Characteristics and outcomes of COVID-19 patients presumed to be treated with sotrovimab in NHS hospitals in England.

BACKGROUND: The impact of the constantly evolving severe acute respiratory syndrome coronavirus 2 on the effectiveness of early coronavirus disease 2019 (COVID-19) treatments is unclear. Here, we report characteristics and acute clinical outcomes of patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and predominance of Omicron subvariants (BA.1, BA.2, and BA.5) in England. METHODS: Retrospective cohort study using data from the Hospital Episode Statistics database from January 1-July 31, 2022. Included patients received a mAb delivered by a National Health Service (NHS) hospital as a day-case, for which the primary diagnosis was COVID-19. Patients were presumed to have received sotrovimab based on NHS data showing that 99.98% of COVID-19-mAb-treated individuals received sotrovimab during the study period. COVID-19-attributable hospitalizations were reported overall and across six distinct periods of Omicron subvariant prevalence. Subgroup analyses were conducted in patients with severe renal disease and active cancer. RESULTS: Among a total of 10,096 patients, 1.0% (n = 96) had a COVID-19-attributable hospitalization, 4.6% (n = 465) had a hospital visit due to any cause, and 0.3% (n = 27) died due to any cause during the acute period. COVID-19-attributable hospitalization rates were consistent among subgroups, and no significant differences were observed across periods of Omicron subvariant predominance. CONCLUSIONS: Levels of COVID-19-attributable hospitalizations and deaths were low in mAb-treated patients and among subgroups. Similar hospitalization rates were observed whilst Omicron BA.1, BA.2, and BA.5 were predominant, despite reported reductions in in vitro neutralization activity of sotrovimab against BA.2 and BA.5.

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 and BA.5 subvariant predominance: a systematic literature review.

PURPOSE: To evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance. METHODS: Electronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022 to February 27, 2023. RESULTS: The 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions. They included > 1.7 million high-risk patients with COVID-19, of whom approximately 41,000 received sotrovimab (range n = 20-5979 during BA.2 and n = 76-1383 during BA.5 predominance). Four studies compared the effectiveness of sotrovimab with untreated or no monoclonal antibody treatment controls, two compared sotrovimab with other treatments, and three single-arm studies compared outcomes during BA.2 and/or BA.5 versus BA.1. Five studies descriptively reported rates of clinical outcomes in patients treated with sotrovimab. Rates of COVID-19-related hospitalization or mortality (0.95-4.0% during BA.2; 0.5-2.0% during BA.5) and all-cause mortality (1.7-2.0% during BA.2; 3.4% during combined BA.2 and BA.5 periods) among sotrovimab-treated patients were consistently low. During BA.2, a lower risk of all-cause hospitalization or mortality was reported across studies with sotrovimab versus untreated cohorts. Compared with other treatments, sotrovimab was associated with a lower (molnupiravir) or similar (nirmatrelvir/ritonavir) risk of COVID-19-related hospitalization or mortality during BA.2 and BA.5. There was no significant difference in outcomes between the BA.1, BA.2 and BA.5 periods. CONCLUSIONS: This systematic literature review suggests continued effectiveness of sotrovimab in preventing severe clinical outcomes during BA.2 and BA.5 predominance, both against active/untreated comparators and compared with BA.1 predominance.

Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk COVID-19 patients in north west London: a retrospective cohort study.

BACKGROUND: We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance. METHODS: Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed. RESULTS: We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively. CONCLUSIONS: Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.

Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19: Evidence from the US National COVID Cohort Collaborative (N3C).

BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has been an unprecedented healthcare crisis, one that threatened to overwhelm health systems and prompted an urgent need for early treatment options for patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. Randomised clinical trials established the safety and efficacy of monoclonal antibodies (mAbs) early in the pandemic; in vitro data subsequently led to use of the mAbs being discontinued, without clear evidence on how these data were linked to outcomes. In this study, we describe and compare real-world outcomes for patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19 treated with sotrovimab versus untreated patients. METHODS: Electronic health records from the National COVID Cohort Collaborative (N3C) were used to identify US patients (aged ≥ 12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (27 September 2021-30 April 2022) who met Emergency Use Authorization (EUA) high-risk criteria. Patients receiving the mAb sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort, with the day of infusion as the index date. Untreated patients (no evidence of early mAb treatment, prophylactic mAb or oral antiviral treatment) were assigned to the untreated cohort, with an imputed index date based on the time distribution between diagnosis and sotrovimab infusion in the sotrovimab cohort. The primary endpoint was hospitalisation or death (both all-cause) within 29 days of index, reported as descriptive rate and adjusted [via inverse probability of treatment weighting (IPTW)] odds ratio (OR) and 95% confidence interval (CI). RESULTS: Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis period, 4992 met the criteria for the sotrovimab cohort, and 541,325 were included in the untreated cohort. Before weighting, significant differences were noted between the cohorts; for example, patients in the sotrovimab cohort were older (60 years versus 54 years), were more likely to be white (85% versus 75%) and met more EUA criteria (mean 3.1 versus 2.2) versus the untreated cohort. The proportions of patients with 29-day hospitalisation or death were 3.5% (176/4992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts, respectively (unadjusted OR: 0.78; 95% CI: 0.67, 0.91; p = 0.001). In adjusted analysis, sotrovimab was associated with a 25% reduction in the odds of hospitalisation or death compared with the untreated cohort (IPTW-adjusted OR: 0.75; 95% CI: 0.61, 0.92; p = 0.005). CONCLUSIONS: Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalisation, mortality) in the period 27 September 2021-30 April 2022, which included Delta and Omicron BA.1 variants and an early surge of Omicron BA.2 variant.

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review.

PURPOSE: Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab, with variable fold changes in neutralization potency for the Omicron BA.2 sublineage and onward. The correlation between reduced in vitro activity and clinical efficacy outcomes is unknown. A systematic literature review (SLR) evaluated the effectiveness of sotrovimab on severe clinical outcomes during Omicron BA.2 predominance. METHODS: Electronic databases were searched for peer-reviewed journals, preprint articles, and conference abstracts published from January 1-November 3, 2022. RESULTS: Five studies were included, which displayed heterogeneity in study design and population. Two UK studies had large samples of patients during BA.2 predominance: one demonstrated clinical effectiveness vs molnupiravir during BA.1 (adjusted hazard ratio [aHR] 0.54, 95% CI 0.33-0.88; p = 0.014) and BA.2 (aHR 0.44, 95% CI 0.27-0.71; p = 0.001); the other reported no difference in the clinical outcomes of sotrovimab-treated patients when directly comparing sequencing-confirmed BA.1 and BA.2 cases (HR 1.17, 95% CI 0.74-1.86). One US study showed a lower risk of 30-day all-cause hospitalization/mortality for sotrovimab compared with no treatment during the BA.2 surge in March (adjusted relative risk [aRR] 0.41, 95% CI 0.27-0.62) and April 2022 (aRR 0.54, 95% CI 0.08-3.54). Two studies from Italy and Qatar reported low progression rates but were either single-arm descriptive or not sufficiently powered to draw conclusions on the effectiveness of sotrovimab. CONCLUSION: This SLR showed that the effectiveness of sotrovimab was maintained against Omicron BA.2 in both ecological and sequencing-confirmed studies, by demonstrating low/comparable clinical outcomes between BA.1 and BA.2 periods or comparing against an active/untreated comparator.

Prevalent new user designs: A literature review of current implementation practice.

PURPOSE: Prevalent new user (PNU) designs extend the active comparator new user design by allowing for the inclusion of initiators of the study drug who were previously on a comparator treatment. We performed a literature review summarising current practice. METHODS: PubMed was searched for studies applying the PNU design since its proposal in 2017. The review focused on three components. First, we extracted information on the overall study design, including the database used. We summarised information on implementation of the PNU design, including key decisions relating to exposure set definition and estimation of time-conditional propensity scores. Finally, we reviewed the analysis strategy of the matched cohort. RESULTS: Nineteen studies met the criteria for inclusion. Most studies (73%) implemented the PNU design in electronic health record or registry databases, with the remaining using insurance claims databases. Of 15 studies including a class of prevalent users, 40% deviated from the original exposure set definition proposals in favour of a more complex definition. Four studies did not include prevalent new users but used other aspects of the PNU framework. Several studies lacked details on exposure set definition (n = 2), time-conditional propensity score model (n = 2) or integration of complex analytical techniques, such as the high-dimensional propensity score algorithm (n = 3). CONCLUSION: PNU designs have been applied in a range of therapeutic and disease areas. However, to encourage more widespread use of this design and help shape best practice, there is a need for improved accessibility, specifically through the provision of analytical code alongside guidance to support implementation and transparent reporting.

Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the USA.

INTRODUCTION: Sotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-world clinical effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality was evaluated for the period when the prevalence of circulating SARS-CoV-2 variants changed between Delta and Omicron in the USA. METHODS: A retrospective analysis was conducted of de-identified patients diagnosed with COVID-19 between 1 September 2021 to 30 April 2022 in the FAIR Health National Private Insurance Claims database. Patients meeting high-risk criteria were divided into two cohorts: sotrovimab and not treated with a mAb ("no mAb"). All-cause hospitalizations and facility-reported mortality ≤ 30 days of diagnosis ("30-day hospitalization or mortality") were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality in each cohort. RESULTS: Compared with the no mAb cohort (n = 1,514,868), the sotrovimab cohort (n = 15,633) was older and had a higher proportion of patients with high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, the sotrovimab cohort had a 55% lower risk of 30-day hospitalization or mortality (RR 0.45, 95% CI 0.41-0.49) and an 85% lower risk of 30-day mortality (RR 0.15, 95% CI 0.08-0.29). Monthly, from September 2021 to April 2022, the RR reduction for 30-day hospitalization or mortality in the sotrovimab cohort was maintained, ranging from 46% to 71% compared with the no mAb cohort; the RR estimate in April 2022 was uncertain, with wide confidence intervals due to the small sample size. CONCLUSION: Sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and mortality versus no mAb treatment. Clinical effectiveness persisted during Delta and early Omicron variant waves and among all high-risk subgroups assessed.

Treatment patterns, healthcare resource use, and costs associated with uncomplicated urinary tract infection among female patients in the United States.

BACKGROUND: We evaluated associations between antibiotic prescription and healthcare resource use and costs (Part A), and between antibiotic switching and healthcare resource use, costs, and uncomplicated urinary tract infection recurrence (Part B) in female patients with uncomplicated urinary tract infection in the United States. METHODS: This retrospective cohort study of linked Optum and Premier Healthcare Database data included female patients ≥12 years old with an uncomplicated urinary tract infection diagnosis (index date), who were prescribed antibiotics during an outpatient/emergency department visit between January 1, 2013 and December 31, 2018. In Part A, patients were stratified by antibiotic prescription appropriateness: appropriate and optimal (compliant with Infectious Diseases Society of America 2011 guidelines for drug class/treatment duration) versus inappropriate/suboptimal (inappropriate drug class/treatment duration per Infectious Diseases Society of America 2011 guidelines, and/or treatment failure). In Part B, patients were stratified by treatment pattern (antibiotic switch vs no antibiotic switch). Healthcare resource use and costs during index episode (within 28 days of index date) and 12-month follow-up were compared. RESULTS: Of 5870 patients (mean age 44.5 years), 2762 (47.1%) had inappropriate/suboptimal prescriptions and 567 (9.7%) switched antibiotic. Inappropriate/suboptimal prescriptions were associated with higher healthcare resource use (mean number of ambulatory care and pharmacy claims [both p < 0.001]), and higher total mean cost (inpatient, outpatient/emergency department, ambulatory visits, and pharmacy costs) per patient ($2616) than appropriate and optimal prescriptions ($649; p < 0.001) (Part A). Antibiotic switching was associated with more pharmacy claims and higher total mean costs (p ≤ 0.01), and a higher incidence of recurrent uncomplicated urinary tract infection (18.9%) than no antibiotic switching (14.2%; p < 0.001) (Part B). CONCLUSIONS: Inappropriate/suboptimal prescriptions and antibiotic switching were associated with high costs, ambulatory care, and pharmacy claims, suggesting a need for improved uncomplicated urinary tract infection prescribing practices in the United States.

Disease burden of primary biliary cholangitis and associated pruritus based on a cross-sectional US claims analysis.

OBJECTIVE: In order to identify areas of unmet need in patients with primary biliary cholangitis (PBC), this study sought to use real-world observational healthcare data to characterise the burden in patients with PBC and in PBC patients with a recorded diagnosis of pruritus. DESIGN: This retrospective, cross-sectional database study compared prevalence of prespecified comorbidities and medications in the PBC population and PBC-pruritus subpopulation with non-cases using an indirect standardisation approach. The PBC population was identified from the US IBM MarketScan Commercial Claims and Medicare Supplemental Database during 2016 using International Classification of Diseases 10th Revision, Clinical Modification codes (≥2 claims for PBC); the PBC-pruritus subpopulation additionally had ≥1 claim for pruritus during this period. Non-cases had no claims for PBC. Indirect age-sex standardised prevalence ratios (iSPR) and 95% confidence intervals (CIs) were calculated for prespecified comorbidities and medications recorded during 2017. RESULTS: The PBC population (N=1963) and PBC-pruritus subpopulation (N=139) had significantly higher prevalence of fatigue (19.9%, iSPR (95% CI): 1.51 (1.36 to 1.66); 26.6%, 2.10 (1.48 to 2.90)), depression/anxiety (21.3%, 1.09 (0.99 to 1.20); 28.1%, 1.46 (1.04 to 2.00)) and sleep-related issues (6.9%, 1.18 (0.99 to 1.40); 14.4%, 2.58 (1.58 to 3.99)) compared with non-cases. Bile acid sequestrants were prescribed in 5.8% and 18.0% of the PBC and PBC-pruritus populations, respectively. In general, a higher prevalence of comorbidities and medication use was observed in the PBC-pruritus subpopulation compared with the PBC population and non-cases. CONCLUSION: Despite availability of treatments for PBC, the PBC population had a higher burden of comorbidities than non-cases. This burden was even greater among the PBC-pruritus subpopulation, with a particularly high prevalence of sleep disorders and depression/anxiety. Despite this, pruritus remains undertreated highlighting a need for treatments specifically indicated for cholestatic pruritus.

The increasing incidence and prevalence of hypereosinophilic syndrome in the United Kingdom.

INTRODUCTION: Data on the burden of hypereosinophilic syndrome (HES) are limited. This study investigated the incidence and prevalence of HES using real-world data from patients in the United Kingdom. METHODS: Primary care data from the Clinical Practice Research Datalink were analyzed. The patients of interest were identified using medical codes specific for HES. Annual incidence rates and prevalence were estimated for the years 2010-2018 (inclusive) using patients observed for a minimum period of one year. RESULTS: Between 2010 and 2018, 93 patients were identified with HES. During the study period the incidence of HES ranged from less than 0.04, 95% confidence interval (CI) (0.01-0.07) to 0.17, 95% CI (0.10-0.26) per 100,000 person-years and the prevalence ranged from 0.15, 95% CI (0.10-0.25) to 0.89, 95% CI (0.74-1.09) cases per 100,000 persons. Sensitivity analyses varying the minimum observation period required to identify HES patients gave similar results. CONCLUSION: These results provide estimates of the burden of HES in the United Kingdom and indicate that whilst HES is a very rare disease, there is evidence that is increasingly being recorded in UK primary care.

Treatment patterns among non-active users of maintenance asthma medication in the United Kingdom: a retrospective cohort study in the Clinical Practice Research Datalink.

Objective: To describe patient characteristics, treatment patterns and healthcare utilization (HCU) of non-active users of maintenance asthma medications in the United Kingdom.Methods: Retrospective, cohort analysis of patients with asthma, aged ≥ 6 years who were non-active users of maintenance therapy (no prescription for inhaled corticosteroids (ICS), combined ICS/long-acting beta agonists (ICS/LABA) or 'other' bronchodilatory therapies in last 12 months) were identified in the Clinical Practice Research Datalink (2012-2015) and followed-up for 2 years after a new prescription for an asthma maintenance medication (index date). Patient characteristics, most common maintenance treatment sequences and HCU were described.Results: 55,293 patients were identified (ICS: 46,297, ICS/LABA: 8,367; Other: 629). Mean age was 37 years and 56% were female. During follow-up, the most common treatment sequences across groups implied intermittent use, comprising periods of maintenance therapy interspersed with maintenance-free periods. During year 1 and year 2 of follow-up, the proportion of patients prescribed OCS was 19% and 13%, prescribed ≥ 4 short-acting bronchodilators (SABD) was 24% and 19%, having ≥ 3 asthma-related primary care consultations/year was 59% and 36% and experiencing ≥ 1 exacerbation/year was 15% and 11%, respectively.Conclusions: In previously non-active users of asthma maintenance medication subsequently commenced on maintenance therapy, intermittent use was common during the 2-year follow-up despite the potential need for regular use as evidenced by patient HCU and SABD usage patterns. This highlights the need for regular patient assessment and education on medication adherence to ensure appropriateness of prescribing to maintain asthma control.

Rapid testing and treatment for sexually transmitted infections improve patient care and yield public health benefits.

A service evaluation of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing and result notification in patients attending a rapid testing service (Dean Street Express [DSE]) compared with those attending an existing 'standard' sexual health clinic (56 Dean Street [56DS]), and modelling the impact of the new service from 1 June 2014 to 31 May 2015. PRIMARY OUTCOME: time from patients' sample collection to notification of test results at DSE compared with 56DS. Secondary outcomes estimated using a model: number of transmissions prevented and the number of new partner visits avoided and associated cost savings achieved due to rapid testing at DSE. In 2014/15, there were a total of 81,352 visits for CT/NG testing across 56DS (21,086) and DSE (60,266). Rapid testing resulted in a reduced mean time to notification of 8.68 days: 8.95 days for 56DS (95% CI 8.91-8.99) compared to 0.27 days for DSE (95% CI 0.26-0.28). Our model estimates that rapid testing at DSE would lead to 196 CT and/or NG transmissions prevented (2.5-97.5% centile range = 6-956) and lead to annual savings attributable to reduced numbers of partner attendances of £124,283 (2.5-97.5% centile range = £4260-590,331). DSE, a rapid testing service for asymptomatic infections, delivers faster time to result notification for CT and/or NG which enables faster treatment, reduces infectious periods and leads to fewer transmissions, partner attendances and clinic costs.

Access to general practice and visits to accident and emergency departments in England: cross-sectional analysis of a national patient survey.

BACKGROUND: The annual number of unplanned attendances at accident and emergency (A&E) departments in England increased by 11% (2.2 million attendances) between 2008-2009 and 2012-2013. A national review of urgent and emergency care has emphasised the role of access to primary care services in preventing A&E attendances. AIM: To estimate the number of A&E attendances in England in 2012-2013 that were preceded by the attending patient being unable to obtain an appointment or a convenient appointment at their general practice. DESIGN AND SETTING: Cross-sectional analysis of a national survey of adults registered with a GP in England. METHOD: The number of general practice consultations in England in 2012-2013 was estimated by extrapolating the linear trend of published data for 2000-2001 to 2008-2009. This parameter was multiplied by the ratio of attempts to obtain a general practice appointment that resulted in an A&E attendance to attempts that resulted in a general practice consultation estimated using the GP Patient Survey 2012-2013. A sensitivity analysis varied the number of consultations by ±12% and the ratio by ±25%. RESULTS: An estimated 5.77 million (99.9% confidence interval = 5.49 to 6.05 million) A&E attendances were preceded by the attending patient being unable to obtain a general practice appointment or a convenient appointment, comprising 26.5% of unplanned A&E attendances in England in 2012-2013. The sensitivity analysis produced values between 17.5% and 37.2% of unplanned A&E attendances. CONCLUSION: A large number of A&E attendances are likely to be preceded by unsuccessful attempts to obtain convenient general practice appointments in England each year.

Reducing inappropriate accident and emergency department attendances: a systematic review of primary care service interventions.

BACKGROUND: Inappropriate attendances may account for up to 40% of presentations at accident and emergency (A&E) departments. There is considerable interest from health practitioners and policymakers in interventions to reduce this burden. AIM: To review the evidence on primary care service interventions to reduce inappropriate A&E attendances. DESIGN AND SETTING: Systematic review of UK and international primary care interventions. METHOD: Studies published in English between 1 January 1986 and 23 August 2011 were identified from PubMed, the NHS Economic Evaluation Database, the Cochrane Collaboration, and Health Technology Assessment databases. The outcome measures were A&E attendances, patient satisfaction, clinical outcome, and intervention cost. Two authors reviewed titles and abstracts of retrieved results, with adjudication of disagreements conducted by the third. Studies were quality assessed using the Scottish Intercollegiate Guidelines Network checklist system where applicable. RESULTS: In total, 9916 manuscripts were identified, of which 34 were reviewed. Telephone triage was the single best-evaluated intervention. This resulted in negligible impact on A&E attendance, but exhibited acceptable patient satisfaction and clinical safety; cost effectiveness was uncertain. The limited available evidence suggests that emergency nurse practitioners in community settings and community health centres may reduce A&E attendance. For all other interventions considered in this review (walk-in centres, minor injuries units, and out-of-hours general practice), the effects on A&E attendance, patient outcomes, and cost were inconclusive. CONCLUSION: Studies showed a negligible effect on A&E attendance for all interventions; data on patient outcomes and cost-effectiveness are limited. There is an urgent need to examine all aspects of primary care service interventions that aim to reduce inappropriate A&E attendance.

Defining primary care sensitive conditions: a necessity for effective primary care delivery?

Primary care is a major component of England's National Health Service (NHS), responsible for approximately 300 million consultations per year with GPs in England, which represents 70-90% of all patient contacts with the NHS. In addition to providing healthcare to the registered population, GPs are charged with coordination and gatekeeping of access to services provided by secondary care, tertiary care and other allied healthcare providers. As GPs will be assuming a key role in commissioning health services in England, there is a clear opportunity to re-model care delivery to maximize outcomes, cost efficiency and patient access by focusing on diseases that are most amenable to management in primary care. It is essential that there is evidence to inform what conditions are most sensitive to management in primary care - commonly referred to as primary care sensitive conditions or ambulatory care sensitive conditions. Such definitions would aid resource planning, drafting of local management protocols and simplification of the interface between primary and secondary care for a number of chronic conditions. Indeed, inappropriate utilization of secondary care resources is likely to represent a significant opportunity cost to healthcare providers and may be less desirable for patients.

Increasing the age for the legal purchase of tobacco in England: impacts on socio-economic disparities in youth smoking.

BACKGROUND: The minimum age for the legal purchase of tobacco increased from 16 to 18 years in England, Scotland and Wales on 1 October 2007. The authors examined the impact of this legislation on disparities in smoking behaviour and access to cigarettes among youth in England. METHODS: A multivariate logistic regression analysis was carried out adjusting for secular trends in regular smoking using data from the Smoking, Drinking and Drug Use Survey, a national survey of 11-15 year olds. The primary outcome measure was regular smoking and the predictor variables were the law increasing the minimum age for purchase and eligibility for free school meals (FSM). RESULTS: Increasing the minimum age for purchase was associated with a significant reduction in regular smoking among youth (adjusted OR 0.67; 95% CI 0.55 to 0.81, p=0.0005). This effect was not significantly different in pupils eligible for FSM compared with those that were not (adjusted OR 1.29; 95% CI 0.95 to 1.76, p=0.10 for interaction term). The percentage of pupils who stated that they found it difficult to buy cigarettes from a shop did not increase in those eligible for FSM (25.2% to 33.3%; p=0.21) but did increase significantly in others (21.2% to 36.9%; p<0.01) between 2006 and 2008. No differences in ease of purchase were found between pupils eligible for FSM and those not before or after the legislation (2006: p=0.34, 2008: p=0.55). CONCLUSIONS: Increasing the age for the legal purchase of tobacco was associated with reduced regular smoking among youth in England and appeared to have a similar impact in different socio-economic groups.

Colorectal cancer: no longer the issue in familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal cancer (CRC) syndrome with an untreated lifetime prevalence of CRC close to 100% and extracolonic manifestations (ECM) of increasing clinical significance. This study examined the effect of systematic callup and prophylactic colectomy on FAP survival. Patients diagnosed, treated and followed-up at our institution were analysed. 'Callups' were those identified via the callup system; 'probands' were those identified by other means. Proportions were analysed by Chi-squared or Fischer's exact test. Mortality rates were indirectly standardised to the UK population. Survival curves from birth were estimated by Kaplan-Meier. A total of 439 patients (293 callups, 146 probands) were analysed. Crude mortality rates (CMRs) of callups and probands were 4.85 per 1,000 person years (PY) and 9.71 per 1,000 PY, respectively-a rate ratio of 0.50 (95% CI 0.34-0.72, P = 0.0001). The standardised mortality ratio (SMR) of callups was non-significantly lower than probands (4.12 vs. 4.70). Callups experienced non-significantly lower age-band specific SMR up to 45 years. More probands died of CRC (42.4 vs. 22.5%, P = 0.025), whereas more callups died of ECM (30.6 vs. 13.4%, P = 0.027). Median survival was 64 years for callups and 60 years for probands; survival curves did not differ significantly (P = 0.253). The crude mortality rate of callups is approximately half that of probands. As fewer callups die of CRC, a greater proportion die of ECMs. Callups experienced non-significantly reduced mortality up to 45 years. Whilst the FAP callup system reduces CRC risk, mortality attributable to ECMs needs to be addressed.

Surgical prophylaxis in familial adenomatous polyposis: do pre-existing desmoids outside the abdominal cavity matter?

Desmoid tumours (DT) are myofibroblastic proliferations found in 10-25% of familial adenomatous polyposis (FAP) patients, either intra-abdominally (IA), in the abdominal wall (AW) or elsewhere (extra-abdominal (EA)). Most DT occur following prophylactic colectomy but occasionally patients present with pre-operative DT. Mutations 3' to codon 1444, predispose to DT and attenuated phenotype, leading to a potential strategy of delaying surgery in patients at high risk of DT. Here we assess if the existence of a pre-operative AW-DT or EA-DT predisposes to IA-DT following laparotomy. Data were collected on FAP patients undergoing primary surgery at St Mark's Hospital. Patients were stratified into those having no DT, EA-DT or AW-DT pre-operatively. Relative-risks were calculated and proportions compared using Fisher's exact-test. 587 FAP patients were identified; nine discovered with IA-DT intra-operatively were excluded. 5(0.9%) and 6(1%) of the remainder had a pre-operative EA-DT and AW-DT, respectively; one (0.2%) had both. Six of these 12 developed a post-operative IA-DT. 566(98%) had no pre-operative DT, 50(9%) of these developed IA-DT post-operatively; median time to tumour was 2 (IQR, 1-3.5) years. A pre-operative AW-DT predisposed to IA-DT post-operatively (RR = 7.6, 95% CI 4.0-14.1, P = 0.0009) whilst EA-DT did not (RR = 2.3, 0.4-13.3, P = 0.38). A 3' mutation was significantly associated with post-operative IA-DT in the 'no pre-operative DT' group (P = 0.002). The presence of a DT external to the abdominal cavity pre-operatively, poses a clinical challenge with regards to surgical decision-making. Patients with an AW-DT pre-operatively may warrant a conservative surgical approach, to minimize post-operative IA-DT risk.