A case of Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim.

PURPOSE: To report a case of endogenous Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim. CASE REPORT: A 57-year-old man developed disseminated Lomentospora prolificans with right endophthalmitis on the background of immunosuppression following lung transplantation for interstitial lung disease. He was treated with early vitrectomy, intravitreal voriconazole, and systemic Olorofim, voriconazole and terbinafine. His symptoms improved and remained stable in the right eye. Eight weeks later the patient represented with Lomentopora prolificans endophthalmitis in the left eye when systemic voriconazole and terbinafine treatment were withdrawn. Despite aggressive treatment he ultimately succumbed due to vascular complications of extensive disseminated disease. CONCLUSION: We report a rare case of disseminated Lomentosporosis with panophthalmitis in an immunocompromised host with prolonged survival on systemic Olorofim, voriconazole and terbinafine in conjunction with pars plana vitrectomy and intravitreal voriconazole. Early suspicion of an opportunistic fungal infection is critical, as managing disseminated disease is often unsuccessful. Despite presumed inherent resistance, intravitreal and systemic voriconazole appeared to limit disease progression in the right eye. The potential synergistic effects of combined antifungal therapy with orotomides warrant further investigation.

Long-term outcomes (beyond 5 years) of liver transplant recipients-A transatlantic multicenter study.

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44-58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.

What, Where, and How to Collect Real-World Data and Generate Real-World Evidence to Support Drug Reimbursement Decision-Making in Asia: A reflection Into the Past and A Way Forward.

BACKGROUND: Globally, there is increasing interest in the use of real-world data (RWD) and real-world evidence (RWE) to inform health technology assessment (HTA) and reimbursement decision-making. Using current practices and case studies shared by eleven health systems in Asia, a non-binding guidance that seeks to align practices for generating and using RWD/RWE for decision-making in Asia was developed by the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) Working Group, addressing a current gap and needs among HTA users and generators. METHODS: The guidance document was developed over two face-to-face workshops, in addition to an online survey, a face-to-face interview and pragmatic search of literature. The specific focus was on what, where and how to collect RWD/ RWE. RESULTS: All 11 REALISE member jurisdictions participated in the online survey and the first in-person workshop, 10 participated in the second in-person workshop, and 8 participated in the in-depth face-to-face interviews. The guidance document was iteratively reviewed by all working group members and the International Advisory Panel. There was substantial variation in: (a) sources and types of RWD being used in HTA, and (b) the relative importance and prioritization of RWE being used for policy-making. A list of national-level databases and other sources of RWD available in each country was compiled. A list of useful guidance on data collection, quality assurance and study design were also compiled. CONCLUSION: The REALISE guidance document serves to align the collection of better quality RWD and generation of reliable RWE to ultimately inform HTA in Asia.

COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes. METHODS: Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described. RESULTS: Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes. CONCLUSIONS: During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.

The incidence of Kawasaki disease using hospital admissions data for England 2006-2021.

OBJECTIVE: To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. METHODS: We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. RESULTS: We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged <5 years was 8.9 (95% CI: 8.6, 9.2)/100 000 person-years; in children aged 5-9, 2.4 (95% CI: 2.3, 2.6)/100 000 person-years; and in children aged 10-15, 0.6 (95% CI: 0.6, 0.7). Male : female ratio was 1.5 : 1. Incidence was higher among non-White than White ethnicities [adjusted IRR 2.1 (2.0-2.2) for Asian, 3.0 (2.8-3.3) for Black and 4.5 (4.2-4.8) for other ethnicities]. The incidence increased with socioeconomic deprivation; the adjusted IRR of the least deprived IMD quintile compared with the most deprived quintile was 0.81 (0.77-0.84). CONCLUSIONS: Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.

Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination.

OBJECTIVES: Coronavirus 2019 vaccine responses in rare autoimmune rheumatic diseases (RAIRDs) remain poorly understood; in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in RAIRD patients compared with healthy controls (HCs). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2-specific T cell responses were measured and compared with those of HCs. Activation-induced marker and deep phenotyping assays were used to identify differences in T cells between high and no/low antibody groups, followed by multidimensional clustering. RESULTS: A total of 50 patients with RAIRDs were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). The median anti-spike levels were significantly lower in RAIRD patients compared with HCs (P < 0.0001). Fifteen (33%) patients had undetectable levels and 26 (57%) had levels lower than the lowest HC. Rituximab in the last 12 months (P = 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (P = 0.03) and spike-specific CD4+ T cells (P = 0.02) between no/low antibody vs high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with no/low antibodies have diminished numbers and poor quality of memory T cells that lack proliferative and functional capacities.

Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study.

Objective: Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD). Methods: Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls. Results: Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03). Conclusion: Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.

Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY.

BACKGROUND: In the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed. METHODS: In a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic. FINDINGS: Between Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 [<0·1%] participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50-67), with rare autoimmune rheumatic diseases was 65 years (54-73), and with lymphoid malignancy was 69 years (61-75). Of the 23 036 participants with serological data, 6583 (28·6%) had received three vaccine doses, 14 234 (61·8%) had received four vaccine doses, and 2219 (9·6%) had received five or more vaccine doses. IgG anti-spike antibodies were undetectable in 2310 (23·3%) of 9927 patients with solid organ transplants, 922 (14·1%) of 6516 patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) of 6593 patients with lymphoid malignancies. In all groups, seropositivity was associated with younger age, higher number of vaccine doses (ie, five vs three), and previous COVID-19. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in recipients of solid organ transplants receiving a combination of an anti-proliferative agent, a calcineurin inhibitor, and steroids, and those with rare autoimmune rheumatic diseases or lymphoid malignancies treated with anti-CD20 therapies. INTERPRETATION: Approximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions. FUNDING: UK Research and Innovation, Kidney Research UK, Blood Cancer UK, Vasculitis UK and the Cystic Fibrosis Trust.

Validation of methods to identify people with idiopathic inflammatory myopathies using hospital episode statistics.

Objective: Hospital episode statistics (HES) are routinely recorded at every hospital admission within the National Health Service (NHS) in England. This study validates diagnostic ICD-10 codes within HES as a method of identifying cases of idiopathic inflammatory myopathies (IIMs). Methods: All inpatient admissions at one NHS Trust between 2010 and 2020 with relevant diagnostic ICD-10 codes were extracted from HES. Hospital databases were used to identify all outpatients with IIM, and electronic care records were reviewed to confirm coding accuracy. Total hospital admissions were calculated from NHS Digital reports. The sensitivity and specificity of each code and code combinations were calculated to develop an optimal algorithm. The optimal algorithm was tested in a sample of admissions at another NHS Trust. Results: Of the 672 individuals identified by HES, 510 were confirmed to have IIM. Overall, the positive predictive value (PPV) was 76% and sensitivity 89%. Combination algorithms achieved PPVs between 89 and 94%. HES can also predict the presence of IIM-associated interstitial lung disease (ILD) with a PPV of 79% and sensitivity of 71%. The optimal algorithm excluded children (except JDM code M33.0), combined M33.0, M33.1, M33.9, M36.0, G72.4, M60.8 and M33.2, and included M60.9 only if it occurred alongside an ILD code (J84.1, J84.9 or J99.1). This produced a PPV of 88.9% and sensitivity of 84.2%. Retesting this algorithm at another NHS Trust confirmed a high PPV (94.4%). Conclusion: IIM ICD-10 code combinations in HES have high PPVs and sensitivities. Algorithms tested in this study could be applied across all NHS Trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM.

COVID-19 infection and hospitalization risk according to vaccination status and DMARD treatment in patients with rheumatoid arthritis.

OBJECTIVES: The objectives of this study were to investigate the incidence of COVID-19 hospitalization in unvaccinated and vaccinated patients with RA compared with matched controls, and in patients with RA according to DMARD treatment. METHODS: This was a Danish nationwide matched-cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalization (Danish National Patient Register) and first-time positive SARS-CoV-2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PYs) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. RESULTS: In total, 28 447 unvaccinated patients and 568 940 comparators had IRs for COVID-19 hospitalization of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PYs, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding IRs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PYs (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV-2 and 1.09 (0.92-1.14) among vaccinated RA patients. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalization compared with conventional DMARD-treated patients. CONCLUSION: The incidence of COVID-19 hospitalization was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. METHODS: A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. RESULTS: The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. CONCLUSION: At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Estimating the clinical prevalence of Wilson's disease in the UK.

BACKGROUND & AIMS: The clinical prevalence of Wilson's disease (WD) in the UK remains unknown. The estimated genetic prevalence in the UK, 142/million, is higher than the clinical prevalence (15/million) reported in other European studies. The aim of this study was to estimate the clinical prevalence of WD utilising readily available laboratory and clinical data. METHOD: Patients with WD who attended Nottingham University Hospital NHS Trust (NUH) between 2011 and 2018 were identified using multiple sources of case ascertainment: serum ceruloplasmin, 24-hour urinary copper, 'Wilson' in liver biopsy report, hospital prescription for penicillamine/trientine/zinc and admission coded with ICD-10 Code E83.0 (disorder of copper metabolism). Potential cases were identified using the Leipzig score, diagnosis was confirmed in hospital records and the point prevalence was calculated using the Office for National Statistics mid-2017 population estimates. RESULTS: A total of 1,794 patients were identified from ≥1 source; 19 patients had WD, of whom 11 were from within the study catchment area and alive at the time of point prevalence estimation. Twenty-nine patients had a Leipzig score ≥2 without a diagnosis of WD, but none had WD on screening (n = 16). The overall prevalence of WD was 15.5/million; males 16.9/million and females 14.1/million. CONCLUSION: This is the first UK population-based study to assess the clinical prevalence of WD. The reported clinical prevalence is lower than the UK genetic prevalence, but comparable to the clinical prevalence reported in Europe. The case ascertainment approach used in this study may be cost-effective, and similar practises could be adopted nationally. LAY SUMMARY: Our study estimates the clinical prevalence of Wilson's disease, a rare genetic disorder of copper metabolism, in the UK. The estimated clinical prevalence is this study is markedly lower than the estimated UK genetic prevalence.

A systematic review and meta-analysis of the incidence rate of Takayasu arteritis.

OBJECTIVES: Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated with substantial morbidity and mortality, notably due to its effects on the cardiovascular system. It has a poorly understood global epidemiology. Our objective was to systematically review the available evidence in order to calculate the incidence rate of TAK. METHODS: Three databases (MEDLINE, PubMed and Embase) were searched in November 2019 and the results were screened by two reviewers. A random effects meta-analysis was then conducted in R to calculate the overall incidence rate. Heterogeneity was assessed using I2. The quality of the studies was assessed using an adapted Newcastle-Ottawa scale. Further subgroup analyses were performed by quality, sex, research setting and geographical location. Publication bias was assessed using a Begg's funnel plot. RESULTS: The incidence rate for TAK was 1.11 per million person-years (95% CI 0.70-1.76). The heterogeneity in the data was extremely high in all analyses, which suggests that there was considerable variation in incidence rates across the different populations studied. TAK was found to be more common in women (incidence rate 2.01 per million person-years, 95% CI 1.39-2.90). CONCLUSIONS: TAK is an extremely rare disease. It affects women more commonly than men. There is considerable variation in the incidence rate between populations. We suggest that future research should focus on discrete populations in order to better identify genetic and environmental risk factors.

Primary care consultations after hospitalisation for pneumonia: a large population-based cohort study.

BACKGROUND: Up to 70% of patients report ongoing symptoms 4 weeks after hospitalisation for pneumonia; the impact on primary care is poorly understood. AIM: To investigate the frequency of primary care consultations after hospitalisation for pneumonia, and the reasons for consultation. DESIGN AND SETTING: A population-based cohort study in England using a UK primary care database of anonymised medical records (Clinical Practice Research Datalink [CPRD]) linked to Hospital Episode Statistics (HES). METHOD: Adults with the first International Classification of Diseases, 10th Revision (ICD-10) code for pneumonia (J12-J18) recorded in HES between July 2002 and June 2017 were included. Primary care consultation within 30 days of discharge was identified as the recording of any medical Read code (excluding administration-related codes) in CPRD. Competing-risks regression analyses were conducted to determine the predictors of consultation and antibiotic use at consultation; death and readmission were competing events. Reasons for consultation were examined. RESULTS: Of 56 396 adults, 55.9% (n = 31 542) consulted primary care within 30 days of hospital discharge. The rate of consultation was highest within 7 days (4.7 per 100 person-days). The strongest predictor for consultation was a higher number of primary care consultations in the year before index admission (adjusted subhazard ratio [sHR] 8.98, 95% confidence interval [CI] = 6.42 to 12.55). The most common reason for consultation was for a respiratory disorder (40.7%, n = 12 840), 11.8% for pneumonia specifically. At consultation, 31.1% (n = 9823) received further antibiotics. Penicillins (41.6%, n = 5753/13 829) and macrolides (21.9%, n = 3029/13 829) were the most common antibiotics prescribed. CONCLUSION: Following hospitalisation for pneumonia, a significant proportion of patients consulted primary care within 30 days, highlighting the morbidity experienced by patients during recovery from pneumonia.

Cost-effectiveness analysis of the nonavalent human papillomavirus vaccine for the prevention of cervical cancer in Singapore.

BACKGROUND: The nonavalent human papillomavirus (HPV) vaccine has been shown to extend protection against oncogenic HPV types 31/33/45/52/58 (HPV-OV) not covered by the bivalent and quadrivalent HPV vaccines. Besides its clinical benefit, evidence on the economic value of the nonavalent vaccine is required to inform local vaccination strategies and funding decisions. This study evaluated the cost-effectiveness of replacing the bivalent vaccine with the nonavalent vaccine in the national school-based HPV vaccination programme in Singapore. METHODS: An existing age-structured dynamic transmission model coupled with stochastic individual-based simulations was adapted to project the health and economic impact of vaccinating 13-year-old girls with two doses of the nonavalent or bivalent HPV vaccines in Singapore. Direct costs (in Singapore dollars, S$) were obtained from public healthcare institutions in Singapore, while health state utilities were sourced from the literature. Incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime horizon, from a healthcare system perspective. Probabilistic sensitivity analysis was performed to obtain the ICERs and corresponding variations across variable uncertainty. Particularly, this study tested the scenarios of lifelong and 20-year vaccine-induced protection, assumed 96.0% and 22.3% cross-protection against HPV-OV by nonavalent and bivalent vaccines respectively, and fixed vaccine prices per dose at S$188 for nonavalent and S$61.50 for bivalent vaccines. RESULTS: Compared with the bivalent vaccine, the use of the nonavalent vaccine was associated with an ICER of S$61,629 per quality-adjusted life year gained in the base case. The result was robust across a range of plausible input values, and to assumptions regarding the duration of vaccine protection. CONCLUSION: Given the high ICER, the nonavalent vaccine is unlikely to represent a cost-effective option compared with the bivalent vaccine for school-based HPV vaccination of 13-year old female students in Singapore. Substantial price reductions would be required to justify its inclusion in the school-based programme in the future.

Estimation of the burden of shielding among a cross-section of patients attending rheumatology clinics with SLE-data from the BSR audit of systemic lupus erythematosus.

OBJECTIVES: We aimed to estimate what proportion of people with SLE attending UK rheumatology clinics would be categorized as being at high risk from coronavirus disease 2019 (COVID-19) and therefore asked to shield, and explore what implications this has for rheumatology clinical practice. METHODS: We used data from the British Society for Rheumatology multicentre audit of SLE, which included a large, representative cross-sectional sample of patients attending UK Rheumatology clinics with SLE. We calculated who would receive shielding advice using the British Society for Rheumatology's risk stratification guidance and accompanying scoring grid, and assessed whether ethnicity and history of nephritis were over-represented in the shielding group. RESULTS: The audit included 1003 patients from 51 centres across all 4 nations of the UK. Overall 344 (34.3%) patients had a shielding score ≥3 and would have been advised to shield. People with previous or current LN were 2.6 (1.9-3.4) times more likely to be in the shielding group than people with no previous LN (P < 0.001). Ethnicity was not evenly distributed between the groups (chi-squared P < 0.001). Compared with White people, people of Black ethnicity were 1.9 (1.3-2.8) and Asian 1.9 (1.3-2.7) times more likely to be in the shielding group. Increased risk persisted after controlling for LN. CONCLUSION: Our study demonstrates the large number of people with SLE who are likely to be shielding. Implications for clinical practice include considering communication across language and cultural differences, and ways to conduct renal assessment including urinalysis, during telephone and video consultations for patients who are shielding.

A landscape analysis of health technology assessment capacity in the Association of South-East Asian Nations region.

BACKGROUND: Progress towards achieving Universal Health Coverage and institutionalizing healthcare priority setting through health technology assessment (HTA) in the Association of South-East Asian Nations (ASEAN) region varies considerably across countries because of differences in healthcare expenditure, political support, access to health information and technology infrastructure. To explore the status and capacity of HTA in the region, the ASEAN Secretariat requested for member countries to be surveyed to identify existing gaps and to propose solutions to help countries develop and streamline their priority-setting processes for improved healthcare decision-making. METHODS: A mixed survey questionnaire with open- and closed-ended questions relating to HTA governance, HTA infrastructure, supply and demand of HTA and global HTA networking opportunities in each country was administered electronically to representatives of HTA nodal agencies of all ASEAN members. In-person meetings or email correspondence were used to clarify or validate any unclear responses. Results were collated and presented quantitatively. RESULTS: Responses from eight out of ten member countries were analysed. The results illustrate that countries in the ASEAN region are at different stages of HTA institutionalization. While Malaysia, Singapore and Thailand have well-established processes and methods for priority setting through HTA, other countries, such as Cambodia, Indonesia, Lao PDR, Myanmar, the Philippines and Vietnam, have begun to develop HTA systems in their countries by establishing nodal agencies or conducting ad-hoc activities. DISCUSSION AND CONCLUSION: The study provides a general overview of the HTA landscape in ASEAN countries. Systematic efforts to mitigate the gaps between the demand and supply of HTA in each country are required while ensuring adequate participation from stakeholders so that decisions for resource allocation are made in a fair, legitimate and transparent manner and are relevant to each local context.

Cost-effectiveness of pertuzumab and trastuzumab biosimilar combination therapy as initial treatment for HER2-positive metastatic breast cancer in Singapore.

BACKGROUND: This study evaluates the cost-effectiveness of pertuzumab with trastuzumab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore. METHODS: A partitioned survival model with three health states was developed to evaluate the cost-effectiveness of trastuzumab biosimilar and docetaxel with or without pertuzumab from a healthcare system perspective over a 15-year time horizon for patients with HER2-positive MBC. Key clinical inputs were derived from the CLEOPATRA trial. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. RESULTS: The base-case resulted in an incremental cost-effectiveness ratio (ICER) of SGD366,658 (USD272,244) per quality-adjusted life-year (QALY) gained. One-way sensitivity analyses showed that the ICER was sensitive to utilities in the progression-free state, price of pertuzumab and time horizon. When the price for trastuzumab reference biologic (branded) was applied, the ICER was even higher (SGD426,996 [USD317,045]/QALY). CONCLUSION: Although trastuzumab biosimilar reduced the cost of the pertuzumab combination regimen, the ICER remained high and was not cost effective in Singapore's context. As pertuzumab contributed 80% of the overall combination treatment cost, price reductions for pertuzumab will be required to improve the cost-effectiveness of combination treatment to an acceptable level.