Psychosocial and sexual health among men with and without HIV who have sex with men: A cross-sectional nationwide study in Denmark.

OBJECTIVES: The HIV/AIDS epidemic has disproportionately affected men who have sex with men (MSM) since its onset. Despite important medical advancements in treatment, the enduring effects of living with HIV continue to adversely impact the health and well-being of this population. This cross-sectional nationwide study examined psychosocial and sexual health among MSM in Denmark, comparing those living with and without HIV. METHODS: Data from MSM living with HIV were collected from the SHARE study, a Danish nationwide survey that investigated psychosocial, sexual and reproductive health among people with HIV, and compared with data from MSM without HIV, retrieved from the nationally representative cohort study, Project SEXUS. Associations between HIV status and psychosocial and sexual health outcomes were examined using logistic regression models while controlling for potentially confounding variables. RESULTS: Among 369 MSM with HIV and 1002 MSM without HIV, logistic regression analyses revealed that living with HIV was significantly associated with having current symptoms of anxiety and depression and greater dissatisfaction with one's body. Additionally, MSM with HIV significantly more often than MSM without HIV reported low sexual desire, sexual inactivity, a lack of sexual needs in the last year and erectile dysfunction. Having received payment for sex was more frequently reported by MSM with HIV, as was sexualised drug use, including chemsex drugs. CONCLUSION: Compared with MSM without HIV, MSM with HIV in Denmark report a higher burden of mental health and sex life challenges.

Biomarkers for identification of high-risk coronary artery plaques in patients with suspected coronary artery disease.

BACKGROUND: Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether increased levels of Troponin I (TnI) and C-reactive protein (CRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) is not well described. We assessed the association between 1) TnI and 2) CRP with quantified coronary plaque burden, luminal diameter stenosis, and HRP in patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred for coronary computed tomography angiography (CCTA). METHODS: The CCTA from 1615 patients were analyzed using a semiautomatic software for coronary artery plaque characterization. Patients with high TnI (>6 â€‹ng/L) and high CRP (>2 â€‹mg/L) were identified. Associations of TnI and CRP with plaque burden, stenosis (≥50% luminal diameter stenosis on CCTA), and HRP were investigated. RESULTS: TnI and CRP were both positively correlated with total plaque burden (TnI rs â€‹= â€‹0.14, p â€‹< â€‹0.001; CRP rs â€‹= â€‹0.08, p â€‹< â€‹0.001). In multivariate logistic regression analyses, high TnI was associated with stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p â€‹= â€‹0.034), the presence of HRP (OR 1.79, 95% CI: 1.17-2.74, p â€‹= â€‹0.008), and the subtypes of HRP; low attenuation plaque (OR 1.93, 95% CI: 1.24-3.00, p â€‹= â€‹0.003), and positive remodeling (OR 1.51, 95% CI: 1.07-2.13, p â€‹= â€‹0.018). For CRP, only stenosis and napkin ring sign correlated significantly. CONCLUSION: In patients with suspected CAD, TnI and CRP are associated with HRP features. These findings may suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and affect patient management. GOV IDENTIFIER: NCT02264717.

Perception and Emotional Experiences of Infant Feeding Among Women Living With HIV in a High-Income Setting: A Longitudinal Mixed Methods Study.

BACKGROUND: The recommendation of breastfeeding avoidance for women living with HIV in high-income settings may be influenced by cultural beliefs and come at an emotional cost. This multicenter, longitudinal, convergent mixed methods study aimed to compare differences in attitudes, concerns, and experiences surrounding breastfeeding in women living with HIV of Nordic and non-Nordic origin. SETTING: High-income setting. METHODS: Pregnant women living with HIV in the Nordic countries Denmark, Finland, and Sweden were recruited in 2019-2020. Quantitative data on attitudes surrounding infant feeding were assessed using the Positive Attitudes Concerning Infant Feeding questionnaire completed in the third trimester (T1), and 3 (T2) and 6 (T3) months postpartum. Women who completed the survey were also invited to participate in semistructured interviews at T1 and T3. The findings from the quantitative survey and qualitative interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the data sets and to draw metainferences. RESULTS: In total, 44 women completed the survey, of whom 31 also participated in qualitative interviews. The merged analyses identified three overarching domains representing commonalities across the quantitative and qualitative data: emotional impact, justifying not breastfeeding, and coping strategies. Not being able to breastfeed was emotionally challenging. Cultural expectations influenced the women's experiences and the strategies they used to justify their infant feeding choice. CONCLUSIONS: For women living with HIV in Nordic countries not breastfeeding was a complex, multilayered process substantially influenced by social and cultural expectations.

Psychiatric Diagnoses Among HIV-Exposed and HIV-Unexposed Uninfected Children: A Danish Nationwide Cohort Study.

This nationwide registry-based cohort study aimed to compare the risk of psychiatric diagnoses among HIV-exposed uninfected (HEU) children with a matched comparison group of HIV-unexposed uninfected (HUU) children, born in Denmark. We hypothesized that HEU children had an increased risk of psychiatric diagnoses and that this increased risk may differ by sex and age. All HEU children born in Denmark between year 2000 and 2020 were included. Each HEU child was matched by year of birth, maternal age at birth, and maternal immigration status to 10 HUU children. The primary outcome was risk of any psychiatric diagnosis (International Classification of Diseases, 10th Revision F00-F99). Incidence rate ratios (IRRs) were estimated using Poisson regression. Analyses stratifying by sex and age were also conducted. In total, 550 HEU children and 5500 HUU children were included. HEU children had an increased risk of any psychiatric disorder [IRR 1.45; 95% confidence interval (CI): 1.04-2.04] in the unadjusted analysis, but in the adjusted analysis, the risk was only significant for children aged 6-11 years [adjusted incidence rate ratio (aIRR) 1.93; 95% CI: 1.14-3.28]. Stratifying by sex, girls aged 6-11 years had an increased risk of any psychiatric disorder (aIRR 3.04; 95% CI: 1.27-7.28), while boys had an increased risk at age 12-20 years (aIRR 2.47; 95% CI: 1.18-5.17). In conclusion, HEU girls aged 6-11 years and HEU boys aged 12-20 years had an increased risk of any psychiatric disorder compared with HUU girls and boys, respectively. These findings highlight the importance of addressing the mental health needs of HEU children/adolescents.

Multiplex immunofluorescence staining of coverslip-mounted paraffin-embedded tissue sections.

Animal and human tissues are used extensively in physiological and pathophysiological research. Due to both ethical considerations and low availability, it is essential to maximize the use of these tissues. Therefore, the aim was to develop a new method allowing for multiplex immunofluorescence (IF) staining of kidney sections in order to reuse the same tissue section multiple times. The paraffin-embedded kidney sections were placed onto coated coverslips and multiplex IF staining was performed. Five rounds of staining were performed where each round consisted of indirect antibody labelling, imaging on a widefield epifluorescence microscope, removal of the antibodies using a stripping buffer, and then re-staining. In the final round, the tissue was stained with hematoxylin/eosin. Using this method, tubular segments in the nephron, blood vessels, and interstitial cells were labeled. Furthermore, by placing the tissue on coverslips, confocal-like resolution was obtained using a conventional widefield epifluorescence microscope and a 60x oil objective. Thus, using standard reagents and equipment, paraffin-embedded tissue was used for multiplex IF staining with increased Z-resolution. In summary, this method offers time-saving multiplex IF staining and allows for the retrieval of both quantitative and spatial expressional information of multiple proteins and subsequently for an assessment of the tissue morphology. Due to the simplicity and integrated effectivity of this multiplex IF protocol, it holds the potential to supplement standard IF staining protocols and maximize use of tissue.

Psychosocial, sexual, reproductive and menopausal health in women with and without HIV in a high-income setting.

OBJECTIVES: To investigate psychosocial, sexual, reproductive and menopausal health in women with HIV (WWH) compared to women without HIV (WWOH) in Denmark. DESIGN: A nationwide cross-sectional study. METHODS: Data was retrieved from the SHARE study , a Danish nationwide cross-sectional survey examining psychosocial, sexual and reproductive health in people with HIV. Data from WWH, collected in 2021-2022, was matched 1:10 on age to a comparison group of WWOH from the nationally representative cohort study Project SEXUS . Associations between HIV status and psychosocial and sexual health outcomes were assessed by adjusted odds ratios (aOR) with 95% confidence intervals (95% CIs) obtained in logistic regression analyses controlling for potential confounding variables. The severity of menopausal symptoms in WWH was compared to published reference norms. RESULTS: Among 144 WWH and 1440 WWOH, recurrent loneliness was significantly more common among WWH (aOR 2.22 [95% CI: 1.25-3.96]), and WWH had significantly fewer children and close friends (aOR 0.52 [95% CI: 0.28-0.96] for 3-9 vs. 0-2 close friends). Symptoms of anxiety and depression did not differ between groups. Lack of sexual desire (aOR 2.90 [95% CI: 1.29-6.50]), low FSFI-6 score indicating sexual dysfunction (aOR 3.40 [95% CI: 1.33-8.69]), lubrication dysfunction (aOR 8.24 [95% CI: 2.83-24.00]) and genital pain dysfunction (aOR 5.13 [95% CI: 1.26-20.86]) were significantly more common in WWH compared to WWOH. No differences were seen in menopausal characteristics. CONCLUSIONS: WWH in Denmark have fewer children and close friends, and more often report recurrent loneliness, lacking sexual desire and sexual dysfunction compared to WWOH. No differences were evident in menopausal characteristics.

Use of antiretroviral therapy in pregnancy and association with birth outcome among women living with HIV in Denmark: A nationwide, population-based cohort study.

OBJECTIVE: To describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes. METHODS: A population-based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes. RESULTS: In total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased odds of preterm birth, small for gestational age or low birth weight. First-trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23-11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13-9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes. CONCLUSIONS: Pregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and NRTI + PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors.

Psychosocial health in pregnancy and postpartum among women living with - and without HIV and non-pregnant women living with HIV living in the Nordic countries - Results from a longitudinal survey study.

BACKGROUND: The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. METHODS: In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019-2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. RESULTS: A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. CONCLUSIONS: A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions.

The experience of pregnancy among women living with HIV in Nordic countries: A qualitative narrative enquiry.

OBJECTIVE: The success of antiretroviral therapy has resulted in the normalization of pregnancy among women living with HIV and a very low risk of perinatal transmission of HIV. Despite these advances, women living with HIV still face complex medical and psychosocial issues during pregnancy. The purpose of this study is to describe experiences of pregnancy and the relevance of social support among women living with HIV in Nordic countries. METHODS: This qualitative study examined data from pregnant women living with HIV from sites in Denmark, Sweden and Finland from 2019 to 2020. Data were collected in the third trimester via individual interviews using a hybrid, narrative/semistructured format. The transcribed interviews were analyzed using narrative thematic analysis. RESULTS: In total, 31 women living with HIV were enrolled, of whom 61% originated from an African country and 29% from a Nordic country. The analysis generated four primary narrative themes: just a normal pregnancy, unique considerations and concerns, interactions with healthcare, and social support. Women living with HIV have a strong desire to have normal pregnancies and to be treated like any other pregnant woman. However, this normality is fragile, and being pregnant and living with HIV does come with unique considerations and concerns, such as fear of transmission, antiretroviral therapy, and the need for specialized care, which are fundamental to the women's experiences. Interactions with healthcare providers and social support influence their experiences in both positive and negative ways. CONCLUSION: The findings emphasize a sense of normality in pregnancy among women living with HIV. However, pregnancy does come with unique considerations and concerns, which highly influence the women's experience of pregnancy. Healthcare providers should focus on person-centered care, ensuring continuity and that women living with HIV do not feel discriminated against throughout their pregnancy.

Incidence of Chronic Obstructive Pulmonary Disease in People With Human Immunodeficiency Virus and Their Parents and Siblings in Denmark.

BACKGROUND: People with human immunodeficiency virus (PWH) may be at increased risk of several respiratory syndromes including chronic obstructive pulmonary disease (COPD). In matched cohort studies, we examined risk factors for COPD in PWH and their parents and siblings compared with population controls. METHODS: Using data from national registries, competing risk regression models were constructed and used to calculate adjusted hazard ratios (aHRs) for COPD. We evaluated the effect of human immunodeficiency virus characteristics, smoking, and educational attainment on COPD incidence in PWH. RESULTS: A total of 226 PWH and 1029 population controls were diagnosed with COPD during 63 661 and 562 171 person-years of follow-up. PWH had increased risk of being diagnosed with COPD compared to controls (aHR, 2.02 [95% confidence interval, 1.75-2.33]). Parents and siblings of PWH were also more likely to be diagnosed with COPD compared to controls. CD4+ T-cell counts were not associated with COPD, but unsuppressed viral replication, smoking status, and educational attainment were associated with COPD in PWH. No COPD diagnoses were registered in PWH with high educational attainment and absence of smoking. CONCLUSIONS: PWH have an increased risk of being diagnosed with COPD, as have their parents and siblings. This seems to be driven primarily by smoking and low socioeconomic status.

The Use and Efficacy of Biological Therapies for Inflammatory Bowel Disease in a Danish Tertiary Centre 2010-2020.

Background: Patients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center. Methods: We included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre. Their medical records were reviewed. Results: The population consisted of 327 Crohn's disease (CD) patients, 291 ulcerative colitis (UC) patients, and 3 patients with IBD unclassified (IBDU). The median follow-up was 3 years (interquartile range = 2-5) after initiating therapy. The annual number of patients initiating biological therapy rose from 29 (2010) to 85 (2019). Most patients (457, 73.6%) received 1 biological drug; 164 (26.4%) patients received 2 or more biologicals. Primary lack of response was observed in 36.4% (106/291) and 17.4% (57/327) of UC and CD patients; loss of response was observed in 27.1% (79/291) and 31.5% (103/327) of UC and CD patients, respectively. The 5-year surgery rates were 26.6% and 20.4% in UC and CD patients, respectively. Multivariate Cox regression showed that treatment with thiopurine reduced the likelihood of needing to switch biological therapy, requiring surgery or corticosteroids in UC patients (HR: 0.745, 95% CI: 0.559-0.993), but not in CD patients (HR: 0.996, 95% CI: 0.736-1.349). Conclusions: The annual number of IBD patients initiated on biological therapy increased considerably between 2010 and 2020. One-quarter of these patients required surgery after 5 years. Our findings suggest a beneficial effect of concurrent thiopurines for UC patients receiving biologicals, but this was not found for CD patients. This effect in UC patients was not observed when we included patients initiating thiopurines up to 6 months after the introduction of biological therapy.

Predicting in vivo performance of fenofibrate amorphous solid dispersions using in vitro non-sink dissolution and dissolution permeation setup.

Amorphous solid dispersion (ASD) is emerging as a useful formulation strategy to increase the bioavailability of active pharmaceutical ingredients with poor solubility. In vitro dissolution testing under non-sink conditions has often been used to evaluate the ability of ASDs to generate and maintain supersaturation to predict the in vivo performance. However, such a single compartment dissolution setup can fail to predict the oral bioavailability, due to an interdependence between precipitation and permeation. Hence, the use of two compartment dissolution-permeation setups is emerging. In this study, three ASDs containing fenofibrate as model drug substance were developed using Soluplus®, and Hypromellose Acetate Succinate in two different grades (high and low), respectively. The aim was to compare the use of a small-scale in vitro non-sink dissolution setup and a small-scale in vitro dissolution-permeation setup to predict the in vivo oral exposure of the ASDs in rats. The maximum concentration (Cmax) and area under curve (AUC) obtained in the in vitro studies were used to predict the in vivo rank order of the formulations. The results showed that the two in vitro studies resulted in the same rank order based on both Cmax and AUC. Interestingly, Cmax resulted in a better in vitro/in vivo correlation than the in vitro AUC, and based on the in vitro Cmax, the in vivo rank order was predicted.

Characterizing Cutaneous Drug Delivery Using Open-Flow Microperfusion and Mass Spectrometry Imaging.

Traditionally, cutaneous drug delivery is studied by skin accumulation or skin permeation, while alternative techniques may enable the interactions between the drug and the skin to be studied in more detail. Time-resolved skin profiling for pharmacokinetic monitoring of two Janus Kinase (JAK) inhibitors, tofacitinib and LEO 37319A, was performed using dermal open-flow microperfusion (dOFM) for sampling of perfusate in an ex vivo and in vivo setup in pig skin. Additionally, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) was performed to investigate depth-resolved skin distributions at defined time points ex vivo in human skin. By dOFM, higher skin concentrations were observed for tofacitinib compared to LEO 37319A, which was supported by the lower molecular weight, higher solubility, lipophilicity, and degree of protein binding. Using MALDI-MSI, the two compounds were observed to show different skin distributions, which was interpreted to be caused by the difference in the ability of the two molecules to interact with the skin compartments. In conclusion, the techniques assessed time- and depth-resolved skin concentrations and were able to show differences in the pharmacokinetic profiles of two JAK inhibitors. Thus, evidence shows that the two techniques can be used as complementary methods to support decision making in drug development.

The Danish HIV Birth Cohort (DHBC) - a nationwide, prospective cohort.

PURPOSE: The purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark and their children, in the era of antiretroviral therapy and other interventions for treatment and prophylaxis. PARTICIPANTS: All WLWH giving birth to one or more children in Denmark after 31 December 1999 are included, with consecutive ongoing enrolment, if they are living with HIV and pregnant, or if they are diagnosed with HIV in relation to pregnancy, delivery or shortly after delivery. FINDINGS TO DATE: DHBC has been used to describe trends in the management of pregnancies in WLWH and their outcomes on a nationwide basis, mode of delivery and predictors of emergency caesarean section as well as risk factors during pregnancy in WLWH for birth-related complications compared with women from the general population (WGP). We have found that HIV-exposed, but uninfected (HEU) children born to WLWH had a lower median birth weight and gestational age and were at higher risk of intrauterine growth retardation than children born to WGP. We have investigated risk of in-hospital admission and use of antibiotics during the first 4 years of life among HEU children and showed that HEU children had an increased risk of overall hospital admission compared with a matched control group of unexposed children.Further, we compared anthropometric outcomes in children with a matched control group of children not exposed to HIV. FUTURE PLANS: To continuously investigate the significance of HIV infection and antiretroviral therapy in pregnancy and after delivery in WLWH in Denmark and their HEU children and compare these findings with children born to WGP.

Short and long-term effectiveness and safety of vedolizumab in treatment-refractory patients with ulcerative colitis and Crohn's disease - a real-world two-center cohort study.

OBJECTIVES: Real-world data about sustained clinical remission (SCR) and treatment optimization with vedolizumab for ulcerative colitis (UC) and Crohn's disease (CD) are scarce. We aimed to investigate the short and long-term effectiveness and safety of vedolizumab in a real-world cohort in Denmark. METHODS: A retrospective two-center cohort study was conducted between November 2014 and November 2019 with the primary outcomes of clinical remission (CR) at weeks 14, 30, 52 and 104 and SCR defined as CR at week 14 through week 52. RESULTS: The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. Rates of CR at weeks 14, 30, 52 and 104 were 36.6, 35.1, 34.0 and 27.8%, respectively, in UC, and 31.7, 30.1, 26.5 and 22.4% in CD. SCR was achieved in 19.6 and 20.0%, respectively. In UC and CD, optional dosing of vedolizumab at week 10 (odds ratio [OR] = 0.23 (95% confidence interval [CI], 0.03-1.17), and OR = 0.68 (95% CI, 0.22-2.04)), as well as increase of frequency (OR = .26 (95% CI, 0.01-2.86), and OR = 0.19 (95% CI, 0.01-1.45)), were not associated with CR at week 52. Furthermore, combination treatment with azathioprine was not associated with long-term outcomes. However, dose intensification of vedolizumab successfully restored CR in 65.2 and 57.1% of patients with UC and CD experiencing loss of response. CONCLUSIONS: Vedolizumab is effective in achieving and restoring short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10, and simultaneous treatment with azathioprine, did not improve long-term outcomes.

Prevalence and association with birth outcomes of low vitamin D levels among pregnant women living with HIV.

OBJECTIVES: To evaluate the prevalence of low vitamin D levels among well treated pregnant women living with HIV (WLWH) on combination antiretroviral therapy in Denmark, to identify risk factors of low vitamin D levels, and to assess the association between vitamin D status and birth outcomes. DESIGN: Nationwide cohort study. METHODS: All WLWH in Denmark giving birth from 2000 to 2018 with a vitamin D measurement during pregnancy were identified. Risk factors for low vitamin D (deficiency or insufficiency) were assessed using log-binomial regression models, both univariate and adjusted for maternal and HIV factors. The association between vitamin D status and birth outcomes was assessed using linear regression models for continuous outcomes and log-binomial models for binary outcomes. RESULTS: Among 208 WLWH, the prevalence of vitamin D deficiency was 13%, insufficiency 34%, and sufficiency 53%. Being of African origin (RR 2.68, P = 0.01), Asian origin (RR 3.38, P = < 0.01), or having HIV RNA levels more than 50 copies/ml (RR 1.43, P = 0.04) was associated with an increased risk of low vitamin D level. WLWH with vitamin D deficiency had an increased risk of preterm birth (RR 2.66, P = 0.03) and giving birth to small for gestational age (SGA) children (RR 6.83, P = 0.02) compared with WLWH with sufficient vitamin D level. CONCLUSION: Low vitamin D level was prevalent among well treated pregnant WLWH in Denmark, especially among women of African or Asian origin, and women with detectable viral loads. Vitamin D deficiency was associated with an increased risk of preterm birth and SGA.

Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin.

In skin penetration studies, HPLC-MS/MS analysis on extracts of heat-separated epidermis and dermis provides an estimate of the amount of drug penetrated. In this study, MALDI-MSI enabled qualitative skin distribution analysis of endogenous molecules and the drug molecule, tofacitinib and quantitative analysis of the amount of tofacitinib in the epidermis. The delivery of tofacitinib to the skin was investigated in a Franz diffusion cell using three different formulations (two oil-in-water creams, C1 and C2 and an aqueous gel). Further, in vitro release testing (IVRT) was performed and resulted in the fastest release of tofacitinib from the aqueous gel and the lowest from C2. In the ex vivo skin penetration and permeation study, C1 showed the largest skin retention of tofacitinib, whereas, lower retention and higher permeation were observed for the gel and C2. The quantitative MALDI-MSI analysis showed that the content of tofacitinib in the epidermis for the C1 treated samples was comparable to HPLC-MS/MS analysis, whereas, the samples treated with C2 and the aqueous gel were below LOQ. The study demonstrates that MALDI-MSI can be used for the quantitative determination of drug penetration in epidermis, as well as, to provide valuable information on qualitative skin distribution of tofacitinib.

MALDI mass spectrometry imaging as a complementary analytical method for improved skin distribution analysis of drug molecule and excipients.

In cutaneous drug delivery, it is widely accepted that the choice of excipients affects the delivery of a drug molecule to the skin. MALDI mass spectrometry imaging (MALDI-MSI) is an imaging technique which enables the simultaneous detection of multiple compounds. MALDI-MSI was applied to study the penetration of tofacitinib and excipients in porcine skin from two formulations with sodium lauryl sulphate (SLS) and dexpanthenol (DXP) using Franz diffusion cells. Further, the receptor media was collected for analysis of the permeated amounts of tofacitinib and excipients. The MALDI images showed DXP to be co-localized with tofacitinib in the epidermal and deep dermal region while SLS was distributed in the entire skin compartment. The permeation of tofacitinib for the two formulations was similar after 24 h, whereas, the percentage of permeated DXP was higher than for SLS. This study provided an overview of the skin penetration and permeation of drug molecule and excipients. MALDI-MSI showed differences in the DXP and SLS distribution. This indicates that the excipients interact with the skin through different mechanisms. Compound-specific imaging methods such as MALDI-MSI are potential tools to increase the understanding of the complex interplay between skin, excipients and the drug molecule for optimized cutaneous drug delivery.

Children Exposed or Unexposed to Human Immunodeficiency Virus: Weight, Height, and Body Mass Index During the First 5 Years of Life-A Danish Nationwide Cohort.

BACKGROUND: Exposures to human immunodeficiency (HIV) and antiretroviral therapy in utero may have adverse effects on infant growth. Among children born in Denmark and aged 0-5 years, we aimed to compare anthropometric outcomes in HIV-exposed but uninfected (HEU) children with those in children not exposed to HIV. METHODS: In a nationwide register-based study we included all singleton HEU children born in Denmark in 2000-2016. HEU children were individually matched by child sex, parity, and maternal place of birth to 5 singleton controls born to mothers without HIV. Weight-for-age z (WAZ) scores, length-for-age z (LAZ) scores, and weight-for-length or body mass index-for-age z scores were generated according to the World Health Organization standards and the Fenton growth chart for premature infants. Differences in mean z scores were analyzed using linear mixed models, both univariate and adjusted for social and maternal factors. RESULTS: In total, 485 HEU children and 2495 HIV-unexposed controls were included. Compared with controls, HEU children were smaller at birth, with an adjusted difference in mean WAZ and LAZ scores of -0.29 (95% confidence interval [CI], -.46 to -.12) and -0.51 (95% CI, -.71 to -.31), respectively (both P ≤ .001). Over time, there was a trend toward increasing WAZ and LAZ scores in HEU children, and there was no significant difference in adjusted WAZ scores after age 14 days (-0.13 [95% CI, -.27 to .01]; P = .07) and LAZ scores after age 6 months (-0.15 [95% CI, -.32 to .02]; P = .08). CONCLUSION: Compared with a matched control group, HEU children were smaller at birth, but this difference decreased with time and is not considered to have a negative effect on the health and well-being of HEU children during early childhood.