Intersecting structural and psychosocial conditions: investigating injection drug use and HIV among transgender women.

BACKGROUND: Transgender women continue to face a significant burden of health disparities with HIV infection as a critical public health concern. Substance use is higher among transgender women compared to cisgender women. However, little is known about transgender women who inject drugs and risk for HIV in the United States. The objectives were to explore HIV prevalence, injection-related behaviors, and HIV prevention and care outcomes among transgender women who inject drugs and to compare transgender women to a general sample of people who inject drugs (PWID). METHODS: Participants from National HIV Behavioral Surveillance were recruited via respondent-driven sampling, interviewed, and tested for HIV infection in 2019-2020. Log-linked Poisson regression models were used to test for associations between injection drug use and selected characteristics. RESULTS: Among 1,561 transgender women, 7% injected drugs in the past 12 months. HIV prevalence was higher among transgender women who inject (aPR=1.5, 95%CI=1.2-1.8) than those who do not. Multiple psychosocial conditions were associated with injection drug use. Among transgender women with HIV, those who inject were less likely to take antiretroviral therapy (aPR=0.8, 95%CI=0.7-1.0) than those who do not. Methamphetamine was the most commonly injected drug (67%); most accessed a syringe services program (66%). CONCLUSION: Transgender women who inject have substantial challenges related to health outcomes including high HIV prevalence and exposure to psychosocial conditions, such as homelessness, incarceration, and exchange sex, that may exacerbate risks associated with injection drug use. This population may benefit from increased access to non-judgmental and culturally competent harm reduction services.

A machine-learning based model for automated recommendation of individualized treatment of rifampicin-resistant tuberculosis.

BACKGROUND: Rifampicin resistant tuberculosis remains a global health problem with almost half a million new cases annually. In high-income countries patients empirically start a standardized treatment regimen, followed by an individualized regimen guided by drug susceptibility test (DST) results. In most settings, DST information is not available or is limited to isoniazid and fluoroquinolones. Whole genome sequencing could more accurately guide individualized treatment as the full drug resistance profile is obtained with a single test. Whole genome sequencing has not reached its full potential for patient care, in part due to the complexity of translating a resistance profile into the most effective individualized regimen. METHODS: We developed a treatment recommender clinical decision support system (CDSS) and an accompanying web application for user-friendly recommendation of the optimal individualized treatment regimen to a clinician. RESULTS: Following expert stakeholder meetings and literature review, nine drug features and 14 treatment regimen features were identified and quantified. Using machine learning, a model was developed to predict the optimal treatment regimen based on a training set of 3895 treatment regimen-expert feedback pairs. The acceptability of the treatment recommender CDSS was assessed as part of a clinical trial and in a routine care setting. Within the clinical trial setting, all patients received the CDSS recommended treatment. In 8 of 20 cases, the initial recommendation was recomputed because of stock out, clinical contra-indication or toxicity. In routine care setting, physicians rejected the treatment recommendation in 7 out of 15 cases because it deviated from the national TB treatment guidelines. A survey indicated that the treatment recommender CDSS is easy to use and useful in clinical practice but requires digital infrastructure support and training. CONCLUSIONS: Our findings suggest that global implementation of the novel treatment recommender CDSS holds the potential to improve treatment outcomes of patients with RR-TB, especially those with 'difficult-to-treat' forms of RR-TB.

SARS-CoV-2 Seropositivity in Nursing Home Staff and Residents during the First SARS-CoV-2 Wave in Flanders, Belgium.

(1) Background: early in the COVID-19 pandemic, reverse transcription polymerase chain reaction (RT-PCR) testing was limited. Assessing seroprevalence helps understand prevalence and reinfection risk. However, such data are lacking for the first epidemic wave in Belgian nursing homes. Therefore, we assessed SARS-CoV-2 seroprevalence and cumulative RT-PCR positivity in Belgian nursing homes and evaluated reinfection risk. (2) Methods: we performed a cross-sectional study in nine nursing homes in April and May 2020. Odds ratios (ORs) were calculated to compare the odds of (re)infection between seropositive and seronegative participants. (3) Results: seroprevalence was 21% (95% CI: 18-23): 22% (95% CI: 18-25) in residents and 20% (95% CI: 17-24) in staff. By 20 May 2020, cumulative RT-PCR positivity was 16% (95% CI: 13-21) in residents and 8% (95% CI: 6-12) in staff. ORs for (re)infection in seropositive (compared to seronegative) residents and staff were 0.22 (95% CI: 0.06-0.72) and 3.15 (95% CI: 1.56-6.63), respectively. (4) Conclusion: during the first wave, RT-PCR test programmes underestimated the number of COVID-19 cases. The reinfection rate in residents was 3%, indicating protection, while it was 21% in staff, potentially due to less cautious health behaviour. Future outbreaks should use both RT-PCR and serological testing for complementary insights into transmission dynamics.

Follow-Up of SARS-CoV-2 Antibody Levels in Belgian Nursing Home Residents and Staff Two, Four and Six Months after Primary Course BNT162b2 Vaccination.

When COVID-19 vaccines were implemented, nursing home residents (NHRs) and staff (NHS) in Belgium were prioritized for vaccination. To characterize the vaccine response over time in this population and to identify poorly responding groups, we assessed antibody concentrations two (T1), four (T2) and six months (T3) after primary course BNT162b2 vaccination in six groups of infection-naive/infection-primed NHRs/NHS, with/without comorbidity (NHRs only). Participant groups (N = 125 per group) were defined within a national serosurveillance study in nursing homes, based on questionnaire data. Dried blood spots were analyzed using ELISA for the quantification of SARS-CoV-2 S1RBD IgG antibodies. Among all groups, antibody concentrations significantly decreased between T1 and T2/T3, all with a ≥70% decrease at T3, except for infection-primed staff (-32%). Antibody concentrations among infection-naive NHRs were 11.96 times lower than those among infection-primed NHR, while the latter were comparable (x1.05) to infection-primed NHS. The largest proportion [13% (95% CI: 11-24%)] of vaccine non-responders was observed in the group of infection-naive NHRs with comorbidities. A longer interval between infection and vaccination (≥3 months) elicited higher antibody responses. Our data retrospectively show the necessity of timely COVID-19 booster vaccination. Infection-naive NHRs require special attention regarding immune monitoring in future epidemics or pandemics.

Understanding adaptive responses in PrEP service delivery in Belgian HIV clinics: a multiple case study using an implementation science framework.

INTRODUCTION: In Belgium, oral HIV pre-exposure prophylaxis (PrEP) is primarily provided in specialized clinical settings. Optimal implementation of PrEP services can help to substantially reduce HIV transmission. However, insights into implementation processes, and their complex interactions with local context, are limited. This study examined factors that influence providers' adaptive responses in the implementation of PrEP services in Belgian HIV clinics. METHODS: We conducted a qualitative multiple case study on PrEP care implementation in eight HIV clinics. Thirty-six semi-structured interviews were conducted between January 2021 and May 2022 with a purposive sample of PrEP care providers (e.g. physicians, nurses, psychologists), supplemented by 50 hours of observations of healthcare settings and clinical interactions. Field notes from observations and verbatim interview transcripts were thematically analysed guided by a refined iteration of extended Normalisation Process Theory. RESULTS: Implementing PrEP care in a centralized service delivery system required considerable adaptive capacity of providers to balance the increasing workload with an adequate response to PrEP users' individual care needs. As a result, clinic structures were re-organized to allow for more efficient PrEP care processes, compatible with other clinic-level priorities. Providers adapted clinical and policy norms on PrEP care (e.g. related to PrEP prescribing practices and which providers can deliver PrEP services), to flexibly tailor care to individual clients' situations. Interprofessional relationships were reconfigured in line with organizational and clinical adaptations; these included task-shifting from physicians to nurses, leading them to become increasingly trained and specialized in PrEP care. As nurse involvement grew, they adopted a crucial role in responding to PrEP users' non-medical needs (e.g. providing psychosocial support). Moreover, clinicians' growing collaboration with sexologists and psychologists, and interactions with PrEP users' family physician, became crucial in addressing complex psychosocial needs of PrEP clients, while also alleviating the burden of care on busy HIV clinics. CONCLUSIONS: Our study in Belgian HIV clinics reveals that the implementation of PrEP care presents a complex-multifaceted-undertaking that requires substantial adaptive work to ensure seamless integration within existing health services. To optimize integration in different settings, policies and guidelines governing PrEP care implementation should allow for sufficient flexibility and tailoring according to respective local health systems.

Second trimester vaginal Candida colonization among pregnant women attending antenatal care in Bukavu, Democratic Republic of the Congo: prevalence, clinical correlates, risk factors and pregnancy outcomes.

Introduction: Vaginal Candida colonization (CC) can lead to vulvovaginal candidiasis, the second most prevalent vaginal condition worldwide, and has been associated with adverse birth outcomes. However, no data on CC in the Democratic Republic of the Congo are available. We investigated the prevalence, Candida species, clinical correlates, risk factors and pregnancy outcomes in women with CC in the second trimester of pregnancy. Material and methods: In Bukavu, the Democratic Republic of the Congo, pregnant women were recruited during antenatal care between 16 and 20 weeks of gestation from January 2017 to October 2017 and followed until delivery. Sociodemographics, sexual behavioral, hygienic and clinical characteristics, microbiological data and pregnancy outcomes were collected. Candida detection and speciation was performed with microscopy (Gram-stained smears and wet-mount) and/or quantitative PCR. Multivariate regression models were used to estimate the different associations with CC. Results: The prevalence of CC by wet mount, microscopy of Gram-stain smears and qPCR was 27.9%, 28.1% and 38.2%, respectively. C. albicans was the most prevalent Candida species (91.0%). Previous genital infections, an intermediate vaginal microbiota, bacterial vaginosis, and the use of pit toilets were risk factors for CC. Clinically, CC was associated with itching only. Women with CC had twice the odds for preterm birth, if Candida concentration was high, the odds were four times higher. Conclusions: In Bukavu, the Democratic Republic of the Congo, the prevalence of CC was high and associated with microbiological and modifiable risk factors. Screening and treatment for CC during antenatal care should be investigated as a possible strategy to reduce preterm birth.

Antibiotic or gastric acid inhibitor use during pregnancy and postpartum depression: Population-based cohort study.

INTRODUCTION: Postpartum depression is one of the most common non-obstetric postnatal complications. As the microbiome (and gut-brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth). MATERIAL AND METHODS: This population-based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016. Women with history of depression were excluded. Multivariable logistic regression models were used to assess the impact of antibiotics and gastric acid inhibitors and other risk factors, presented as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Overall, 29% of all 10 666 women with postpartum depression were exposed to antibiotics and 6.2% to gastric acid inhibitors, compared to, respectively, 21% and 3.2% of 613 205 women without postpartum depression. Antibiotic use during pregnancy was associated with postpartum depression (OR 1.43, 95% CI 1.37-1.49), particularly for quinolones and other antibacterials (including nitroimidazole derivatives). Gastric acid inhibition was associated with an even higher risk than antibiotics (OR 2.04, 95% CI 1.88-2.21). Both antibiotics and gastric acid inhibitors suggested higher risk with increased dose in a dose-response analysis. CONCLUSIONS: The use of antibiotics and gastric acid inhibition drugs during pregnancy appeared to be associated with a higher risk of postpartum depression. However, it is important to consider that other predisposing factors could contribute to this increased risk, even after excluding individuals with a history of depression.

Clostridioides difficile infection, recurrence and the associated healthcare consumption in Sweden between 2006 and 2019: a population-based cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). METHODS: This Swedish nationwide population-based cohort study (2006-2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. RESULTS: Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40-18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16-9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84-4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31-3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (< 65 years) than the older (≥ 65 years), and in those with fewer comorbidities, but similar between sexes. Compared to those without recurrence, individuals with recurrence particularly showed a higher rate of hospital admissions (IRR = 1.18, 95% 1.12-1.24). Compared to community-acquired CDI, those with hospital-acquired CDI presented with a higher rate of hospital admissions (IRR = 7.29, 95% CI 6.68-7.96) and a longer length of stay (IRR = 7.64, 95% CI 7.07-8.26). CONCLUSION: CDI was associated with increased health consumption in all affected patient groups. The majority of the CDI burden could be contributed to hospital-acquired CDI (~ 9/10), older patients (~ 3/4) and those with multiple comorbidities (~ 6/10 Charlson score ≥ 3), with 1/5 of the total CDI burden contributed to individuals with recurrence. Yet, relatively speaking the burden was higher among the younger and those with fewer comorbidities, compared to their peers without CDI.

Clostridioides difficile recurrence in individuals with and without cancer: a Swedish population-based cohort study.

PURPOSE: Patients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored. METHODS: This Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006-2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status. RESULTS: Compared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73-0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43-1.74; Cancer history: OR = 1.45, 95% CI 1.36-1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76-0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97-1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found. CONCLUSION: The population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high.

Fasciola spp. in Southeast Asia: A systematic review.

BACKGROUND: Fasciolosis is an emerging public health threat in a number of regions worldwide. To date, we lack an overview of both its occurrence and distribution in Southeast Asia across all actors involved in the life cycle, which impedes the development of disease control measures. Therefore, our objective was to collect recent information on the distribution and the prevalence of Fasciola spp. and the associated risk factors for infection in humans, animals, snails and plant carriers in Southeast Asia. METHODOLOGY: Bibliographic and grey literature databases as well as reference lists of important review articles were searched for relevant records published between January 1st, 2000, and June 30th, 2022. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting systematic reviews. A total of 3,887 records were retrieved, of which 100 were included in the final analysis. PRINCIPAL FINDINGS: The studies focused mainly on one host species (96.0%), with Fasciola spp. infection in animals being the most studied (72.0%), followed by humans (21.0%). Based on the used inclusion and exclusion criteria, reports were retrieved describing the presence of Fasciola spp. infection in seven out of 11 countries in Southeast Asia. Depending on the diagnostic tool applied, the prevalence of Fasciola spp. infection ranged between 0.3% and 66.7% in humans, between 0% and 97.8% in animals, and between 0% and 66.2% in snails. There were no studies reporting the presence of metacercariae on plant carriers. CONCLUSIONS/SIGNIFICANCE: Our study reconfirms that Fasciola spp. infections are widespread and highly prevalent in Southeast Asia, but it remains difficult to accurately assess the true occurrence of Fasciola spp. in absence of well-designed surveys covering all hosts. As next steps we propose to assess the occurrence of the infection across all actors involved in the transmission, to identify associated risk factors and to estimate the burden of the disease to support national and international decision makers.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

BACKGROUND: Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. OBJECTIVES: To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. METHODS: Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. RESULTS: Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. CONCLUSION: Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Rapid detection of S. pyogenes and S. pneumoniae in pleural fluid for diagnosis of parapneumonic empyema.

The aim of this study was to assess the reliability of rapid antigen detection tests (RADT) for Streptococcus pyogenes (GAS) and Streptococcus pneumoniae on pleural fluid samples for diagnosis of parapneumonic effusion/empyema (PPE) and their potential for improving pathogen identification rates. Sixty-three pleural samples were included from 54 patients on which GAS and S. pneumoniae RADT (BinaxNOW), culture, 16S rRNA PCR, and S. pneumoniae-specific PCR were performed. GAS RADT showed a sensitivity of 95.2% and a specificity of 100%. Pneumococcal RADT showed a sensitivity of 100% and specificity of 88.6%. Both RADT increased the pathogen identification rate in PPE compared to culture.

HIV Pre-exposure Prophylaxis (PrEP) Care in Belgium: A mixed-methods Study on PrEP Users' Experiences and Service Delivery Preferences.

In Belgium, HIV pre-exposure prophylaxis (PrEP) services are mainly provided through specialised HIV clinics. To optimise PrEP uptake and retention in care, we require insights into users' perspectives on PrEP care. We aimed to elicit experiences with, and preferences for, PrEP service delivery among PrEP users in Belgium, including willingness to involve their family physician (FP) in PrEP care. We adopted a sequential mixed-methods design. We used a web-based longitudinal study among 326 PrEP users that consisted of two questionnaires at six-month intervals, and complemented this with 21 semi-structured interviews (September 2020-January 2022). We conducted descriptive analyses and logistic regression to examine factors associated with willingness to involve their FP in PrEP care. Interviews were analysed using thematic analysis. Survey respondents reported high satisfaction with care received in HIV clinics [median score 9 (IQR 8-10), 10='very satisfied']. Interviews revealed the importance of regular HIV/STI screening, and the expertise and stigma-free environment of HIV clinics. Yet, they also contextualised service delivery barriers reported in the questionnaire, including the burden of cost and challenges integrating PrEP visits into their private and professional lives. Although 63.8% (n = 208/326) of baseline respondents preferred attending an HIV clinic for PrEP follow-up, 51.9% (n = 108/208) of participants in the follow-up questionnaire reported to be willing to have their FP involved in PrEP care. Participants reporting trust in FPs' PrEP and sexual health expertise, or who didn't feel judged by their FP, were more likely to be willing to involve them in PrEP care. Therefore, we recommend a differentiated PrEP service delivery approach, including involving FPs, to make PrEP care more client-centred.

Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling.

Phospholipase A/acyltransferase 3 (PLAAT3) is a phospholipid-modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). It is a potential drug target for metabolic syndrome, as Plaat3 deficiency in mice protects against diet-induced obesity. We identified seven patients from four unrelated consanguineous families, with homozygous loss-of-function variants in PLAAT3, who presented with a lipodystrophy syndrome with loss of fat varying from partial to generalized and associated with metabolic complications, as well as variable neurological features including demyelinating neuropathy and intellectual disability. Multi-omics analysis of mouse Plaat3-/- and patient-derived WAT showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in the signaling of peroxisome proliferator-activated receptor gamma (PPARγ), the master regulator of adipocyte differentiation. Accordingly, CRISPR-Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARγ. These findings establish PLAAT3 deficiency as a hereditary lipodystrophy syndrome with neurological manifestations, caused by a PPARγ-dependent defect in WAT differentiation and function.

Using serial cross-sectional surveys to create a retrospective nested cohort to determine HIV incidence from 20 US cities.

OBJECTIVE: To estimate HIV incidence using successive cross-sectional surveys by creating retrospective nested cohorts among MSM, people who inject drugs (PWID), and heterosexually active persons (HET). DESIGN: Cohorts were created among participants who had at least one repeat observation across four surveillance cycles from National HIV Behavioral Surveillance in 20 US cities. METHODS: Repeat participants were identified using a combination of date of birth, race/ethnicity, metropolitan statistical area, and gender. The analysis was limited to participants who tested negative for HIV at baseline and were assumed to be at risk between cycles. We calculated person-years at risk from the individual time between cycles and used the total number of seroconversions to estimate incidence and a Poisson distribution to approximate variance. Rate ratios were calculated using age, gender, race/ethnicity, and region. RESULTS: From 2008 to 2019, successive surveys recaptured nested cohorts of 1747 MSM, 3708 PWID, and 1396 HET. We observed an incidence rate of 2.5 per 100 person-years [95% confidence interval (CI) 2.1-2.8) among MSM; 0.6 per 100 person-years (95% CI 0.5-0.7) among PWID; and 0.3 per 100 person-years (95% CI 0.1-0.4) among HET. HIV incidence was higher among younger MSM, black MSM (compared with white MSM), and PWID residing in the South and territories (compared with the Midwest). CONCLUSION: These estimates are consistent with previously published incidence estimates from prospective cohort studies among these populations. Using repeat cross-sectional surveys to simulate a cohort, may serve as another strategy in estimating HIV incidence.

No Significant Association between 25-OH Vitamin D Status and SARS-CoV-2 Antibody Response after COVID-19 Vaccination in Nursing Home Residents and Staff.

Vitamin D is an essential nutrient for various physiological functions, including immunity. While it has been suggested that higher vitamin D levels/supplementation are associated with a better immune response to COVID-19 vaccination, conflicting data exist. Therefore, we aimed to investigate the association between vitamin D (25-hydroxyvitamin D) deficiency/supplementation, and SARS-CoV-2 antibody responses post-vaccination in nursing home residents (NHRs) and staff (NHS). Blood samples were collected from 115 NHRs and 254 NHS at baseline and 14 days after primary course BNT162b2 vaccination. Baseline samples were assessed for serum 25-hydroxyvitamin D levels, while follow-up samples were analyzed for spike protein S1 receptor-binding domain (S1RBD) IgG antibody concentrations and 50% pseudoneutralization titers. Vitamin D supplementation status was obtained from NHRs medical records. We compared immune responses between (severe) vitamin D-deficient and -sufficient NHRs/NHS and between supplemented and non-supplemented NHRs, stratified for history of SARS-CoV-2 infection and participant type. No significant differences in either binding or neutralizing COVID-19 vaccine antibody response were found between groups. The prevalence of vitamin D deficiency (<20 ng/mL) was 45% (95% CI: 36-54%) among NHRs and 60% (95% CI: 54-66%) among NHS. Although we showed that vitamin D status may not be related to a better COVID-19 vaccine antibody response, addressing the high prevalence of vitamin D deficiency in the nursing home population remains important.

Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study.

OBJECTIVES: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age. METHODS: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs. RESULTS: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were ≥65 years, and 54.9% were female. CDI was associated with a 3- to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities. DISCUSSION: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups.

Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study.

INTRODUCTION: Antibiotics represent the most common type of medication used during pregnancy and infancy. Antibiotics have been proposed as a possible factor in changes in microbiota composition, which may play a role in the aetiology of autism and attention deficit/hyperactivity disorder (ADHD). Our aim was to investigate the association between maternal and early-life antibiotic use and autism and ADHD in childhood. METHODS: This Swedish nation-wide population-based cohort study included all first live singleton births (N = 483,459) between January 2006 and December 2016. The association of dispensed antibiotics with autism and ADHD in children aged ≤ 11 years was estimated by applying multivariable logistic regression and generalised estimating equations models. RESULTS: Of the mothers, 25.9% (n = 125,106) were dispensed ≥1 antibiotic during the exposure period (from 3 months pre-conception to delivery), and 41.6% (n = 201,040) of the children received ≥ 1 antibiotic in early life (aged ≤ 2 years). Penicillin was the most prescribed antibiotic class (17.9% of mothers, 38.2% of children). Maternal antibiotic use was associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.09-1.23] and ADHD (OR = 1.29, 95% CI 1.21-1.36) in childhood. Early-life exposure to antibiotics showed an even stronger association [autism (OR = 1.46, 95% CI 1.38-1.55); ADHD (OR = 1.90, 95% CI 1.80-2.00)]. Both maternal and childhood-exposure sub-analyses suggested a dose-response relationship. CONCLUSION: Maternal and early-life antibiotic use was associated with an increased risk of autism and ADHD in childhood. However, differences were noted by exposure period and antibiotic classes.

Antibiotics are commonly prescribed to pregnant women, infants, and toddlers. Antibiotic use during pregnancy may alter the maternal microbiota, which can influence the microbial colonisation of the gastrointestinal system of the foetus. It has been claimed that antibiotic use during pregnancy may have an effect on the gut-brain axis and, as a result, neurodevelopment. Neurodevelopmental disorder (NDD) is a category of illnesses characterised by functional impairments that manifest early in development. The most frequent NDDs are autism and attention-deficit/hyperactivity disorder (ADHD). In this large Swedish nation-wide study, we assessed whether antibiotic use during pregnancy and/or early in life affects the risk of developing autism and ADHD. The study found that both maternal antibiotic usage, as well as early childhood antibiotic use, were associated with an increased risk of autism and ADHD in children. These associations were altered by the quantity, type, and timing of antibiotic exposure.

ERN ReCONNET points to consider for treating patients living with autoimmune rheumatic diseases with antiviral therapies and anti-SARS-CoV-2 antibody products.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

A machine-learning based model for automated recommendation of individualized treatment of rifampicin-resistant tuberculosis.

Background: Rifampicin resistant tuberculosis remains a global health problem with almost half a million new cases annually. In high-income countries patients empirically start a standardized treatment regimen, followed by an individualized regimen guided by drug susceptibility test (DST) results. In most settings, DST information is not available or is limited to isoniazid and fluoroquinolones. Whole genome sequencing could more accurately guide individualized treatment as the full drug resistance profile is obtained with a single test. Whole genome sequencing has not reached its full potential for patient care, in part due to the complexity of translating a resistance profile into the most effective individualized regimen. Methods: We developed a treatment recommender clinical decision support system (CDSS) and an accompanying web application for user-friendly recommendation of the optimal individualized treatment regimen to a clinician. Results: Following expert stakeholder meetings and literature review, nine drug features and 14 treatment regimen features were identified and quantified. Using machine learning, a model was developed to predict the optimal treatment regimen based on a training set of 3895 treatment regimen-expert feedback pairs. The acceptability of the treatment recommender CDSS was assessed as part of a clinical trial and in a routine care setting. Within the clinical trial setting, all patients received the CDSS recommended treatment. In 8 of 20 cases, the initial recommendation was recomputed because of stock out, clinical contra-indication or toxicity. In routine care setting, physicians rejected the treatment recommendation in 7 out of 15 cases because it deviated from the national TB treatment guidelines. A survey indicated that the treatment recommender CDSS is easy to use and useful in clinical practice but requires digital infrastructure support and training. Conclusions: Our findings suggest that global implementation of the novel treatment recommender CDSS holds the potential to improve treatment outcomes of rifampicin resistant tuberculosis.