Analytical performance and user-friendliness of four commercially available point-of-care devices for C-reactive protein.

INTRODUCTION: Proper implementation of Point-of-Care testing (POCT) for C-reactive protein (CRP) in primary care can decrease the inappropriate use of antibiotics, thereby tackling the problem of growing antimicrobial resistance. OBJECTIVE: The analytical performance and user-friendliness of four POCT-CRP assays were evaluated: QuikRead go easy, LumiraDx, cobas b 101 and Afinion 2. MATERIALS AND METHODS: Imprecision was evaluated using plasma pools in addition to manufacturer-specific control material. Trueness was assessed by verification of traceability to ERM-DA474/IFCC in parallel to method comparison towards the central laboratory CRP method (cobas c 503) using i) retrospectively selected plasma samples (n = 100) and ii) prospectively collected capillary whole blood samples (n = 50). User-friendliness was examined using a questionnaire. RESULTS: Between-day imprecision on plasma pools varied from 4.5 % (LumiraDx) to 11.5 % (QuikRead). Traceability verification revealed no significant difference between cobas c 503 CRP results and the ERM-DA474/IFCC certified value. cobas b 101 and Afinion achieved the best agreement with the central laboratory method. LumiraDx and QuikRead revealed a negative mean difference, with LumiraDx violating the criterion of > 95 % of POCT-CRP-results within ± 20 % of the comparison method. Regarding user-friendliness, Afinion obtained the highest Likert-scores. CONCLUSION: The analytical performance and user-friendliness of POCT-CRP devices varies among manufacturers, emphasizing the need for quality assurance supervised by a central laboratory.

Temporal trends in antibiotic prescribing and serious and nonserious infections in children presenting to general practice: a registry-based longitudinal cohort study of 162 507 individuals.

BACKGROUND: It is crucial to understand the trends in paediatric antibiotic prescribing and serious and nonserious infections to improve antibiotic prescribing practices for children in ambulatory care. OBJECTIVES: Assessing trends in paediatric antibiotic prescribing and infection incidence in general practice from 2002 to 2022. METHODS: In this retrospective cohort study using INTEGO network data from 162 507 patients in Flanders (Belgium), we calculated antibiotic prescribing rates and proportions alongside incidence rates of serious and nonserious infections, stratified by age (0-1, 2-6, 7-12 years) and municipality. We performed autoregressive moving average time-series analyses and seasonality analyses. RESULTS: From 2002 to 2022, antibiotic prescribing rate decreased significantly: 584/1000 person-years (PY) (95% CI 571-597) to 484/1000PY (95% CI 478-491); so did antibiotic overall prescribing proportion: 46.3% (95% CI 45.1-47.6) to 23.3% (95% CI 22.9-23.7) (59.3% amoxicillin and 17.8% broad spectrum). Prescribing proportions dropped significantly for nonserious (45.6% to 20.9%) and increased for serious infections (64.1% to 69.8%). Proportions significantly dropped for acute suppurative otitis media (74.7% to 64.1%), upper respiratory tract infections (44.9% to 16.6%), bronchitis/bronchiolitis (73.6% to 44.1%) and acute tonsillopharyngitis (59.5% to 21.7%), while significantly increasing for pneumonia (65.2% to 80.2%). Nonserious and serious infection incidence rates increased from 785/1000PY and 34.2/1000PY to 1223/1000PY and 64.1/1000PY, respectively. Blood and CRP testing proportions increased significantly. CONCLUSIONS: Antibiotic prescribing in general practice for children declined from 2002 to 2022. Further targeted antibiotic stewardship initiatives are needed to reduce the use of broad-spectrum antibiotics and antibiotic prescribing for conditions such as otitis media and bronchitis/bronchiolitis.

Accuracy of respiratory muscle assessments to predict weaning outcomes: a systematic review and comparative meta-analysis.

BACKGROUND: Several bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit. It remains unclear which assessments perform best in predicting weaning success. The primary aim of this systematic review and meta-analysis was to summarize and compare the accuracy of the following assessments to predict weaning success: maximal inspiratory (PImax) and expiratory pressures, diaphragm thickening fraction and excursion (DTF and DE), end-expiratory (Tdiee) and end-inspiratory (Tdiei) diaphragm thickness, airway occlusion pressure (P0.1), electrical activity of respiratory muscles, and volitional and non-volitional assessments of transdiaphragmatic and airway opening pressures. METHODS: Medline (via Pubmed), EMBASE, Web of Science, Cochrane Library and CINAHL were comprehensively searched from inception to 04/05/2023. Studies including adult mechanically ventilated patients reporting data on predictive accuracy were included. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate the SROC curves of each assessment method. Meta-regression was used to compare SROC curves. Sensitivity analyses were conducted by excluding studies with high risk of bias, as assessed with QUADAS-2. Direct comparisons were performed using studies comparing each pair of assessments within the same sample of patients. RESULTS: Ninety-four studies were identified of which 88 studies (n = 6296) reporting on either PImax, DTF, DE, Tdiee, Tdiei and P0.1 were included in the meta-analyses. The sensitivity to predict weaning success was 63% (95% CI 47-77%) for PImax, 75% (95% CI 67-82%) for DE, 77% (95% CI 61-87%) for DTF, 74% (95% CI 40-93%) for P0.1, 69% (95% CI 13-97%) for Tdiei, 37% (95% CI 13-70%) for Tdiee, at fixed 80% specificity. Accuracy of DE and DTF to predict weaning success was significantly higher when compared to PImax (p = 0.04 and p < 0.01, respectively). Sensitivity and direct comparisons analyses showed that the accuracy of DTF to predict weaning success was significantly higher when compared to DE (p < 0.01). CONCLUSIONS: DTF and DE are superior to PImax and DTF seems to have the highest accuracy among all included respiratory muscle assessments for predicting weaning success. Further studies aiming at identifying the optimal threshold of DTF to predict weaning success are warranted. TRIAL REGISTRATION: PROSPERO CRD42020209295, October 15, 2020.

ADNEX risk prediction model for diagnosis of ovarian cancer: systematic review and meta-analysis of external validation studies.

Objectives: To conduct a systematic review of studies externally validating the ADNEX (Assessment of Different Neoplasias in the adnexa) model for diagnosis of ovarian cancer and to present a meta-analysis of its performance. Design: Systematic review and meta-analysis of external validation studies. Data sources: Medline, Embase, Web of Science, Scopus, and Europe PMC, from 15 October 2014 to 15 May 2023. Eligibility criteria for selecting studies: All external validation studies of the performance of ADNEX, with any study design and any study population of patients with an adnexal mass. Two independent reviewers extracted the data. Disagreements were resolved by discussion. Reporting quality of the studies was scored with the TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) reporting guideline, and methodological conduct and risk of bias with PROBAST (Prediction model Risk Of Bias Assessment Tool). Random effects meta-analysis of the area under the receiver operating characteristic curve (AUC), sensitivity and specificity at the 10% risk of malignancy threshold, and net benefit and relative utility at the 10% risk of malignancy threshold were performed. Results: 47 studies (17 007 tumours) were included, with a median study sample size of 261 (range 24-4905). On average, 61% of TRIPOD items were reported. Handling of missing data, justification of sample size, and model calibration were rarely described. 91% of validations were at high risk of bias, mainly because of the unexplained exclusion of incomplete cases, small sample size, or no assessment of calibration. The summary AUC to distinguish benign from malignant tumours in patients who underwent surgery was 0.93 (95% confidence interval 0.92 to 0.94, 95% prediction interval 0.85 to 0.98) for ADNEX with the serum biomarker, cancer antigen 125 (CA125), as a predictor (9202 tumours, 43 centres, 18 countries, and 21 studies) and 0.93 (95% confidence interval 0.91 to 0.94, 95% prediction interval 0.85 to 0.98) for ADNEX without CA125 (6309 tumours, 31 centres, 13 countries, and 12 studies). The estimated probability that the model has use clinically in a new centre was 95% (with CA125) and 91% (without CA125). When restricting analysis to studies with a low risk of bias, summary AUC values were 0.93 (with CA125) and 0.91 (without CA125), and estimated probabilities that the model has use clinically were 89% (with CA125) and 87% (without CA125). Conclusions: The results of the meta-analysis indicated that ADNEX performed well in distinguishing between benign and malignant tumours in populations from different countries and settings, regardless of whether the serum biomarker, CA125, was used as a predictor. A key limitation was that calibration was rarely assessed. Systematic review registration: PROSPERO CRD42022373182.

Vaccine hesitancy for the COVID-19 vaccine booster dose among nursing home staff fully vaccinated with the primary vaccination course in Belgium.

In Belgium, nursing home (NH) staff (NHS) and residents were prioritised for the initial COVID-19 vaccination and successive booster doses. The vaccination campaign for the first booster started in September 2021 in Belgian NH. Our first study about vaccine hesitancy towards the COVID-19 vaccine in Belgian NHS already showed a degree of fear for the primary vaccination course (T1). This new study aims to evaluate vaccine hesitancy to get the first booster (T2) in a population of fully vaccinated (with two doses) NHS. A random stratified sample of NHS who received the primary vaccination course (N = 954) completed an online questionnaire on COVID-19 booster hesitancy (between 25/11/2021 and 22/01/2022). NHS who hesitated or refused the booster were asked for the main reason for their hesitation/refusal. Overall, 21.0 % of our population hesitated before, were still hesitating or refused the booster, NHS that were not hesitant at T1 being 5.7 times less likely to hesitate to get the first booster dose (Adjusted OR 0.179, 95 % CI: 0.120, 0.267). Although there was a slight reduction (23.5 % to 20.1 %) in the proportion of NHS who hesitated/refused vaccination at T1 compared to T2 (p = 0.034), the fear of unknown effects was the principal reason for hesitation/refusal, already mentioned in our first study. NHS were not reassured concerning their initial fears. Given the likelihood that booster vaccinations will be necessary over the coming years, a communication strategy specific to NHS should be implemented.

The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice.

BACKGROUND: The DAWN antivirals trial was a multicentric, randomised placebo-controlled trial evaluating antiviral medication for COVID-19 in general practice. The trial was prematurely terminated because of insufficient recruitment. AIM: To explore which factors contributed to the premature termination. DESIGN & SETTING: General practice in Belgium. METHOD: Patients were randomised to camostat or placebo (patients and physicians blinded) between June 2021 and July 2022; a third arm evaluating molnupiravir (open label) was opened in March 2022. The outcome assessor was blinded for all comparisons except for the patient reported outcomes in case of molnupiravir. The authors analysed available trial data and evaluated trial context, implementation, and mechanisms of impact based on semi-structured interviews with trial stakeholders. RESULTS: The trial recruited 44 participants; 19 were allocated to camostat (median age 55 years), 8 to molnupiravir (median age 60 years), and 17 to placebo (median age 56 years). There were no serious adverse events in either group. Most difficulties were related to the pandemic context: disruption to routine clinical services; multiple changes to the service model for COVID-19 patients; overwhelmed clinical staff; delays of trial medication; and staff shortages in the sponsor and clinical team. In addition, regulatory approval processes were lengthy and led to additional study procedures. It was felt that the trial started too late, when vaccinations had already begun. CONCLUSION: The DAWN antivirals trial was stopped prematurely. Although many barriers were related to the pandemic itself, hurdles such as a small and inexperienced sponsor and clinical teams, delays in regulatory processes, and research capacity in routine settings could be overcome by established research infrastructure and standardisation of processes.

Towards an international consensus on safety netting advice for acutely ill children presenting to ambulatory care: a modified e-Delphi procedure.

OBJECTIVE: Develop a consensus on the content and form of safety netting advice (SNA) for parents of acutely ill children. DESIGN: Four-round modified e-Delphi using online questionnaires and feedback among clinical and research experts. SETTING: Ambulatory care in high-income countries. PARTICIPANTS: Forty-one experts from 13 countries: 3 emergency physicians, 15 general practitioners, 4 nurses and 19 paediatricians. RESULTS: The experts defined the content of SNA as advice on the normal, expected disease course of the provisional diagnosis, diagnostic uncertainty, alarm signs that indicate the need for medical help and information on where and how to find such help. Regarding the form of the SNA, the experts agree that a reliable source should give SNA verbally with paper or digital written or video/image resources at every appropriate healthcare encounter in a short and simple empowering fashion, specific to the child's situation and seek confirmatory feedback from parents. CONCLUSIONS: SNA needs to contain advice on the expected disease course, alarm signs and where and how to find help. It should be given verbally with written resources by a reliable healthcare professional or digital platform. Short, simple and specific, SNA needs to empower the parent whose understanding of the advice should be checked. The effectiveness of SNA resources coproduced by parents and experts should be assessed in different settings and those providing SNA require up-to-date and reliable training.

Factors associated with inappropriateness of antibiotic prescriptions for acutely ill children presenting to ambulatory care in high-income countries: a systematic review and meta-analysis.

BACKGROUND: Acutely ill children are at risk of unwarranted antibiotic prescribing. Data on the appropriateness of antibiotic prescriptions provide insights into potential tailored interventions to promote antibiotic stewardship. OBJECTIVES: To examine factors associated with the inappropriateness of antibiotic prescriptions for acutely ill children presenting to ambulatory care in high-income countries. METHODS: On 8 September 2022, we systematically searched articles published since 2002 in MEDLINE, Embase, CENTRAL, Web of Science, and grey literature databases. We included studies with acutely ill children presenting to ambulatory care settings in high-income countries reporting on the appropriateness of antibiotic prescriptions. The quality of the studies was evaluated using the Appraisal tool for Cross-Sectional Studies and the Newcastle-Ottawa Scale. Pooled ORs were calculated using random-effects models. Meta-regression, sensitivity and subgroup analysis were also performed. RESULTS: We included 40 articles reporting on 30 different factors and their association with inappropriate antibiotic prescribing. 'Appropriateness' covered a wide range of definitions. The following factors were associated with increased inappropriate antibiotic prescribing: acute otitis media diagnosis [pooled OR (95% CI): 2.02 (0.54-7.48)], GP [pooled OR (95% CI) 1.38 (1.00-1.89)] and rural setting [pooled OR (95% CI) 1.47 (1.08-2.02)]. Older patient age and a respiratory tract infection diagnosis have a tendency to be positively associated with inappropriate antibiotic prescribing, but pooling of studies was not possible. CONCLUSIONS: Prioritizing acute otitis media, GPs, rural areas, older children and respiratory tract infections within antimicrobial stewardship programmes plays a vital role in promoting responsible antibiotic prescribing. The implementation of a standardized definition of appropriateness is essential to evaluate such programmes.

C-reactive protein point-of-care testing and complementary strategies to improve antibiotic stewardship in children with acute respiratory infections in primary care.

This paper provides the perspective of an international group of experts on the role of C-reactive protein (CRP) point-of-care testing (POCT) and complementary strategies such as enhanced communication skills training and delayed prescribing to improve antibiotic stewardship in the primary care of children presenting with an acute illness episode due to an acute respiratory tract infection (ARTI). To improve antibiotics prescribing decisions, CRP POCT should be considered to complement the clinical assessment of children (6 months to 14 years) presenting with an ARTI in a primary care setting. CRP POCT can help decide whether a serious infection can be ruled out, before deciding on further treatments or management, when clinical assessment is unconclusive. Based on the evidence currently available, a CRP value can be a valuable support for clinical reasoning and facilitate communication with patients and parents, but the clinical assessment should prevail when making a therapy or referral decision. Nearly half of children tested in the primary care setting can be expected to have a CRP value below 20 mg/l, in which case it is strongly suggested to avoid prescribing antibiotics when the clinical assessment supports ruling out a severe infection. For children with CRP values greater than or equal to 20 mg/l, additional measures such as additional diagnostic tests, observation time, re-assessment by a senior decision-maker, and specialty referrals, should be considered.

The menstrual cycle and the COVID-19 pandemic.

BACKGROUND: The impact of COVID-19 virus on menstrual cycles in unvaccinated women is limited. OBJECTIVE: To investigate the prevalence of changes to menstrual cycle characteristics, hormonal symptoms and lifestyle changes prior to and during the COVID-19 pandemic. METHODS: A retrospective online cross-sectional survey completed by social media users between July 2020 to October 2020. Participants were living in the United Kingdom (UK), premenopausal status and, or over 18 years of age. MAIN OUTCOME(S) AND MEASURES(S): The primary outcome was to assess changes to menstrual cycle characteristics during the pandemic following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Secondary outcomes included assessment of hormonal and lifestyle changes. RESULTS: 15,611 social media users completed the survey. Of which, 75% of participants experienced a change in their menstrual cycle, with significantly greater proportions reporting irregular menstrual cycles (P<0·001), bleeding duration more than seven days (P<0·001), longer mean cycle length (P<0·001) and overall bleeding duration (P<0·001). Over half the participants reported worsening of premenstrual symptoms including low mood/depression, anxiety and irritability. When stratified according to COVID-19 infection, there was no significant difference in menstrual cycle changes. CONCLUSION: The COVID-19 pandemic resulted in considerable variation in menstrual cycle characteristics and hormonal symptoms. This appears to be related to societal and lifestyle changes resulting from the pandemic, rather than to the virus itself. We believe this may have an impact on the individual, as well as national economy, healthcare, and population levels, and therefore suggest this should be taken into consideration by governments, healthcare providers and employers when developing pandemic recovery plans.

Best practice guidance for antibiotic audit and feedback interventions in primary care: a modified Delphi study from the Joint Programming Initiative on Antimicrobial resistance: Primary Care Antibiotic Audit and Feedback Network (JPIAMR-PAAN).

BACKGROUND: Primary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A&F) is often used to reduce inappropriate antibiotic prescribing. The design and implementation of A&F may impact its effectiveness. There are no best practice guidelines for peer comparison A&F in antibiotic prescribing in primary care. OBJECTIVE: To develop best practice guidelines for peer comparison A&F for antibiotic prescribing in primary care in high income countries by leveraging international expertise via the Joint Programming Initiative on Antimicrobial Resistance-Primary Care Antibiotic Audit and Feedback Network. METHODS: We used a modified Delphi process to achieve convergence of expert opinions on best practice statements for peer comparison A&F based on existing evidence and theory. Three rounds were performed, each with online surveys and virtual meetings to enable discussion and rating of each best practice statement. A five-point Likert scale was used to rate consensus with a median threshold score of 4 to indicate a consensus statement. RESULTS: The final set of guidelines include 13 best practice statements in four categories: general considerations (n = 3), selecting feedback recipients (n = 1), data and indicator selection (n = 4), and feedback delivery (n = 5). CONCLUSION: We report an expert-derived best practice recommendations for designing and evaluating peer comparison A&F for antibiotic prescribing in primary care. These 13 statements can be used by A&F designers to optimize the impact of their quality improvement interventions, and improve antibiotic prescribing in primary care.

Guidance on C-reactive protein point-of-care testing and complementary strategies to improve antibiotic prescribing for adults with lower respiratory tract infections in primary care.

The world faces the threat of increasing antimicrobial resistance, and there is growing consensus that swift action must be taken to improve the rational use of antibiotics and increase the stewardship of antibiotics to safeguard this key resource in modern healthcare. This paper provides the perspective of an international group of experts on the role of C-reactive protein point-of-care testing (CRP POCT) and other complementary strategies to improve antibiotic stewardship in primary care, with regards to the diagnosis and treatment of adult patients presenting symptoms of lower respiratory tract infections (LRTIs). It provides guidance regarding the clinical assessment of symptoms in combination with C-reactive protein (CRP) results, at the point of care, to support the management decision, and discusses enhanced patient communication and delayed prescribing as complementary strategies to decrease the inappropriate use of antibiotics. Recommendation: CRP POCT should be promoted to improve the identification of adults presenting with symptoms of LRTIs in primary care who might gain additional benefit from antibiotic treatment. Appropriateness of antibiotic use can be maximized when CRP POCT is used together with complementary strategies such as enhanced communication skills training and delayed prescribing in addition to routine safety netting.

Clinical effectiveness of rehabilitation in ambulatory care for patients with persisting symptoms after COVID-19: a systematic review.

BACKGROUND: Lingering symptoms after acute COVID-19 present a major challenge to ambulatory care services. Since there are reservations regarding their optimal management, we aimed to collate all available evidence on the effects of rehabilitation treatments applicable in ambulatory care for these patients. METHODS: On 9 May 2022, we systematically searched articles in COVID-19 collections, Embase, MEDLINE, Cochrane Library, Web of Science, CINAHL, PsycArticles, PEDro, and EuropePMC. References were eligible if they reported on the clinical effectiveness of a rehabilitation therapy applicable in ambulatory care for adult patients with persisting symptoms continuing 4 weeks after the onset of COVID-19. The quality of the studies was evaluated using the CASP cohort study checklist and the Cochrane Risk of Bias Assessment Tool. Summary of Findings tables were constructed and the certainty of evidence was assessed using the GRADE framework. RESULTS: We included 38 studies comprising 2,790 participants. Physical training and breathing exercises may reduce fatigue, dyspnoea, and chest pain and may improve physical capacity and quality of life, but the evidence is very weak (based on 6 RCTs and 12 cohort studies). The evidence underpinning the effect of nutritional supplements on fatigue, dyspnoea, muscle pain, sensory function, psychological well-being, quality of life, and functional capacity is very poor (based on 4 RCTs). Also, the evidence-base is very weak about the effect of olfactory training on sensory function and quality of life (based on 4 RCTs and 3 cohort studies). Multidisciplinary treatment may have beneficial effects on fatigue, dyspnoea, physical capacity, pulmonary function, quality of life, return to daily life activities, and functional capacity, but the evidence is very weak (based on 5 cohort studies). The certainty of evidence is very low due to study limitations, inconsistency, indirectness, and imprecision. CONCLUSIONS: Physical training, breathing exercises, olfactory training and multidisciplinary treatment can be effective rehabilitation therapies for patients with persisting symptoms after COVID-19, still with high uncertainty regarding these effects. These findings can guide ambulatory care practitioners to treat these patients and should be incorporated in clinical practice guidelines. High-quality studies are needed to confirm our hypotheses and should report on adverse events.

Validation of a rapid SARS-CoV-2 antibody test in general practice.

OBJECTIVES: To validate a rapid serological test (RST) for SARS-CoV-2 antibodies used in seroprevalence studies in healthcare providers, including primary healthcare providers (PHCPs) in Belgium. DESIGN: A phase III validation study of the RST (OrientGene) within a prospective cohort study. SETTING: Primary care in Belgium. PARTICIPANTS: Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages patients were eligible in the seroprevalence study. For the validation study, all participants who tested positive (376) on the RST at the first testing timepoint (T1) and a random sample of those who tested negative (790) and unclear (24) were included. INTERVENTION: At T2, 4 weeks later, PHCPs performed the RST with fingerprick blood (index test) immediately after providing a serum sample to be analysed for the presence of SARS-CoV-2 immunoglobulin G antibodies using a two-out-of-three assay (reference test). PRIMARY AND SECONDARY OUTCOME MEASURES: The RST accuracy was estimated using inverse probability weighting to correct for missing reference test data, and considering unclear RST results as negative for the sensitivity and positive for the specificity. Using these conservative estimates, the true seroprevalence was estimated both for T2 and RST-based prevalence values found in a cohort study with PHCPs in Belgium. RESULTS: 1073 paired tests (403 positive on the reference test) were included. A sensitivity of 73% (a specificity of 92%) was found considering unclear RST results as negative (positive). For an RST-based prevalence at T1 (13.9), T2 (24.9) and T7 (70.21), the true prevalence was estimated to be 9.1%, 25.9% and 95.7%, respectively. CONCLUSION: The RST sensitivity (73%) and specificity (92%) make an RST-based seroprevalence below (above) 23% overestimate (underestimate) the true seroprevalence. TRIAL REGISTRATION NUMBER: NCT04779424.

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.

BACKGROUND: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. METHODS: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. FINDINGS: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. INTERPRETATION: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. FUNDING: Research Foundation Flanders.

Prospective Performance Evaluation of the miDiagnostics COVID-19 PCR Test for Rapid SARS-CoV-2 Detection on Nasopharyngeal Swabs.

Rapid diagnosis or exclusion of SARS-CoV-2 infection is essential for correct medical management decisions regarding COVID-19. High-throughput laboratory-based reverse transcriptase (RT)-PCR testing is accurate with longer turnaround times, while rapid antigen tests show moderate sensitivity. In search of a fast and reliable COVID-19 test, we aimed to validate the rapid miDiagnostics COVID-19 PCR test. We recruited symptomatic and asymptomatic participants in a mobile COVID-19 test center in Belgium. We collected three nasopharyngeal samples from each participant. The index sample was tested on the miDiagnostics COVID-19 PCR reader, the reference sample was tested on the reference TaqPath COVID-19 PCR test in the Belgian Reference Center for Respiratory Pathogens of University Hospitals Leuven, and a third sample was collected for discordance testing with the PerkinElmer SARS-CoV-2 PCR kit. A total of 770 participants yielded 763 sets of included nasopharyngeal samples. Overall positive percent agreement and negative percent agreement of the miDiagnostics COVID-19 PCR test were 95.5% (92.6% to 97.4%) and 94.9% (92.3 to 96.8%), rising to 98.6% (96.5% to 99.6%) and 96.5% (92.6% to 98.7%) in symptomatic patients. Discordance testing reclassified 15 of 21 false-positive cases as true positive. A retest of the miDiagnostics PCR test was performed in 61 tests (7.4%) due to a technical error. The miDiagnostics COVID-19 PCR test showed excellent clinical accuracy. The fast and reliable results allow for rapid correct diagnosis and tailored medical management decisions regarding COVID-19.

Clinical prediction models for serious infections in children: external validation in ambulatory care.

BACKGROUND: Early distinction between mild and serious infections (SI) is challenging in children in ambulatory care. Clinical prediction models (CPMs), developed to aid physicians in clinical decision-making, require broad external validation before clinical use. We aimed to externally validate four CPMs, developed in emergency departments, in ambulatory care. METHODS: We applied the CPMs in a prospective cohort of acutely ill children presenting to general practices, outpatient paediatric practices or emergency departments in Flanders, Belgium. For two multinomial regression models, Feverkidstool and Craig model, discriminative ability and calibration were assessed, and a model update was performed by re-estimation of coefficients with correction for overfitting. For two risk scores, the SBI score and PAWS, the diagnostic test accuracy was assessed. RESULTS: A total of 8211 children were included, comprising 498 SI and 276 serious bacterial infections (SBI). Feverkidstool had a C-statistic of 0.80 (95% confidence interval 0.77-0.84) with good calibration for pneumonia and 0.74 (0.70-0.79) with poor calibration for other SBI. The Craig model had a C-statistic of 0.80 (0.77-0.83) for pneumonia, 0.75 (0.70-0.80) for complicated urinary tract infections and 0.63 (0.39-0.88) for bacteraemia, with poor calibration. The model update resulted in improved C-statistics for all outcomes and good overall calibration for Feverkidstool and the Craig model. SBI score and PAWS performed extremely weak with sensitivities of 0.12 (0.09-0.15) and 0.32 (0.28-0.37). CONCLUSIONS: Feverkidstool and the Craig model show good discriminative ability for predicting SBI and a potential for early recognition of SBI, confirming good external validity in a low prevalence setting of SBI. The SBI score and PAWS showed poor diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02024282. Registered on 31 December 2013.

Cost-effectiveness of point-of-care interventions to tackle inappropriate prescribing of antibiotics in high- and middle-income countries: a systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is propagated by widespread inappropriate use of antibiotics. In response, point-of-care interventions (POCIs) have been developed in primary care to preserve antibiotic effectiveness. Many of these POCIs are adopted based on their clinical value. However, assessment of their cost-effectiveness is crucial as well. OBJECTIVES: To summarize the evidence on cost-effectiveness of POCIs aimed at tackling inappropriate antibiotic prescriptions in primary care in middle- and high-income countries. We also evaluate the quality of the evidence with particular attention to how these economic evaluations faced the challenge of capturing the impact of these POCIs on AMR. METHODS: Six scientific databases (MEDLINE, Embase, Web of Science, NHS EED, NHS HTA, the Cochrane Library) were searched for eligible articles published from 1999 to 2022. Their quality was appraised by means of the Drummond and CHEERS checklist. RESULTS: Twenty-nine articles met the selection criteria. Using their own (implicit) definitions of cost-effectiveness, evidence reported that point-of-care testing, scoring tools, electronic interventions, communication training, and multidimensional and educational interventions are more cost-effective than standard care. In contrast, studies found dipstick testing and audit-and-feedback interventions to be not cost-effective. Data synthesis took a narrative approach as eligible studies were not similar and/or reliable enough to pool their results through meta-analysis. CONCLUSIONS: More high-quality evidence is needed to attain a thorough understanding of the cost-effectiveness of POCIs. Heterogeneity in terms of interventions and efficiency measures complicates comparing and generalizing results. Methodological recommendations are urgently needed to economically evaluate POCIs, focusing on how AMR should be accounted for.