Rapid Point of Care Testing (POCT) for influenza could be used to provide information on influenza vaccine effectiveness (IVE) as well as influencing clinical decision-making in primary care.
We ...undertook a test negative case control study to estimate the overall and age-specific (6 months-17 years, 18-64 years, ≥65 years old) IVE against medically attended POCT-confirmed influenza. The study took place over the winter of 2019-2020 and was nested within twelve general practices that are part of the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), the English sentinel surveillance network.
648 POCT were conducted. 193 (29.7%) of those who were swabbed had received the seasonal influenza vaccine. The crude unadjusted overall IVE was 46.1% (95% CI: 13.9-66.3). After adjusting for confounders the overall IVE was 26.0% (95% CI: 0-65.5). In total 211 patients were prescribed an antimicrobial after swab testing. Given a positive influenza POCT result, the odds ratio (OR) of receiving an antiviral was 21.1 (95%CI: 2.4-182.2, p = <0.01) and the OR of being prescribed an antibiotic was 0.6 (95%CI: 0.4-0.9, p = <0.01).
Using influenza POCT in a primary care sentinel surveillance network to estimate IVE is feasible and provides comparable results to published IVE estimates. A further advantage is that near patient testing of influenza is associated with improvements in appropriate antiviral and antibiotic use. Larger, randomised studies are needed in primary care to see if these trends are still present and to explore their impact on outcomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute gastroenteritis (AGE) is a highly transmissible condition spreading rapidly between individuals and within households. Rotavirus vaccination was introduced in the UK in 2013. The study ...objectives were to investigate how acute gastroenteritis incidence changed over 25 years and household incidence of AGE since 2013.
Repeated cross-sectional study of Royal College of General Practitioners Research and Surveillance Centre network. We used a negative binomial model to report incidence rate ratio (IRR) using the last 5 years data. We also conducted a retrospective cohort analysis, using a shared gamma frailty model (2013-2017). We explored the impact of child under 5- years, household size, socioeconomic status quintile, and rurality.
In the cross-sectional analysis, the IRR of AGE in households with a child of under 5 years was 12.20 (95%CI 11.08-13.45-, p < 0.001) compared with households without; the IRR fell across IMD quintiles, for example there is a 37% decrease in incidence comparing IMD quintile 1 to quintile 5 (95%CI -0.52-0.76, p < 0.001), The cohort study revealed that the presence of an under 5 in the household was associated with a higher risk of household presentation (HR = 6.29, 95% CI 5.61-7.06, p < 0.001). In addition, we observe a reduction in risk of presentation from the most to the least deprived socioeconomic quintile (second quintile: HR = 0.74 (95%CI 0.59-0.92), to least deprived quintile, HR = 0.55 (95%CI 0.41-0.74). We saw a lower association with male gender, white ethnicity and living outside London, but an increased association with increasing household size.
The incidence of AGE has changed over time: pre-school children, larger households, and living in London were associated with higher rates, and male gender and higher economic status associated with lower rates.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral ...anticoagulants (DOACs) or warfarin treatment. We conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72-1.63, p = 0.69) and all-cause mortality 0.93 (0.81-1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71-1.6 p = 0.75) for stroke and 0.93 (0.8-1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38-0.01, p = 0.001); which persisted over seven years of follow-up. In this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several new classes of glucose-lowering medications have been introduced in the past two decades. Some, such as sodium-glucose cotransporter 2 inhibitors (SGLT2s), have evidence of improved ...cardiovascular outcomes, while others, such as dipeptidyl peptidase-4 inhibitors (DPP4s), do not. It is therefore important to identify their uptake in order to find ways to support the use of more effective treatments.
To analyse the uptake of these new classes among patients with type 2 diabetes.
This was a retrospective repeated cross-sectional analysis in primary care. Rates of medication uptake in Australia, Canada, England, and Scotland were compared.
Primary care Electronic Medical Data on prescriptions (Canada, UK) and dispensing data (Australia) from 2012 to 2017 were used. Individuals aged ≥40 years on at least one glucose-lowering drug class in each year of interest were included, excluding those on insulin only. Proportions of patients in each nation, for each year, on each class of medication, and on combinations of classes were determined.
Data from 238 619 patients were included in 2017. The proportion of patients on sulfonylureas (SUs) decreased in three out of four nations, while metformin decreased in Canada. Use of combinations of metformin and new drug classes increased in all nations, replacing combinations involving SUs. In 2017, more patients were on DPP4s (between 19.1% and 27.6%) than on SGLT2s (between 10.1% and 15.3%).
New drugs are displacing SUs. However, despite evidence of better outcomes, the adoption of SGLT2s lagged behind DPP4s.
Direct observation of the household spread of influenza and respiratory infections is limited; much of our understanding comes from mathematical models. The study aims to determine household ...incidence of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections within a primary care routine data and identify factors associated with the diseases' incidence.
We conducted two five-year retrospective analyses of influenza-like illness (ILI), lower (LRTI) and upper (URTI) respiratory infections using the England Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network database; a cross-sectional study reporting incident rate ratio (IRR) from a negative binomial model and a retrospective cohort study, using a shared gamma frailty survival model, reporting hazard ratios (HR). We reported the following household characteristics: children < 5 years old, each extra household member, gender, ethnicity (reference white), chronic disease, pregnancy, and rurality.
The IRR where there was a child < 5 years were 1·62 (1·38-1·89, p < 0·0001), 2·40 (2.04-2.83, p < 0·0001) and 4·46 (3.79-5.255, p < 0·0001) for ILI, LRTI and URTI respectively. IRR also increased with household size, rurality and presentations and by female gender, compared to male. Household incidence of URTI and LRTI changed little between years whereas influenza did and were greater in years with lower vaccine effectiveness. The HR where there was a child < 5 years were 2·34 (95%CI 1·88-2·90, p < 0·0001), 2·97 (95%CI 2·76-3·2, p < 0·0001) and 10·32 (95%CI 10.04-10.62, p < 0·0001) for ILI, LRTI and URTI respectively. HR were increased with female gender, rurality, and increasing household size.
Patterns of household incidence can be measured from routine data and may provide insights for the modelling of disease transmission and public health policy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vaccine co-administration can facilitate the introduction of new vaccines in immunisation schedules and improve coverage. We analysed real life data to quantify the extent of routine paediatric ...vaccine co-administrations as recommended and as never recommended in the immunisation schedule in England, and assessed factors for recommended and never recommended vaccine co-administrations.
Immunisation data for all scheduled routine paediatric vaccines between 2008 and 2018 was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).
We included 6′257′828 doses administered to 1′005′827 children. Twenty-one percent of vaccines were given separately, 79% were co-administered. Sixty-four percent of vaccines scheduled for co-administration were co-administered as recommended while 15% were administered separately. Among all vaccine co-administrations, 75% happened as recommended in the schedule, 4% were never recommended, while 21% deviated from the schedule. Vaccine co-administration according to the schedule varied greatly between vaccines. Forty-eight percent of English children received at least one of their vaccine co-administrations not as recommended in the immunisation schedule, with 19% of children receiving none of their co-administered vaccines as recommended. Late administration of one or more vaccines increased the odds for deviated co-administrations (OR 1.60) and strongly increased the odds for never recommended co-administrations (OR 5.34). Differences between genders, NHS regions, and IMD quintiles were statistically significant but small.
Suboptimal co-administration rates for routine paediatric vaccines are a missed opportunity and should be optimised by concerted public health action.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric ...vaccinations according to the NHS’s immunisation schedule and potential factors of schedule adherence. Immunisation data was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We collected vaccine types, doses, and dates for all routine paediatric vaccines between 2008 and 2018: DTaP/IPV/Hib/HepB, DTaP/IPV/Hib, DTaP/IPV, dTaP/IPV, Td/IPV, MMR, PCV, MenB, MenC, MenACWY, Hib/MenC, RV, HPV. Adherence to the immunisation schedule was calculated for each vaccine and dose. Differences in adherence between genders, NHS regions, and IMD quintiles were analysed. Our study included 6′257′828 vaccinations in 1′005′827 children. Seventy-five percent of first doses were administered within one (for vaccines scheduled in the first year of life) or two months (for vaccines scheduled later in life) following the recommended age, 19% too late and 6% too early. About half of the subsequent doses were given timely. The time between first and second doses was too short for 36% of vaccinations while 13% of second doses were administered too long after the first dose. Third doses were administered timely for 45%, too short for 37%, and too long for 18% of vaccinations. Differences in immunisation schedule adherence between girls and boys were negligible, except for HPV, and differences between the four main NHS regions were small. Overall, immunisation schedule adherence improved slightly with decreasing deprivation according to the Index of Multiple Deprivation. Efforts are required to improve the timeliness of paediatric vaccinations and to assure adequate protection against vaccine preventable diseases. We propose developing a compound measure combining coverage and adherence to provide a better indication of the protection against vaccine preventable diseases in a community.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IntroductionAs new vaccines are developed more vaccine coadministrations vaccines are being offered to make delivery more practical for health systems and patients. We compared the safety of ...coadministered vaccines with separate vaccination for 20 coadministrations by considering nine types of adverse events following immunisation (AEFI).MethodsReal-life immunisation and adverse event data for this observational cohort study were extracted from the Oxford-Royal College of General Practitioners Research and Surveillance Centre for children registered in the database between 2008 and 2018. We applied the self-controlled case series method to calculate relative incidence ratios (RIR) for AEFI. These RIRs compare the RI of AEFI following coadministration with the RI following separate administration of the same vaccines.ResultsWe assessed 3 518 047 adverse events and included 5 993 290 vaccine doses given to 958 591 children. 17% of AEFI occurred less and 11% more frequently following coadministration than would have been expected based on the RIs following separate vaccinations, while there was no significant difference for 72% of AEFI. We found amplifying interaction effects for AEFI after five coadministrations comprising three vaccines: for fever (RIR 1.93 (95% CI 1.63 to 2.29)), rash (RIR 1.49 (95% CI 1.29 to 1.74)), gastrointestinal events (RIR 1.31 (95% CI 1.14 to 1.49)) and respiratory events (RIR 1.27 (1.17–1.38)) following DTaP/IPV/Hib+MenC+ PCV; gastrointestinal events (RIR 1.65 (95% CI 1.35 to 2.02)) following DTaP/IPV/Hib+MenC+ RV; fever (RIR 1.44 (95% CI 1.09 to 1.90)) and respiratory events (RIR 1.40 (95% CI 1.25 to 1.57)) following DTaP/IPV/Hib+PCV+ RV; gastrointestinal (RIR 1.48 (95% CI 1.20 to 1.82)) and respiratory events (RIR 1.43 (95% CI 1.26 to 1.63)) following MMR+Hib/MenC+PCV; gastrointestinal events (RIR 1.68 (95% CI 1.07 to 2.64)) and general symptoms (RIR 11.83 (95% CI 1.28 to 109.01)) following MMR+MenC+PCV. Coadministration of MMR+PCV led to more fever (RIR 1.91 (95% CI 1.83 to 1.99)), neurological events (RIR 2.04 (95% CI 1.67 to 2.49)) and rash (RIR 1.06 (95% CI 1.01 to 1.11)) compared with separate administration, DTaP/IPV/Hib+MMR to more musculoskeletal events (RIR 3.56 (95% CI 1.21 to 10.50)) and MMR+MenC to more fever (RIR 1.58 (95% CI 1.37 to 1.82)). There was no indication that unscheduled coadministrations are less safe than scheduled coadministrations.ConclusionReal-life RIRs of AEFI justify coadministering routine childhood vaccines according to the immunisation schedule. Further research into the severity of AEFI following coadministration is required for a complete understanding of the burden of these AEFI.
Background
The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) has provided in-pandemic evidence that azithromycin and doxycycline were not beneficial in the ...early primary care management of coronavirus 2019 disease (COVID-19).
Aim
To explore the extent of in-pandemic azithromycin and doxycycline use, and the scope for trial findings impacting on practice.
Design & setting
Crude rates of prescribing and respiratory tract infections (RTI) in 2020 were compared with 2019, using the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).
Method
Negative binomial models were used to compare azithromycin and doxycycline prescribing, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years, and 95% confidence intervals (95% CI).
Results
Azithromycin prescriptions increased 7% in 2020 compared with 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4%, respectively) while ILI rose slightly (6.4%). The overall percentage of RTI-prescribed azithromycin rose from 0.51% in 2019 to 0.72% in 2020 (risk difference 0.214%; 95% CI = 0.211 to 0.217); doxycycline rose from 11.86% in 2019 to 15.79% in 2020 (risk difference 3.93%; 95% CI = 3.73 to 4.14). The adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR = 1.22; 95% CI = 1.19 to 1.26;
P
<0.0001). For every unit rise in confirmed COVID-19 there was an associated 3% rise in prescription (IRR = 1.03; 95% CI = 1.02 to 1.03;
P
<0.0001); whereas these measures were static for doxycycline.
Conclusion
PRINCIPLE demonstrates scope for improved antimicrobial stewardship during a pandemic.
Familial hypercholesterolaemia (FH) is an inherited lipid disorder causing premature heart disease, which is severely underdiagnosed. Improving the identification of people with FH in primary care ...settings would help to reduce avoidable heart attacks and early deaths.
To evaluate the accuracy of the familial hypercholesterolaemia case ascertainment identifcation tool (FAMCAT) for identifying FH in primary care.
A retrospective cohort study of 1 030 183 patients was undertaken. Data were extracted from the UK Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. Patient were aged >16 years.
The FAMCAT algorithm was compared with methods of FH detection recommended by national guidelines (Simon Broome diagnostic criteria, Dutch Lipid Clinic Network DLCN Score, and cholesterol levels >99
centile). Discrimination and calibration were assessed by area under the receiver operating curve (AUC) and by comparing observed versus predicted cases.
A total of 1707 patients had a diagnosis of FH. FAMCAT showed a high level of discrimination (AUC = 0.844, 95% confidence interval CI = 0.834 to 0.854), performing significantly better than Simon Broome criteria (AUC = 0.730, 95% CI = 0.719 to 0.741), DLCN Score (AUC = 0.766, 95% CI = 0.755 to 0.778), and screening cholesterols >99 th centile (AUC = 0.579, 95% CI = 0.571 to 0.588). Inclusion of premature myocardial infarction (MI) and fitting cholesterol as a continuous variable improved the accuracy of FAMCAT (AUC = 0.894, 95% CI = 0.885 to 0.903).
Better performance of the FAMCAT algorithm, compared with other approaches for case finding of FH in primary care, such as Simon Broome criteria, DLCN criteria or very high cholesterol levels, has been confirmed in a large population cohort.
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