy, Safety and Tolerability of Fixed Dose Combination (FDC) of FF/UMEC/VI With the FDC of FF/VI and UMEC/VI; Administered Once-daily Via a Dry Powder Inhaler (DPI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT02164513
Recruitment Status : Completed
First Posted : June 16, 2014
Results First Posted : October 10, 2018
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: fluticasone furoate (FF)
Drug: vilanterol (VI)
Drug: umeclidinium bromide (UMEC)
Enrollment 10355
Recruitment Details Participants with chronic obstructive pulmonary disease (COPD), were randomized to the study. Study was conducted from 30 June 2014 to 17 July 2017, at total of 971 sites in 37 countries.
Pre-assignment Details  
Arm/Group Title FF/UMEC/VI FF/VI UMEC/VI
Hide Arm/Group Description The eligible participants in this arm received Fluticasone Furoate (FF)/Umeclidinium (UMEC)/Vilanterol (VI) as a fixed dose combination (FDC) as 100 microgram (µcg)/62.5µcg/25µcg once daily (QD) via a dry powder inhaler (DPI), in the morning, for duration of 52 weeks. The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks. The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Period Title: Overall Study
Started 4151 4134 2070
Completed Investigational Product (IP) 3393 3094 1504
Not Completed IP 758 1040 566
Withdrew IP (WIP): Adverse Event 249 325 186
WIP: Lack of Efficacy 163 313 172
Withdrew IP: Protocol Deviation 32 41 19
WIP (Other): Stopping Criteria Reached 4 1 2
WIP: Study Closed/Terminated 5 2 5
WIP: Lost to Follow-up 21 25 14
WIP: Investigator Discretion 33 36 15
WIP: Withdrawal by Participant 250 296 153
WIP :Did Not Complete Study Treatment 1 1 0
Completed 3714 3598 1775
Not Completed 437 536 295
Reason Not Completed
Adverse Event             162             180             111
Other: Study Closed or terminated             5             2             4
Lost to Follow-up             30             36             22
Physician Decision             47             57             28
Withdrawal by Subject             192             261             130
Other: Reason not provided by site             1             0             0
Arm/Group Title FF/UMEC/VI FF/VI UMEC/VI Total
Hide Arm/Group Description The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks. The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks. The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 4151 4134 2070 10355
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4151 participants 4134 participants 2070 participants 10355 participants
65.3  (8.24) 65.3  (8.30) 65.2  (8.26) 65.3  (8.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4151 participants 4134 participants 2070 participants 10355 participants
Female
1385
  33.4%
1386
  33.5%
714
  34.5%
3485
  33.7%
Male
2766
  66.6%
2748
  66.5%
1356
  65.5%
6870
  66.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4151 participants 4134 participants 2070 participants 10355 participants
American Indian or Alaska Native
87
   2.1%
86
   2.1%
45
   2.2%
218
   2.1%
Asian - Central/South Asian Heritage
6
   0.1%
3
   0.1%
1
   0.0%
10
   0.1%
Asian - East Asian Heritage
362
   8.7%
374
   9.0%
177
   8.6%
913
   8.8%
Asian - Japanese Heritage
151
   3.6%
152
   3.7%
82
   4.0%
385
   3.7%
Asian - South East Asian Heritage
149
   3.6%
147
   3.6%
75
   3.6%
371
   3.6%
Black or African American
122
   2.9%
99
   2.4%
43
   2.1%
264
   2.5%
Native Hawaiian or other Pacific Islander
2
   0.0%
3
   0.1%
2
   0.1%
7
   0.1%
White - Arabic/North African Heritage
31
   0.7%
45
   1.1%
24
   1.2%
100
   1.0%
White - White/Caucasian/European Heritage
3200
  77.1%
3179
  76.9%
1604
  77.5%
7983
  77.1%
Multiple
41
   1.0%
45
   1.1%
17
   0.8%
103
   1.0%
Unknown
0
   0.0%
1
   0.0%
0
   0.0%
1
   0.0%
1.Primary Outcome
Title Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI and FF/VI
Hide Description The annual rate of moderate or severe COPD exacerbations which occurred during treatment was assessed. Moderate exacerbations were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations were defined as exacerbations that required hospitalization or resulted in death. Analysis performed using a generalized linear model assuming a negative binomial distribution. ITT population was used which comprised of all randomized participants, excluding those who were randomized in error. Only those participants with non-missing co-variates were included in the analysis.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title FF/UMEC/VI FF/VI UMEC/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 4145 4133 2069
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per participant per year
0.91
(0.87 to 0.95)
1.07
(1.02 to 1.12)
1.21
(1.14 to 1.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, UMEC/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons.
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.70 to 0.81
Estimation Comments Covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted Forced expiratory volume in 1 second (FEV1) (Screening) were used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, FF/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.80 to 0.90
Estimation Comments Covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted Forced expiratory volume in 1 second (FEV1) (Screening) were used.
2.Secondary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1), at Week 52 Comparing FF/UMEC/VI With FF/VI
Hide Description FEV1 was defined as the amount of air a person exhales in one second. Change from Baseline was calculated as the value of FEV1 at Week 52 minus the value at Baseline. Baseline for trough FEV1 was defined as Day 1 (Pre-dose). Only those participants with non-missing co-variates were included in the analysis. The analysis was performed using a Repeated measures model with covariates of treatment group, smoking status (Screening), geographical region, visit, Baseline, Baseline by visit and treatment group by visit interactions.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title FF/UMEC/VI FF/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 3366 3060
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.094  (0.0042) -0.003  (0.0044)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, FF/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The adjusted p-value at Week 52 should be compared against a reference level of 0.05 in order to infer statistical significance for the comparison of FF/UMEC/VI versus (vs) FF/VI at Week 52.
Method Mixed Models Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.097
Confidence Interval (2-Sided) 95%
0.085 to 0.109
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0061
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in St. George’s Respiratory Questionnaire for (SGRQ) Total Score at Week 52 Comparing FF/UMEC/VI With FF/VI
Hide Description SGRQ is a disease specific-questionnaire, designed to measure impact of respiratory disease and its treatment on a COPD participant’s Health Related Quality of Life (HRQoL). SGRQ contains 14 questions with total of 40 items grouped into three domains (Symptoms, Activity, and Impacts). The overall summary score along with scores for the individual domains of symptoms, activity and impacts were assessed. Score was calculated by summing the pre-assigned weights of answers, dividing by sum of maximum weights for items in SGRQ. Total scores ranged from 0 to 100. A decrease in score indicates improvement in HRQoL and higher score implies worse quality of life. Change from Baseline was calculated as total score at Week 52 minus value at Baseline. Baseline was defined as Day 1. Minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Only those participants with non-missing co-variates were included in the analysis.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title FF/UMEC/VI FF/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 3318 3026
Least Squares Mean (Standard Error)
Unit of Measure: Scores on SGRQ scale
-5.5  (0.23) -3.7  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, FF/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The adjusted p-value at Week 52 should be compared against a reference level of 0.05 in order to infer statistical significance for the comparison of FF/UMEC/VI vs FF/VI at Week 52.
Method Mixed Models Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-2.4 to -1.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With FF/VI and With UMEC/VI
Hide Description This measures the number of days, to the first onset of moderate or severe exacerbations. Moderate exacerbations, were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations, were defined as exacerbations that required hospitalization or resulted in death. The Hazard ratio from Cox proportional hazards model with covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted FEV1 (Screening), have been reported. Only those participants with non-missing co-variates were included in the analysis. First quartile and median time to onset are taken from the Kaplan-Meier estimates. If <25% (and <50%) of participants experienced the event within a treatment then Q1 (and median) time to onset are displayed as NA (not applicable) for that treatment.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title FF/UMEC/VI FF/VI UMEC/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 1959 2039 1036
Measure Type: Number
Unit of Measure: Days
First quartile time to onset 112 81 73
Median time to onset NA [1]  NA [1]  306
[1]
If <25% (and <50%) of participants experienced the event within a treatment then Q1 (and median) time to onset are displayed as NA (not applicable) for that treatment.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, FF/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The adjusted p-values should be compared against a reference level of 0.05 in order to infer statistical significance for either of the comparisons.
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.80 to 0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, UMEC/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.78 to 0.91
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Annual Rate of On-treatment Moderate/Severe Exacerbations Comparing FF/UMEC/VI With UMEC/VI in the Subset of Participants With a Blood Eosinophil Count >=150 Cells Per Microliter
Hide Description The annual rate of moderate or severe COPD exacerbations during the treatment, for participants with blood eosinophil count >=150 cells per microliter , has been reported. Moderate exacerbations, were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations were defined as exacerbations that required hospitalization or resulted in death. Only those participants with non-missing co-variates and non-missing eosinophil, at Baseline were included in the analysis.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/UMEC/VI UMEC/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 2296 1195
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per participant per year
0.95
(0.90 to 1.01)
1.39
(1.29 to 1.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, UMEC/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.62 to 0.75
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to First On-treatment Moderate/Severe Exacerbation Comparing FF/UMEC/VI With UMEC/VI in the Subset of Particpants With a Blood Eosinophil Count >=150 Cells Per Microliter at Baseline
Hide Description This measures the number of days, to the first onset of moderate or severe exacerbations for participants with blood eosinophil count >=150 cells per microliter, at Baseline has been reported. Moderate exacerbations, were defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization or resulting in death). Severe exacerbations, were defined as exacerbations that required hospitalization or resulted in death. Only those participants with non-missing co-variates and non missing eosinophils at Baseline were included in the analysis. First quartile and median time to onset are taken from the Kaplan-Meier estimates. If <25% (and <50%) of participants experienced the event within a treatment then Q1 (and median) time to onset are displayed as NA (not applicable) for that treatment.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/UMEC/VI UMEC/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 2296 1195
Measure Type: Number
Unit of Measure: Days
First quartile time to onset 107 55
Median time to onset NA [1]  253
[1]
If <25% (and <50%) of participants experienced the event within a treatment then Q1 (and median) time to onset are displayed as NA (not applicable) for that treatment.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, UMEC/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.70 to 0.85
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Annual Rate of On-treatment Severe Exacerbations Comparing FF/UMEC/VI With FF/VI and With UMEC/VI
Hide Description The annual rate of severe COPD exacerbations during the treatment, has been reported. Severe exacerbations were defined as exacerbations that required hospitalization or resulted in death. The covariates of treatment group, sex, exacerbation history (<=1, >=2 moderate/severe), smoking status (Screening), geographical region and post-bronchodilator percent predicted FEV1 (Screening) were used. Only those participants with non-missing co-variates were included in the analysis
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title FF/UMEC/VI FF/VI UMEC/VI
Hide Arm/Group Description:
The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks.
The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
Overall Number of Participants Analyzed 4145 4133 2069
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per participant per year
0.13
(0.12 to 0.14)
0.15
(0.13 to 0.16)
0.19
(0.17 to 0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, FF/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments [Not Specified]
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.76 to 1.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/UMEC/VI, UMEC/VI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.56 to 0.78
Estimation Comments [Not Specified]
Time Frame On-treatment Serious adverse events (SAEs) and Adverse events (AEs) are reported from the first dose of randomized medication up to Week 52.
Adverse Event Reporting Description All AEs and SAEs in the ITT Population were reported. The number of on-treatment deaths are reported from date of first dose of study medication up to the day after the last date of study medication.
 
Arm/Group Title FF/UMEC/VI 100/62.5/25 FF/VI 100/25 UMEC/VI 62.5/25
Hide Arm/Group Description The eligible participants in this arm received FF/UMEC/VI as a FDC as 100 µcg/62.5µcg/25µcg, QD via a DPI, in the morning, for duration of 52 weeks. The eligible participants in this arm received FF/VI 100µcg/25µcg QD via DPI, in the morning for duration of 52 weeks. The eligible participants in this arm received UMEC/VI 62.5µcg/25µcg QD via DPI, in the morning for duration of 52 weeks.
All-Cause Mortality
FF/UMEC/VI 100/62.5/25 FF/VI 100/25 UMEC/VI 62.5/25
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   68/4151 (1.64%)      76/4134 (1.84%)      49/2070 (2.37%)    
Show Serious Adverse Events Hide Serious Adverse Events
FF/UMEC/VI 100/62.5/25 FF/VI 100/25 UMEC/VI 62.5/25
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   895/4151 (21.56%)      850/4134 (20.56%)      470/2070 (22.71%)    
Blood and lymphatic system disorders       
Anaemia  1  1/4151 (0.02%)  1 4/4134 (0.10%)  4 0/2070 (0.00%)  0
Autoimmune haemolytic anaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Coagulopathy  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Haemorrhagic disorder  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Iron deficiency anaemia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Leukocytosis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Microcytic anaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Thrombocytopenia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Cardiac disorders       
Acute coronary syndrome  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 3/2070 (0.14%)  3
Acute left ventricular failure  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Acute myocardial infarction  1  13/4151 (0.31%)  14 8/4134 (0.19%)  8 6/2070 (0.29%)  6
Angina pectoris  1  2/4151 (0.05%)  3 3/4134 (0.07%)  3 2/2070 (0.10%)  2
Angina unstable  1  7/4151 (0.17%)  8 6/4134 (0.15%)  6 2/2070 (0.10%)  2
Aortic valve incompetence  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Aortic valve stenosis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Arteriosclerosis coronary artery  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Atrial fibrillation  1  21/4151 (0.51%)  24 13/4134 (0.31%)  13 6/2070 (0.29%)  6
Atrial flutter  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Atrial tachycardia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Atrial thrombosis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Atrioventricular block  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Atrioventricular block complete  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 2/2070 (0.10%)  2
Atrioventricular dissociation  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Bradycardia  1  3/4151 (0.07%)  3 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Cardiac arrest  1  4/4151 (0.10%)  4 2/4134 (0.05%)  2 2/2070 (0.10%)  2
Cardiac disorder  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cardiac failure  1  12/4151 (0.29%)  12 7/4134 (0.17%)  8 3/2070 (0.14%)  3
Cardiac failure acute  1  2/4151 (0.05%)  3 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Cardiac failure chronic  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 2/2070 (0.10%)  2
Cardiac failure congestive  1  21/4151 (0.51%)  28 12/4134 (0.29%)  12 7/2070 (0.34%)  10
Cardiac valve disease  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Cardio-respiratory arrest  1  4/4151 (0.10%)  4 4/4134 (0.10%)  4 5/2070 (0.24%)  5
Cardiogenic shock  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cardiomyopathy  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Cardiopulmonary failure  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Congestive cardiomyopathy  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Cor pulmonale  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Cor pulmonale chronic  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Coronary artery disease  1  4/4151 (0.10%)  4 2/4134 (0.05%)  2 3/2070 (0.14%)  3
Coronary artery insufficiency  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Coronary artery occlusion  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Coronary artery stenosis  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 2/2070 (0.10%)  2
Ischaemic cardiomyopathy  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Left ventricular failure  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Mitral valve incompetence  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Myocardial infarction  1  10/4151 (0.24%)  10 6/4134 (0.15%)  6 7/2070 (0.34%)  7
Myocardial ischaemia  1  5/4151 (0.12%)  6 1/4134 (0.02%)  1 3/2070 (0.14%)  3
Palpitations  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Pericardial effusion  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Prinzmetal angina  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Right ventricular failure  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Sinus arrest  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Sinus node dysfunction  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Supraventricular extrasystoles  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Supraventricular tachycardia  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Tachyarrhythmia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Tachycardia  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Tricuspid valve incompetence  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Ventricular arrhythmia  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Ventricular extrasystoles  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Ventricular fibrillation  1  2/4151 (0.05%)  2 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Ventricular tachycardia  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Congenital, familial and genetic disorders       
Developmental hip dysplasia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hydrocele  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Myocardial bridging  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Odontogenic cyst  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Ear and labyrinth disorders       
Meniere's disease  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Vertigo  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Vestibular disorder  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Endocrine disorders       
Adrenal mass  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hyperthyroidism  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Eye disorders       
Amaurosis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cataract  1  3/4151 (0.07%)  3 5/4134 (0.12%)  5 2/2070 (0.10%)  2
Cataract nuclear  1  2/4151 (0.05%)  3 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Conjunctival haemorrhage  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Diplopia  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Retinal detachment  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Vitreous haemorrhage  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gastrointestinal disorders       
Abdominal adhesions  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Abdominal compartment syndrome  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Abdominal discomfort  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Abdominal distension  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Abdominal hernia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Abdominal pain  1  3/4151 (0.07%)  3 4/4134 (0.10%)  4 2/2070 (0.10%)  2
Abdominal pain lower  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Abdominal pain upper  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Anal fistula  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Ascites  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Colitis  1  2/4151 (0.05%)  3 3/4134 (0.07%)  3 1/2070 (0.05%)  1
Colitis ulcerative  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Constipation  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Crohn's disease  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Diarrhoea  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Diarrhoea haemorrhagic  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Diverticulum intestinal  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Diverticulum intestinal haemorrhagic  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Duodenal ulcer  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Duodenitis  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Dysphagia  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Erosive duodenitis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Erosive oesophagitis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Faecaloma  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Gastric polyps  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gastric ulcer  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Gastric ulcer haemorrhage  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Gastric ulcer perforation  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Gastritis  1  4/4151 (0.10%)  5 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Gastritis erosive  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Gastrointestinal haemorrhage  1  1/4151 (0.02%)  1 4/4134 (0.10%)  4 0/2070 (0.00%)  0
Gastrointestinal inflammation  1  0/4151 (0.00%)  0 1/4134 (0.02%)  2 0/2070 (0.00%)  0
Gastrooesophageal reflux disease  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Haematemesis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Haemorrhoids  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Ileus  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Incarcerated inguinal hernia  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Incarcerated umbilical hernia  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Inguinal hernia  1  6/4151 (0.14%)  6 4/4134 (0.10%)  4 1/2070 (0.05%)  1
Intestinal obstruction  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Intestinal perforation  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Intestinal polyp  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Irritable bowel syndrome  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Large intestinal obstruction  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Large intestine polyp  1  2/4151 (0.05%)  2 2/4134 (0.05%)  2 2/2070 (0.10%)  2
Lower gastrointestinal haemorrhage  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Nausea  1  1/4151 (0.02%)  3 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pancreatic cyst  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Pancreatic failure  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pancreatitis  1  3/4151 (0.07%)  4 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Pancreatitis acute  1  4/4151 (0.10%)  4 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Peritoneal haemorrhage  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Rectal haemorrhage  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Retroperitoneal fibrosis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Small intestinal obstruction  1  2/4151 (0.05%)  2 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Umbilical hernia  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Upper gastrointestinal haemorrhage  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Vomiting  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
General disorders       
Asthenia  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Chest discomfort  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Chest pain  1  5/4151 (0.12%)  5 3/4134 (0.07%)  3 7/2070 (0.34%)  7
Complication associated with device  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Condition aggravated  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Death  1  3/4151 (0.07%)  3 5/4134 (0.12%)  5 2/2070 (0.10%)  2
General physical health deterioration  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hernia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Impaired healing  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Implant site fibrosis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Incarcerated hernia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Medical device site haemorrhage  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Multiple organ dysfunction syndrome  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Non-cardiac chest pain  1  8/4151 (0.19%)  8 10/4134 (0.24%)  10 1/2070 (0.05%)  1
Oedema peripheral  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pain  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Peripheral swelling  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Pyrexia  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 2/2070 (0.10%)  2
Stent-graft endoleak  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Sudden cardiac death  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Sudden death  1  3/4151 (0.07%)  3 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Systemic inflammatory response syndrome  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Hepatobiliary disorders       
Biliary colic  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Cholecystitis  1  3/4151 (0.07%)  3 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Cholecystitis acute  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Cholecystitis chronic  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Cholelithiasis  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 5/2070 (0.24%)  5
Gallbladder perforation  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Gallbladder polyp  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hepatitis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Immune system disorders       
Allergy to arthropod sting  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Anaphylactic reaction  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 2/2070 (0.10%)  2
Anaphylactic shock  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Drug hypersensitivity  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Infections and infestations       
Abdominal abscess  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Abscess  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Acute sinusitis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Anal abscess  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Appendiceal abscess  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Appendicitis  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Appendicitis perforated  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Arthritis bacterial  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Aspergillus infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Bacterial sepsis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Bronchiolitis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Bronchitis  1  10/4151 (0.24%)  10 10/4134 (0.24%)  11 3/2070 (0.14%)  3
Bronchitis bacterial  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Carbuncle  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cellulitis  1  6/4151 (0.14%)  6 1/4134 (0.02%)  4 3/2070 (0.14%)  3
Cellulitis staphylococcal  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Cholecystitis infective  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Clostridial infection  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Clostridium difficile colitis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Clostridium difficile infection  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Colonic abscess  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Corona virus infection  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Cystitis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Device related infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Diarrhoea infectious  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Diverticulitis  1  3/4151 (0.07%)  3 3/4134 (0.07%)  3 1/2070 (0.05%)  1
Empyema  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Endocarditis bacterial  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Enteritis infectious  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Enterocolitis infectious  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Erysipelas  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Escherichia urinary tract infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Fungal oesophagitis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Gangrene  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gastroenteritis  1  1/4151 (0.02%)  1 5/4134 (0.12%)  5 2/2070 (0.10%)  2
Gastroenteritis salmonella  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Gastroenteritis viral  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
H1N1 influenza  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Haemophilus infection  1  3/4151 (0.07%)  3 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Helicobacter gastritis  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Helicobacter infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hepatitis C  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Herpes zoster  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Infected skin ulcer  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Infected varicose vein  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Infection  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Infectious colitis  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Infectious pleural effusion  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Infective exacerbation of bronchiectasis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease  1  8/4151 (0.19%)  8 19/4134 (0.46%)  20 7/2070 (0.34%)  8
Influenza  1  7/4151 (0.17%)  7 6/4134 (0.15%)  6 5/2070 (0.24%)  5
Kidney infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Laryngitis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Liver abscess  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lower respiratory tract infection  1  7/4151 (0.17%)  8 4/4134 (0.10%)  4 4/2070 (0.19%)  5
Lung abscess  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Lung infection  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Meningitis viral  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Mycobacterial infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Mycoplasma infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Nosocomial infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Oesophageal candidiasis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Oral infection  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Orchitis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Osteomyelitis  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Osteomyelitis acute  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Parainfluenzae virus infection  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Parotitis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Peritonitis  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Pharyngotonsillitis  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Pneumococcal sepsis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pneumonia  1  184/4151 (4.43%)  198 152/4134 (3.68%)  165 54/2070 (2.61%)  55
Pneumonia bacterial  1  2/4151 (0.05%)  3 9/4134 (0.22%)  9 0/2070 (0.00%)  0
Pneumonia fungal  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Pneumonia haemophilus  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pneumonia influenzal  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Pneumonia klebsiella  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Pneumonia necrotising  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pneumonia pneumococcal  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pneumonia pseudomonal  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Pneumonia staphylococcal  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Postoperative wound infection  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Pseudomonas infection  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Pulmonary tuberculosis  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Pyelonephritis acute  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Respiratory syncytial virus infection  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Respiratory tract infection  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Respiratory tract infection bacterial  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Respiratory tract infection viral  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Rhinovirus infection  1  1/4151 (0.02%)  1 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Sepsis  1  9/4151 (0.22%)  10 8/4134 (0.19%)  8 6/2070 (0.29%)  6
Sepsis syndrome  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Septic shock  1  4/4151 (0.10%)  4 2/4134 (0.05%)  2 3/2070 (0.14%)  3
Sinusitis  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Soft tissue infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Staphylococcal infection  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Streptococcal infection  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Subacute endocarditis  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Subcutaneous abscess  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Subdiaphragmatic abscess  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Superinfection  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Tonsillitis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Tooth abscess  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Tracheobronchitis  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Tuberculosis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Upper respiratory tract infection  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Urinary tract infection  1  4/4151 (0.10%)  4 7/4134 (0.17%)  7 4/2070 (0.19%)  4
Urosepsis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Viral upper respiratory tract infection  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Injury, poisoning and procedural complications       
Alcohol poisoning  1  4/4151 (0.10%)  4 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Animal bite  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Ankle fracture  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Chemical peritonitis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  2 0/2070 (0.00%)  0
Chest injury  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Comminuted fracture  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Conjunctival laceration  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Contusion  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Craniocerebral injury  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Facial bones fracture  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Fall  1  0/4151 (0.00%)  0 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Femoral neck fracture  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Femur fracture  1  2/4151 (0.05%)  2 3/4134 (0.07%)  3 1/2070 (0.05%)  1
Fibula fracture  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Foot fracture  1  3/4151 (0.07%)  4 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Foreign body  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Foreign body aspiration  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gastrointestinal disorder postoperative  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gun shot wound  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hand fracture  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Head injury  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Heat illness  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hip fracture  1  4/4151 (0.10%)  4 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Humerus fracture  1  4/4151 (0.10%)  4 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Incisional hernia  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Jaw fracture  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Joint injury  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Limb injury  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lower limb fracture  1  3/4151 (0.07%)  3 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Lumbar vertebral fracture  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Meniscus injury  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Multiple injuries  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Muscle rupture  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Overdose  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Pelvic fracture  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Post procedural haematoma  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Post procedural haematuria  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Post procedural haemorrhage  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Post procedural stroke  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Postoperative respiratory failure  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Procedural complication  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Procedural pain  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Radius fracture  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Rib fracture  1  9/4151 (0.22%)  10 3/4134 (0.07%)  3 1/2070 (0.05%)  1
Seroma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Skin injury  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Soft tissue injury  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Spinal compression fracture  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Spinal fracture  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Splenic rupture  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Stress fracture  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Tendon rupture  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Thermal burn  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Tibia fracture  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Toxicity to various agents  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Ulna fracture  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Upper limb fracture  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Wound dehiscence  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Wound evisceration  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Investigations       
Biopsy prostate  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Blood glucose increased  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Blood pressure increased  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
C-reactive protein increased  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Fibrin D dimer increased  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hepatic enzyme increased  1  3/4151 (0.07%)  3 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Occult blood positive  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Prostatic specific antigen increased  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Streptococcus test positive  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Transaminases increased  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Troponin increased  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Weight decreased  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Metabolism and nutrition disorders       
Acetonaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Dehydration  1  4/4151 (0.10%)  4 5/4134 (0.12%)  5 2/2070 (0.10%)  2
Diabetes mellitus  1  3/4151 (0.07%)  3 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Diabetes mellitus inadequate control  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Fluid overload  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gout  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hyperglycaemia  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hyperglycaemic hyperosmolar nonketotic syndrome  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Hyperkalaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hyperlipidaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hypocalcaemia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hypoglycaemia  1  3/4151 (0.07%)  3 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hypokalaemia  1  7/4151 (0.17%)  7 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hyponatraemia  1  5/4151 (0.12%)  5 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Hypophagia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hypovolaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Iron deficiency  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lactic acidosis  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Metabolic acidosis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Obesity  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Type 2 diabetes mellitus  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Vitamin B12 deficiency  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  4/4151 (0.10%)  4 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Back pain  1  2/4151 (0.05%)  2 1/4134 (0.02%)  2 0/2070 (0.00%)  0
Bone infarction  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Bursitis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Costochondritis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Dupuytren's contracture  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Femoroacetabular impingement  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Groin pain  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Intervertebral disc disorder  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Intervertebral disc protrusion  1  1/4151 (0.02%)  1 3/4134 (0.07%)  3 3/2070 (0.14%)  3
Lumbar spinal stenosis  1  1/4151 (0.02%)  1 2/4134 (0.05%)  3 1/2070 (0.05%)  1
Muscle haemorrhage  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Musculoskeletal chest pain  1  2/4151 (0.05%)  3 4/4134 (0.10%)  4 0/2070 (0.00%)  0
Musculoskeletal pain  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Neck pain  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Osteoarthritis  1  9/4151 (0.22%)  9 5/4134 (0.12%)  6 1/2070 (0.05%)  1
Osteonecrosis  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Osteoporosis  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Pain in extremity  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Rhabdomyolysis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Rotator cuff syndrome  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Spinal column stenosis  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 2/2070 (0.10%)  2
Spinal deformity  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Spinal ligament ossification  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Spinal osteoarthritis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Spondylitis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Spondylolisthesis  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Vertebral foraminal stenosis  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 2/2070 (0.10%)  2
Adenocarcinoma gastric  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Adenocarcinoma of colon  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
B-cell lymphoma  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Basal cell carcinoma  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Benign breast neoplasm  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Benign fallopian tube neoplasm  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Bladder cancer  1  0/4151 (0.00%)  0 4/4134 (0.10%)  5 0/2070 (0.00%)  0
Bladder neoplasm  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Bladder transitional cell carcinoma  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Bladder transitional cell carcinoma stage I  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Bone neoplasm  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Brain neoplasm  1  2/4151 (0.05%)  2 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Breast cancer  1  2/4151 (0.05%)  2 2/4134 (0.05%)  2 2/2070 (0.10%)  2
Bronchial carcinoma  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Cervix carcinoma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Colon cancer  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Colon cancer stage I  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Epiglottic carcinoma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Fibroma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Gastric cancer  1  0/4151 (0.00%)  0 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Gastrointestinal neoplasm  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Glottis carcinoma  1  0/4151 (0.00%)  0 1/4134 (0.02%)  2 0/2070 (0.00%)  0
Haemangioma of spleen  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Hepatic angiosarcoma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hepatic cancer metastatic  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Hepatic neoplasm  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hepatocellular carcinoma  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Invasive ductal breast carcinoma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Laryngeal cancer  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Laryngeal squamous cell carcinoma  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Lung adenocarcinoma  1  4/4151 (0.10%)  4 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lung adenocarcinoma stage III  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Lung cancer metastatic  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 0/2070 (0.00%)  0
Lung carcinoma cell type unspecified stage I  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lung carcinoma cell type unspecified stage IV  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lung neoplasm  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Lung neoplasm malignant  1  6/4151 (0.14%)  6 10/4134 (0.24%)  10 2/2070 (0.10%)  2
Lung squamous cell carcinoma stage II  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Lymphoma  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Malignant neoplasm of ampulla of Vater  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Malignant neoplasm of unknown primary site  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Metastases to bone  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Metastases to central nervous system  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Metastases to liver  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Metastases to lung  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Metastases to lymph nodes  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Monoclonal gammopathy  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Myelodysplastic syndrome  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Neoplasm  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Neuroendocrine carcinoma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Neuroendocrine tumour of the lung  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Non-small cell lung cancer  1  2/4151 (0.05%)  2 3/4134 (0.07%)  3 1/2070 (0.05%)  1
Oesophageal carcinoma  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Oral neoplasm  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Pancreatic carcinoma  1  3/4151 (0.07%)  3 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Pancreatic neoplasm  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Papilloma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Plasma cell myeloma  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Prostate cancer  1  4/4151 (0.10%)  4 4/4134 (0.10%)  4 1/2070 (0.05%)  1
Pyogenic granuloma  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Rectal adenocarcinoma  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Sarcoma  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Small cell lung cancer  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Small cell lung cancer metastatic  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Small intestine carcinoma  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Soft tissue sarcoma  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Squamous cell carcinoma of lung  1  3/4151 (0.07%)  3 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Squamous cell carcinoma of the cervix  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Squamous cell carcinoma of the oral cavity  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Throat cancer  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Tonsil cancer  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Transitional cell carcinoma  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 1/2070 (0.05%)  1
Urethral cancer  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Vulval cancer  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Nervous system disorders       
Aphasia  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Ataxia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Brain stem ischaemia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Brain stem stroke  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Carotid artery occlusion  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Carotid artery stenosis  1  4/4151 (0.10%)  4 1/4134 (0.02%)  1 1/2070 (0.05%)  1
Cerebellar infarction  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cerebral amyloid angiopathy  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cerebral haemorrhage  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Cerebral infarction  1  3/4151 (0.07%)  3 3/4134 (0.07%)  3 0/2070 (0.00%)  0
Cerebral ischaemia  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Cerebrovascular accident  1  7/4151 (0.17%)  7 6/4134 (0.15%)  7 3/2070 (0.14%)  3
Cerebrovascular disorder  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Cerebrovascular insufficiency  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Cognitive disorder  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Dizziness  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Encephalopathy  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Guillain-Barre syndrome  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Haemorrhage intracranial  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Headache  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 2/2070 (0.10%)  2
Hemiparesis  1  1/4151 (0.02%)  1 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hypoaesthesia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Hypoxic-ischaemic encephalopathy  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Intracranial aneurysm  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Ischaemic stroke  1  4/4151 (0.10%)  4 5/4134 (0.12%)  5 0/2070 (0.00%)  0
Lacunar infarction  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Loss of consciousness  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Mental impairment  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Metabolic encephalopathy  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Migraine  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Myoclonus  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Paraesthesia  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Parkinson's disease  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Peripheral nerve paresis  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Post herpetic neuralgia  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Presyncope  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Radicular syndrome  1  1/4151 (0.02%)  3 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Sciatica  1  3/4151 (0.07%)  4 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Seizure  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Simple partial seizures  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Syncope  1  6/4151 (0.14%)  6 5/4134 (0.12%)  5 3/2070 (0.14%)  3
Tension headache  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Thalamic infarction  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Transient ischaemic attack  1  8/4151 (0.19%)  8 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Psychiatric disorders       
Affective disorder  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Alcoholism  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Anxiety  1  1/4151 (0.02%)  1 2/4134 (0.05%)  2 3/2070 (0.14%)  3
Completed suicide  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Confusional state  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Delirium  1  1/4151 (0.02%)  1 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Depression  1  2/4151 (0.05%)  2 4/4134 (0.10%)  4 1/2070 (0.05%)  1
Depression suicidal  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Insomnia  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Major depression  1  2/4151 (0.05%)  2 0/4134 (0.00%)  0 0/2070 (0.00%)  0
Mental status changes  1  2/4151 (0.05%)  2 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Psychotic disorder due to a general medical condition  1  0/4151 (0.00%)  0 0/4134 (0.00%)  0 1/2070 (0.05%)  1
Substance-induced psychotic disorder  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0
Suicide attempt  1  0/4151 (0.00%)  0 1/4134 (0.02%)  1 0/2070 (0.00%)  0