Diagnosis and Management of Sore Throat in Young Adults

Background: Sore throat is one of the most common presentations in primary care, especially in young adults. This thesis aimed to further research in the area of improving the diagnosis and management of sore throat in young adults, with a particular focus on infectious mononucleosis (IM) and Group A Beta Haemolytic Streptococcus (GABHS). There were four broad objectives; 1) to systematically review the effectiveness of antiviral therapy for infectious mononucleosis (IM), 2) to derive and externally validate a clinical prediction rule (CPR) to aid in the positive diagnosis of IM caused by Epstein Barr Virus (EBV), 3) to validate the Centor score CPR (a widely used CPR for the diagnosis of GABHS sore throat) in an Irish setting, and 4) to explore potential associations between IM caused by EBV and fatigue and time missed from college / work in younger adults. Methods: A systematic review of the effectiveness of antivirals for IM was carried out, according to Cochrane methodology. A prospective cohort study with six-month follow-up was conducted in seven student health centres in Ireland. A CPR for the diagnosis of EBV was developed and internally validated in the thesis cohort and externally validated in a geographically separate cohort. The Centor score CPR was validated in this research cohort. The cohort study data was also used to explore outcomes (fatigue scores and time missed from college or work) of participants diagnosed with EBV IM versus those with sore throat from other aetiology.  Results: The systematic review included seven randomised controlled trials (RCTs) with a total of 333 participants. There were small statistically significant improvements in the treatment group for two of the twelve outcomes; 'time to clinical recovery as assessed by physician' and 'duration of lymphadenopathy, however these may not be clinically meaningful. A total of 348 young adults (42 (12.8%) EBV positive) were recruited to the cohort study. Response rates at three month follow up were 68.7% and at six month follow up were 56.3%, with similar rates in EBV positive and EBV negative participants. Four CPR models were developed for the diagnosis of EBV. The models performed reasonably well in internal validation and similarly when validated externally. When the Centor score was validated in this study population, it was found to have only fair performance. The cohort study was underpowered,  but a large percentage of those in both EBV and non-EBV sore throat groups (56% and 42% respectively) reported fatigue six months following acute illness. The odds ratio for missing 10 or more days (compared to 0-9 days) for EBV positive versus EBV negative patients was 3.58 (95% CI 1.47 to 8.71). Conclusions: The presentation of sore throat is a very common one in primary care. This thesis adds to the literature in the area by examining its diagnosis and management in young adults, especially focussing on two conditions; IM caused by EBV and GABHS sore throat. This thesis describes tools that can aid in the diagnostic process, suggests strategies for management, depending on which underlying pathology is suspected and highlights evidence gaps in the management of IM.</p

Oseltamivir for coronavirus illness: post-hoc exploratory analysis of an open-label, pragmatic, randomised controlled trial in European primary care from 2016 to 2018

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.</div