Real-world evidence from Germany and the United States: Treatment initiation on low-efficacy versus high-efficacy therapies in patients with multiple sclerosis.

BACKGROUND: The hit-hard-and-early (HHAE) strategy where treatment is initiated with high-efficacy therapies opposed to low-efficacy therapies presents a potential paradigm shift in multiple sclerosis (MS) management. This study aimed to assess the adoption of the HHAE strategy in Germany and the United States (US) from 2020 to 2022 based on real-world data. METHODS: The analysis was based on longitudinal, patient-level data from Germany and the US. For Germany, data was extracted from the Permea platform covering approximately 44 % of all German community pharmacy dispensing. For the US, data from the Komodo Healthcare Map™ was utilized, covering medical benefit data from around 88 % of the US patient population. Patients ≥18 years old and who had at least 2 prescriptions for MS-related disease-modifying drugs (DMDs) between January 2020 and December 2022 were included. To approximate therapy beginners, a washout period of one year before treatment start was applied, excluding all patients who had an MS-related DMD prescription or claim in 2019. Cohort entry date was the day of the first MS-related DMD dispense or claim. DMDs were classified as high-efficacy and low-efficacy based on the Multiple Sclerosis Therapy Consensus Group (MSTCG). Group differences were assessed with two-sided χ2-square and t-tests. RESULTS: 29,604 MS therapy beginners were identified in the German and 49,791 MS therapy beginners were identified in the US dataset. 29.6 % of MS therapy beginners in Germany and 61.6 % in the US followed the HHAE strategy. Between 2020 and 2022, a significant 14 % increase in the HHAE strategy was observed in both countries (p < 0.0001). High-efficacy therapy beginners switched from their initially prescribed therapy less frequently than low-efficacy therapy beginners: 6.9 % of high-efficacy vs. 19.5 % of low-efficacy therapy beginners in Germany (p < 0.0001) and 5.5 % of high-efficacy vs. 25.0 % low-efficacy therapy beginners in the US (p < 0.0001) switched from their first prescribed DMD. CONCLUSION: Between 2020 and 2022, the adoption of the HHAE strategy increased in both countries, with the US exhibiting nearly double the adoption rates. High-efficacy therapy beginners were less likely to switch from their initially prescribed medication than low-efficacy therapy beginners. Real world evidence can provide valuable insights into rapidly changing treatment patterns in patients with MS.

Diagnostic delay in Hidradenitis suppurativa investigated using data from social media and from statutory health insurances.

BACKGROUND: The chronic inflammatory skin disease hidradenitis suppurativa (HS) leads to severe pain and reduced quality of life. Nonetheless, it often takes years until a correct diagnosis is made. In this analysis, disease-related experiences and pathways of patients with HS were investigated and compared with the physicians' perspective. METHODS: Public posts on forums and social media as well as results of a survey conducted among dermatologists and their patients on the actual medical care reality of HS in Germany were analysed. Furthermore, claims data from German health insurance companies were evaluated. RESULTS: Patients with HS suffer from a 43.3% reduction in working ability. Dermatology (26.5%) was the most frequently consulted specialty, with HS diagnosed predominantly in the inpatient setting (43.8%). Abscesses were described as the most frequent alternative diagnosis in HS patients (53.2%). Patient-reported changes of physicians in dermatology (34.1%) and surgery (42.4%) occurred predominantly within the specialty. Dermatology received most referrals from general practitioners (67.1%), but only 12.1% from surgeons. CONCLUSION: There is an urgent need to reduce the delay in diagnosis and the prolonged burden of disease in patients with HS. Therefore, awareness of the disease, its detection and treatment which goes beyond dermatology should be promoted, if possible as part of medical studies.

Data on Ocrelizumab Treatment Collected by MS Patients in Germany Using Brisa App.

BACKGROUND: With a rising number of multiple sclerosis (MS) cases and increasing pressure on health systems, digital companion apps like Brisa, designed specifically for people with MS, can play an important role in the patient journey. These apps enable the collection of real-time longitudinal data that are critical to our understanding of the pathophysiology and progression of MS. METHODS: This retrospective, descriptive analysis consists of data from Brisa users who registered between 6 August 2021 and 8 September 2022. Of the unique users, 37.7% (n = 1593) fulfilled the inclusion criteria including information about medication and demographics and tracked one or more symptoms and/or patient-reported outcomes. Users were classified as moderate-efficacy treatment users, high-efficacy treatment users and ocrelizumab users, and the reporting frequency and scores of symptoms and patient-reported outcomes were analyzed. RESULTS: The largest cohort of Brisa users (405) reported treatment with ocrelizumab and were mostly diagnosed 2-5 years before the survey. The most reported MS symptoms were similar between OUs (ocrelizumab users), HETUs (high-efficacy treatment users) and METUs (moderate-efficacy treatment users). OUs on average reported symptoms and answered questionnaires more frequently. Baseline scores between HETUs and OUs were similar, whereas baseline scores of METUs were slightly lower in comparison. In a further analysis of OUs, disability scores increased with age; users aged 26-45 years had higher pain scores than 18-25-year-olds. No significant differences were found in quality of life, bowel control and vision between age groups. CONCLUSION: These findings show that the characteristics of the Brisa cohort are similar to the results of other studies and registries and can provide a representative overview of everyday disease management. Thereby, these results can bridge the gap between clinical research and real patient experience, but they also raise new questions, such as how often the hard-and-early therapy approach is already used and whether baseline characteristics and reasons for choosing a particular treatment contribute to the different outcomes over time. Answering these questions requires further research and analysis.

Shifting from the treat-to-target to the early highly effective treatment approach in patients with multiple sclerosis - real-world evidence from Germany.

Background: While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients with poor prognostic factors, it remains unclear whether this approach has been adopted by a broad range of MS providers in Germany yet. Objective: To assess the adoption of the early highly effective treatment (EHT) compared to the treat-to-target treatment approach with the option of escalating treatment efficacy over time in Germany based on real-world evidence data. Design: Patient-level pharmacy dispensing data from the Permea platform were analysed from 2020 to 2022. Methods: In total, 29,529 therapy beginners (>18 years) were included to analyse shifts in treatment approaches over time and switching behaviour. Medication classification adhered to the German Society of Neurology guidelines and designated fumarates, glatiramer acetate, teriflunomide and interferons as low-efficacy category 1 medications; cladribine and S1P-modulators as medium-efficacy category 2 medications; and alemtuzumab, natalizumab, ocrelizumab, ofatumumab and rituximab (off-label) as high-efficacy category 3 medications. Results: Our results show that 70.0% of patients redeemed their first prescription for category 1 medication, 16.3% for category 2 and 13.7% for category 3 medications. The proportion of prescriptions filled shifted from 2020 to 2022 with a decrease of 14.7% for category 1 drugs and an increase of 12.5% for category 3 drugs. 93.2% of patients stayed on their initially prescribed medication category. 3.2% of category 1 and 3.7% of category 2 therapy beginners escalated to category 3 medication. 3.4% of category 3 medication users de-escalated their treatment to category 1 or category 2. Conclusion: While most individuals started their treatment according to the treat-to-target approach and remained on their initially prescribed medication category, there has been a steadily increasing shift towards the EHT approach since 2020. These insights demonstrate that, while not officially recommended by German guidelines, MS providers increasingly adopt the EHT approach.

The IMPACT of the COVID-19 Pandemic on Prescription Drug Use in Patients with Psoriasis Vulgaris in Germany.

INTRODUCTION: Real-world evidence (RWE) data is increasingly important to generate rapid insights to effectively manage patient populations. Disruptions like the coronavirus disease 2019 (COVID-19) pandemic may negatively impact the choice of medications used for managing chronic diseases such as psoriasis (PSO). Here, we explored the effect of the COVID-19 pandemic on the sales volumes of treatment guideline-based PSO medication in Germany. METHODS: Patient-level pharmacy dispensing data from the Permea platform, covering approximately 44% of all community pharmacy dispensing in Germany, were analysed from 2019 through to 2021. Patient demographics and PSO indicated medication sales were assessed specifically before and during the pandemic in Germany. RESULTS: We included 6,865,852 sold PSO related drugs from April 2019 to March 2021. Medication sales increased during the pandemic compared with before the pandemic for treatment classes of first-line biological and second-line drugs. The increase was observed across all age groups, but monthly variations could not be detected. Furthermore, we observed increased sales in first-line biological and second-line medications when comparing low to high COVID-19 incidence state. CONCLUSION: Throughout the COVID-19 pandemic the PSO indicated medication sales increased for first-line biological and second-line treatment. This shows that despite the pandemic impact, there continues to be an increase in sales volume for biologics. Only German federal states with intermittently very high COVID-19 incidences show a stagnation in sales volume. The reasons for this need to be investigated in further studies to possibly gain a better understanding of the concerns and uncertainties of patients with PSO.

Drug switching in axial spondyloarthritis patients in Germany - a social listening analysis.

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which primarily affects the axial skeleton resulting in chronic back pain and stiffness. According to the guideline, the first-line treatment includes non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-pharmacological treatment. Second line treatment involves biological disease-modifying antirheumatic drugs (bDMARDs) such as tumour necrosis factor and interleukin-17 inhibitors. Objectives: The aim of this social media listening research project was to analyse switches of medication and the reasons thereof to gain valuable insights into real-life journeys of patients suffering from axSpA. Methods: Publicly available posts in German-speaking disease-specific forums were scanned for disease-specific keywords and commonly used drugs by axSpA patients on the Permea platform. Posts containing at least two key words were selected and switches between medications were manually labelled. A total of 287 scraped posts between 01 July 2010 and 04 Feb 2022 were analysed. Results: The largest group of described medication switches was initially using bDMARDs. Switches to a different bDMARD, termination of medication and switches to glucocorticoids were most frequently named. Patients on NSAIDs switched to glucocorticoids, a different NSAID or bDMARD, whereas patients on csDMARDs most frequently changed to bDMARDs. In all medication groups the main reason for switching was insufficient efficacy and side effects. Additionally, for the medication groups bDMARDs, csDMARDs and corticosteroids, pregnancy and lactation were given as a reason for switching, whereas patients in the NSAID group never mentioned pregnancy and breastfeeding as a reason for switching treatment. Conclusion: Our analysis shows medication switches based on real-life patient experiences shared with peers in a social listening setting. We also show medication switches differing from advised guidelines. Gathering real-life insights into patients' journey dealing with chronic diseases allows us to understand, and thereby improve patient care and treatment.

Performance of the VitaPCR rapid molecular test for SARS-CoV-2 screening at hospital admission.

OBJECTIVE: To evaluate the diagnostic accuracy of rapid VitaPCR™ (Credo) assay as screening test in emergency department (ED) patients prior to transfer or medical interventions. METHODS: In this prospective study 6642 oropharyngeal swabs from nonpreselected ED patients were tested for SARS-CoV-2 with (1) extraction-free VitaPCR and (2) extraction-based reference assays (Aptima®, cobas®, Xpert®Xpress). RESULTS: The median TAT of VitaPCR was 47 minutes (IQR: 38-59), while reference assays required 6.2 hours (IQR: 4.4-13.3). VitaPCR's sensitivity, specificity, PPV and NPV was 77.9%, 99.9%, 97.9%, and 98.9% in relation to Hologic Panther TMA; 78.3%, 99.8%, 96.4%, and 98.5% compared to Roche cobas6800 PCR; 71.2%, 99.2%, 94.9%, and 94.3% using Cepheid GeneXpert PCR as reference. CONCLUSION: High-sensitivity testing is needed to limit nosocomial spread and identify asymptomatic COVID-19 patients. However, time advantage of the VitaPCR must be weighed against its significantly lower sensitivity, especially when used in high-risk environments such as hospitals.

Correlation and differences of patient-reported outcomes vs. Likert-Rating of MS symptoms in a real-world cohort using a digital patient app.

Background: Multiple Sclerosis (MS) is a chronic and progressive neurological autoimmune disease currently affecting 250,000 individuals in Germany. Patients suffering from the disease can be severely impaired in their day-to-day activities. BRISA is a digital app specifically designed to help MS patients monitor their disease by regularly tracking symptoms. Lengthy and time-consuming questionnaires for patient-reported outcomes (PRO) are the standard method to assess the patients' current condition. Here, we examine whether simplified versions of these questionnaires can provide comparable information regarding individual symptom presentations in BRISA users. Methods: 828 users were included in the analysis. Patients who provided onboarding information and answered at least one questionnaire and the corresponding simplified smiley symptoms assessment were included. Correlation of questionnaire and symptom scores was calculated using Pearson's correlation. Results: Our analysis cohort predominantly consisted of female, 26-55-year-olds. Relapsing-remitting MS (RRMS) was the most common MS type recorded. Most patients were diagnosed 2-5 years ago. Questionnaires regarding fatigue and vision impairment were among the most answered, those regarding bowel movement and sexual satisfaction received fewest responses. Overall, the scores from questionnaires and symptoms correlated positively. Scoring correlation could also be shown across the subgroups divided by gender, age groups, type of MS, and time since diagnosis of the disease. Conclusion: Scores recorded from traditional PRO questionnaires can be reflected more easily as a trend in a simplified scale using smileys. Nevertheless, traditional questionnaires are needed to also maintain a more objective assessment. In conclusion, the patient will benefit most from an adaptive combination of regular traditional PRO questionnaire assessments and simplified symptom recording.

The influence of the COVID-19 pandemic on the prescription of multiple sclerosis medication in Germany.

BACKGROUND: Real-word evidence from diverse data sources is increasingly important in terms of generating rapid insights to effectively manage patient populations, especially during major public health disruptions such as the ongoing COVID-19 pandemic. Patients with chronic and inflammatory diseases - such as multiple sclerosis (MS) - were reported to experience potentially negative effects due to the use of immunosuppressive drugs in combination with a COVID-19 infection. In this research, we explored the impact of the COVID-19 pandemic on medication use in patients with MS in Germany. METHODS: Patient-level pharmacy dispensing data from the Permea platform - covering approximately 44% of all community pharmacy dispensing in Germany - were analysed from 2019 - 2021. Longitudinal use patterns of MS medication and antidepressants and patient demographics were assessed. Daily variation in MS medication use was specifically studied around the dates of the first and second lockdowns in Germany. RESULTS: We included data from 539,400 prescriptions which included at least 1 MS drug. The medication data showed a stable level of monthly prescriptions for MS medication at 2.02 ± 0.03 prescriptions per pharmacy during the study period. Although there was a sharp increase in daily prescriptions before the first lockdown (from an average 660.08 ± 137.59 daily prescriptions in the observed period to a maximum dispensing number of 998 daily prescriptions), the overall number of prescriptions remained at pre-pandemic levels (603 ± 90.31 daily prescriptions in 2019). Similar trends were observed for monthly co-prescribed antidepressant use per pharmacy (0.10 ± 0.01 in 2019-0.11 ± 0.02 in 2020). CONCLUSION: Throughout the COVID-19 pandemic, the use of MS medications and co-prescribed antidepressants was stable. These insights from real-world data demonstrate the value of evidence-based insights for managing patient care.

Factors associated with an increased risk of SARS-CoV-2 infection in healthcare workers in aerosol-generating disciplines.

BACKGROUND: Healthcare workers (HCWs) are at a high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate risk factors for SARS-CoV-2 infection among HCWs in medical disciplines with AGP. METHODS: A nationwide questionnaire-based study in private practices and hospital settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCWs and potential risk factors of infection were investigated. RESULTS: 2070 healthcare facilities with 25113 employees were included in the study. The overall infection rate among HCWs was 4.7%. Multivariate analysis showed that regions with higher incidence rates had a significantly increased risk of infection. Furthermore, hospital setting and HCWs in gastrointestinal endoscopy (GIE) had more than double the risk of infection (OR 2.63; 95% CI 2.50-2.82, p<0.01 and OR 2.35; 95% CI 2.25-2.50, p<0.01). For medical facilities who treated confirmed SARS-CoV-2 cases, there was a tendency towards higher risk of infection (OR 1.39; 95% CI 1.11-1.63, p=0.068). CONCLUSION: Both factors within and outside medical facilities appear to be associated with an increased risk of infection among HCWs. Therefore, GIE and healthcare delivery setting were related to increased infection rates. Regions with higher SARS-CoV-2 incidence rates were also significantly associated with increased risk of infection.

One year of COVID-19 pandemic: Health care workers' infection rates and economical burden in medical facilities for oral and maxillofacial surgery.

The aim of this study was to create an overview on the COVID-associated burdens faced by the oral and maxillofacial surgery (OMS) workforce during 1 year of the pandemic. OMS hospitals and private practices nationwide were surveyed regarding health care worker (HCW) screening, infection status, pre-interventional testing, personal protective equipment (PPE), and economic impact. Participants were recruited via the German Society for Oral and Maxillofacial Surgery. A total of 11 hospitals (416 employees) and 55 private practices (744 employees) participated. The HCW infection rate was significantly higher in private practices than in clinics (4.7% vs. 1.4%, p<0.01), although most infections in HCW occurred in private environment (hospitals 88.2%, private practice 66.7%). Pre-interventional testing was performed significantly less for outpatients in private practices than in hospitals (90.7% vs. 36.4%, p<0.01). Polymerase chain reaction (PCR) was used significantly more for inpatients in hospitals than in private practices (100.0% vs. 27.3%, p<0.01). FFP2/3 use rose significantly in hospitals (0% in second quarter vs. 46% in fourth quarter, p<0.05) and private practices (15% in second quarter vs. 38% in fourth quarter, p<0.01). The decrease in procedures (≤50%) was significantly higher in hospitals than in private practices (90.9% vs. 40.0%, p<0.01). Despite higher infection rates in private practices, declining procedures and revenue affected hospitals more. Future COVID-related measures must adjust the infrastructure especially for hospitals to prevent further straining of staff and finances.

Artificial Intelligence-Based Detection of Pneumonia in Chest Radiographs.

Artificial intelligence is gaining increasing relevance in the field of radiology. This study retrospectively evaluates how a commercially available deep learning algorithm can detect pneumonia in chest radiographs (CR) in emergency departments. The chest radiographs of 948 patients with dyspnea between 3 February and 8 May 2020, as well as 15 October and 15 December 2020, were used. A deep learning algorithm was used to identify opacifications associated with pneumonia, and the performance was evaluated by using ROC analysis, sensitivity, specificity, PPV and NPV. Two radiologists assessed all enrolled images for pulmonal infection patterns as the reference standard. If consolidations or opacifications were present, the radiologists classified the pulmonal findings regarding a possible COVID-19 infection because of the ongoing pandemic. The AUROC value of the deep learning algorithm reached 0.923 when detecting pneumonia in chest radiographs with a sensitivity of 95.4%, specificity of 66.0%, PPV of 80.2% and NPV of 90.8%. The detection of COVID-19 pneumonia in CR by radiologists was achieved with a sensitivity of 50.6% and a specificity of 73%. The deep learning algorithm proved to be an excellent tool for detecting pneumonia in chest radiographs. Thus, the assessment of suspicious chest radiographs can be purposefully supported, shortening the turnaround time for reporting relevant findings and aiding early triage.

SARS-CoV-2 Vaccination Rate and SARS-CoV-2 Infection of Health Care Workers in Aerosol-Generating Medical Disciplines.

Healthcare workers (HCW) who perform aerosol-generating procedures (AGP) are at high risk of SARS-CoV-2 infection. Data on infection rates and vaccination are limited. A nationwide, cross-sectional study focusing on AGP-related specialties was conducted between 3 May 2021 and 14 June 2021. Vaccination rates among HCW, perception of infection risk, and infection rates were analyzed, focusing on the comparison of gastrointestinal endoscopy (GIE) and other AGP-related specialties (NON-GIE), from the beginning of the pandemic until the time point of the study. Infections rates among HCW developed similarly to the general population during the course of the pandemic, however, with significantly higher infections rates among the GIE specialty. The perceived risk of infection was distributed similarly among HCW in GIE and NON-GIE (91.7%, CI: 88.6−94.4 vs. 85.8%, CI: 82.4−89.0; p < 0.01) with strongest perceived threats posed by AGPs (90.8%) and close patient contact (70.1%). The very high vaccination rate (100−80%) among physicians was reported at 83.5%, being significantly more frequently reported than among nurses (56.4%, p < 0.01). GIE had more often stated very high vaccination rate compared with NON-GIE (76.1% vs. 65.3%, p < 0.01). A significantly higher rate of GIE was reported to have fewer concerns regarding infection risk after vaccination than NON-GIE (92.0% vs. 80.3%, p < 0.01).

A fluorometric assay to determine the protective effect of glucose-6-phosphate dehydrogenase (G6PD) against a Plasmodium spp. infection in females heterozygous for the G6PD gene: proof of concept in Plasmodium falciparum.

OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency offers some protection against malaria; however, the degree of protection is poorly described and likely to vary with G6PD genotype and Plasmodium species. We present a novel approach to quantify the differential invasion rates of P. falciparum between G6PD deficient and normal red blood cells (RBCs) in an ex vivo model. A flow-cytometry based assay was developed to distinguish G6PD deficient and normal, parasitized and non-parasitized RBCs within the same sample. Venous blood collected from a G6PD heterozygous female was infected and cultured ex vivo with a laboratory strain of P. falciparum (FC27). RESULTS: Aliquots of infected blood were assayed at schizont and subsequent synchronized ring stages. At schizont stage, 84.9% of RBCs were G6PD deficient of which 0.4% were parasitized compared to 2.0% of normal RBCs. In the subsequent ring stage, 90.4% of RBCs were deficient and 0.2% of deficient and 0.9% of normal cells respectively were parasitized. The pooled Odds Ratio for a deficient RBC to be parasitized was 0.2 (95% confidence interval: 0.18-0.22, p < 0.001) compared to a normal cell. Further studies are warranted to explore preferential parasitization with different G6PD variants and Plasmodium species.

[Impact of Covid 19 on endoscopy in Germany]. / Ein Jahr Covid-19: Testung, Verwendung von Schutzausrüstung und Auswirkungen auf die Gastrointestinale Endoskopie in Deutschland.

BACKGROUND: Practices and hospitals are facing great challenges in coping with the COVID-19-pandemic. So far, data on the impact of the pandemic on gastroenterological facilities are lacking, especially on a temporal course. A database is lacking, especially for the outpatient care sector. University Hospital of Augsburg was commissioned to generate data on this as a part of the collaborative project B-FAST of the Network of University Medicine (NUM). METHODS: Gastroenterological institutions nationwide were surveyed by an online questionnaire. Recruitment was carried out via the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the Professional Association of Gastroenterologists in Private Practice (bng). This manuscript provides an overview of data on the use of protective equipment, pre-interventional testing of patients, staff screening and economic impact over the course of the pandemic. RESULTS: 429 facilities answered the questionnaire. Practices tested their patients pre-interventionally significantly less often than clinics (7.8% vs. 82.6%). In clinics, inpatients (93.1%) were tested significantly more often than outpatients (72.2%). The use of personal protective equipment (PPE) increased significantly during the pandemic. It was shown that over 70% of facilities screened their staff for SARS-CoV-2 without cause. Clinics cancelled elective procedures significantly more often than practices in quarter 4/2020. Procedures and turnover decreased in 2020 compared to the previous year. However, fewer facilities were affected by a loss of revenue than expected in previous studies. CONCLUSION: Our data demonstrate the variable implementation of pre-interventional SARS-CoV-2 testing in outpatient and inpatient care. The use of adequate PPE and staff screening increased during the pandemic.

Evaluation of the ESGE recommendations for COVID-19 pre-endoscopy risk-stratification in a high-volume center in Germany.

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) has defined COVID-19 infection prevention and control strategies within the endoscopy unit. These include pre-endoscopic questionnaire-based risk-stratification as well as pre-procedure viral testing. Real-life data on the effectiveness of these measures are presented here. Patients and methods Data from the outpatient endoscopic unit of the University Hospital Augsburg between July 1, 2020 and December 31, 2020 including the second pandemic wave were reviewed retrospectively. All patients were assessed with a pre-endoscopic risk-stratification questionnaire as well as viral testing using an antigen point-of-care test (Ag-POCT) in conjunction with a standard polymerase chain reaction (PCR) test. Highly elective procedures were postponed. The theoretically expected number of SARS-CoV-2-positive patients was simulated and compared with the actual number. In addition, endoscopy staff was evaluated with a rapid antibody test to determine the number of infections among the personnel. Results In total, 1029 procedures, 591 questionnaires, 591 Ag-POCTs, and 529 standard PCR tests were performed in 591 patients. 247 procedures in 142 patients were postponed. One Ag-POCT was positive but with a negative PCR test, while one PCR test was positive but with a negative Ag-POCT. This was lower than the theoretically expected number of COVID-19-positive patients (n = 15). One of 43 employees (2.3 %) in the outpatient endoscopy unit was seropositive. Conclusions Pre-endoscopic risk management including questionnaire-based risk stratification and viral testing seems to be an effective tool in combination with personal protective equipment for SARS-CoV-2 infection prevention and control within the endoscopy unit even in a high-prevalence setting.

Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision.

Certain clinical indications and treatments such as the use of rasburicase in cancer therapy and 8-aminoquinolines for Plasmodium vivax malaria treatment would benefit from a point-of-care test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three studies were conducted to evaluate the performance of one such test: the STANDARD™ G6PD Test (SD BIOSENSOR, South Korea). First, biological interference on the test performance was evaluated in specimens with common blood disorders, including high white blood cell (WBC) counts. Second, the test precision on fingerstick specimens was evaluated against five individuals of each, deficient, intermediate, and normal G6PD activity status. Third, clinical performance of the test was evaluated at three point-of-care settings in the United States. The test performed equivalently to the reference assay in specimens with common blood disorders. High WBC count blood samples resulted in overestimation of G6PD activity in both the reference assay and the STANDARD G6PD Test. The STANDARD G6PD Test showed good precision on multiple fingerstick specimens from the same individual. The same G6PD threshold values (U/g Hb) were applied for a semiquantitative interpretation for fingerstick- and venous-derived results. The sensitivity/specificity values (95% confidence intervals) for the test for G6PD deficiency were 100 (92.3-100.0)/97 (95.2-98.2) and 100 (95.7-100.0)/97.4 (95.7-98.5) for venous and capillary specimens, respectively. The same values for females with intermediate (> 30% to ≤ 70%) G6PD activity were 94.1 (71.3-99.9)/88.2 (83.9-91.7) and 82.4 (56.6-96.2)/87.6(83.3-91.2) for venous and capillary specimens, respectively. The STANDARD G6PD Test enables point-of-care testing for G6PD deficiency.

Performance of antigen testing for diagnosis of COVID-19: a direct comparison of a lateral flow device to nucleic acid amplification based tests.

OBJECTIVES: The gold standard for diagnosing an infection with SARS-CoV-2 is detection of viral RNA by nucleic acid amplification techniques. Test capacities, however, are limited. Therefore, numerous easy-to-use rapid antigen tests based on lateral flow technology have been developed. Manufacturer-reported performance data seem convincing, but real-world data are missing. METHODS: We retrospectively analysed all prospectively collected antigen tests results performed between 23.06.2020 and 26.11.2020, generated by non-laboratory personnel at the point-of-care from oro- or nasopharyngeal swab samples at the University Hospital Augsburg and compared them to concomitantly (within 24 h.) generated results from molecular tests. RESULTS: For a total of 3630 antigen tests, 3110 NAAT results were available. Overall, sensitivity, specificity, NPV and PPV of antigen testing were 59.4%, 99.0%, 98.7% and 64.8%, respectively. Sensitivity and PPV were lower in asymptomatic patients (47.6% and 44.4%, respectively) and only slightly higher in patients with clinical symptoms (66.7% and 85.0%, respectively). Some samples with very low Ct-values (minimum Ct 13) were not detected by antigen testing. 31 false positive results occurred. ROC curve analysis showed that reducing the COI cut-off from 1, as suggested by the manufacturer, to 0.9 is optimal, albeit with an AUC of only 0.66. CONCLUSION: In real life, performance of lateral-flow-based antigen tests are well below the manufacturer's specifications, irrespective of patient's symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged. This does not preclude their usefulness in large-scale screening programs to reduce transmission events on a population-wide scale.

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test's sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%-100.0%; capillary 93.8%-100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%-99.1%) and 97.8% on capillary (95% CI 97.0%-98.5%). At the 70% threshold, the test's sensitivity was 96.9% on venous specimens (95% CI 83.8%-99.9%) and 94.3% on capillary (95% CI 80.8%-99.3%). Specificity was 96.5% (95% CI 95.0%-97.6%) and 92.3% (95% CI 90.3%-94.0%) on venous and capillary specimens, respectively. CONCLUSION/SIGNIFICANCE: The STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (identifier: NCT04033640).