Elizabeth Orton

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Background Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. Methodology/Principal Findings Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I2 and publication bias was assessed using Beggs funnel plot and Eggers regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.16–0.34; p<0.001) and laboratory confirmed influenza infection (OR = 0.15; 95% CI = 0.03–0.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. Conclusions/Significance Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.

Independent risk factors for injury in pre-school children: three population-based nested case-control studies using routine primary care data

Background Injuries in childhood are largely preventable yet an estimated 2,400 children die every day because of injury and violence. Despite this, the factors that contribute to injury occurrence have not been quantified at the population scale using primary care data. We used The Health Improvement Network (THIN) database to identify risk factors for thermal injury, fractures and poisoning in pre-school children in order to inform the optimal delivery of preventative strategies. Methods We used a matched, nested case-control study design. Cases were children under 5 with a first medically recorded injury, comprising 3,649 thermal injury cases, 4,050 fracture cases and 2,193 poisoning cases, matched on general practice to 94,620 control children. Results Younger maternal age and higher birth order increased the odds of all injuries. Children’s age of highest injury risk varied by injury type; compared with children under 1 year, thermal injuries were highest in those age 1-2 (OR = 2.43, 95%CI 2.23–2.65), poisonings in those age 2-3 (OR = 7.32, 95%CI 6.26–8.58) and fractures in those age 3-5 (OR = 3.80, 95%CI 3.42–4.23). Increasing deprivation was an important modifiable risk factor for poisonings and thermal injuries (tests for trend p≤0.001) as were hazardous/harmful alcohol consumption by a household adult (OR = 1.73, 95%CI 1.26–2.38 and OR = 1.39, 95%CI 1.07–1.81 respectively) and maternal diagnosis of depression (OR = 1.45, 95%CI 1.24–1.70 and OR = 1.16, 95%CI 1.02–1.32 respectively). Fracture was not associated with these factors, however, not living in single-adult household reduced the odds of fracture (OR = 0.88, 95%CI 0.82–0.95). Conclusions Maternal depression, hazardous/harmful adult alcohol consumption and socioeconomic deprivation represent important modifiable risk factors for thermal injury and poisoning but not fractures in preschool children. Since these risk factors can be ascertained from routine primary care records, pre-school children’s frequent visits to primary care present an opportunity to reduce injury risk by implementing effective preventative interventions from existing national guidelines.

Identification of incident poisoning, fracture and burn events using linked primary care, secondary care and mortality data from England: implications for research and surveillance

Background English national injury data collection systems are restricted to hospitalisations and deaths. With recent linkage of a large primary care database, the Clinical Practice Research Datalink (CPRD), with secondary care and mortality data, we aimed to assess the utility of linked data for injury research and surveillance by examining recording patterns and comparing incidence of common injuries across data sources. Methods The incidence of poisonings, fractures and burns was estimated for a cohort of 2 147 853 0–24 year olds using CPRD linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality data between 1997 and 2012. Time-based algorithms were developed to identify incident events, distinguishing between repeat follow-up records for the same injury and those for a new event. Results We identified 42 985 poisoning, 185 517 fracture and 36 719 burn events in linked CPRD-HES-ONS data; incidence rates were 41.9 per 10 000 person-years (95% CI 41.4 to 42.4), 180.8 (179.8–181.7) and 35.8 (35.4–36.1), respectively. Of the injuries, 22 628 (53%) poisonings, 139 662 (75%) fractures and 33 462 (91%) burns were only recorded within CPRD. Only 16% of deaths from poisoning (n=106) or fracture (n=58) recorded in ONS were recorded within CPRD and/or HES records. None of the 10 deaths from burns were recorded in CPRD or HES records. Conclusions It is essential to use linked primary care, hospitalisation and deaths data to estimate injury burden, as many injury events are only captured within a single data source. Linked routinely collected data offer an immediate and affordable mechanism for injury surveillance and analyses of population-based injury epidemiology in England.

Risk factors for scald injury in children under 5 years of age: A case-control study using routinely collected data

Scald injury is common, accounting for half of all burns in pre-school children. Most scalds are preventable and health professionals can play an important role in targeting interventions to those at greatest risk. However, the potential for routinely collected medical data to be used to identify high risk children has not been well explored. We used a matched case-control study to identify risk factors for first scald injury in children under 5 using a large, nationally representative database of routinely collected primary care records. Among 986 cases and 9240 controls, male gender, age (2 years), higher birth order, single-parent families and increasing index of material deprivation were associated with increased odds of scald injury. Older maternal age at childbirth was associated with decreased odds of scald injury. Children at risk of scald injury can be identified from routinely collected primary care data and primary care practitioners can use this information to target evidence-based safety interventions.

Persistence of Health Inequalities in Childhood Injury in the UK; A Population-Based Cohort Study of Children under 5

Background Injury is a significant cause of childhood death and can result in substantial long-term disability. Injuries are more common in children from socio-economically deprived families, contributing to health inequalities between the most and least affluent. However, little is known about how the relationship between injuries and deprivation has changed over time in the UK. Methods We conducted a cohort study of all children under 5 registered in one of 495 UK general practices that contributed medical data to The Health Improvement Network database between 1990–2009. We estimated the incidence of fractures, burns and poisonings by age, sex, socio-economic group and calendar period and adjusted incidence rate ratios (IRR) comparing the least and most socio-economically deprived areas over time. Estimates of the UK annual burden of injuries and the excess burden attributable to deprivation were derived from incidence rates. Results The cohort of 979,383 children experienced 20,804 fractures, 15,880 burns and 10,155 poisonings, equating to an incidence of 75.8/10,000 person-years (95% confidence interval 74.8–76.9) for fractures, 57.9 (57.0–58.9) for burns and 37.3 (35.6–38.0) for poisonings. Incidence rates decreased over time for burns and poisonings and increased for fractures (p<0.001 test for trend for each injury). They were significantly higher in more deprived households (IRR test for trend p<0.001 for each injury type) and these gradients persisted over time. We estimate that 865 fractures, 3,763 burns and 3,043 poisonings could be prevented each year in the UK if incidence rates could be reduced to those of the most affluent areas. Conclusions The incidence of burns and poisonings declined between 1990 and 2009 but increased for fractures. Despite these changes, strong socio-economic inequalities persisted resulting in an estimated 9,000 additional medically-attended injuries per year in under-5s.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta‐analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta‐analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta‐analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

Children at risk of medicinal and non-medicinal poisoning: a population-based case-control study in general practice

BACKGROUND Preschool children have a high risk of poisoning. While medicines prescribed by primary care are potential poisoning agents, the risk factors for poisoning from medication are not well described. AIM To identify risk factors for medicinal and non-medicinal poisoning in preschool children. DESIGN AND SETTING Population-based nested case-control study using The Health Improvement Network primary care database 1988-2004. METHOD Conditional logistic regression was used to identify child, maternal, and social risk factors for medicinal (1316 cases) and non-medicinal poisoning (503 cases), using 17 709 controls matched on general practice. RESULTS Poisoning by medicines was independently associated with deprivation (test for trend P<0.001), maternal age (P<0.001), birth order (P<0.001), maternal alcohol misuse (odds ratio [OR] = 5.44, 95% confidence interval [CI] = 1.99 to 14.91), and perinatal depression (OR = 1.54, 95% CI = 1.26 to 1.88). Living in a household with two or more adults lowered the odds of injury compared to single-parent households (OR = 0.85, 95% CI = 0.74 to 0.96) and the odds varied by age, being highest in 2 year olds (OR = 9.61, 95% CI = 7.73 to 11.95). Non-medicinal poisoning was associated with deprivation (P = 0.001), maternal age (P<0.001), and birth order (P<0.001). The odds were raised in 1 year olds (OR = 5.44, 95% CI = 4.07 to 7.26) and 2 year olds (OR = 5.07, 95% CI = 3.73 to 6.90) compared to those aged <1 year. CONCLUSION Primary care data can be used to target interventions to children at risk of poisoning. This is pertinent when prescribing for children/family members, as prescribed medications may become poisoning agents. Prompt identification of maternal depression and alcohol misuse, and delivery of poisoning-prevention interventions at this stage may help prevent poisonings.

Risk factors for long-bone fractures in children up to 5 years of age: a nested case–control study

Aim To investigate risk factors for first long-bone fractures in children up to 5 years old in order to provide evidence about which families could benefit from injury prevention interventions. Methods Population-based matched nested case–control study using The Health Improvement Network, a UK primary care research database, 1988–2004. Maternal, household and child risk factors for injury were assessed among 2456 children with long-bone fractures (cases). 23 661controls were matched to cases on general practice. Adjusted ORs and 95% CIs were estimated using conditional logistic regression. Results Fractures of long-bones were independently associated with younger maternal age and higher birth order, with children who were the fourth-born in the family, or later, having a threefold greater odds of fracture compared to first-born children (adjusted OR 3.12, 95% CI 2.08 to 4.68). Children over the age of 1 year had a fourfold (13–24 months, adjusted OR 4.09 95% CI 3.51 to 4.76) to fivefold (37+ months, adjusted OR 4.88 95% CI 4.21 to 5.66) increase in the odds of a long-bone fracture compared to children aged 0–12 months. Children in families with a history of maternal alcohol misuse had a raised odds of long-bone fracture (adjusted OR 2.33, 95% CI 1.13 to 4.82) compared to those with no documented history. Conclusions Risk factors for long-bone fractures in children less than 5 years old included age above 1 year, increasing birth order, younger maternal age and maternal alcohol misuse. These risk factors should be used to prioritise families and communities for injury prevention interventions.

Venous thromboembolism in adults screened for sickle cell trait: a population-based cohort study with nested case–control analysis

Objective To determine whether sickle cell carriers (‘sickle cell trait’) have an increased risk of venous thromboembolism (VTE). Design Cohort study with nested case–control analysis. Setting General population with data from 609 UK general practices in the Clinical Practice Research Datalink (CPRD). Participants All individuals registered with a CPRD general practice between 1998 and 2013, with a medical record of screening for sickle cell between 18 and 75 years of age. Main outcomes measures Incidence of VTE per 10 000 person-years (PY) among sickle cell carriers and non-carriers; and adjusted OR for VTE among sickle cell carriers compared with non-carriers. Results We included 30 424 individuals screened for sickle cell, with a follow-up time of 179 503 PY, identifying 55 VTEs in 6758 sickle cell carriers and 125 VTEs in 23 666 non-carriers. VTE incidence among sickle cell carriers (14.9/10 000 PY; 95% CI 11.4 to 19.4) was significantly higher than non-carriers (8.8/10 000 PY; 95% CI 7.4 to 10.4). Restricting analysis to confirmed non-carriers was non-significant, but performed on a small sample. In the case–control analysis (180 cases matched to 1775 controls by age and gender), sickle cell carriers remained at increased risk of VTE after adjusting for body mass index, pregnancy, smoking status and ethnicity (OR 1.78, 95% CI 1.18 to 2.69, p=0.006), with the greatest risk for pulmonary embolism (PE) (OR 2.27, 95% CI 1.17 to 4.39, p=0.011). Conclusions Although absolute numbers are small, in a general population screened for sickle cell, carriers have a higher incidence and risk of VTE, particularly PE, than non-carriers. Clinicians should be aware of this elevated risk in the clinical care of sickle cell carriers, or when discussing carrier screening, and explicitly attend to modifiable risk factors for VTE in these individuals. More complete primary care coding of carrier status could improve analysis.

Changes in poisonings among adolescents in the UK between 1992 and 2012: a population based cohort study

Background Poisonings are a common cause of morbidity and mortality among adolescents. Yet surveillance data indicating current incidence rates (IRs) and time trends are lacking, making policy development and service planning difficult. We utilised population based primary care data to estimate adolescent poisoning rates according to intent across the UK. Methods A cohort study of 1 311 021 adolescents aged 10–17 years, between 1992 and 2012, was conducted using routine primary care data from The Health Improvement Network. IRs and adjusted IRRs with 95% CIs were calculated for all poisonings, intentional, unintentional, unknown intent and alcohol related poisonings, by age, sex, calendar time and socioeconomic deprivation. Results Overall poisoning incidence increased by 27% from the period 1992–1996 to 2007–2012, with the largest increases in intentional poisonings among females aged 16–17 years (IR 391.4/100 000 person years (PY), CI 328.9 to 465.7 for age 17 years in 1992–1996; 767.0/100 000 PY, CI 719.5 to 817.7 in 2007–2012) and alcohol related poisonings in females aged 15–16 years (IR 65.7/100 000 PY, CI 43.3 to 99.8 rising to 130.0/100 000 PY, CI 110.0 to 150.0 for age 15 years). A strong socioeconomic gradient for all poisonings persisted over time, with higher rates among the more deprived (IRR 2.63, CI 2.41 to 2.88 for the most vs least deprived quintile in 2007–2012). Conclusions Adolescent poisonings, especially intentional poisonings, have increased substantially over time and remain associated with health inequalities. Social and psychological support for adolescents should be targeted at more deprived communities, and child and adolescent mental health and alcohol support service provision should be commissioned to reflect the changing need.