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"Butler, Christopher C"
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The challenge of antimicrobial resistance
by
Butler, Christopher C.
,
San Tan, Pui
,
Pouwels, Koen B.
in
Animals
,
Anti-Bacterial Agents - pharmacology
,
Antibiotic resistance
2019
The accelerating tide of antimicrobial resistance (AMR) is a major worldwide policy concern. Like climate change, the incentives for individual decision-makers do not take into account the costs to society at large. AMR represents an impending “tragedy of the commons,” and there is an immediate need for collective action to prevent future harm. Roope et al. review the issues associated with AMR from an economics perspective and draw parallels with climate change. A major stumbling block for both challenges is to build consensus about the best way forward when faced with many uncertainties and inequities. Science , this issue p. eaau4679 As antibiotic consumption grows, bacteria are becoming increasingly resistant to treatment. Antibiotic resistance undermines much of modern health care, which relies on access to effective antibiotics to prevent and treat infections associated with routine medical procedures. The resulting challenges have much in common with those posed by climate change, which economists have responded to with research that has informed and shaped public policy. Drawing on economic concepts such as externalities and the principal–agent relationship, we suggest how economics can help to solve the challenges arising from increasing resistance to antibiotics. We discuss solutions to the key economic issues, from incentivizing the development of effective new antibiotics to improving antibiotic stewardship through financial mechanisms and regulation.
Journal Article
C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations
by
Llor, Carl
,
Kirby, Nigel
,
Gillespie, David
in
Aged
,
Anti-Bacterial Agents - therapeutic use
,
Antibiotics
2019
In this randomized trial, C-reactive protein testing was used as a point-of-care aid in determining whether antibiotic therapy was warranted in patients with an acute exacerbation of COPD. Among 653 outpatients, there was significantly less use of antibiotics with CRP guidance, with no evidence of any worse outcome.
Journal Article
Incidence and antibiotic prescribing for clinically diagnosed urinary tract infection in older adults in UK primary care, 2004-2014
by
Butler, Christopher C.
,
Paranjothy, Shantini
,
Jones, Hywel M.
in
Adults
,
Aged
,
Aged, 80 and over
2018
Urinary tract infections (UTI) are an important cause of morbidity and antibiotic use in older adults but there are little data describing disease burden in primary care. The aim of this study was to estimate the incidence of clinically diagnosed UTI and examine associated empirical antibiotic prescribing. We conducted a retrospective observational study using linked health records from almost one million patients aged ≥65 years old, registered with 393 primary care practices in England. We estimated incidence of clinically diagnosed UTI between March 2004 and April 2014, and used multilevel logistic regression to examine trends in empiric antibiotic prescribing. Of 931,945 older adults, 196,358 (21%) had at least one clinically diagnosed UTI over the study period. In men, the incidence of clinically diagnosed UTI per 100 person-years at risk increased from 2.81 to 3.05 in those aged 65-74, 5.90 to 6.13 in those aged 75-84, and 8.08 to 10.54 in those aged 85+. In women, incidence increased from 9.03 to 10.96 in those aged 65-74, 11.35 to 14.34 in those aged 75-84, and 14.65 to 19.80 in those aged 85+. Prescribing of broad-spectrum antibiotics decreased over the study period. There were increases in the proportion of older men (from 45% to 74%) and women (from 55% to 82%) with UTI, prescribed a UTI specific antibiotic. There were also increases in the proportion of older men (42% to 69%) and women (15% to 26%) prescribed antibiotics for durations recommended by clinical guidelines. This is the first population-based study describing the burden of UTI in UK primary care. Our findings suggest a need to better understand reasons for increasing rates of clinically diagnosed UTI and consider how best to address this important clinical problem.
Journal Article
Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial
by
Kemp, Alison
,
Ronaldson, Sarah
,
Montgomery, Alan A
in
Adolescent
,
Birth Weight
,
Breast Feeding
2016
Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth.
We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866.
Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64–1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI −47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99–1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77–1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother–child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention.
Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge.
Department of Health Policy Research Programme.
Journal Article
Experiences and concerns of health workers throughout the first year of the COVID-19 pandemic in the UK: A longitudinal qualitative interview study
by
Butler, Christopher C.
,
Wanat, Marta
,
Sheard, Sally
in
Audio data
,
Autumn
,
Clinical Competence
2022
To identify the experiences and concerns of health workers (HWs), and how they changed, throughout the first year of the COVID-19 pandemic in the UK.
Longitudinal, qualitative study with HWs involved in patient management or delivery of care related to COVID-19 in general practice, emergency departments and hospitals. Participants were identified through snowballing. Semi-structured telephone or video interviews were conducted between February 2020 and February 2021, audio-recorded, summarised, and transcribed. Data were analysed longitudinally using framework and thematic analysis.
We conducted 105 interviews with 14 participants and identified three phases corresponding with shifts in HWs' experiences and concerns. (1) Emergency and mobilisation phase (late winter-spring 2020), with significant rapid shifts in responsibilities, required skills, and training, and challenges in patient care. (2) Consolidation and preparation phase (summer-autumn 2020), involving gradual return to usual care and responsibilities, sense of professional development and improvement in care, and focus on learning and preparing for future. (3) Exhaustion and survival phase (autumn 2020-winter 2021), entailing return of changes in responsibilities, focus on balancing COVID-19 and non-COVID care (until becoming overwhelmed with COVID-19 cases), and concerns about longer-term impacts of unceasing pressure on health services. Participants' perceptions of COVID-19 risk and patient/public attitudes changed throughout the year, and tiredness and weariness turned into exhaustion.
Results showed a long-term impact of the COVID-19 pandemic on UK HWs' experiences and concerns related to changes in their roles, provision of care, and personal wellbeing. Despite mobilisation in the emergency phase, and trying to learn from this, HWs' experiences seemed to be similar or worse in the second wave partly due to many COVID-19 cases. The findings highlight the importance of supporting HWs and strengthening system-level resilience (e.g., with resources, processes) to enable them to respond to current and future demands and emergencies.
Journal Article
Obesity in Recovery From Influenza‐Like Illness and Effectiveness of Oseltamivir
2025
Results from observational studies have shown that obesity has a mild to moderate association with influenza-like illness (ILI) severity and hospitalization risk. Using data from the ALIC
E Randomized Clinical Trial (RCT), this study investigated the relationship between obesity and ILI severity, time to recovery, and oseltamivir effectiveness in the obese population.
A total of 2622 adults (≥ 18 years old) from the ALIC
E RCT were categorized by body mass index (BMI) into under/normal weight (BMI < 25 kg/m
), overweight (BMI ≥ 25 kg/m
and < 30 kg/m
), and obesity (BMI ≥ 30 kg/m
). ILI symptom severity, time to recovery, and oseltamivir effectiveness were assessed across these weight groups.
At presentation, ILI symptom severity was not different between weight groups. However, time to recovery was longer for obese patients compared to under/normal weight patients, with adjusted HR 0.88 (95% CI 0.79-0.99). The mean time to recovery was 6.6 days (95% CI 6.0-7.1) for obese patients, 6.2 days (95% CI 5.8-6.6) for overweight, and 5.7 days (95% CI 5.4-6.1) for under/normal weight patients. Obese patients had similar benefits from oseltamivir treatment compared to under/normal weight patients, with an average of 0.8 days gained from oseltamivir (95% CI 0.7-1) and 0.5 days (95% CI 0.4-0.7), respectively.
ILI symptom severity at presentation was equally distributed between the three weight groups. However, their time to recovery was approximately 1 day longer compared to under/normal weight patients. The effectiveness of oseltamivir appears to be similar between the two groups.
Journal Article
Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial
2013
Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older.
Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated “moderately bad” or worse. Secondary outcomes were symptom severity in days 2–4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N).
1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated “moderately bad” or worse (hazard ratio 1·06, 95% CI 0·96–1·18; p=0·229) nor mean symptom severity (1·69 with placebo vs 1·62 with amoxicillin; difference −0·07 [95% CI −0·15 to 0·007]; p=0·074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15·9%] of 1021 patients vs 194 [19·3%] of 1006; p=0·043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11–174; p=0·025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595).
When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms.
European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
Journal Article
Risk of adverse outcomes following urinary tract infection in older people with renal impairment: Retrospective cohort study using linked health record data
by
Butler, Christopher C.
,
Paranjothy, Shantini
,
Farewell, Daniel
in
Aged
,
Aged, 80 and over
,
Analysis
2018
Few studies have investigated the risk of adverse outcomes in older people with renal impairment presenting to primary care with a urinary tract infection (UTI). The aim of this study was to determine the risk of adverse outcomes in patients aged ≥65 years presenting to primary care with a UTI, by estimated glomerular filtration rate (eGFR) and empirical prescription of nitrofurantoin versus trimethoprim.
This was a retrospective cohort study using linked health record data from 795,484 patients from 393 general practices in England, who were aged ≥65 years between 2010 and 2016. Patients were entered into the cohort if they presented with a UTI and had a creatinine measurement in the 24 months prior to presentation. We calculated an eGFR to estimate risk of adverse outcomes by renal function, and propensity-score matched patients with eGFRs <60 mL/minute/1.73 m2 to estimate risk of adverse outcomes between those prescribed trimethoprim and nitrofurantoin. Outcomes were 14-day risk of reconsultation for urinary symptoms and same-day antibiotic prescription (proxy for treatment nonresponse), hospitalisation for UTI, sepsis, or acute kidney injury (AKI), and 28-day risk of death. Of 123,607 eligible patients with a UTI, we calculated an eGFR for 116,945 (95%). Median age was 76 (IQR, 70-83) years and 32,428 (28%) were male. Compared to an eGFR of >60 mL/minute/1.73 m2, patients with an eGFR of <60 mL/minute/1.73 m2 had greater odds of hospitalisation for UTI (adjusted odds ratios [ORs] ranged from 1.14 [95% confidence interval (CI) 1.01-1.28, p = 0.028], for eGFRs of 45-59, to 1.68 [95% CI 1.01-2.82, p < 0.001] for eGFRs <15) and AKI (adjusted ORs ranged from 1.57 [95% CI 1.29-1.91, p < 0.001], for eGFRs of 45-59, to 4.53 [95% CI 2.52-8.17, p < 0.001] for eGFRs <15). Compared to an eGFR of >60 mL/minute/1.73 m2, patients with an eGFR <45 had significantly greater odds of hospitalisation for sepsis, and those with an eGFR <30 had significantly greater odds of death. Compared to trimethoprim, nitrofurantoin prescribing was associated with lower odds of hospitalisation for AKI (ORs ranged from 0.62 [95% CI 0.40-0.94, p = 0.025], for eGFRs of 45-59, to 0.45 [95% CI 0.25-0.81, p = 0.008] for eGFRs <30). Nitrofurantoin was not associated with greater odds of any adverse outcome. Our study lacked data on urine microbiology and antibiotic-related adverse events. Despite our design, residual confounding may still have affected some of our findings.
Older patients with renal impairment presenting to primary care with a UTI had an increased risk of UTI-related hospitalisation and death, suggesting a need for interventions that reduce the risk of these adverse outcomes. Nitrofurantoin prescribing was not associated with an increased risk of adverse outcomes in patients with an eGFR <60 mL/minute/1.73 m2 and could be used more widely in this population.
Journal Article
Understanding how community antiretroviral delivery influences engagement in HIV care: a qualitative assessment of the Centralised Chronic Medication Dispensing and Distribution programme in South Africa
by
Butler, Christopher C
,
Shozi, Hlengiwe
,
Tonkin-Crine, Sarah
in
Anti-HIV Agents - therapeutic use
,
Anti-Retroviral Agents - therapeutic use
,
Antiretroviral drugs
2020
IntroductionProviding antiretroviral therapy (ART) for millions of people living with HIV requires efficient, client-centred models of differentiated ART delivery. In South Africa, the Centralised Chronic Medication Dispensing and Distribution (CCMDD) programme allows over 1 million people to collect chronic medication, including ART, from community pick-up points. We aimed to explore how CCMDD influences engagement in HIV care.MethodsWe performed in-depth interviews and focus group discussions with clients receiving ART and healthcare workers in Durban, South Africa. We analysed transcripts using deductive thematic analysis, with a framework informed by ‘theories of practice’, which highlights the materialities, competencies, meanings and other life practices that underpin clients’ engagement in HIV care.ResultsBetween March 2018 to August 2018 we undertook 25 interviews and four focus groups with a total of 55 clients, and interviewed eight healthcare workers. The material challenges of standard clinic-based ART provision included long waiting times, poor confidentiality and restricted opening hours, which discouraged clients from engagement. In contrast, CCMDD allowed quicker and more convenient ART collection in the community. This required the development of new competencies around accessing care, and helped change the meanings associated with HIV, by normalising treatment collection. CCMDD was seen as a reward by clients for taking ART well, and helped reduce disruption to other life practices such as employment. At private pharmacies, some clients reported receiving inferior care compared with paying customers, and some worried about inadvertently revealing their HIV status. Clients and healthcare workers had to negotiate problems with CCMDD implementation, including some pharmacies reaching capacity or only allowing ART collection at restricted times.ConclusionsIn South Africa, CCMDD overcame material barriers to attending clinics, changed the meanings associated with collecting ART and was less disruptive to other social practices in clients’ lives. Expansion of community-based ART delivery programmes may help to facilitate engagement in HIV care.Trial registration numberSTREAM study clinical trial registration: NCT03066128, registered February 2017.
Journal Article