Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

BACKGROUND: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. AIM: To explore the factors associated with the overruling of initial procalcitonin guidance. DESIGN AND SETTING: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. METHOD: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. RESULTS: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03-3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32-9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34-23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18-4.37); and the GP's number of years of experience (aOR per year 1.05, 1.01-1.09). CONCLUSIONS: Overruling of procalcitonin guidance was associated with GPs' socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.

Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: A prospective comparative clinical trial.

BACKGROUND: Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. METHODS: In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. RESULTS: Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. CONCLUSIONS: RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

Diagnostic Performance of Individual Symptoms to Predict SARS-CoV-2 RT-PCR Positivity and Symptom Persistence among Suspects Presenting in Primary Care during the First Wave of COVID-19.

This study aimed to estimate the diagnostic performance of patient symptoms and to describe the clinical course of RT-PCR-positive compared with RT-PCR-negative patients in primary care. Symptomatic COVID-19 suspects were assessed clinically at the initial consultation in primary care between March and May 2020, followed by phone consultations over a span of at least 28 days. Sensitivity and specificity were estimated for each symptom using the initial RT-PCR result as a reference standard. The proportions of symptomatic patients according to the RT-PCR test results were compared over time, and time to recovery was estimated. Out of 883 patients, 13.9% had a positive RT-PCR test, and 17.4% were not tested. Most sensitive symptoms were cough, myalgia, and a history of fever, while most specific symptoms were fever for ≥4 days, hypo/anosmia, and hypo/ageusia. At the final follow up (median time 55 days, range 28-105 days), 44.7% of patients still reported symptoms in the RT-PCR-positive group, compared with 18.3% in the negative group (p < 0.001), mostly with hypo/anosmia (16.3%), dyspnea (12.2%), and fatigue (10.6%). The discriminative value of individual symptoms for diagnosing COVID-19 was limited. Almost half of the SARS-CoV-2-positive patients still reported symptoms at least 28 days after the initial consultation.

Procalcitonin and lung ultrasonography point-of-care testing to determine antibiotic prescription in patients with lower respiratory tract infection in primary care: pragmatic cluster randomised trial.

OBJECTIVE: To assess whether point-of care procalcitonin and lung ultrasonography can safely reduce unnecessary antibiotic treatment in patients with lower respiratory tract infections in primary care. DESIGN: Three group, pragmatic cluster randomised controlled trial from September 2018 to March 2020. SETTING: 60 Swiss general practices. PARTICIPANTS: One general practitioner per practice was included. General practitioners screen all patients with acute cough; patients with clinical pneumonia were included. INTERVENTIONS: Randomisation in a 1:1:1 of general practitioners to either antibiotics guided by sequential procalcitonin and lung ultrasonography point-of-care tests (UltraPro; n=152), procalcitonin guided antibiotics (n=195), or usual care (n=122). MAIN OUTCOMES: Primary outcome was proportion of patients in each group prescribed an antibiotic by day 28. Secondary outcomes included duration of restricted activities due to lower respiratory tract infection within 14 days. RESULTS: 60 general practitioners included 469 patients (median age 53 years (interquartile range 38-66); 278 (59%) were female). Probability of antibiotic prescription at day 28 was lower in the procalcitonin group than in the usual care group (0.40 v 0.70, cluster corrected difference -0.26 (95% confidence interval -0.41 to -0.10)). No significant difference was seen between UltraPro and procalcitonin groups (0.41 v 0.40, -0.03 (-0.17 to 0.12)). The median number of days with restricted activities by day 14 was 4 days in the procalcitonin group and 3 days in the usual care group (difference 1 day (95% confidence interval -0.23 to 2.32); hazard ratio 0.75 (95% confidence interval 0.58 to 0.97)), which did not prove non-inferiority. CONCLUSIONS: Compared with usual care, point-of-care procalcitonin led to a 26% absolute reduction in the probability of 28 day antibiotic prescription without affecting patients' safety. Point-of-care lung ultrasonography did not further reduce antibiotic prescription, although a potential added value cannot be excluded, owing to the wide confidence intervals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03191071.

The role of general practitioners in managing the COVID-19 pandemic in a private healthcare system.

BACKGROUND: The canton of Vaud's public health authorities, in Switzerland, invited general practitioners (GPs) to participate in managing suspected COVID-19 patients and continue caring for their non-COVID-19 patients. However, this course of action was not mandatory. The present study's objective was to describe and understand how involved GPs were in dealing with the COVID-19 pandemic's first wave. METHODS: This mixed-methods study combined a retrospective quantitative survey and a qualitative explanatory investigation. All of the canton's GPs were invited to participate in the quantitative survey via an online questionnaire including sections on: specific organization regarding COVID-19 activities and suspected COVID-19 patients, activities relating to non-COVID-19 patients, consequences on the practice's professional staff, and opinions about the public health authorities' pandemic crisis management. The qualitative investigation involved interviews with 10 volunteer GPs. RESULTS: The participation rate was 41%. One third of GPs chose not to reorganize their practice for the specific management of suspected COVID-19 patients. The number of weekly activities and interventions decreased by over 50% at 44% of practices, mostly due to a lack of patients. Even in an extraordinary crisis, GPs maintained their choice of whether to become involved, as their private and independent status allowed them to do. However, those who chose to be involved felt frustrated that the public health authorities did not recognize them as major health providers in the management of the pandemic. CONCLUSION: This study illustrated the complexity and limitations of a primary care system based completely on private healthcare providers.

Which strategy for using medical and community masks? A prospective analysis of their environmental impact.

INTRODUCTION: The use of personal protective equipment, especially medical masks, increased dramatically during the COVID-19 crisis. Medical masks are made of synthetic materials, mainly polypropylene, and a majority of them are produced in China and imported to the European market. The urgency of the need has so far prevailed over environmental considerations. OBJECTIVE: Assess the environmental impact of different strategies for the use of face mask. METHOD: A prospective analysis was conducted to assess the environmental impact of different strategies for the use of medical and community masks. Eight scenarios, differentiating the typologies of masks and the modes of reuse are compared using three environmental impact indicators: the Global Warming Potential (GWP100), the ecological scarcity (UBP method, from German 'Umweltbelastungpunkte') and the plastic leakage (PL). This study attempts to provide clear recommendations that consider both the environmental impact and the protective effectiveness of face masks used in the community. RESULTS: The environmental impact of single-use masks is the most unfavourable, with a GWP of 0.4-1.3 kg CO2 eq., depending on the transport scenario, and a PL of 1.8 g, for a 1 month protection against COVID-19. The use of home-made cotton masks and prolonged use of medical masks through wait-and-reuse are the scenarios with the lowest impact. CONCLUSION: The use of medical masks with a wait and reuse strategy seems to be the most appropriate when considering both environmental impact and effectiveness. Our results also highlight the need to develop procedures and the legal/operational framework to extend the use of protective equipment during a pandemic.

An Online Influenza Surveillance System for Primary Care Workers in Switzerland: Observational Prospective Pilot Study.

BACKGROUND: A better understanding of the influenza epidemiology among primary care workers could guide future recommendations to prevent transmission in primary care practices. Therefore, we designed a pilot study to assess the feasibility of using a work-based online influenza surveillance system among primary care workers. Such an approach is of particular relevance in the context of the coronavirus disease (COVID-19) pandemic, as its findings could apply to other infectious diseases with similar mechanisms of transmission. OBJECTIVE: This study aims to determine the feasibility of using a work-based online influenza surveillance system for primary care workers in Switzerland. METHODS: Physicians and staff of one walk-in clinic and two selected primary care practices were enrolled in this observational prospective pilot study during the 2017-2018 influenza season. They were invited to record symptoms of influenza-like illness in a weekly online survey sent by email and to self-collect a nasopharyngeal swab in case any symptoms were recorded. Samples were tested by real-time polymerase chain reaction for influenza A, influenza B, and a panel of respiratory pathogens. RESULTS: Among 67 eligible staff members, 58% (n=39) consented to the study and 53% (n=36) provided data. From the time all participants were included, the weekly survey response rate stayed close to 100% until the end of the study. Of 79 symptomatic episodes (mean 2.2 episodes per participant), 10 episodes in 7 participants fitted the definition of an influenza-like illness case (attack rate: 7/36, 19%). One swab tested positive for influenza A H1N1 (attack rate: 3%, 95% CI 0%-18%). Swabbing was considered relatively easy. CONCLUSIONS: A work-based online influenza surveillance system is feasible for use among primary care workers. This promising methodology could be broadly used in future studies to improve the understanding of influenza epidemiology and other diseases such as COVID-19. This could prove to be highly useful in primary care settings and guide future recommendations to prevent transmission. A larger study will also help to assess asymptomatic infections.