An assessment of potential unintended consequences following a national antimicrobial stewardship programme in England: an interrupted time series analysis

Background: The 'Quality Premium' (QP) introduced in England in 2015 aimed to financially reward local healthcare commissioners for targeted reductions in primary care antibiotic prescribing. We aimed to evaluate possible unintended clinical outcomes related to this QP. Methods: Using Clinical Practice Research Datalink and Hospital Episode Statistics datasets, we examined general practitioner (GP) consultations (visits) and emergency hospital admissions related to a series of pre-defined conditions of unintended consequences of reduced prescribing. Monthly age and sex-standardised rates were calculated using a direct method of standardisation. We used segmented regression analysis of interrupted time series to evaluate the impact of the QP on seasonally adjusted outcome rates. Results: We identified 27,334 GP consultations and over five million emergency hospital admissions with pre-defined conditions. There was no evidence that the QP was associated with changes in GP consultation and hospital admission rates for the selected conditions combined. However, when each condition was considered separately, a significant increase in hospital admission rates was noted for quinsy, and significant decreases were seen for hospital-acquired pneumonia, scarlet fever, pyelonephritis and complicated urinary tract conditions. A significant decrease in GP consultation rates was estimated for empyema and scarlet fever. No significant changes were observed for other conditions. Conclusions: Findings from this study show that overall there was no significant association between the intervention and unintended clinical consequences, with the exception of a few specific conditions, most of which could be explained through other parallel policy changes or should be interpreted with caution due to small numbers

Impact of Caesarean section on subsequent fertility: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between a Caesarean section and subsequent fertility? SUMMARY ANSWER: Most studies report that fertility is reduced after Caesarean section compared with vaginal delivery. However, studies with a more robust design show smaller effects and it is uncertain whether the association is causal. WHAT IS KNOWN ALREADY: A previous systematic review published in 1996 summarizing six studies including 85 728 women suggested that Caesarean section reduces subsequent fertility. The included studies suffer from severe methodological limitations. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis of cohort studies comparing subsequent reproductive outcomes of women who had a Caesarean section with those who delivered vaginally. PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of Cochrane Library, Medline, Embase, CINAHL Plus and Maternity and Infant Care databases were conducted in December 2011 to identify randomized and non-randomized studies that compared the subsequent fertility outcomes after a Caesarean section and after a vaginal delivery. Eighteen cohort studies including 591 850 women matched the inclusion criteria. Risk of bias was assessed by the Newcastle-Ottawa scale (NOS). Data extraction was done independently by two reviewers. The meta-analysis was based on a random-effects model. Subgroup analyses were performed to assess whether the estimated effect was influenced by parity, risk adjustment, maternal choice, cohort period, and study quality and size. MAIN RESULTS AND THE ROLE OF CHANCE: The impact of Caesarean section on subsequent pregnancies could be analysed in 10 studies and on subsequent births in 16 studies. A meta-analysis suggests that patients who had undergone a Caesarean section had a 9% lower subsequent pregnancy rate [risk ratio (RR) 0.91, 95% confidence interval (CI) (0.87, 0.95)] and 11% lower birth rate [RR 0.89, 95% CI (0.87, 0.92)], compared with patients who had delivered vaginally. Studies that controlled for maternal age or specifically analysed primary elective Caesarean section for breech delivery, and those that were least prone to bias according to the NOS reported smaller effects. LIMITATIONS, REASONS FOR CAUTION: There is significant variation in the design and methods of included studies. Residual bias in the adjusted results is likely as no study was able to control for a number of important maternal characteristics, such as a history of infertility or maternal obesity. WIDER IMPLICATIONS OF THE FINDINGS: Further research is needed to reduce the impact of selection bias by indication through creating more comparable patient groups and applying risk adjustment

Descriptive epidemiology of Escherichia coli bacteraemia in England, April 2012 to March 2014

We determined the incidence, risk factors and antimicrobial susceptibility associated with Escherichia coli bacteraemia in England over a 24 month period. Case data were obtained from the national mandatory surveillance database, with susceptibility data linked from LabBase2, a voluntary national microbiology database. Between April 2012 and March 2014, 66,512 E. coli bacteraemia cases were reported. Disease incidence increased by 6% from 60.4 per 100,000 population in 2012-13 to 63.5 per 100,000 population in 2013-14 (p < 0.0001). Rates of E. coli bacteraemia varied with patient age and sex, with 70.5% (46,883/66,512) of cases seen in patients aged ≥ 65 years and 52.4% (33,969/64,846) of cases in females. The most common underlying cause of bacteraemia was infection of the genital/urinary tract (41.1%; 27,328/66,512), of which 98.4% (26,891/27,328) were urinary tract infections (UTIs). The majority of cases (76.1%; 50,617/66,512) had positive blood cultures before or within two days of admission and were classified as community onset cases, however 15.7% (10,468/66,512) occurred in patients who had been hospitalised for over a week. Non-susceptibility to ciprofloxacin, third-generation cephalosporins, piperacillin-tazobactam, gentamicin and carbapenems were 18.4% (8,439/45,829), 10.4% (4,256/40,734), 10.2% (4,694/46,186), 9.7% (4,770/49,114) and 0.2% (91/42,986), respectively. Antibiotic non-susceptibility was higher in hospital-onset cases than for those presenting from the community (e.g. ciprofloxacin non-susceptibility was 22.1% (2,234/10,105) for hospital-onset vs 17.4% (5,920/34,069) for community-onset cases). Interventions to reduce the incidence of E. coli bacteraemia will have to target the community setting and UTIs if substantial reductions are to be realised

Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis

Objectives: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs). Method: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD), between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium. Results: Prescribing rates decreased over the six year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1,000 RTI consultations) (p<0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after two years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change two years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats. Conclusions: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients

Speciation of common Gram-negative pathogens using a highly multiplexed high resolution melt curve assay

The identification of the bacterial species responsible for an infection remains an important step for the selection of antimicrobial therapy. Gram-negative bacteria are an important source of hospital and community acquired infections and frequently antimicrobial resistant. Speciation of bacteria is typically carried out by biochemical profiling of organisms isolated from clinical specimens, which is time consuming and delays the initiation of tailored treatment. Whilst molecular methods such as PCR have been used, they often struggle with the challenge of detecting and discriminating a wide range of targets. High resolution melt analysis is an end-point qPCR detection method that provides greater multiplexing capability than probe based methods. Here we report the design of a high resolution melt analysis assay for the identification of six common Gram-negative pathogens; Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Salmonella Sp, and Acinetobacter baumannii, and a generic Gram-negative specific 16S rRNA control. The assay was evaluated using a well characterised collection of 113 clinically isolated Gram-negative bacteria. The agreement between the HRM assay and the reference test of PCR and sequencing was 98.2% (Kappa 0.96); the overall sensitivity and specificity of the assay was 97.1% (95% CI: 90.1–99.7%) and 100% (95% CI: 91.78–100%) respectively

Respiratory antibacterial prescribing in primary care and the COVID-19 pandemic in England, winter season 2020–21

Background Antibacterial prescribing for respiratory tract infections (RTIs) accounts for almost half of all prescribing in primary care. Nearly a quarter of antibacterial prescribing in primary care is estimated to be inappropriate, the greatest being for RTIs. The COVID-19 pandemic has changed the provision of healthcare services and impacted the levels of antibacterials prescribed. Objectives To describe the changes in community antibacterial prescribing for RTIs in winter 2020–21 in England. Methods RTI antibacterial prescribing was measured in prescription items/1000 population for primary care from January 2014 and in DDDs/1000 population/day for the totality of RTI prescribing [combined with Accident & Emergency (A&E) in secondary care], from January 2016 to February 2021. Trends were assessed using negative binomial regression and seasonally adjusted interrupted time-series analysis. Results Antibacterials prescribed for RTIs reduced by a further 12.4% per season compared with pre-COVID (P < 0.001). In winter 2020–21, RTI prescriptions almost halved compared with the previous winter in 2019–20 (P < 0.001). The trend observed for total RTI prescribing (primary care with A&E) was similar to that observed in the community alone. Conclusions During COVID-19, RTI prescribing reduced in the community and the expected rise in winter was not seen in 2020–21. We found no evidence that RTI prescribing shifted from primary care to A&E in secondary care. The most likely explanation is a decrease in RTIs and presentations to primary care associated with national prevention measures for COVID-19

Seasonal changes in the incidence of Escherichia coli bloodstream infection: variation with region and place of onset.

Previous research has shown that Escherichia coli infection rates peak in the summer; however, to date there has been no investigation as to whether this is seen in both hospital and community-onset cases, and how this differs across regions. We investigated and quantified E. coli bloodstream infection (BSI) seasonality. A generalized additive Poisson model was fitted to mandatory E. coli BSI surveillance data reported in England. There was no impact of seasonality in hospital-onset cases; however, for the community-onset cases, there was statistically significant seasonal variation over time nationally. When examined regionally, seasonality was significant in the North of England only. This variation resulted in an absolute increase of 0.06 (95% CI 0.02-0.1) cases above the mean (3.25) in each hospital trust for each week of the peak summer season, and a decrease of (-) 0.07 (95% CI -0.1 to -0.03) in the autumn. We estimate that fewer than one hospital bed-day per week per hospital is lost because of seasonal increases during the summer. Our findings highlight the need to understand the distinct community and hospital dynamics of E. coli BSI, and to explore the regional differences driving the variation in incidence, in order to design and implement effective control measures

Respiratory antibacterial prescribing in primary care and the COVID-19 pandemic in England, winter season 2020–21

Background Antibacterial prescribing for respiratory tract infections (RTIs) accounts for almost half of all prescribing in primary care. Nearly a quarter of antibacterial prescribing in primary care is estimated to be inappropriate, the greatest being for RTIs. The COVID-19 pandemic has changed the provision of healthcare services and impacted the levels of antibacterials prescribed. Objectives To describe the changes in community antibacterial prescribing for RTIs in winter 2020–21 in England. Methods RTI antibacterial prescribing was measured in prescription items/1000 population for primary care from January 2014 and in DDDs/1000 population/day for the totality of RTI prescribing [combined with Accident & Emergency (A&E) in secondary care], from January 2016 to February 2021. Trends were assessed using negative binomial regression and seasonally adjusted interrupted time-series analysis. Results Antibacterials prescribed for RTIs reduced by a further 12.4% per season compared with pre-COVID (P

Comparison of three CT-guided epidural steroid injection approaches in 104 patients with cervical radicular pain: transforaminal anterolateral, posterolateral, and transfacet indirect.

The treatment of persistent cervical radicular pain (CRP) by CT-guided epidural steroid injections (CTESI) by a transforaminal anterolateral (TFA) approach is associated with rare but serious complications. Two recently described transforaminal posterolateral (TFP) and transfacet indirect (TFT) approaches may be safer options, but have not been extensively evaluated. We compared the efficacy of three CTESI approaches (TFA, TFP, and TFT) in the treatment of persistent CRP (&gt;6 weeks). Patients were prospectively assessed for pain using the visual analog scale (VAS) and for functional disability by the Neck Disability Index (NDI) before treatment, then 6 weeks and 6 months after CTESI. A total of 104 patients were included (n = 30 TFA, n = 36 TFP, and n = 38 TFT approaches). Each group was found to have a statistically significant improvement at 6 weeks (median VAS values: 7 (2-9) at D0 and 2 (3-6) at 6 weeks p &lt; 0.01; median NDI values: 38 (24-50) at D0 and 29 (18-42) at 6 weeks (p &lt; 0.01)), and at 6 months (median VAS values: 7 (2-9) at D0 and 4 (2-6) at 6 months (p &lt; 0.01); median NDI values: 38 (24-50) at D0 and 28 (13-40) at 6 months (p &lt; 0.01)). No significant difference was observed in the decrease in VAS and NDI scores among the three approaches at 6 weeks (p = 0.635 and p = 0.54 for VAS and NDI respectively) or 6 months (p = 0.704 and p = 0.315 for VAS and NDI respectively). No major complications were noted. The results of CTESI using the TFP or TFT approach are similar to those for TFA in the treatment of persistent CRP and could be a safer option