Vulvovaginal yeast infections during pregnancy and perinatal outcomes: systematic review and meta-analysis.

BACKGROUND: Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast infections are likely to cause more inflammation than asymptomatic. The objective of this study was to investigate associations between symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and perinatal outcomes. METHODS: We did a systematic review and searched eight databases until 01 July 2022. We included studies reporting on pregnant women with and without laboratory confirmed vulvovaginal yeast infection and preterm birth or eight other perinatal outcomes. We used random effects meta-analysis to calculate summary odds ratios (OR), 95% confidence intervals (CI) and prediction intervals for the association between yeast infection and outcomes. We described findings from studies with multivariable analyses. We assessed the risk of bias using published tools. RESULTS: We screened 3909 references and included 57 studies. Only 22/57 studies reported information about participant vulvovaginal symptoms. Preterm birth was an outcome in 35/57 studies (49,161 women). In 32/35 studies with available data, the summary OR from univariable analyses was 1.01 (95% CI 0.84-1.21, I2 60%, prediction interval 0.45-2.23). In analyses stratified by symptom status, we found ORs of 1.44 (95% CI 0.92-2.26) in two studies with ≥ 50% symptomatic participants, 0.84 (95% CI 0.45-1.58) in seven studies with < 50% symptomatic participants, and 1.12 (95% CI 0.94-1.35) in four studies with asymptomatic participants. In three studies with multivariable analysis, adjusted ORs were greater than one but CIs were compatible with there being no association. We did not find associations between vulvovaginal yeast infection and any secondary outcome. Most studies were at high risk of bias in at least one domain and only three studies controlled for confounding. CONCLUSIONS: We did not find strong statistical evidence of an increased risk for preterm birth or eight other adverse perinatal outcomes, in pregnant women with either symptomatic or asymptomatic vulvovaginal yeast infection. The available evidence is insufficient to make recommendations about testing and treatment of vulvovaginal yeast infection in pregnancy. Future studies should assess vulvovaginal symptoms, yeast organism loads, concomitant vaginal or cervical infections, and microbiota using state-of-the-art diagnostics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020197564.

Detection of SARS-CoV-2 infection in the general population by three prevailing rapid antigen tests: cross-sectional diagnostic accuracy study.

BACKGROUND: Rapid antigen diagnostic tests (Ag-RDTs) are the most widely used point-of-care tests for detecting SARS-CoV-2 infection. Since the accuracy may have altered by changes in SARS-CoV-2 epidemiology, indications for testing, sampling and testing procedures, and roll-out of COVID-19 vaccination, we evaluated the performance of three prevailing SARS-CoV-2 Ag-RDTs. METHODS: In this cross-sectional study, we consecutively enrolled individuals aged >16 years presenting for SARS-CoV-2 testing at three Dutch public health service COVID-19 test sites. In the first phase, participants underwent either BD-Veritor System (Becton Dickinson), PanBio (Abbott), or SD-Biosensor (Roche Diagnostics) testing with routine sampling procedures. In a subsequent phase, participants underwent SD-Biosensor testing with a less invasive sampling method (combined oropharyngeal-nasal [OP-N] swab). Diagnostic accuracies were assessed against molecular testing. RESULTS: Six thousand nine hundred fifty-five of 7005 participants (99%) with results from both an Ag-RDT and a molecular reference test were analysed. SARS-CoV-2 prevalence and overall sensitivities were 13% (188/1441) and 69% (129/188, 95% CI 62-75) for BD-Veritor, 8% (173/2056) and 69% (119/173, 61-76) for PanBio, and 12% (215/1769) and 74% (160/215, 68-80) for SD-Biosensor with routine sampling and 10% (164/1689) and 75% (123/164, 68-81) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72-83% and 54-56%, respectively. Above a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities were 86% (125/146, 79-91) for BD-Veritor, 89% (108/121, 82-94) for PanBio, and 88% (160/182, 82-92) for SD-Biosensor with routine sampling and 84% (118/141, 77-89) with OP-N sampling. Specificities were >99% for all tests in most analyses. Sixty-one per cent of false-negative Ag-RDT participants returned for testing within 14 days (median: 3 days, interquartile range 3) of whom 90% tested positive. CONCLUSIONS: Overall sensitivities of three SARS-CoV-2 Ag-RDTs were 69-75%, increasing to ≥86% above a viral load cut-off. The decreased sensitivity among asymptomatic participants and high positivity rate during follow-up in false-negative Ag-RDT participants emphasise the need for education of the public about the importance of re-testing after an initial negative Ag-RDT should symptoms develop. For SD-Biosensor, the diagnostic accuracy with OP-N and deep nasopharyngeal sampling was similar; adopting the more convenient sampling method might reduce the threshold for professional testing.

Head-to-head comparison of the accuracy of saliva and nasal rapid antigen SARS-CoV-2 self-testing: cross-sectional study.

BACKGROUND: The diagnostic accuracy of unsupervised self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We studied the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT in the general population. METHODS: This large cross-sectional study consecutively included unselected individuals aged ≥ 16 years presenting for SARS-CoV-2 testing at three public health service test sites. Participants underwent molecular test sampling and received two self-tests (the Hangzhou AllTest Biotech saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform themselves at home. Diagnostic accuracy of both self-tests was assessed with molecular testing as reference. RESULTS: Out of 2819 participants, 6.5% had a positive molecular test. Overall sensitivities were 46.7% (39.3-54.2%) for the saliva Ag-RDT and 68.9% (61.6-75.6%) for the nasal Ag-RDT. With a viral load cut-off (≥ 5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, these sensitivities increased to 54.9% (46.4-63.3%) and 83.9% (76.9-89.5%), respectively. For the nasal Ag-RDT, sensitivities were 78.5% (71.1-84.8%) and 22.6% (9.6-41.1%) in those symptomatic and asymptomatic at the time of sampling, which increased to 90.4% (83.8-94.9%) and 38.9% (17.3-64.3%) after applying the viral load cut-off. In those with and without prior SARS-CoV-2 infection, sensitivities were 36.8% (16.3-61.6%) and 72.7% (65.1-79.4%). Specificities were > 99% and > 99%, positive predictive values > 70% and > 90%, and negative predictive values > 95% and > 95%, for the saliva and nasal Ag-RDT, respectively, in most analyses. Most participants considered the self-performing and result interpretation (very) easy for both self-tests. CONCLUSIONS: The Hangzhou AllTest Biotech saliva self Ag-RDT is not reliable for SARS-CoV-2 detection, overall, and in all studied subgroups. The SD Biosensor nasal self Ag-RDT had high sensitivity in individuals with symptoms and in those without prior SARS-CoV-2 infection but low sensitivity in asymptomatic individuals and those with a prior SARS-CoV-2 infection which warrants further investigation.

Feasibility and acceptability of frequent vaginal self-sampling at home by Rwandan women at high risk of urogenital tract infections.

OBJECTIVES: To establish temporal links between vaginal microbiota (VMB) data and incident clinical events, frequent longitudinal vaginal sampling is required. Self-collection of swabs at the participant's home may be useful to avoid overburdening research clinics and participants. One-off vaginal self-sampling for STI or cervical cancer screening programmes has been shown to be feasible and acceptable to women in multiple studies, including in sub-Saharan Africa, but the feasibility and acceptability of frequent longitudinal vaginal sampling in the context of VMB sequencing studies is unknown. METHODS: Twelve participants of a randomised clinical trial in Kigali, Rwanda, self-collected vaginal swabs three times a week for a month. We studied feasibility by comparing DNA concentrations, proportions of samples with >1000 16S rRNA amplicon sequencing reads and VMB composition outcomes of self-collected swabs with clinician-collected swabs. We evaluated the acceptability of self-collection using structured face-to-face interviews and a focus group discussion. RESULTS: The participants collected vaginal swabs at 131 different time points. One woman stopped self-sampling after one try due to a social harm. All self-sampled swabs generated >1000 rRNA amplicon sequencing reads, and the DNA concentration of self-sampled swabs and clinician-sampled swabs did not differ significantly (Kruskal-Wallis p=0.484). Self-sampled and clinician-sampled swabs generated similar VMB composition data. Participants reported feeling very comfortable during self-sampling (11/12; 91.7%) and that self-sampling had become easier over time (12/12; 100%). They mentioned reduced travel time and travel costs as advantages of self-sampling at home. CONCLUSIONS: Frequent longitudinal vaginal sampling at home is feasible and acceptable to participants, even in the context of a low-resource setting, as long as adequate counselling is provided. TRIAL REGISTRATION NUMBER: NCT02459665.

Interventions to control nosocomial transmission of SARS-CoV-2: a modelling study.

BACKGROUND: Emergence of more transmissible SARS-CoV-2 variants requires more efficient control measures to limit nosocomial transmission and maintain healthcare capacities during pandemic waves. Yet the relative importance of different strategies is unknown. METHODS: We developed an agent-based model and compared the impact of personal protective equipment (PPE), screening of healthcare workers (HCWs), contact tracing of symptomatic HCWs and restricting HCWs from working in multiple units (HCW cohorting) on nosocomial SARS-CoV-2 transmission. The model was fit on hospital data from the first wave in the Netherlands (February until August 2020) and assumed that HCWs used 90% effective PPE in COVID-19 wards and self-isolated at home for 7 days immediately upon symptom onset. Intervention effects on the effective reproduction number (RE), HCW absenteeism and the proportion of infected individuals among tested individuals (positivity rate) were estimated for a more transmissible variant. RESULTS: Introduction of a variant with 56% higher transmissibility increased - all other variables kept constant - RE from 0.4 to 0.65 (+ 63%) and nosocomial transmissions by 303%, mainly because of more transmissions caused by pre-symptomatic patients and HCWs. Compared to baseline, PPE use in all hospital wards (assuming 90% effectiveness) reduced RE by 85% and absenteeism by 57%. Screening HCWs every 3 days with perfect test sensitivity reduced RE by 67%, yielding a maximum test positivity rate of 5%. Screening HCWs every 3 or 7 days assuming time-varying test sensitivities reduced RE by 9% and 3%, respectively. Contact tracing reduced RE by at least 32% and achieved higher test positivity rates than screening interventions. HCW cohorting reduced RE by 5%. Sensitivity analyses show that our findings do not change significantly for 70% PPE effectiveness. For low PPE effectiveness of 50%, PPE use in all wards is less effective than screening every 3 days with perfect sensitivity but still more effective than all other interventions. CONCLUSIONS: In response to the emergence of more transmissible SARS-CoV-2 variants, PPE use in all hospital wards might still be most effective in preventing nosocomial transmission. Regular screening and contact tracing of HCWs are also effective interventions but critically depend on the sensitivity of the diagnostic test used.

Health-related quality of life in patients with immune mediated inflammatory diseases: A cross-sectional, multidisciplinary study.

Immune mediated inflammatory diseases (IMIDs) have similarities in pathophysiology and treatment. Not much is known, however, about health-related quality of life (HR-QoL) in IMIDs. We assessed and compared HR-QoL, using the validated EuroQoL 5-dimensions 5-levels questionnaire, in an observational cohort comprising 530 patients (67.5% female, mean age 49 years (95% CI 35.9-50.9), mean disease duration 31.0 months (95% CI 27.2-34.8)), with the following IMIDs: connective tissue diseases (32.6%), uveitis (20.8%), inflammatory arthritis (17.7%), psoriasis (15.5%), vasculitis (6.2%), primary antiphospholipid syndrome (4.2%), and autoinflammatory diseases (2.8%). Patients used either no anti-inflammatory therapy (31.5%), monotherapy (28.7%), or a combination of anti-inflammatory drugs (39.8%). The mean HR-QoL utility score was 0.75 (95% CI 0.72-0.78). Multinominal logistic regression analysis showed a statistically significant association between a very low HR-QoL (utility score (<0.70)) and female sex, rheumatological IMID or psoriasis, smoking or having smoked in the past, and current biological disease modifying anti-rheumatic drugs use.

Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure.

BACKGROUND: Metronidazole is the first-line treatment for bacterial vaginosis, but cure rates are suboptimal and recurrence rates high. OBJECTIVES: To evaluate the impact of a standard course of oral metronidazole treatment (500 mg twice per day for 7 days) on the vaginal microbiota of Rwandan bacterial vaginosis patients using microscopy and 16S rRNA gene sequencing, and to evaluate correlates of treatment failure. STUDY DESIGN: HIV-negative, nonpregnant women aged 18-45 years with bacterial vaginosis and/or Trichomonas vaginalis (N=68) were interviewed and sampled before and after metronidazole treatment. They were also screened, and treated if applicable, for other urogenital infections. The vaginal microbiota was assessed by Gram stain Nugent scoring, Illumina 16S rRNA HiSeq sequencing (relative abundances), and BactQuant 16S gene quantitative polymerase chain reaction (estimated concentrations). Only women with a pretreatment Nugent score of 7-10 and a valid posttreatment Nugent score (N=55) were included in metronidazole treatment failure analyses, with treatment failure defined as a posttreatment Nugent score of 4-10. RESULTS: The bacterial vaginosis cure rate by Nugent scoring was 54.5%. The mean total vaginal bacterial concentration declined from 6.59 to 5.85 log10/µL (P<.001), which was mostly due to a reduction in mean bacterial vaginosis-associated anaerobes concentration (all bacterial vaginosis-associated anaerobe taxa combined) from 6.23 to 4.55 log10/µL (P<.001). However, only 16.4% of women had a bacterial vaginosis anaerobes concentration reduction of more than 50%, and only 3 women had complete eradication. The mean concentration of lactobacilli (all species combined) increased from 4.98 to 5.56 log10/µL (P=.017), with L. iners being the most common species pre- and posttreatment. The mean concentration of pathobionts (defined as Proteobacteria, streptococci, staphylococci, enterococci, and a few others) did not change significantly: from 1.92 log10/µL pretreatment to 2.01 log10/µL posttreatment (P=.939). Pretreatment pathobionts concentration, and having a pretreatment vaginal microbiota type containing more than 50% Gardnerella vaginalis (compared with less than 50%), were associated with increased likelihood of treatment failure, but the latter did not reach statistical significance (P=.044 and P=.084, respectively). CONCLUSIONS: Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments.

Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

BACKGROUND: Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. METHODS AND FINDINGS: We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations. CONCLUSIONS: Combining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

Correction: Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

[This corrects the article DOI: 10.1371/journal.pmed.1002511.].

The vaginal microbiome and sexually transmitted infections are interlinked: Consequences for treatment and prevention.

In a Perspective for our Collection on STI research, Janneke van de Wijgert discusses the latest on how the vaginal microbiota predisposes women to acquisition of STIs and discusses future potential for clinical intervention.

Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.

BACKGROUND: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. METHODS AND FINDINGS: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. CONCLUSIONS: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in african sex workers.

BACKGROUND: The observed association between Depo-Provera injectable use and increased HIV acquisition may be caused by hormone-induced increased susceptibility to other sexually transmitted infections (STIs) or changes in the cervicovaginal microbiota (VMB), accompanied by genital immune activation and/or mucosal remodeling. METHODS: Rwandan female sex workers (n = 800) were interviewed about contraceptive use and sexual behavior and were tested for STIs, bacterial vaginosis by Nugent score and pregnancy, at baseline. A subset of 397 HIV-negative, nonpregnant women were interviewed and tested again at regular intervals for 2 years. The VMB of a subset of 174 women was characterized by phylogenetic microarray. Outcomes of STI and VMB were compared between women with hormonal exposures (reporting oral contraceptive or injectable use, or testing positive for pregnancy) and controls (not reporting hormonal contraception and not pregnant). RESULTS: Oral contraceptive use was associated with increased human papillomavirus prevalence (adjusted odds ratio [aOR], 3.10; 1.21-7.94) and Chlamydia trachomatis incidence (aOR, 6.13; 1.58-23.80), injectable use with increased herpes simplex virus-2 prevalence (aOR, 2.13; 1.26-3.59) and pregnancy with lower HIV prevalence (aOR, 0.45; 0.22-0.92) but higher candidiasis incidence (aOR, 2.14; 1.12-4.09). Hormonal status was not associated with Nugent score category or phylogenetic VMB clustering, but oral contraceptive users had lower semiquantitative vaginal abundance of Prevotella, Sneathia/Leptotrichia amnionii, and Mycoplasma species. CONCLUSIONS: Oral contraceptive and injectable use were associated with several STIs but not with VMB composition. The increased herpes simplex virus-2 prevalence among injectable users might explain the potentially higher HIV risk in these women, but more research is needed to confirm these results and elucidate biological mechanisms.

Correlates of the molecular vaginal microbiota composition of African women.

BACKGROUND: Sociodemographic, behavioral and clinical correlates of the vaginal microbiome (VMB) as characterized by molecular methods have not been adequately studied. VMB dominated by bacteria other than lactobacilli may cause inflammation, which may facilitate HIV acquisition and other adverse reproductive health outcomes. METHODS: We characterized the VMB of women in Kenya, Rwanda, South Africa and Tanzania (KRST) using a 16S rDNA phylogenetic microarray. Cytokines were quantified in cervicovaginal lavages. Potential sociodemographic, behavioral, and clinical correlates were also evaluated. RESULTS: Three hundred thirteen samples from 230 women were available for analysis. Five VMB clusters were identified: one cluster each dominated by Lactobacillus crispatus (KRST-I) and L. iners (KRST-II), and three clusters not dominated by a single species but containing multiple (facultative) anaerobes (KRST-III/IV/V). Women in clusters KRST-I and II had lower mean concentrations of interleukin (IL)-1α (p < 0.001) and Granulocyte Colony Stimulating Factor (G-CSF) (p = 0.01), but higher concentrations of interferon-γ-induced protein (IP-10) (p < 0.01) than women in clusters KRST-III/IV/V. A lower proportion of women in cluster KRST-I tested positive for bacterial sexually transmitted infections (STIs; ptrend = 0.07) and urinary tract infection (UTI; p = 0.06), and a higher proportion of women in clusters KRST-I and II had vaginal candidiasis (ptrend = 0.09), but these associations did not reach statistical significance. Women who reported unusual vaginal discharge were more likely to belong to clusters KRST-III/IV/V (p = 0.05). CONCLUSION: Vaginal dysbiosis in African women was significantly associated with vaginal inflammation; the associations with increased prevalence of STIs and UTI, and decreased prevalence of vaginal candidiasis, should be confirmed in larger studies.

Within-episode repeat antibiotic prescriptions in patients with respiratory tract infections: A population-based cohort study.

BACKGROUND: Antimicrobial stewardship interventions mainly focus on initial antibiotic prescriptions, with few considering within-episode repeat prescriptions. We aimed to describe the magnitude, type and determinants of within-episode repeat antibiotic prescriptions in patients presenting to primary care with respiratory tract infections (RTIs). METHODS: We conducted a population-based cohort study among 530 sampled English general practices within the Clinical Practice Research Datalink (CPRD). All individuals with a primary care RTI consultation for which an antibiotic was prescribed between March 2018 and February 2022. Main outcome measurement was repeat antibiotic prescriptions within 28 days of a RTI visit stratified by age (children vs. adults) and RTI type (lower vs. upper RTI). Multivariable logistic regression and principal components analyses were used to identify risk factors and patient clusters at risk for within-episode repeat prescriptions. FINDINGS: 905,964 RTI episodes with at least one antibiotic prescription were identified. In adults, 19.9% (95% CI 19.3-20.5%) had at least one within-episode repeat prescription for a lower RTI, compared to 10.5% (95% CI 10.3-10.8%) for an upper RTI. In children, this was around 10% irrespective of RTI type. The majority of repeat prescriptions occurred a median of 10 days after the initial prescription and was the same antibiotic class in 48.3% of cases. Frequent RTI related GP visits and prior within-RTI-episode repeat antibiotic prescriptions were main factors associated with repeat prescriptions in both adults and children irrespective of RTI type. Young (<2 years) and older (65+) age were associated with repeat prescriptions. Among those aged 2-64 years, allergic rhinitis, COPD and oral corticosteroids were associated with repeat prescriptions. INTERPRETATIONS: Repeat within-episode antibiotic use accounts for a significant proportion of all antibiotics prescribed for RTIs, with same class antibiotics unlikely to confer clinical benefit and is therefore a prime target for future antimicrobial stewardship interventions.

High adherence to intermittent and continuous use of a contraceptive vaginal ring among women in a randomized controlled trial in Kigali, Rwanda.

Background: The introduction of female-initiated drug-delivery methods, including vaginal rings, have proven to be a promising avenue to address sexually transmitted infections and unintended pregnancies, which disproportionally affects women and girls in sub-Saharan Africa. Efficient uptake of existing and new technologies such as vaginal rings requires in depth understanding of product adherence. This remains a major challenge as data on adherence to vaginal rings from African countries is limited. In this study, we explored adherence of contraceptive vaginal ring (NuvaRing®) use in Kigali, Rwanda using a mixed methods approach. Methods: We collected quantitative and qualitative data at multiple time points from women participating in a clinical trial exploring the safety and acceptability of either intermittent or continuous use of the NuvaRing®. Various adherence categories were used including monthly and cumulative adherence measurement. The quantitative data were analysed using R and the qualitative data were analysed using a deductive, content-analytical approach based on categories related to the quantitative adherence measures. All data were compared and triangulated. Results: Data from 120 enrolled participants showed that self-reported adherence was high at every study visit in both study groups. At first study visit 80% of the intermittent ring users and 79.7% of the continuous ring users reported perfect adherence (assessed as "the ring was never out"). Reporting of ring expulsions and removals were highest (28.3%) at the beginning of the trial. Self-reported perfect ring adherence increased during the study and reports of ring expulsions and removals declined as familiarity with this contraceptive method increased. The percentage of women with perfect cumulative adherence was non-significantly higher in the intermittent (61.7%) than in the continuous use group (54.3%). The low rate of discrepant adherence data after triangulation (6%) is in line with the perception of the participants as adherent throughout the study. Conclusions: Self-reported adherence in both study groups was high with removals and expulsions being within the expected product range. Comprehensive adherence data triangulation allowed for a deeper understanding of context-driven behaviour that shaped adherence patterns and challenges. Our data categorisation and triangulation approach has shown potential for implementation in future vaginal ring studies aiming to better understand and measure adherence.

Health-related quality of life during the COVID-19 pandemic: The impact of restrictive measures using data from two Dutch population-based cohort studies.

OBJECTIVES: We describe health-related quality of life during the COVID-19 pandemic in the general Dutch population and correlations with restrictive measures. METHODS: Data were obtained from 18-85 year-old participants of two population-based cohort studies (February 2021-July 2022): PIENTER Corona (n = 8,019) and VASCO (n = 45,413). Per cohort, mean scores of mental and physical health and health utility from the SF-12 were calculated by age group, sex and presence of a medical risk condition. Spearman correlations with stringency of measures were calculated. RESULTS: Both cohorts showed comparable results. Participants <30 years had lowest health utility and mental health score, and highest physical health score. Health utility and mental health score increased with age (up to 79 years), while physical health score decreased with age. Women and participants with a medical risk condition scored lower than their counterparts. Fluctuations were small over time but most pronounced among participants <60 years, and correlated weakly, but mostly positively with measure stringency. CONCLUSIONS: During the Dutch COVID-19 epidemic, health utility and mental health scores were lower and fluctuated strongest among young adults compared to older adults. In our study population, age, sex and presence of a medical risk condition seemed to have more impact on health scores than stringency of COVID-19 non-pharmaceutical interventions.

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.