Validity of Routine Health Data To Identify Safety Outcomes of Interest For Covid-19 Vaccines and Therapeutics in the Context of the Emerging Pandemic: A Comprehensive Literature Review.

Introduction: Regulatory guidance encourages transparent reporting of information on the quality and validity of electronic health record data being used to generate real-world benefit-risk evidence for vaccines and therapeutics. We aimed to provide an overview of the availability of validated diagnostic algorithms for selected safety endpoints for Coronavirus disease 2019 (COVID-19) vaccines and therapeutics in the context of the emerging pandemic prior to December 2020. Methods: We reviewed the literature up to December 2020 to identify validation studies for various safety events of interest, including myocardial infarction, arrhythmia, myocarditis, acute cardiac injury, vasculitis/vasculopathy, venous thromboembolism, stroke, respiratory distress syndrome (RDS), pneumonitis, cytokine release syndrome (CRS), multiple organ dysfunction syndrome, and renal failure. We included studies published between 2015 and 2020 that were considered high quality assessed with QUADAS and that reported positive predictive values (PPVs). Results: Out of 43 identified studies, we found that diagnostic algorithms for cardiovascular outcomes were supported by the highest number of validation studies (n=17). Accurate algorithms are available for myocardial infarction (median PPV 80%; IQR 22%), arrhythmia (PPV range >70%), venous thromboembolism (median PPV: 73%) and ischaemic stroke (PPV range ≥85%). We found a lack of validation studies for less common respiratory and cardiac safety outcomes of interest (eg, pneumonitis and myocarditis), as well as for COVID-specific complications (CRS, RDS). Conclusion: There is a need for better understanding of barriers to conducting validation studies, including data governance restrictions. Regulatory guidance should promote embedding validation within real-world EHR research used for decision-making.

Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study.

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. OBJECTIVE: To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. METHODS: A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. RESULTS: In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p = 0.219). CONCLUSION: There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population.

Healthcare resource utilisation and cost of pneumococcal disease from 2003 to 2019 in children ≤17 years in England.

OBJECTIVE: To estimate healthcare resource utilisation (HCRU) and costs associated with pneumococcal disease (PD) in children aged ≤17 years in England from 2003-2019. METHODS: A retrospective study in children aged ≤17 years was conducted using the Clinical Practice Research Datalink Gold primary care database and Hospital Episodes Statistics Admitted Patient Care database from 2003-2019. Episodes of invasive pneumococcal disease (IPD) were identified in hospital, pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) episodes in primary care and in hospital, and acute otitis media (AOM) episodes in primary care. General practitioner (GP) visits and inpatient admission yearly rates were calculated per 1,000 persons. The average inpatient and primary care cost per episode were calculated. The Mann-Kendall test was used to assess monotonic time trends. RESULTS: 1,500,686 children were followed from 2003-2019. The highest average inpatient cost per episode [£34,255 (95%CI 27,222-41,288)] was in IPD, followed by ACP [£3,549 (95%CI 3,405-3,693)] and PP [£1,498 (95%CI 1,153-1,843)]. The highest primary care costs per episode were in AOM [£48.7 (95%CI 48.7-48.7)], followed by PP [£38.4 (95%CI 37.0-39.7)] and ACP [£28.6 (95%CI 28.2-29.1)]. The highest inpatient admission and GP visits yearly rates were observed in children aged <2 years. Across years, a significant decrease in GP visits yearly rates was observed for PP, ACP and AOM in children overall (p-value<0.001). A decrease in primary care costs was observed for ACP (p-value<0.001). There was an increasing trend in AOM primary care costs (p-value<0.001). No significant trends were observed in inpatient admission yearly rates in PP, ACP or IPD and inpatient costs per episode in PP, ACP and IPD. CONCLUSION: From 2003-2019, primary care HCRU and costs decreased (except for PP cost), but no trends in inpatient HCRU and costs were observed. The economic burden of pneumonia, IPD and AOM remains substantial in children aged ≤17 years in England.

Healthcare resource utilization and cost of pneumococcal disease in children in Germany, 2014-2019: a retrospective cohort study.

BACKGROUND: Since the introduction of higher valency pneumococcal conjugate vaccines in 2009, recent estimates on the economic burden of pediatric pneumococcal disease (PD) in Germany have been lacking. This study estimates healthcare resource utilization (HCRU) and medical cost associated with PDs in children < 16 years old in Germany from 2014-2019. METHODS: A nationally representative sample from the Institute for Applied Health Research (InGef) German claims database was used, covering approximately 5% of the total German population. Episodes of pneumococcal pneumonia (PP), all-cause pneumonia (ACP), invasive pneumococcal disease (IPD), and acute otitis media (AOM) in children aged < 16 years were identified using ICD-10-GM codes. HCRU was estimated from annual rates of outpatient visits, outpatient antibiotic prescriptions and inpatient admissions, divided by person-years (PY) at-risk. Average direct medical costs per episode were estimated as the total cost of all HCRU, divided by the total number of episodes. The Mann-Kendall test was used to assess monotonic time trends from 2014-2019. RESULTS:  During 2014-2019, 916,805 children aged < 16 years were followed up for a total of 3,608,716 PY. The average costs per episode for out-versus inpatient care associated with PP and ACP were €67 (95% CI 58-76) versus €2,606 (95% CI 1,338-3,873), and €63 (95% CI 62-63) versus €620 (95% CI 598-641), respectively. For IPD, the average medical cost per episode for out-versus inpatients were €30 (95% CI 19-42) versus €6,051 (95% CI 3,323-8,779), respectively. There were no significant trends in HCRU or costs for IPD or pneumonia over the study period, except for a significant reduction in ACP outpatient visits. A significant decrease in rate of outpatient visits and antibiotic prescribing for recurrent AOM was observed, in addition to an increase in rates of hospital admissions for simple AOM. This was paralleled by a significant increase in inpatient costs per episode for treating AOM overall, and simple AOM, over the study period. CONCLUSIONS:  The HCRU and cost per episode of pneumonia and IPD did not vary significantly from 2014-2019, but increased for AOM. The economic burden of pneumonia, IPD, and AOM remains substantial in Germany.

Incidence of pneumococcal disease from 2003 to 2019 in children ≤17 years in England.

BACKGROUND: Pneumococcal disease is a leading cause of communicable disease morbidity and mortality globally. We aimed to estimate invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) incidence rates (IRs) in children aged 0-17 years in England from 2003 to 2019. METHODS: A retrospective study in children ≤17 years old from 2003 to 2019 using the Clinical Practice Research Datalink (CPRD) Gold and Hospital Episodes Statistics Admitted Patient Care (HES APC) databases. IPD episodes were identified in hospital records (HES APC). PP (caused by Streptococcus pneumoniae only) and ACP episodes (caused by any pathogen) were identified in primary care (CPRD) and in hospital records (HES APC). Annual IRs by age-group were calculated as the number of episodes/person-years (PY) at risk, with 95% confidence intervals (95% CI). Interrupted time series analyses were conducted to assess changes in IRs across the post-PCV7 (2007-2009), early post-PCV13 (2011-2014) and late post-PCV13 (2015-2019) periods compared to the pre-PCV7 period (2003-2005) using generalized linear models. RESULTS: 170 IPD episodes, 769 PP episodes and 12,142 ACP episodes were identified in 1,500,686 children in 2003-2019. The overall IPD, PP and ACP IRs (per 100,000 PY) were 2.29 (95% CI 1.96-2.66), 10.34 (95% CI 9.62-11.10) and 163.37 (95% CI 160.47-166.30), respectively. The highest IPD, PP and ACP IRs were observed in children aged < 2 years compared to older children (2-4 and 5-17 years). IPD IRs decreased between the pre-PCV7 period and the late post-PCV13 period from 3.28 (95% CI 2.42-4.33) to 1.41 (95% CI 0.80-2.29), IRR 0.28 (95% CI 0.09-0.90), p-value 0.033. PP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 14.65 (95% CI 12.77-16.72) to 3.87 (95% CI 2.81-5.20), IRR 0.19 (95% CI 0.09-0.38), p-value < 0.001. ACP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 167.28 (95% CI 160.78-173.96) to 124.96 (95% CI 118.54-131.63), IRR 0.77 (95% CI 0.66-0.88), p-value < 0.001. CONCLUSIONS: The clinical burden of IPD, PP and ACP declined in children in England aged 0-17 years between 2003 and 2019, especially in the late post-PCV13 period. This study highlights the importance of PCV vaccination in reducing the burden of PD and ACP in children in England.

Incidence of acute otitis media from 2003 to 2019 in children ≤ 17 years in England.

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the UK. PCVs are active immunization for the prevention of invasive disease, pneumonia and acute otitis media (AOM) caused by Streptococcus pneumoniae in children. The aim of this observational study was to estimate incidence rates (IRs) of AOM in children ≤17 years from 2003 to 2019 in England, before and after the introduction of pneumococcal conjugate vaccines (PCVs). METHODS: AOM episodes were identified using Read diagnosis codes in children aged ≤17 years in the Clinical Practice Research Datalink (CPRD) Gold database from 2003 to 2019. Annual IRs with 95% confidence intervals (CI) by age group were calculated as the number of episodes/person-years (PY) at risk. Interrupted time series analyses were conducted to estimate incidence rate ratios (IRR) across post-PCV7 (2007-2009), early post-PCV13 (2011-2014) and late post-PCV13 (2015-2019) periods compared to the pre-PCV7 period (2003-2005) using generalized linear models. RESULTS: From 2003 to 2019, 274,008 all-cause AOM episodes were identified in 1,500,686 children. The overall AOM IR was 3690.9 (95% CI 3677.1-3704.8) per 100,000 PY. AOM IRs were highest in children aged < 5 years and decreased by age; < 2 years: 8286.7 (95% CI 8216.8-8357.1); 2-4 years: 7951.8 (95% CI 7902.5-8001.4); 5-17 years: 2184.4 (95% CI 2172.1-2196.8) (per 100,000 PY). Overall AOM IRs declined by 40.3% between the pre-PCV7 period and the late-PCV13 period from 4451.9 (95% CI 4418.1-4485.9) to 2658.5 (95% CI 2628.6-2688.7) per 100,000 PY, and across all age groups. IRRs indicated a significant decrease in AOM IRs in all the post-vaccination periods, compared to the pre-PCV7 period: post-PCV7 0.87 (95% CI 0.85-0.89), early post-PCV13 0.88 (95% CI 0.86-0.91), and late post-PCV13 0.75 (95% CI 0.73-0.78). CONCLUSIONS: The AOM IRs declined during the 2003-2019 period; however, the clinical burden of AOM remains substantial among children ≤17 years in England.

Clinical and economic burden of pneumococcal disease among individuals aged 16 years and older in Germany.

This study assessed the incidence rate of all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD) and associated medical costs among individuals aged ≥16 in the German InGef database from 2016 to 2019. Incidence rate was expressed as the number of episodes per 100 000 person-years (PY). Healthcare resource utilisation was investigated by age group and by risk group (healthy, at-risk, high-risk). Direct medical costs per ACP/IPD episode were estimated as the total costs of all inpatient and outpatient visits. The overall incidence rate of ACP was 1345 (95% CI 1339-1352) and 8.25 (95% CI 7.76-8.77) per 100 000 PY for IPD. For both ACP and IPD, incidence rates increased with age and were higher in the high-risk and at-risk groups, in comparison to the healthy group. ACP inpatient admission rate increased with age but remained steady across age-groups for IPD. The mean direct medical costs per episode were €8075 (95% CI 7121-9028) for IPD and €1454 (95% CI 1426-1482) for ACP. The aggregate direct medical costs for IPD and ACP episodes were estimated to be €8.5 million and €248.9 million respectively. The clinical and economic burden of IPD and ACP among German adults is substantial regardless of age.

Pneumococcal vaccination coverage in individuals (16-59 years) with a newly diagnosed risk condition in Germany.

BACKGROUND: Despite recommendations from the German Standing Committee on Vaccination (STIKO), pneumococcal vaccination coverage remains low in vulnerable populations. This study estimated the pneumococcal vaccination coverage rate (VCR) and timing among individuals aged 16-59 years in Germany who were recommended to receive pneumococcal vaccination, according to STIKO. METHODS: A retrospective cohort analysis was conducted using the German InGef database. Individuals aged 16 to 59 years diagnosed with at least one "at-risk" (chronic disease) or "high-risk" (e.g., immunocompromising) condition considered to be at-risk of pneumococcal infection were identified at the time of first diagnosis, between January 1, 2016 and December 31, 2018, and followed up until December 31, 2019. The percentage of cumulative pneumococcal VCR with 95% confidence interval (CI) was reported for each calendar year of follow-up. RESULTS: There were 334,292 individuals followed for a median of 2.38 (interquartile range (IQR) 1.63-3.13) person years. For individuals aged 16-59 years diagnosed with an incident risk condition in 2016, pneumococcal VCR increased from 0.44% (95% CI 0.41-0.48) in 2016 to 1.24% (95% CI 1.18-1.30) in 2019. In 2019, VCRs were higher in individuals with high-risk conditions compared with at-risk conditions (2.24% (95% CI 2.09-2.40) vs. 0.90% (95% CI 0.85-0.96)). In 2019, VCRs were higher in individuals aged 50 to 59 years compared with individuals aged 16 to 49 years (2.25% (95% CI 2.10-2.41) vs. 0.90% (95% CI 0.84-0.96)). Similar trends were observed in individuals with newly diagnosed risk conditions identified in 2017 and in 2018. Older age, influenza vaccination and increasing number of risk conditions increased the likelihood of pneumococcal vaccination. Median time to vaccination from diagnosis of the risk condition was shorter for high-risk conditions (369.5 days (IQR 155.8-702.0)) compared to at-risk conditions (435.5 days (IQR 196.3-758.8)). CONCLUSION: Despite recommendations from STIKO, pneumococcal vaccination coverage remains very low and with long delays in vulnerable individuals aged 16-59 in Germany. Further efforts are required to increase immunization levels and shorten time to vaccination among individuals 16-59 years of age developing conditions with higher susceptibility to pneumococcal infection.

Incidence of acute otitis media in children < 16 years old in Germany during 2014-2019.

BACKGROUND: Acute otitis media (AOM) remains a common infection in children despite the introduction of pneumococcal conjugate vaccines. This study estimated AOM incidence rates (IRs) over time in children < 16 years old in Germany following PCV13 introduction. METHODS: AOM episodes were identified in the InGef healthcare claims database from 2014-2019 in children aged < 16 years. Each AOM episode was classified as either simple or recurrent. Recurrent AOM was defined as 3 or more episodes identified within a 6-month period; or 4 or more episodes within a 12-month period with at least one episode in the prior 6 months. AOM-related surgical procedures within 12 months and complications within 21 days of an AOM episode were also identified. Annual IRs were calculated as number of episodes/child-years (CY) at risk. 95% Confidence intervals (95%CI) were calculated using the Wilson method. The Mann-Kendall test was used to assess trends over time. RESULTS: Between 2014 and 2019, the study population comprised 916,805 children with 327,726 AOM episodes, of which 15% (49,011) of all episodes were identified as recurrent AOM and 85% (278,715) as simple AOM. There were significant declines in AOM (p = 0.003) in the study population overall and in all age groups over the study period; from 101 (95%CI 101-102)/1000 CY to 79 (95%CI 78-80)/1000 CY in the total study population, from 209 (95%CI 206-212)/1000 CY to 147 (95%CI 145-150)/1000 CY in < 2-year-olds, from 239 (95%CI 237-242) to 179 (95%CI 177-182)/1000 CY in 2-4-year-olds, and from 50 (95%CI 49-50) to 38 (95%CI 37-39)/1000 CY in 5-15-year-olds. No significant trends were identified for AOM-related surgical procedures over the study period; however, AOM-related complications overall increased (p = 0.003). CONCLUSION: Between 2014 and 2019, AOM incidence overall declined in children aged 0-15 years in Germany. Over the study period, the incidence of complicated AOM cases increased, however the incidence of AOM-related surgical procedures remained constant. Despite the impact of PCV13, the burden associated with AOM in Germany remains substantial.

Impact of comorbidities on the safety and effectiveness of hip and knee arthroplasty surgery.

AIMS: Access to joint replacement is being restricted for patients with comorbidities in a number of high-income countries. However, there is little evidence on the impact of comorbidities on outcomes. The purpose of this study was to determine the safety and effectiveness of hip and knee arthroplasty in patients with and without comorbidities. METHODS: In total, 312,079 hip arthroplasty and 328,753 knee arthroplasty patients were included. A total of 11 common comorbidities were identified in administrative hospital records. Safety risks were measured by assessing length of hospital stay (LOS) and 30-day emergency readmissions and mortality. Effectiveness outcomes were changes in Oxford Hip or Knee Scores (OHS/OKS) (scale from 0 (worst) to 48 (best)) and in health-related quality of life (EQ-5D) (scale from 0 (death) to 1 (full health)) from immediately before, to six months after, surgery. Regression analysis was used to estimate adjusted mean differences (LOS, change in OHS/OKS/EQ-5D) and risk differences (readmissions and mortality). RESULTS: Patients with comorbidities had a longer LOS and higher readmission and mortality rates than patients without. In hip arthroplasty patients with heart disease, for example, LOS was 1.20 days (95% confidence interval (CI) 1.15 to 1.25) longer and readmission rate was 1.52% (95% CI 1.34% to 1.71%) and mortality 0.19% (95% CI 0.15% to 0.23%) higher. Similar patterns were observed for knee arthroplasty patients. Patients without comorbidities reported large improvements in function (mean improvement OHS 21.3 (SD 9.91) and OKS 15.9 (SD 10.0)). Patients with comorbidities reported only slightly smaller improvements. In patients with heart disease, mean improvement in OHS was 0.39 (95% CI 0.27 to 0.51) and in OKS 0.56 (95% CI 0.45 to 0.67) less than in patients without comorbidities. There were no significant differences in EQ-5D improvement. CONCLUSION: Comorbidities were associated with small increases in adverse safety risks but they have little impact on pain or function in patients undergoing hip or knee arthroplasty. These results do not support restricting access to hip and knee arthroplasty for patients with common comorbidities. Cite this article: Bone Joint J 2021;103-B(1):56-64.

Access to hip and knee replacement surgery in patients with chronic diseases according to patient-reported pain and functional status.

BACKGROUND: An increasing number of patients undergoing hip or knee replacement have chronic diseases. It has been suggested that the presence of chronic diseases may affect access to this type of surgery in the English National Health Service (NHS). We examined the access to hip and knee replacement surgery in patients with and without chronic diseases according to preoperative patient-reported pain, functional status and symptom duration. METHODS: We analysed data of 640,832 patients who had hip or knee surgery between 2009 and 2016 in England. Multivariable regression was used to estimate the impact of 11 chronic diseases on severity of joint problems as measured on a scale from 0 to 48 by Oxford Hip (OHS) and Knee Scores (OKS) just before surgery and on likelihood of long-standing joint problems (> 5 years pre-operatively). RESULTS: Patients with chronic diseases reported more severe joint problems than patients without (OHS differences ranged from 1.1 [95% CI 0.93, 1.2] to 2.5 [95% CI 2.3, 2.7] and OKS differences from 0.5 [95% CI 0.3, 0.7] to 2.6 [95% CI 2.4, 2.7] for the 11 chronic diseases) but the differences remain small. When analysed separately, patients with chronic diseases reported both more severe pain and poorer functional status. Six chronic diseases in hip patients and two in knee patients increased the likelihood that they had long-standing joint problems. The severity of joint problems just before surgery increased with the number of chronic diseases (OHS differences; one chronic disease (1.5 [95% CI 1.4, 1.5]) to four or more (5.8 [95% CI 5.6, 6.0])). CONCLUSIONS: Patients with chronic diseases reported more severe joint problems immediately before hip or knee replacement surgery suggesting they have hip or knee replacement later in the course of their joint disease.

The agreement between chronic diseases reported by patients and derived from administrative data in patients undergoing joint arthroplasty.

BACKGROUND: This study examined the agreement between patient-reported chronic diseases and hospital administrative records in hip or knee arthroplasty patients in England. METHODS: Survey data reported by 676,428 patients for the English Patient Reported Outcome Measures (PROMs) programme was linked to hospital administrative data. Sensitivity and specificity of 11 patient-reported chronic diseases were estimated with hospital administrative data as reference standard. RESULTS: Specificity was high (> 90%) for all 11 chronic diseases. However, sensitivity varied by disease with the highest found for 'diabetes' (87.5%) and 'high blood pressure' (74.3%) and lowest for 'kidney disease' (18.8%) and 'leg pain due to poor circulation' (26.1%). Sensitivity was increased for diseases that were given as specific examples in the questionnaire (e.g. 'parkinson's disease' (65.6%) and 'multiple sclerosis' (69.5%), compared to 'diseases of the nervous system' (20.9%)). CONCLUSIONS: Patients can give information about the presence of chronic diseases that is consistent with chronic diseases derived from hospital administrative data if the description in the patient questionnaire is precise and if the disease is familiar to most patients and has significant impact on their life. Such patient questionnaires need to be validated before they are used for research and service evaluation projects.

Comorbidities and the referral pathway to access joint replacement surgery: an exploratory qualitative study.

BACKGROUND: Variation in access to joint replacement surgery has been widely reported but less attention has been given to the impact of comorbidities on the patient journey to joint replacement surgery. There is a lack of consensus amongst healthcare professionals and commissioners about how patients with comorbidities should be referred or selected for joint replacement surgery. It is therefore important to understand the views of healthcare professionals on the management, referral and selection of patients with comorbidities for joint replacement surgery. METHODS: An exploratory qualitative study involving semi-structured interviews with 20 healthcare professionals in England across the referral pathway to joint replacement surgery. They were asked to talk about their experiences of referring and selecting patients with comorbidities for joint replacement surgery. The interviews were audio-recorded and transcribed verbatim. Data analysis followed a thematic analysis approach based on the principles of grounded theory. RESULTS: In general, the presence of comorbidities was not seen as a barrier to being referred or selected for joint replacement but was seen as a challenge to manage the patients' journey across the referral pathway. Each professional group, concentrated on different aspects of the patients' condition which appeared to affect how they managed patients with comorbidities. This implied there was a disagreement about roles and responsibilities in the management of patients with comorbidities. None of the professionals believed it was their responsibility to address comorbidities in preparation for surgery. This disagreement was identified as a reason why some patients seem to 'get lost' in the referral system when they were considered to be unprepared for surgery. Patients were then potentially left to manage their own comorbidities before being reconsidered for joint replacement. CONCLUSIONS: At the clinician-level, comorbidities were not perceived as a barrier to accessing joint replacement surgery but at the pathway-level, it may create an implicit barrier such that patients with comorbidities may get 'lost' to the system. Further study is needed to explore the roles and responsibilities of professionals across the current orthopaedic referral pathway which may be less suitable for patients with comorbidities.

Impact of comorbid conditions on outcomes of hip and knee replacement surgery: a systematic review and meta-analysis.

OBJECTIVE: To systematically perform a meta-analysis of the association between different comorbid conditions on safety (short-term outcomes) and effectiveness (long-term outcomes) in patients undergoing hip and knee replacement surgery. DESIGN: Systematic review and meta-analysis. METHODS: Medline, Embase and CINAHL Plus were searched up to May 2017. We included all studies that reported data to allow the calculation of a pooled OR for the impact of 11 comorbid conditions on 10 outcomes (including surgical complications, readmissions, mortality, function, health-related quality of life, pain and revision surgery). The quality of included studies was assessed using a modified Newcastle-Ottawa Scale. Continuous outcomes were converted to ORs using the Hasselblad and Hedges approach. Results were combined using a random-effects meta-analysis. OUTCOMES: The primary outcome was the adjusted OR for the impact of each 11 comorbid condition on each of the 10 outcomes compared with patients without the comorbid condition. Where the adjusted OR was not available the secondary outcome was the crude OR. RESULTS: 70 studies were included with 16 (23%) reporting on at least 100 000 patients and 9 (13%) were of high quality. We found that comorbidities increased the short-term risk of hospital readmissions (8 of 11 conditions) and mortality (8 of 11 conditions). The impact on surgical complications was inconsistent across comorbid conditions. In the long term, comorbid conditions increased the risk of revision surgery (6 of 11 conditions) and long-term mortality (7 of 11 conditions). The long-term impact on function, quality of life and pain varied across comorbid conditions. CONCLUSIONS: This systematic review shows that comorbidities predominantly have an impact on the safety of hip and knee replacement surgery but little impact on its effectiveness. There is a need for high-quality studies also considering the severity of comorbid conditions.