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Abstract Background Chronic rhinosinusitis is an inflammatory disorder in which the role of bacteria remains uncertain. While sinus outflow obstruction is often an initiating event, mucosal inflammation and dysbiosis may persist or develop in sinuses with widely patent surgical openings. Understanding of the relationship between dysbiosis and chronic sinus inflammation is obfuscated by inter-individual microbiota variability and likely intra-individual temporal variation that has yet to be defined. In this study, long-term microbiota stability is investigated within surgically-opened maxillary sinuses of individuals with and without sinus inflammatory disease. Methods Maxillary sinus swabs were performed in 35 subjects with longstanding maxillary antrostomies. Subjects with and without active chronic maxillary sinusitis were included. Repeat swabs were obtained from the same sinuses after a prolonged interval (mean 719 ± 383 days). Patients were categorized based on the inflammatory status of the sinus mucosa at times of sample collection, as assessed by nasal endoscopy. Total DNA from swab eluents was extracted, and the microbiota characterized using 16S rRNA gene sequencing followed by taxonomic classification. Prevalence and abundance of genera were determined by analysis of 16S rRNA gene sequences. Taxa were identified that were stably present between two time points in individual subjects. Results The overall proportion of stable taxa across time points was 24.5 ± 10.6%. This stability index was consistent across patient groups and not correlated with clinical parameters. Highly prevalent taxa, including Staphylococcus, Corynebacterium, Propionibacterium, and Pseudomonas, were often stably present, but varied in relative abundance. Janthinobacterium, Enterobacter, Lactobacillus, and Acinetobacter were prevalent and moderately abundant taxa in healthy sinuses, but not in inflamed sinuses. Moraxella and Haemophilus were present at low prevalence and proportional abundance in chronically or intermittently inflamed sinuses, but not in healthy sinuses. Conclusions A relatively small component of the post-antrostomy maxillary sinus microbiota exhibits long-term stability in individual subjects. Stable bacteria include a limited number of highly prevalent and a larger number of lower prevalence taxa, which vary widely in proportional abundance. The concept of individual-specific core sinus microbiota, durable over time and medical therapy, but fluctuating in proportional abundance, has implications for understanding the role of bacteria in CRS pathogenesis.

Abstract Background Although one of the main drivers of antimicrobial resistance is inappropriate antibiotic prescribing, there are limited resources to support the surveillance of antibiotic consumption in low-income countries. In this study, we aimed to assess antibiotic use and consumption among medical patients of two hospitals in different geographic regions of Sierra Leone. Methods This is a cross-sectional study of adult (18 years or older) patients receiving medical care at two hospitals (34 Military Hospital-MH and Makeni Government Hospital-MGH) between March 2021 and October 2021. After admission to the medical or intensive care unit, patients were sequentially recruited by a nurse from each hospital. Demographic and clinical characteristics and information on the dose of antibiotics, their routes, and frequency of administration and duration were collected using a questionnaire adapted from previous studies and encrypted in EpiCollect software (Epic, Verona WI). A physician reviews and verifies each completed questionnaire. Data analysis was done using STATA version 16. Results The mean age of the 468 patients evaluated in this study was 48.6 years. The majority were women (241, 51.7%) and treated at MGH (245, 52.0%). Clinical diagnosis of bacterial infection was made in only 180 (38.5%) patients. Regardless of the diagnosis, most (442, 94.9%) patients received at least one antibiotic. Of a total 813 doses of antibiotics prescribed by the two hospitals, 424 (52.2%) were administered in MH. Overall, antibiotic consumption was 66.9 defined daily doses (DDDs) per 100 bed-days, with ceftriaxone being the most commonly used antibiotic (277, 34.1%). The ACCESS and WATCH antibiotics accounted for 18.9 DDDs per 100 bed-days (28.2%) and 48.0 DDDs per 100 bed-days (71.7%), respectively. None of the patients were prescribed a RESERVE antibiotics. The antibiotic consumption was lower in MH (61.3 DDDs per 100 bed-days) than MGH (76.5 DDDs per 100 bed-days). Conclusion Antibiotic consumption was highest with ceftriaxone, followed by levofloxacin and metronidazole. Given the high rate of consumption of antibiotics in the WATCH category of the AWaRe classification, there is a need to initiate surveillance of antibiotic consumption and establish hospital-based antibiotic stewardship in these settings.

Abstract Background People who inject drugs (PWID) are disproportionally affected by hepatitis C virus (HCV) infection and many remain undiagnosed. HCV self-testing (HCVST) may be an effective approach to increase testing uptake, but has rarely been used among PWID. We assessed the usability and acceptability of HCVST among PWID in Kenya. Methods We conducted a cross-sectional study nested within a cohort study between August and December 2020 on Kenya’s North Coast region. Participants were handed a prototype oral fluid HCVST kit and asked to conduct the test relying on the instructions for use. Usability was assessed by documenting errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire. Results Among 150 participants, 19% were female and 65.3% had primary level education or lower. 71.3% made at least one error, 56.7% experienced some difficulty during at least one step, and the majority of participants (78%) required assistance during at least one step of the procedure. Most common errors occurred when placing the tube into the stand (18%), collecting the oral fluid sample (24%) and timing of reading results (53%). There was a strong association between presence of symptoms of opiate withdrawals and observed errors (94% vs 62%; p = 0.016) in a sub-group of 74 participants assessed. Inter-reader and inter-operator concordance were 97.7% (kappa: 0.92) and 99.2% (kappa: 0.95), respectively. Acceptability assessed by asking whether participants would choose to use HCVST prior to and after conducting HCVST was 98% and 95%, respectively. Conclusions We found a high acceptability of oral fluid HCVST among PWID. User errors were common and were associated with the presence of withdrawal symptoms among users. Despite errors, most participants were able to obtain and interpret results correctly. These findings suggest that this group of users may benefit from greater messaging and education including options to receive direct assistance when self-testing for HCV.

Abstract Background Hepatitis C virus self-testing (HCVST) is an additional approach that may expand access to HCV testing. We conducted a mixed-methods cross-sectional observational study to assess the usability and acceptability of HCVST among people who inject drugs (PWID), men who have sex with men (MSM) and transgender (TG) people in Tbilisi, Georgia. Methods The study was conducted from December 2019 to June 2020 among PWID at one harm reduction site and among MSM/TG at one community-based organization. We used a convergent parallel mixed-methods design. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire. A subset of participants participated in cognitive and in-depth interviews. Results A total of 90 PWID, 84 MSM and 6 TG were observed performing HCVST. PWID were older (median age 35 vs 24) and had a lower level of education compared to MSM/TG (27% vs 59%). The proportion of participants who completed all steps successfully without assistance was 60% among PWID and 80% among MSM/TG. The most common error was in sample collection and this was observed more often among PWID than MSM/TG (21% vs 6%; p = 0.002). More PWID requested assistance during HCVST compared to MSM/TG (22% vs 8%; p = 0.011). Acceptability was high in both groups (98% vs 96%; p = 0.407). Inter-reader agreement was 97% among PWID and 99% among MSM/TG. Qualitative data from cognitive (n = 20) and in-depth interviews (n = 20) was consistent with the quantitative data confirming a high usability and acceptability. Conclusions HCVST was highly acceptable among key populations in Georgia of relatively high educational level, and most participants performed HCVST correctly. A significant difference in usability was observed among PWID compared to MSM/TG, indicating that PWID may benefit from improved messaging and education as well as options to receive direct assistance when self-testing for HCV.

Abstract Background In 2018, Rwanda launched a 5-year hepatitis C virus (HCV) elimination plan as per the World Health Organization global targets to eliminate HCV by 2030. To improve awareness of HCV status, strategies are needed to ensure easy access to HCV testing by as-yet unreached populations. HCV-self-testing, an innovative strategy, could further increase HCV testing uptake. This assessment explores perceptions around HCV self-testing among members of the public and healthcare workers in Rwanda. Methods A qualitative study was undertaken in Masaka District Hospital, comprising individual interviews, group interviews and participatory action research (PAR) activities. Purposive and snowball sampling methods guided the selection of informants. Informed consent was obtained from all participants. A thematic analysis approach was used to analyse the findings. Results The participants comprised 36 members of the public and 36 healthcare workers. Informants appreciated HCV self-testing as an innovative means of increasing access to HCV testing, as well as an opportunity to test privately and subsequently autonomously decide whether to seek further HCV care. Informants further highlighted the need to make HCV self-testing services free of charge at the nearest health facility. Disadvantages identified included the lack of pre/post-test counselling, as well as the potential psychosocial harm which may result from the use of HCV self-testing. Conclusion HCV self-testing is perceived to be an acceptable method to increase HCV testing in Rwanda. Further research is needed to assess the impact of HCV self-testing on HCV cascade of care outcomes.

Abstract Background The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) continues to be a major public-health burden in this highly stigmatised population. To halt transmission of HCV, rapid HCV self-testing kits represent an innovative approach that could enable PWID to know their HCV status and seek treatment. As no HCV test has yet been licenced for self-administration, it is crucial to obtain knowledge around the factors that may deter or foster delivery of HCV self-testing among PWID in resource-constrained countries. Methods A qualitative study to assess values and preferences relating to HCV self-testing was conducted in mid-2020 among PWID in the Bishkek and Chui regions of Kyrgyzstan. Forty-seven PWID participated in 15 individual interviews, two group interviews (n = 12) and one participatory action-research session (n = 20). Responses were analysed using a thematic analysis approach with 4 predefined themes: awareness of HCV and current HCV testing experiences, and acceptability and service delivery preferences for HCV self-testing. Informants’ insights were analysed using a thematic analysis approach. This research received local ethics approval. Results Awareness of HCV is low and currently PWID prefer community-based HCV testing due to stigma encountered in other healthcare settings. HCV self-testing would be accepted and appreciated by PWID. Acceptability may increase if HCV self-testing: was delivered in pharmacies or by harm reduction associations; was free of charge; was oral rather than blood-based; included instructions with images and clear information on the test’s accuracy; and was distributed alongside pre- and post-testing counselling with linkage to confirmatory testing support. Conclusions HCV self-testing could increase awareness of and more frequent testing for HCV infection among PWID in Kyrgyzstan. It is recommended that peer-driven associations are involved in the delivery of any HCV self-testing. Furthermore, efforts should be maximised to end discrimination against PWID at the healthcare institutions responsible for confirmatory HCV testing and treatment provision.

Abstract Background Viral load (VL) testing is being scaled up in resource-limited settings. However, not all commercially available VL testing methods have been evaluated under field conditions. This study is one of a few to evaluate the Biocentric platform for VL quantification in routine practice in Sub-Saharan Africa. Methods Venous blood specimens were obtained from patients eligible for VL testing at two health facilities in Swaziland from October 2016 to March 2017. Samples were centrifuged at two laboratories (LAB-1, LAB-2) to obtain paired plasma specimens for VL quantification with the national reference method and on the Biocentric platform. Agreement (correlation, Bland–Altman) and accuracy (sensitivity, specificity) indicators were calculated at the VL thresholds of 416 (2.62 log10) and 1000 (3.0 log10) copies/mL. Leftover samples from patients with discordant VL results were re-quantified and accuracy indicators recalculated. Logistic regression was used to compare laboratory performance. Results A total of 364 paired plasma samples (LAB-1: n = 198; LAB-2: n = 166) were successfully tested using both methods. The correlation was high (R = 0.82, p

Abstract Background Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration. Methods Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating intravenous or subcutaneous teicoplanin safety and pharmacokinetics. Results Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7–6.5) after a loading dose of 5 injections 12 h apart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An overdose (Cmin >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven adverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51–183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic inflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p

Background: The HIV epidemic in Kenya remains a significant public health concern, particularly among gay, bisexual, and other men who have sex with men (GBMSM), who continue to bear a disproportionate burden of the epidemic. This study's objective is to describe HIV phylogenetic clusters among different subgroups of Kenyan GBMSM, including those who use physical hotspots, virtual spaces, or a combination of both to find male sexual partners., Methods: Dried blood spots (DBS) were collected from GBMSM in Kisumu, Mombasa, and Kiambu counties, Kenya, in 2019 (baseline) and 2020 (endline). HIV pol sequencing was attempted on all seropositive DBS. HIV phylogenetic clusters were inferred using a patristic distance cutoff of ≤ 0.02 nucleotide substitutions per site. We used descriptive statistics to analyze sociodemographic characteristics and risk behaviors stratified by clustering status., Results: Of the 2,450 participants (baseline and endline), 453 (18.5%) were living with HIV. Only a small proportion of seropositive DBS specimens were successfully sequenced (n = 36/453; 7.9%), likely due to most study participants being virally suppressed (87.4%). Among these sequences, 13 (36.1%) formed eight distinct clusters comprised of seven dyads and one triad. The clusters mainly consisted of GBMSM seeking partners online (n = 10/13; 76.9%) and who tested less frequently than recommended by Kenyan guidelines (n = 11/13; 84.6%)., Conclusions: Our study identified HIV phylogenetic clusters among Kenyan GBMSM who predominantly seek sexual partners online and test infrequently. These findings highlight potential unmet HIV prevention, testing, and treatment needs within this population. Furthermore, these results underscore the importance of tailoring HIV programs to address the diverse needs of GBMSM in Kenya across different venues, including both physical hotspots and online platforms, to ensure comprehensive prevention and care strategies., Competing Interests: Declarations. Ethics approval and consent to participate: The study obtained approval from the Institutional Review Boards of the Kenyatta National Hospital – University of Nairobi, Kenya (P557/08/2018) and the University of Manitoba Health Research Ethics Board, Canada (HS22205). All participants provided written informed consent and were ≥ 18 years of age. Consent for publication Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. Crown.)