Increase in Anxiety-Related Out-of-Hours Primary Care Consultations Since COVID-19: An Observational Study Using Routine Data in Flanders

Background: Survey studies suggest that COVID-19 has had a negative impact on the population's mental well-being. Routine registration data allow a more objective way for investigating such associations, complementary to self-report measures. This study investigates the level of out of hours (OOH) consultations for psychological problems since the start of the COVID-19 pandemic in Flanders, Belgium. Methods: The iCAREdata database is a clinical research database with routine data of OOH care, covering a large area in Flanders, Belgium. After defining the first wave and the second wave of COVID-19 in Flanders in time, we compared the number of consultations regarding psychological problems (in general, anxiety-related, depression-related, and sleep-related) between those periods, the period in between these waves, and the period before the start of COVID-19. Results: A significant rise in OOH consultations due to psychological—and more specifically, anxiety-related—problems is observed since the start of the COVID-19 pandemic in Flanders. Elevated levels are observed until the second wave. This finding is in sharp contrast with the general pattern of lower demand for primary healthcare during this period. The majority of these supplementary consultations happened by phone. Consultations regarding depression-related problems did not change over time. Sleep disturbances in the OOH setting were more common after the first wave. Conclusion: Despite some limitations, a large Flemish database with routine data on OOH care shows an increase in the number of consultations regarding psychological problems in general and anxiety-related problems since the start of the COVID-19-pandemic until the second wave.

Increase in Anxiety-Related Out-of-Hours Primary Care Consultations Since COVID-19: An Observational Study Using Routine Data in Flanders.

Background: Survey studies suggest that COVID-19 has had a negative impact on the population's mental well-being. Routine registration data allow a more objective way for investigating such associations, complementary to self-report measures. This study investigates the level of out of hours (OOH) consultations for psychological problems since the start of the COVID-19 pandemic in Flanders, Belgium. Methods: The iCAREdata database is a clinical research database with routine data of OOH care, covering a large area in Flanders, Belgium. After defining the first wave and the second wave of COVID-19 in Flanders in time, we compared the number of consultations regarding psychological problems (in general, anxiety-related, depression-related, and sleep-related) between those periods, the period in between these waves, and the period before the start of COVID-19. Results: A significant rise in OOH consultations due to psychological-and more specifically, anxiety-related-problems is observed since the start of the COVID-19 pandemic in Flanders. Elevated levels are observed until the second wave. This finding is in sharp contrast with the general pattern of lower demand for primary healthcare during this period. The majority of these supplementary consultations happened by phone. Consultations regarding depression-related problems did not change over time. Sleep disturbances in the OOH setting were more common after the first wave. Conclusion: Despite some limitations, a large Flemish database with routine data on OOH care shows an increase in the number of consultations regarding psychological problems in general and anxiety-related problems since the start of the COVID-19-pandemic until the second wave.

Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections.

Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut-targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the formulation of a throat spray with live lactobacilli exhibiting several in vitro mechanisms of action against respiratory viral infections, including induction of interferon regulatory pathways and direct inhibition of respiratory viruses. Rational selection of Lactobacillaceae strains was based on previously documented beneficial properties, up-scaling and industrial production characteristics, clinical safety parameters, and potential antiviral and immunostimulatory efficacy in the URT demonstrated in this study. Using a three-step selection strategy, three strains were selected and further tested in vitro antiviral assays and in formulations: Lacticaseibacillus casei AMBR2 as a promising endogenous candidate URT probiotic with previously reported barrier-enhancing and anti-pathogenic properties and the two well-studied model strains Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 that display immunomodulatory capacities. The three strains and their combination significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV-229E coronavirus in co-culture models with bacteria, virus, and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway-inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form. Thus, the developed spray with live lactobacilli will be further explored in the clinic as a potential broad-acting live biotherapeutic strategy against respiratory viral diseases.

Randomized, Double-Blind, Placebo-Controlled Trial of a Throat Spray with Selected Lactobacilli in COVID-19 Outpatients.

Primary care urgently needs treatments for coronavirus disease 2019 (COVID-19) patients because current options are limited, while these patients who do not require hospitalization encompass more than 90% of the people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a throat spray containing three Lactobacillaceae strains with broad antiviral properties in a randomized, double-blind, placebo-controlled trial. Before the availability of vaccines, 78 eligible COVID-19 patients were randomized to verum (n = 41) and placebo (n = 37) within 96 h of a positive PCR-based SARS-CoV-2 diagnosis, and a per-protocol analysis was performed. Symptoms and severity were reported daily via an online diary. Combined nose-throat swabs and dried blood spots were collected at regular time points in the study for microbiome, viral load, and antibody analyses. The daily reported symptoms were highly variable, with no added benefit for symptom resolution in the verum group. However, based on 16S V4 amplicon sequencing, the acute symptom score (fever, diarrhea, chills, and muscle pain) was significantly negatively associated with the relative abundance of amplicon sequence variants (ASVs) that included the applied lactobacilli (P < 0.05). Furthermore, specific monitoring of these applied lactobacilli strains showed that they were detectable via quantitative PCR (qPCR) analysis in 82% of the patients in the verum group. At the end of the trial, a trend toward lower test positivity for SARS-CoV-2 was observed for the verum group (2/30; 6.7% positive) than for the placebo group (7/27; 26% positive) (P = 0.07). These data indicate that the throat spray with selected antiviral lactobacilli could have the potential to reduce nasopharyngeal viral loads and acute symptoms but should be applied earlier in the viral infection process and substantiated in larger trials. IMPORTANCE Viral respiratory tract infections result in significant health and economic burdens, as highlighted by the COVID-19 pandemic. Primary care patients represent 90% of those infected with SARS-CoV-2, yet their treatment options are limited to analgesics and antiphlogistics, and few broadly acting antiviral strategies are available. Microbiome or probiotic therapy is a promising emerging treatment option because it is based on the multifactorial action of beneficial bacteria against respiratory viral disease. In this study, an innovative topical throat spray with select beneficial lactobacilli was administered to primary COVID-19 patients. A remote study setup (reducing the burden on hospitals and general practitioners) was successfully implemented using online questionnaires and longitudinal self-sampling. Our results point toward the potential mechanisms of action associated with spray administration at the levels of viral loads and microbiome modulation in the upper respiratory tract and pave the way for future clinical applications of beneficial bacteria against viral diseases.

Role of Self-Sampling for Cervical Cancer Screening: Diagnostic Test Properties of Three Tests for the Diagnosis of HPV in Rural Communities of Cuenca, Ecuador.

BACKGROUND: HPV primary screening has shown effectiveness for cancer prevention; however, gynaecological examination is considered uncomfortable. Self-sampling methods increase the acceptance of screening. The aim of this study is to compare the sensitivity and specificity of clinician sampling versus vaginal and urine self-sampling for HPV diagnosis. METHODS: A diagnostic test study was conducted in a rural parish of Cuenca, Ecuador. A total of 120 women participated. Each participant self-collected urine and vaginal samples and underwent clinician sampling for HPV testing. The latter was considered as the golden standard. All three samples were processed with the same amplification and hybridization protocol for HPV detection (Hybribio) following the manufacturer's instructions. RESULTS: Characteristics of the participants were: median age 35 years; 40.8% married; 46.7% had a primary level of education; and median age of sexual onset, 17.6 years. The prevalence of any type of HPV with clinician sampling was 15.0%, 17.5% with urine sampling and 18.3% with vaginal self-sampling. Self-sampling sensitivity reached 94.4% (IC 74.2-99.9), and specificity 92.1% (IC 85.2-95.9). Urine sampling had a sensitivity of 88.8% (IC 67.2, 96.9), and specificity 94.1% (IC 67.2-96.9). The negative predictive value was 98.9% (IC 94.2-99.8) for vaginal self-sampling and 97.6% (IC 92.6-99.4) for urine sampling. CONCLUSIONS: This study shows that vaginal and urine self-sampling methods have similar sensitivity and specificity compared with clinician sampling for the diagnosis of HPV. The correlation between HPV genotypes among the three tests is satisfactory.

Overprescribing of Topical Ocular Corticosteroids and Antibiotics in Out-of-Hours Primary Care in Belgium.

Prescribing patterns by primary care physicians concerning ophthalmic problems were studied using the iCAREdata, a database containing information from the out-of-hours care setting in the Flanders region of Belgium. A very high percentage of prescribed ophthalmic medication was topical antibiotics (89.4%) with tobramycin as the most prevalent substance and in clear conflict with the prevailing guidelines. In addition, a very substantial fraction of prescribed medication contained corticosteroids (30.4%). This is a potentially unsafe option within the technical infrastructure of this setting, which limits the diagnostic possibilities concerning viral infections or preexisting glaucoma risk. We conclude that more efforts are required to limit unnecessary and inappropriate prescribing behavior to further promote patient safety.

Antibiotic Prescribing Trends in Belgian Out-of-Hours Primary Care during the COVID-19 Pandemic: Observational Study Using Routinely Collected Health Data.

Antibiotic overprescribing is one of the main drivers of the global and growing problem of antibiotic resistance, especially in primary care and for respiratory tract infections (RTIs). RTIs are the most common reason for patients to consult out-of-hours (OOH) primary care. The COVID-19 pandemic has changed the way general practitioners (GPs) work, both during office hours and OOH. In Belgian OOH primary care, remote consultations with the possibility of issuing prescriptions and telephone triage were implemented. We aimed to describe the impact of COVID-19 on GPs' antibiotic prescribing during OOH primary care. In an observational study, using routinely collected health data from GP cooperatives (GPCs) in Flanders, we analyzed GPs' antibiotic prescriptions in 2019 (10 GPCs) and 2020 (20 GPCs) during OOH consultations (telephone and face-to-face). We used autoregressive integrated moving average (ARIMA) modeling to identify any changes after lockdowns were implemented. In total, 388,293 contacts and 268,430 prescriptions were analyzed in detail. The number of antibiotic prescriptions per weekend, per 100,000 population was 11.47 (95% CI: 9.08-13.87) or 42.9% lower after compared to before the implementation of lockdown among all contacts. For antibiotic prescribing per contact, we found a decrease of 12.2 percentage points (95% CI: 10.6-13.7) or 56.5% among all contacts and of 5.3 percentage points (95% CI: 3.7-6.9) or 23.2% for face-to-face contacts only. The decrease in the number of prescriptions was more pronounced for cases with respiratory symptoms that corresponded with symptoms of COVID-19 and for antibiotics that are frequently prescribed for RTIs, such as amoxicillin (a decrease of 64.9%) and amoxicillin/clavulanate (a decrease of 38.1%) but did not appear for others such as nitrofurantoin. The implementation of COVID-19 lockdown measures coincided with an unprecedented drop in the number of antibiotic prescriptions, which can be explained by a decrease in face-to-face patient contacts, as well as a lower number of antibiotics prescriptions per face-to-face patient contact. The decrease was seen for antibiotics used for RTIs but not for nitrofurantoin, the first-choice antibiotic for urinary tract infections.

Cotton and Surgical Face Masks in Community Settings: Bacterial Contamination and Face Mask Hygiene.

During the current COVID-19 pandemic, the use of face masks has become increasingly recommended and even mandatory in community settings. To evaluate the risk of bacterial cross-contamination, this study analyzed the bacterial bioburden of disposable surgical masks and homemade cotton masks, and surveyed the habits and face mask preferences of the Flemish population. Using culture approaches and 16S rRNA gene amplicon sequencing, we analyzed the microbial community on surgical and/or cotton face masks of 13 healthy volunteers after 4 h of wearing. Cotton and surgical masks contained on average 1.46 × 105 CFU/mask and 1.32 × 104 CFU/mask, respectively. Bacillus, Staphylococcus, and Acinetobacter spp. were mostly cultured from the masks and 43% of these isolates were resistant to ampicillin or erythromycin. Microbial profiling demonstrated a consistent difference between mask types. Cotton masks mainly contained Roseomonas, Paracoccus, and Enhydrobacter taxa and surgical masks Streptococcus and Staphylococcus. After 4 h of mask wearing, the microbiome of the anterior nares and the cheek showed a trend toward an altered beta-diversity. According to dedicated questions in the large-scale Corona survey of the University of Antwerp with almost 25,000 participants, only 21% of responders reported to clean their cotton face mask daily. Laboratory results indicated that the best mask cleaning methods were boiling at 100°C, washing at 60°C with detergent or ironing with a steam iron. Taken together, this study suggests that a considerable number of bacteria, including pathobionts and antibiotic resistant bacteria, accumulate on surgical and even more on cotton face masks after use. Based on our results, face masks should be properly disposed of or sterilized after intensive use. Clear guidelines for the general population are crucial to reduce the bacteria-related biosafety risk of face masks, and measures such as physical distancing and increased ventilation should not be neglected when promoting face mask use.

A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity.

BACKGROUNDSARS-CoV-2 infection induces mucin overexpression, further promoting disease. Given that mucins are critical components of innate immunity, unraveling their expression profiles that dictate the course of disease could greatly enhance our understanding and management of COVID-19.METHODSUsing validated RT-PCR assays, we assessed mucin mRNA expression in the blood of patients with symptomatic COVID-19 compared with symptomatic patients without COVID-19 and healthy controls and correlated the data with clinical outcome parameters. Additionally, we analyzed mucin expression in mucus and lung tissue from patients with COVID-19 and investigated the effect of drugs for COVID-19 treatment on SARS-CoV-2-induced mucin expression in pulmonary epithelial cells.RESULTSWe identified a dynamic blood mucin mRNA signature that clearly distinguished patients with symptomatic COVID-19 from patients without COVID-19 based on expression of MUC1, MUC2, MUC4, MUC6, MUC13, MUC16, and MUC20 (AUCROC of 91.8%; sensitivity and specificity of 90.6% and 93.3%, respectively) and that discriminated between mild and critical COVID-19 based on the expression of MUC16, MUC20, and MUC21 (AUCROC of 89.1%; sensitivity and specificity of 90.0% and 85.7%, respectively). Differences in the transcriptional landscape of mucins in critical cases compared with mild cases identified associations with COVID-19 symptoms, respiratory support, organ failure, secondary infections, and mortality. Furthermore, we identified different mucins in the mucus and lung tissue of critically ill COVID-19 patients and showed the ability of baricitinib, tocilizumab, favipiravir, and remdesivir to suppress expression of SARS-CoV-2-induced mucins.CONCLUSIONThis multifaceted blood mucin mRNA signature showed the potential role of mucin profiling in diagnosing, estimating severity, and guiding treatment options in patients with COVID-19.FUNDINGThe Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

COVID-19 Vaccine Acceptance in Azuay Province, Ecuador: A Cross-Sectional Online Survey.

We investigated the COVID-19 vaccination acceptance level in Azuay province, Ecuador through an online survey from 12th to 26th February (before the start of the COVID-19 vaccination campaign in Ecuador). Overall, 1219 respondents participated in the survey. The mean age was 32 ± 13 years; 693 participants (57%) were female. In total, 1109 (91%) of the participants indicated they were willing to be vaccinated with a COVID-19 vaccine, if the vaccine is at least 95% effective; 835 (68.5%) if it is 90% effective and 493 (40.5%) if it is 70% effective; 676 (55.5%) participants indicated they feared side effects and 237 (19.4%) thought the vaccine was not effective. Older age, having had a postgraduate education, a history of a negative COVID-19 test, a high level of worry of contracting COVID-19, believing that COVID-19 infection can be prevented with a vaccine and understanding there is currently an effective vaccine against COVID-19 were associated with higher vaccination acceptance. A vaccination education campaign will be needed to increase the knowledge of Ecuadorians about the COVID-19 vaccine and to increase their trust in the vaccine. People with a lower education level and living in rural areas may need to be targeted during such a campaign.

Organisation and characteristics of out-of-hours primary care during a COVID-19 outbreak: A real-time observational study.

BACKGROUND: During the COVID-19 pandemic, general practitioners worldwide re-organise care in very different ways because of the lack of evidence-based protocols. OBJECTIVE: This paper describes the organisation and the characteristics of consultations in Belgian out-of-hours primary care during five weekends at the peak of a COVID-19 outbreak and compares it to a similar period in 2019. METHODS: Real-time observational study using pseudonymised routine clinical data extracted out of reports from home visits, telephone- and physical consultations (iCAREdata). Nine general practice cooperatives (GPCs) participated covering a population of 1 513 523. RESULTS: All GPCs rapidly re-organised care in order to handle the outbreak and provide a safe working environment. The average consultation rate was 222 per 100 000 citizens per weekend. These consultations were handled by telephone alone in 40% (N = 6293). A diagnosis at risk of COVID-19 was registered in 6692 (43%) consultations,. Out of 5311 physical consultations, 1460 were at risk of COVID-19 of which 443 (30%) did not receive prior telephone consultation to estimate this risk. Compared to 2019, the workload initially increased due to telephone consultations but afterwards declined drastically. The physical consultation rate declined by 45% with a marked decline in diagnoses unrelated to COVID-19. CONCLUSIONS: General practitioners can rapidly re-organise out-of-hours care to handle patient flows during a COVID-19 outbreak. Forty percent of the out-of-hours primary care contacts are handled by telephone consultations alone. We recommend to give a telephone consultation to all patients and not to rely on call takers to differentiate between infectious and regular care. The demand for physical consultations declined drastically provoking questions about patient's safety for care unrelated to COVID-19.

Impact of the COVID-19 pandemic on the core functions of primary care: will the cure be worse than the disease? A qualitative interview study in Flemish GPs.

OBJECTIVES: The current COVID-19 pandemic, as well as the measures taken to control it, have a profound impact on healthcare. This study was set up to gain insights into the consequences of the COVID-19 outbreak on the core competencies of general practice, as they are experienced by general practitioners (GPs) on the frontline. DESIGN, SETTING, PARTICIPANTS: We performed a descriptive study using semistructured interviews with 132 GPs in Flanders, using a topic list based on the WONCA definition of core competencies in general practice. Data were analysed qualitatively using framework analysis. RESULTS: Changes in practice management and in consultation strategies were quickly adopted. There was a major switch towards telephone triage and consults, for covid-related as well as for non-covid related problems. Patient-centred care is still a major objective. Clinical decision-making is largely focused on respiratory assessment and triage, and GPs feel that acute care is compromised, both by their own changed focus and by the fact that patients consult less frequently for non-covid problems. Chronic care is mostly postponed, and this will have consequences that will extend and become visible after the corona crisis. Through the holistic eyes of primary care, the current outbreak-as well as the measures taken to control it-will have a profound impact on psychological and socioeconomic well-being. This impact is already visible in vulnerable people and will continue to become clear in the medium and long terms. GPs think that they are at high risk of getting infected. Dropping out and being unable to contribute their part or becoming virus transmitters are reported to be greater concerns than getting ill themselves. CONCLUSIONS: The current times have a profound impact on the core competences of primary care. Although the vast increase in patients soliciting medical help and the necessary separate covid and non-covid flows have been dealt with, GPs are worried about the continuity of regular care and the consequences of the anticovid measures. These may become a threat for the general health of the population and for the provision of primary healthcare in the near and distant future.