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1.
PLoS One ; 17(3): e0264906, 2022.
Article in English | MEDLINE | ID: covidwho-1745315

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
COVID-19/epidemiology , Delivery of Health Care/trends , Health Personnel/psychology , COVID-19/psychology , Clinical Competence , Disease Management , Hospitals , Humans , Longitudinal Studies , Qualitative Research , United Kingdom/epidemiology
3.
Br J Gen Pract ; 72(716): e217-e224, 2022 03.
Article in English | MEDLINE | ID: covidwho-1608429

ABSTRACT

BACKGROUND: There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. AIM: To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. DESIGN AND SETTING: Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. METHOD: Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. RESULTS: Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. CONCLUSION: Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-and-see policy in most of these patients with flu-like illness seems the best option.


Subject(s)
COVID-19 , Respiratory Tract Infections , Virus Diseases , Adult , Child , Humans , Pandemics , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , SARS-CoV-2 , Virus Diseases/complications , Virus Diseases/diagnosis , Virus Diseases/epidemiology
4.
Lancet ; 398(10303): 843-855, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-1599473

ABSTRACT

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Subject(s)
Budesonide/administration & dosage , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Aged , Bayes Theorem , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
5.
Antibiotics (Basel) ; 10(12)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572351

ABSTRACT

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners' (GPs') perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conducted with 18 GPs at two time-points: autumn 2020 (14 interviews) and spring 2021 (10 interviews). Interviews were audio-recorded, transcribed and analysed thematically, taking a longitudinal approach. Participants reported a lower threshold for antibiotic prescribing (and fewer consultations) for respiratory infections and COVID-19 symptoms early in the pandemic, then returning to more usual (pre-pandemic) prescribing. They perceived the pandemic as having had less impact on antibiotic prescribing for urinary and skin infections. Participants perceived the changing ways of working and consulting (e.g., proportions of remote and in-person consultations) in addition to changing patient presentations and GP workloads as influencing the fluctuations in antibiotic prescribing. This was compounded by decreased engagement with, and priority of, AMS due to COVID-19-related urgent priorities. Re-engagement with AMS is needed, e.g., through reviving antibiotic prescribing feedback and targets/incentives. The pandemic disrupted, and required adaptations in, the usual ways of working and AMS. It is now important to identify opportunities, e.g., for re-organising ways of managing infections and AMS in the future.

7.
Lancet ; 398(10309): 1417-1426, 2021 10 16.
Article in English | MEDLINE | ID: covidwho-1432164

ABSTRACT

BACKGROUND: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298). FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis. INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections. FUNDING: National Institute for Health Research.


Subject(s)
Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Administration, Oral , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Child , Child, Preschool , Double-Blind Method , England , Female , Humans , Infant , Male , Primary Health Care , Treatment Outcome
8.
Front Med (Lausanne) ; 8: 726319, 2021.
Article in English | MEDLINE | ID: covidwho-1441118

ABSTRACT

Background: Minimising primary care professionals' (PCPs) risk of SARS-CoV-2 infection is crucial to ensure their safety as well as functioning health care system. PCPs' perspectives on the support they needed in the early stages of a public health crisis can inform future preparedness. Aim: To understand PCPs' experiences of providing care during the COVID-19 pandemic, with focus on personal risk from COVID-19 and testing. Design and Setting: Qualitative study using semi-structured interviews with PCPs in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece and Sweden, between April and July 2020. Method: Interviews were analysed using a combination of inductive and deductive thematic analysis techniques. Results: Eighty interviews were conducted, showing that PCPs tried to make sense of their risk of both contracting and severity of COVID-19 by assessing individual risk factors and perceived effectiveness of Personal Protective Equipment (PPE). They had limited access to PPE yet continued providing care as their "duty." Some PCPs felt that they were put in high-risk situations when patients or colleagues were not flagging symptoms of COVID-19. Not having access to testing in the initial stages of the pandemic was somewhat accepted but when available, was valued. Conclusion: Access to adequate PPE and testing, as well as training for staff and education for patients about the importance of ensuring staff safety is crucial. Given PCPs' varied response in how they appraised personal risk and their tolerance for working, PCPs may benefit from the autonomy in deciding how they want to work during health emergencies.

9.
BMJ Open ; 11(7): e049257, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1334577

ABSTRACT

OBJECTIVE: To describe primary health care (consultation characteristics and management) for patients contacting their general practitioner (GP) with a respiratory tract infection (RTI) early on in the COVID-19 pandemic in contrasting European countries, with comparison to prepandemic findings. SETTING: Primary care in 16 countries (79 practices), when no routine SARS-CoV-2 testing was generally available. DESIGN AND PARTICIPANTS: Before (n=4376) and early in the pandemic (n=3301), patients with RTI symptoms were registered in this prospective audit study. OUTCOME MEASURES: Consultation characteristics (type of contact and use of PPE) and management characteristics (clinical assessments, diagnostic testing, prescribing, advice and referral) were registered. Differences in these characteristics between countries and between pandemic and prepandemic care are described. RESULTS: Care for patients with RTIs rapidly switched to telephone/video consultations (10% in Armenia, 91% in Denmark), and when consultations were face-to-face, GPs used PPE during 97% (95% CI 96% to 98%) of contacts. Laboratory testing for SARS-CoV-2 in primary care patients with RTIs was rapidly implemented in Denmark (59%) and Germany (31%), while overall testing for C reactive protein decreased. The proportion of patients prescribed antibiotics varied considerably between countries (3% in Belgium, 48% in UK) and was lower during the pandemic compared with the months before, except for Greece, Poland and UK. GPs provided frequent and varied COVID-related advice and more frequently scheduled a follow-up contact (50%, 95% CI 48% to 52%). GPs reported a slightly higher degree of confidence in the likely effectiveness of their management in face-to-face (73% (very) confident, 95% CI 71% to 76%) than in virtual consultations (69%, 95% CI 67% to 71%). CONCLUSIONS: Despite between-country variation in consultation characteristics, access to SARS-CoV-2 laboratory testing and medication prescribing, GPs reported a high degree of confidence in managing their patients with RTIs in the emerging pandemic. Insight in the highly variable pandemic responses, as measured in this multicountry audit, can aid in fine-tuning national action and in coordinating a pan-European response during future pandemic threats.


Subject(s)
COVID-19 , Respiratory Tract Infections , Armenia , Belgium , COVID-19 Testing , Europe/epidemiology , Germany , Greece , Humans , Pandemics , Poland , Primary Health Care , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , SARS-CoV-2
10.
Lancet Respir Med ; 9(9): 1010-1020, 2021 09.
Article in English | MEDLINE | ID: covidwho-1331331

ABSTRACT

BACKGROUND: Doxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support its use. We aimed to assess the efficacy of doxycycline to treat suspected COVID-19 in the community among people at high risk of adverse outcomes. METHODS: We did a national, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in older people (PRINCIPLE) across primary care centres in the UK. We included people aged 65 years or older, or 50 years or older with comorbidities (weakened immune system, heart disease, hypertension, asthma or lung disease, diabetes, mild hepatic impairment, stroke or neurological problem, and self-reported obesity or body-mass index of 35 kg/m2 or greater), who had been unwell (for ≤14 days) with suspected COVID-19 or a positive PCR test for SARS-CoV-2 infection in the community. Participants were randomly assigned using response adaptive randomisation to usual care only, usual care plus oral doxycycline (200 mg on day 1, then 100 mg once daily for the following 6 days), or usual care plus other interventions. The interventions reported in this manuscript are usual care plus doxycycline and usual care only; evaluations of other interventions in this platform trial are ongoing. The coprimary endpoints were time to first self-reported recovery, and hospitalisation or death related to COVID-19, both measured over 28 days from randomisation and analysed by intention to treat. This trial is ongoing and is registered with ISRCTN, 86534580. FINDINGS: The trial opened on April 2, 2020. Randomisation to doxycycline began on July 24, 2020, and was stopped on Dec 14, 2020, because the prespecified futility criterion was met; 2689 participants were enrolled and randomised between these dates. Of these, 2508 (93·3%) participants contributed follow-up data and were included in the primary analysis: 780 (31·1%) in the usual care plus doxycycline group, 948 in the usual care only group (37·8%), and 780 (31·1%) in the usual care plus other interventions group. Among the 1792 participants randomly assigned to the usual care plus doxycycline and usual care only groups, the mean age was 61·1 years (SD 7·9); 999 (55·7%) participants were female and 790 (44·1%) were male. In the primary analysis model, there was little evidence of difference in median time to first self-reported recovery between the usual care plus doxycycline group and the usual care only group (9·6 [95% Bayesian Credible Interval [BCI] 8·3 to 11·0] days vs 10·1 [8·7 to 11·7] days, hazard ratio 1·04 [95% BCI 0·93 to 1·17]). The estimated benefit in median time to first self-reported recovery was 0·5 days [95% BCI -0·99 to 2·04] and the probability of a clinically meaningful benefit (defined as ≥1·5 days) was 0·10. Hospitalisation or death related to COVID-19 occurred in 41 (crude percentage 5·3%) participants in the usual care plus doxycycline group and 43 (4·5%) in the usual care only group (estimated absolute percentage difference -0·5% [95% BCI -2·6 to 1·4]); there were five deaths (0·6%) in the usual care plus doxycycline group and two (0·2%) in the usual care only group. INTERPRETATION: In patients with suspected COVID-19 in the community in the UK, who were at high risk of adverse outcomes, treatment with doxycycline was not associated with clinically meaningful reductions in time to recovery or hospital admissions or deaths related to COVID-19, and should not be used as a routine treatment for COVID-19. FUNDING: UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research.


Subject(s)
Anti-Bacterial Agents/administration & dosage , COVID-19/drug therapy , Doxycycline/administration & dosage , Age Factors , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Doxycycline/adverse effects , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Male , Middle Aged , Minimal Clinically Important Difference , Risk Factors , SARS-CoV-2/isolation & purification , Self Report/statistics & numerical data , Treatment Outcome , United Kingdom/epidemiology
11.
Br J Gen Pract ; 71(709): e634-e642, 2021 08.
Article in English | MEDLINE | ID: covidwho-1299600

ABSTRACT

BACKGROUND: Primary care has a crucial role in responding to the COVID-19 pandemic as the first point of patient care and gatekeeper to secondary care. Qualitative studies exploring the experiences of healthcare professionals during the COVID-19 pandemic have mainly focused on secondary care. AIM: To gain an understanding of the experiences of European primary care professionals (PCPs) working during the first peak of the COVID-19 pandemic. DESIGN AND SETTING: An exploratory qualitative study, using semi-structured interviews in primary care in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece, and Sweden, between April and July 2020. METHOD: Interviews were audiorecorded, transcribed, and analysed using a combination of inductive and deductive thematic analysis techniques. RESULTS: Eighty interviews were conducted with PCPs. PCPs had to make their own decisions on how to rapidly transform services in relation to COVID-19 and non-COVID-19 care. Despite being overwhelmed with guidance, they often lacked access to practical training. Consequently, PCPs turned to their colleagues for moral support and information to try to quickly adjust to new ways of working, including remote care, and to deal with uncertainty. CONCLUSION: PCPs rapidly transformed primary care delivery despite a number of challenges. Representation of primary care at policy level and engagement with local primary care champions are needed to facilitate easy and coordinated access to practical information on how to adapt services, ongoing training, and access to appropriate mental health support services for PCPs. Preservation of autonomy and responsiveness of primary care are critical to preserve the ability for rapid transformation in any future crisis of care delivery.


Subject(s)
COVID-19 , Pandemics , Belgium , Delivery of Health Care , England , Europe/epidemiology , Germany , Humans , Ireland , Netherlands , Poland , Primary Health Care , Qualitative Research , SARS-CoV-2 , Sweden
12.
BMJ Open ; 11(6): e046799, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1276961

ABSTRACT

INTRODUCTION: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications. METHODS AND ANALYSIS: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes. ETHICS AND DISSEMINATION: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN86534580.


Subject(s)
COVID-19 , Aged , Humans , Hydroxychloroquine , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
13.
AIDS ; 35(4): F1-F10, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1135927

ABSTRACT

OBJECTIVE: To assess whether people living with HIV (PLWH) are at increased risk of coronavirus disease 2019 (COVID-19) mortality or adverse outcomes, and whether antiretroviral therapy (ART) influences this risk. DESIGN: Rapid review with meta-analysis and narrative synthesis. METHODS: We searched databases including Embase, Medline, medRxiv and Google Scholar up to 26 August 2020 for studies describing COVID-19 outcomes in PLWH and conducted a meta-analysis of higher quality studies. RESULTS: We identified 1908 studies and included 19 in the review. In a meta-analysis of five studies, PLWH had a higher risk of COVID-19 mortality [hazard ratio 1.95, 95% confidence interval (CI): 1.62-2.34] compared with people without HIV. Risk of death remained elevated for PLWH in a subgroup analysis of hospitalized cohorts (hazard ratio 1.60, 95% CI: 1.12-2.27) and studies of PLWH across all settings (hazard ratio 2.08, 95% CI: 1.69-2.56). Eight other studies assessed the association between HIV and COVID-19 outcomes, but provided inconclusive, lower quality evidence due to potential confounding and selection bias. There were insufficient data on the effect of CD4+ T-cell count and HIV viral load on COVID-19 outcomes. Eleven studies reported COVID-19 outcomes by ART-regimen. In the two largest studies, tenofovir disoproxil fumarate-based regimens were associated with a lower risk of adverse COVID-19 outcomes, although these analyses are susceptible to confounding by co-morbidities. CONCLUSION: Emerging evidence suggests a moderately increased risk of COVID-19 mortality among PLWH. Further investigation into the relationship between COVID-19 outcomes and CD4+ T-cell count, HIV viral load, ART and the use of tenofovir disoproxil fumarate is warranted.


Subject(s)
COVID-19/complications , HIV Infections , Tenofovir/therapeutic use , CD4 Lymphocyte Count , HIV Infections/complications , HIV Infections/drug therapy , Humans , Viral Load
14.
Antivir Ther ; 25(7): 365-376, 2020.
Article in English | MEDLINE | ID: covidwho-1128073

ABSTRACT

BACKGROUND: The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesize the clinical evidence for lopinavir/ritonavir as a treatment for COVID-19. METHODS: We performed a rapid review by searching databases including PubMed, GoogleScholar, medRxiv, ClinicalTrials.gov and the Cochrane COVID-19 Study Register, for COVID-19 studies comparing outcomes between patients who did and did not receive lopinavir/ritonavir. The quality of evidence was assessed using the GRADE criteria. RESULTS: We identified five completed randomized controlled trials (RCTs) and 14 retrospective cohort studies. Two large RCTs of 5,040 and 2,771 hospitalized adults with COVID-19 found no evidence that lopinavir/ritonavir influenced the primary outcome of mortality, or secondary outcomes including progression to mechanical ventilation or time to discharge. Results remained similar in all sub-group analyses including by age, gender, baseline ventilation and time since symptom onset. The three smaller RCTs (n=86-199) also found no evidence of a benefit in the primary outcomes of time to clinical improvement or time to viral clearance. The 14 observational studies included between 50 and 415 participants, and were limited by a lack of adjustment for potential confounding variables. The majority of these studies found no evidence that lopinavir/ritonavir was associated with improved mortality or other clinical outcomes, although results regarding viral clearance were mixed. CONCLUSIONS: Good evidence from large clinical trials does not support using lopinavir/ritonavir to treat COVID-19 amongst hospitalized patients.


Subject(s)
COVID-19/drug therapy , Lopinavir/administration & dosage , Ritonavir/administration & dosage , SARS-CoV-2 , Drug Therapy, Combination , Humans , Randomized Controlled Trials as Topic
15.
Appl Health Econ Health Policy ; 19(4): 521-535, 2021 07.
Article in English | MEDLINE | ID: covidwho-1118292

ABSTRACT

BACKGROUND: In the UK, consultations for prescription medicines are available via private providers such as online pharmacies. However, these providers may have lower thresholds for prescribing certain drugs. This is a particular concern for antibiotics, given the increasing burden of antimicrobial resistance. Public preferences for consultations with online providers are unknown, hence the impact of increased availability of online consultations on antibiotic use and population health is unclear. OBJECTIVE: To conduct a discrete choice experiment survey to understand UK public preferences for seeking online consultations, and the factors that influence these preferences, in the context of having symptoms for which antibiotics may be appropriate. METHODS: In a survey conducted between July and August 2018, general population respondents completed 16 questions in which they chose a primary care consultation via either their local medical centre or an online provider. Consultations were described in terms of five attributes, including cost and similarity to traditional 'face-to-face' appointments. Choices were modelled using regression analysis. RESULTS: Respondents (n = 734) placed a high value on having a consultation via their local medical centre rather than an online provider, and a low value on consultations by phone or video. However, respondents characterised as 'busy young professionals' showed a lower strength of preference for traditional consultations, with a higher concern for convenience. CONCLUSION: Before COVID-19, the UK public had limited appetite for consultations with online providers, or for consultations that were not face-to-face. Nevertheless, prescriptions from online providers should be monitored going forward, particularly for antibiotics, and in key patient groups.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , COVID-19 , Patient Preference/psychology , Patient Preference/statistics & numerical data , Referral and Consultation/statistics & numerical data , Telemedicine/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Surveys and Questionnaires , United Kingdom , Young Adult
16.
JMIR Public Health Surveill ; 7(2): e24341, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1090464

ABSTRACT

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections. OBJECTIVE: The aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research. METHODS: The RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval. RESULTS: The RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford-RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season. CONCLUSIONS: The COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.


Subject(s)
Clinical Protocols , Influenza, Human/prevention & control , Respiratory Tract Infections/prevention & control , Vaccines/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Female , Humans , Influenza, Human/drug therapy , Male , Middle Aged , Population Surveillance/methods , Public Health , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , United Kingdom
17.
Lancet HIV ; 8(3): e158-e165, 2021 03.
Article in English | MEDLINE | ID: covidwho-1062697

ABSTRACT

BACKGROUND: The effect of the COVID-19 pandemic on HIV outcomes in low-income and middle-income countries is poorly described. We aimed to measure the impact of the 2020 national COVID-19 lockdown on HIV testing and treatment in KwaZulu-Natal, South Africa, where 1·7 million people are living with HIV. METHODS: In this interrupted time series analysis, we analysed anonymised programmatic data from 65 primary care clinics in KwaZulu-Natal province, South Africa. We included data from people testing for HIV, initiating antiretroviral therapy (ART), and collecting ART at participating clinics during the study period, with no age restrictions. We used descriptive statistics to summarise demographic and clinical data, and present crude summaries of the main outcomes of numbers of HIV tests per month, ART initiations per week, and ART collection visits per week, before and after the national lockdown that began on March 27, 2020. We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these outcomes, as well as post-lockdown trends. FINDINGS: Between Jan 1, 2018, and July 31, 2020, we recorded 1 315 439 HIV tests. Between Jan 1, 2018, and June 15, 2020, we recorded 71 142 ART initiations and 2 319 992 ART collection visits. We recorded a median of 41 926 HIV tests per month before lockdown (January, 2018, to March, 2020; IQR 37 838-51 069) and a median of 38 911 HIV tests per month after lockdown (April, 2020, to July, 2020; IQR 32 699-42 756). In the Poisson regression model, taking into account long-term trends, lockdown was associated with an estimated 47·6% decrease in HIV testing in April, 2020 (incidence rate ratio [IRR] 0·524, 95% CI 0·446-0·615). ART initiations decreased from a median of 571 per week before lockdown (IQR 498-678), to 375 per week after lockdown (331-399), with an estimated 46·2% decrease in the Poisson regression model in the first week of lockdown (March 30, 2020, to April 5, 2020; IRR 0·538, 0·459-0·630). There was no marked change in the number of ART collection visits (median 18 519 visits per week before lockdown [IQR 17 074-19 922] vs 17 863 visits per week after lockdown [17 509-18 995]; estimated effect in the first week of lockdown IRR 0·932, 95% CI 0·794-1·093). As restrictions eased, HIV testing and ART initiations gradually improved towards pre-lockdown levels (slope change 1·183/month, 95% CI 1·113-1·256 for HIV testing; 1·156/month, 1·085-1·230 for ART initiations). INTERPRETATION: ART provision was generally maintained during the 2020 COVID-19 lockdown, but HIV testing and ART initiations were heavily impacted. Strategies to increase testing and treatment initiation should be implemented. FUNDING: Wellcome Trust, Africa Oxford Initiative.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/prevention & control , HIV Infections/diagnosis , HIV Infections/drug therapy , Mass Screening/statistics & numerical data , Primary Health Care/statistics & numerical data , Adolescent , Adult , Ambulatory Care Facilities , Antiretroviral Therapy, Highly Active , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Interrupted Time Series Analysis , Male , Middle Aged , Public Health Surveillance , SARS-CoV-2 , South Africa , Young Adult
18.
Br J Gen Pract ; 70(696): e444-e449, 2020 07.
Article in English | MEDLINE | ID: covidwho-612102

ABSTRACT

BACKGROUND: Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir. AIM: To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic patients who have tested positive for coronavirus (not including SARS-CoV-2). DESIGN AND SETTING: Exploratory analysis of data from an open-label, pragmatic, randomised controlled trial during three influenza seasons, from 2016 to 2018, in primary care research networks, in 15 European countries. METHOD: Patients aged ≥1 year presenting to primary care with influenza-like illness (ILI), and who tested positive for coronavirus (not including SARS-CoV-2), were randomised to usual care or usual care plus oseltamivir. The primary outcome was time to recovery defined as a return to usual activities, with minor or absent fever, headache, and muscle ache. RESULTS: Coronaviruses (CoV-229E, CoV-OC43, CoV-KU1 and CoV-NL63) were identified in 308 (9%) out of 3266 randomised participants in the trial; 153 of these were allocated to usual care and 155 to usual care plus oseltamivir; the primary outcome was ascertained in 136 and 147 participants, respectively. The median time to recovery was shorter in patients randomised to oseltamivir: 4 days (interquartile range [IQR] 3-6) versus 5 days (IQR 3-8; hazard ratio 1.31; 95% confidence interval = 1.03 to 1.66; P = 0.026). CONCLUSION: Primary care patients with ILI testing positive for coronavirus (not including SARS-CoV-2) recovered sooner when oseltamivir was added to usual care compared with usual care alone. This may be of relevance to the primary care management of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Influenza, Human/drug therapy , Oseltamivir/therapeutic use , Adolescent , Adult , Aged , COVID-19 , Child , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Drug Therapy, Combination , Europe , Female , Fever/virology , Headache/virology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Time Factors , Treatment Outcome , Young Adult
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