Background: Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin disorders that causes great disease burdens world-wide. The demographics and clinical characteristics of AD are different between countries, regions, and age groups yet these differences were not well characterized in China. To get well guidance for AD clinicians, we described the demographics, clinical characteristics, comorbidities, patient-identified aggravating factors and treatment of AD in all-age patients in China. Methods: This study included Chinese individuals diagnosed with AD by accredited clinicians in the department of dermatology of 205 hospitals from 31/34 provincial administrative divisions across China during August, 2021 to September, 2022. All included patients completed dermatologist-lead interviews regarding their general medical history, comorbidities, AD-related aggravating factors and medications. Two-level mixed ordered logistic regression was used to evaluate factors for aggravation of the disease. Results: Overall, 16838 respondents were included in the final analysis with a mean age of 30.94 years (standard deviation, ± 24.08 years). The proportion of patients with severe AD was the highest in patients with onset of AD at ≥60 years old (26.73%). Allergic rhinitis and hypertension were the most common atopic and non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergy and diabetes. There was a high proportion of severe AD in patients who had aggravating factors such as seafood, lamb and beef, chili peppers, alcohol, seasonal changes, and psychological factors. Cross-sectional survey revealed unmet needs of severe AD in treatment strategy, in lack of immunosuppressants’ and biological agents’ application. Conclusion: Treatment of comorbidities and control of aggravating factors significantly contribute to AD management. Improving systemic immunotherapy could reduce the incidence of severe AD.

The mortality rate due to COVID-19 in immunocompromised cases is considerably high. Monoclonal antibody (mAb) therapy is essential in managing SARS-CoV-2 infection, especially in immunocompromised cases. The mutation in the spike protein RBD region of the SARS-CoV-2 leads to the substitution of amino acids resulting in an altered ACE2 binding affinity. The mAbs must be tested in-vitro using standard neutralisation assays designed against emerging SARS-CoV-2 variants to estimate the mAb therapy efficacy. Based on already available data on the mAb efficacy for known SARS-CoV-2 variants, it is plausible to draw inferences for other closely related SARS-CoV-2 variants in circulation owing to the similar spike protein RBD amino acid sequence. In this article, we have attempted to analyse the data of mAb efficacy tested against SARS-CoV-2 variants and extrapolate on other emerging omicron sublineages like BA.2.75, BF.7 and BQ.1.

Background: Allergic rhinoconjunctivitis (ARC), asthma and eczema carry a substantial morbidity. These conditions often co-exist within the same individual and prevalence can differ based on age, ethnicity and gender. Objectives: Using a UK primary care database, we estimated the trends in prevalence over the last decade for ARC, asthma and eczema and associated risk factors. Methods: Longitudinal cohort analysis of the health improvement (THIN) database between 1 st Jan 2010 and 1 st Jan 2019. Logistic regression analysis was used to explore risk factors for diagnosis of these conditions. Results: An average of 4.17 million records per year were analysed, 19.4% were children and 49.75% were male. There was an increase in prevalence of ARC, asthma and eczema amongst adults during the study period, whereas ARC and asthma prevalence amongst children has fallen. By 2018, 1:8 adults and 1:14 children had ARC; asthma was diagnosed in 1:7 adults and 1:10 children whereas eczema was diagnosed in 1:6 adults and 1:4 children respectively. Ethnicity and gender modify the risk of being diagnosed with these conditions. Having other allergies substantially increases the odds of having asthma, eczema and ARC. Conclusion: The population burden of ARC, asthma and eczema in the UK is substantial. These conditions are often associated with other allergies and can, therefore, be complex to manage. These data support calls for improvement of pathways of care for allergy patients in the UK.

Introduction Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution’s harmful effects. Methods Patient data were collected from a single center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM 2.5) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO 2), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. Results From 2010-2018, there were 17 731 ED visits by 1740 children with SCD (64.8% HbSS/HbSβ 0). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Three-day (lags 0-2) rolling mean PM 2.5 and CO levels were associated with daily ED visits among those with SCD (PM 2.5 incident rate ratio (IRR) 1.051 (95% CI 1.010-1.094) per 9.4 µg/m 3 increase; CO 1.088 (1.045-1.132) per 0.5 ppm). NO 2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. Conclusions Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.

Allergic diseases were recently reported related to both SARS-CoV-2 infection and severe COVID-19 through observational studies. However, their causal relationship remains unclear. Herein, we performed univariate and multivariate Mendelian randomization (MR) studies to investigate the causal association between various allergic diseases and COVID-19. Genome-wide association studies (GWAS) summaries were used in this study, with 360838 participants in the allergic disease database, 455449 in asthma, 217914 in allergic rhinitis (AR), and 205764 in atopic dermatitis (AD). In univariate MR analysis, the allergic disease was not causally in connection with SARS‐CoV‐2 infection but have a causal protective effect on severe COVID-19. In contrast, no significant causal effect was found of SARS-CoV-2 infection/severe COVID-19 on the allergic disease. AD, mixed asthma, and childhood asthma were causal protective factors for severe COVID-19. Multivariate MR analysis further revealed the dominant role of asthma in allergic diseases and the dominance of childhood asthma in asthma subtypes. In summary, this study, based on the population genetic variation model, pointed out the protective effect of allergic diseases against severe COVID-19, which may provide some inspiration for further exploration of the pathophysiological mechanisms of COVID-19.

Rotavirus A (RVA) is an important cause of acute gastroenteritis (AGE) in children. This study aims to investigate the molecular epidemiology of RVA children hospitalized with AGE in Chiang Rai, Thailand in 2018-2020 by RT-PCR. Of 302 samples, RVA was detected in 11.6% (35 samples): 11.3% (19/168) in 2018-2019 and 11.9% (16/134) in 2019-2020. Surprisingly, G8P[8] was detected as the predominant genotype at 68.4% in 2018-2019 and 81.2% in 2019-2020. In addition, other genotypes were also detected, including G1P[8] (15.8%), G2P[4] (5.3%), G3P[8] (10.5%) in 2018-2019 and G9P[8] (18.8%) in 2019-2020. Analysis of genomic constellation of G8P[8] strains, represented by RVA/Human-wt/ THA/5CR11/2019/G8P[8], revealed a DS-1-like genetic backbone: G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis of the VP7 gene showed that the DS-1-like G8P[8] strains clustered in a distinct sublineage A together with 13 G8P[8] strains reported from Thailand and China, and these sublineage A G8P[8] strains contained unique amino acid substitutions in two positions (A125S and N147D) on the VP7 antigenic epitopes. Homology modeling of the VP7 capsid protein confirmed that these two amino acid changes were located on the surface exposed area of the virion. Phylogenetic trees of the VP1, VP6, NSP2, NSP3, and NSP4 genes have demonstrated that DS-1-like G8P[8] strains in the present study and 51 DS-1-like G8P[8] reference strains published formerly clustered in separate lineages. To the best of our knowledge, this is the first report of the emergence of novel DS-1-like G8P[8] strains that might have evolved genetically through reassortment events with locally or globally circulating genotypes.

Objectives: Viral blips (VB) have been reported in people with HIV (PWH) after COVID-19 vaccination. Materials and Methods: We performed a retrospective cohort study among virally suppressed PWH vaccinated against COVID-19 with mRNA-1273, comparing the occurrence of VB in the 12 months after the first vaccine shot with those recorded in the 12 months before. The association between several clinical and immunologic variables and VB have been evaluated through logistic regression. Results: Overall, 48 individuals were included in our analysis. No difference was recorded between VB incidence in the 12 months before and after vaccination [11/48 (23%) vs 15/48 (31.3%), p=0.42]. No significant association was detected between selected variables and VB occurrence after vaccination. In a post hoc analysis including also 8 PWH excluded for not reaching the definition of viral suppression, we observed 15 increases of HIV RNA out of 56 PWH (26.8%) before vaccination and 23 increases of HIV RNA out of 56 PWH after vaccination (41.1%). This difference in incidence remained not significant (p=0.10) but a strong association between increases of HIV RNA occurrence before and after vaccination [p=0.02, OR 4.3 (95% CI 1-22-15.17)] was found. Conclusion: Among virally suppressed PWH, COVID-19 vaccination with mRNA-1273 is not associated with increased occurrence of VB.

Background: Orf virus (ORFV) is an important zoonotic parapox virus, with 100% morbidity. It affects mainly domesticated ruminants such as sheep and goats. This study determined the molecular epidemiology of ORFV local as well as imported sheep and goats in Nigeria and evolution of ORFV in Africa. Methods: A total of 30 small ruminants with orf were sampled in a livestock market Abuja Nigeria.Skin scabs from pathological tissues were collected and processed for viral genomic DNA. PCR and Sanger sequencing of B2L gene of ORFV. Phylogenetic analysis, phylogeography, and Bayesian skygird reconstruction (BSK), including mutational changes were performed on B2L gene sequences. Results: An ORFV positivity rate of 67% was determined from samples. Animals <2 years had the highest prevalence of 76.5%.Hundred percent attack rate was observed among the Uda and WAD breeds, followed by Niger 71.4%, Kano Brown 66.7%, Yankasa 25% and Balami 0% breeds. ORFV from Africa breeds clustered into 2 major lineages, Asian and African, with an evolutionary rate of 7.45 × 10 -4, 95% HPD (3.46 × 10 -4 to 1.17 × 10 -3) substitutions/ site/year. Viral population demography showed a constant population growth with a slight rise in viral population growth towards year 2020. Conclusion: We report molecular evolution of ORFV in Africa and identified gap in molecular data; we recommend regional molecular surveillance of ORFV and other zoonotic trans-boundary diseases in global health prevention and control effort.

Objective: The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns, pre- and post-menstrual symptoms in women aged 18-45 years. Design & Setting: Multicentric observational study conducted in six institutes of national importance in different states of India over one year. Population: A total of 5709 female participants fulfilling inclusion criteria were enrolled. Methods: Data about impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on menstrual cycle and its associated symptoms were obtained using an online and offline survey. Main Outcome: COVID-19 vaccination with COVISHILED/COVAXIN resulted in menstrual cycle disturbances. Results: Of 5709 participants, 78.2% received COVISHIELD, 21.8% COVAXIN. Of all, 333(5.8%) developed post-vaccination menstrual disturbances with 32.7% frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleed. 301 participants, noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of menstrual cycle (p=0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to COVISHIELD (5.3%). A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in COVISHIELD group (p=0.031) with generalized weakness and body pains as main complaints (p=0.001). No significant difference was observed in COVID-19 infection incidence with these vaccines. When comparing menstrual abnormalities among those with COVID-19 infection, no significant associations were observed (p >0.05). Conclusions: COVISHILED and COVAXIN resulted in menstrual cycle disturbances and pre-and post-menstrual symptoms. The menstrual irregularities were significantly higher with COVAXIN vaccine.

Aim: This research aimed to study the association of drug interactions and sociodemographic, clinical, and functional characteristics in nonagenarians with hyperpolypharmacy. Methods: This was a secondary analysis of an evaluation performed by the Multiprofessional Care for the Oldest-old Project in 2016, with participants identified with hyperpolypharmacy. Results: Results revealed that 69% of 29 participants had at least one major drug interaction, 41% had 10 or more moderate interactions, and 59% had minor interactions. The study revealed significant relationships for major drug interactions with the characteristics of recurrent urinary tract infections, anxiety, and palpitations. The study found near significance for white color, not good general health and appetite, depression, and impaired cognition. For moderate drug interaction, findings showed a relationship near significance for females, perception of not good general health and appetite, hypertension, diabetes, urinary infection, depression scale change, agitation, pain, fatigue, and a fear of falling. For minor drug interactions, the study revealed significant findings for an association with depression, and apathy or sleepiness. There were findings near significance for an association with white color, diabetes, agitation, pain, fatigue, and cough. Conclusion: Drug interactions are highly prevalent among nonagenarians with hyperpolypharmacy, with clinical and quality of life impact. Thus they must be constantly evaluated for the presence of drug interactions at all levels of care, whether in primary care or in specialized care. A study with larger sample size and longitudinal contour is proposed to prove the importance of our observations.

Mutations at positions 452 and 486 of the spike glycoprotein receptor binding domain (RBD) in the SARS-CoV-2 XBC.1 variant were analysed from the viewpoint of change in hydrophobicity and amino acid charge. A decrease in hydrophobicity due to mutations at positions 452 and 486 in the spike glycoprotein was observed, which might affect the infectivity of the XBC.1 variant. L452M and F486P improve the hACE2-RBD binding affinity, which might negatively impact the efficacy of vaccines against SARS-CoV-2, primarily based on spike glycoprotein. Notably, the mutation L452M in XBC.1 also indicates its probable zoonotic links.

1. A survey on the recent COVID-19 epidemic in China was conducted. 2. The epidemic likely made over 85% of people in China sick in December 2022. 3. The epidemic likely ended in early January 2023. 4. The epidemic had the features of spreading more rapidly and widely and having a higher symptomatic rate than previously thought. 5. The above features could lead to many severe cases and deaths due to the shortages of medical resources. 6. The above features greatly enhanced the population immunity in China, which will accelerate the end of the COVID-19 pandemic and reduce the emergence of risky variants of SARS-CoV-2 in China.

Human adenoviruses (HAdVs) are among the most important etiological agents of acute gastroenteritis (AGE). HAdVs found in 5.2% of children admitted for AGE between 2013 and 2016 in seven different hospitals across four cities of Western India. The dominance of subgroup-F (52.4%) strains was observed, followed by the occurrence of non-enteric adenoviruses of the subgroup A (17.4%), C (11.4%), B (8.2%), and D (3.2%). The subgroup-F strains were predominant in Ahmadabad (78.5%), Mumbai (61.5%), and Surat (57.1%) cities, followed by subgroup A strains.  In Pune city, subgroup B and C strains were detected in 62.5% of AGE patients, with none of the subgroup A strains. Clinically, patients infected with enteric and non-enteric HAdV strains were indistinguishable from each other. However, a high viral load was observed in subgroup-F specimens as compared to non-subgroup-F. The study highlights the need for viral load estimation to ascertain the role of enteric and non-enteric HAdV strains associated with diarrheal etiology.

Objective: Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in women. This study aimed to investigate the epidemiological characteristics of HPV genotypes in women from Yueyang city and to provide a basis for the prevention and treatment of cervical cancer in this city. Methods: A retrospective cross-sectional study was conducted on 125,604 women who had received treatment from eight hospitals in Yueyang city from September 2019 to September 2022. The HPV infection rate of the patients was analyzed. Results: The HPV infection rate was 20.47%, of which the high-risk type (HR-HPV) accounted for 17.47% and the low-risk type (LR-HPV) accounted for 4.97%. Among the HR-HPV subtypes, the top five infection rates, from the highest to the lowest, were HPV 52 (5.11%), HPV 16 (2.71%), HPV 58 (2.55%), HPV 53 (2.39%), and HPV 51 (1.67%). The main LR-HPV infection types were HPV 81 (2.05%), HPV 42 (1.04%), and HPV 43 (0.78%). Among the infected patients, 74% had a single subtype, 18% had two subtypes, and 8% had three or more subtypes. The main infected populations were <25 years old, 55–64 years old, and ≥65 years old, accounting for 26.68%, 29.03%, and 32.28% of the total infected population in this study, respectively. Conclusion: The HPV infection rate in women in Yueyang city was 20.47%, with HR-HPV being dominant. As women aged <25 years, 55–64 years, and ≥65 years are at a relatively higher risk, more attention should be paid to them for prevention and control of HPV infections.

Introduction: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. Objective: To assess the fetal and pregnancy safety associated with Prazosin exposures in early Pregnancy. Methods: Subjects were 11 patients who took Prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between January 1, 2000 to December 31, 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. Results: It was found that 6 /11 (54.5%) subjects did not report any adverse outcomes and were uneventful pregnancies. There were 2 miscarriages. Birthweights were within the normal range for the remaining 9 pregnancies. Adverse events reported were consistent with background population expectation, including: 1 postpartum hemorrhage, 1 case of preeclampsia, 1 preterm birth, 2 NICU admissions, and 2 caesarean sections. Discussion / Conclusion: For these 11 subjects, pregnancy outcomes after exposure to Prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that Prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to Prazosin while pregnant. Therefore, this study contributes valuable data toward monitoring safety of Prazosin in Pregnancy.

Pakistan is one of the 36 water-stressed countries, with less than 1000 cubic per person annual water availability. Factors like global warming, urbanization, and irrigation for agribusiness have come into play in skyrocketing the need for water globally. As a low-middle income country, inhabitants of Pakistan are actively moving toward resolving the water crisis through rainwater harvesting during the monsoon period. Though the practice is simple, feasible, and cost-effective, there are certain health risks associated with it. Due to its virological and microbial quality, rainwater is highly contraindicated for potable use without proper treatment. Pathogens like Campylobacter jejuni, Salmonella spp., Giardia lamblia, hepatitis A virus, rotaviruses, etc, and fecal matter of animals like birds, mammals, and reptiles, contaminate the roof harvested rainwater (RHRW) and result in diseases such as Human enteritis, Acute diarrheal disease, Giardiasis, among many others. Apart from this, the sporadic multi-demics of dengue, malaria, and cholera being directly or indirectly related to the monsoon period impose a burden on Pakistan’s public health sector and improper Rooftop Rainwater Harvesting (RTRWH) adds to the stress. It is now imperative that doctors and public health officials join hands to counsel the public on individual and national levels to contain the recurring outbreaks of these diseases associated with the monsoon period. Procedures of RHRW treatment such as ultra-membrane filtration, UV treatment, safe roofing material, and first-flush diversion devices should be strategically promoted through awareness campaigns. Our article discusses the limitations for potable use of RHRW in this era of multi-demic and suggests strategies to retrieve favorable outcomes to cater to the water scarcity through RTRWH in the state effectively.

Objective To report our recent experience managing ultra-high-risk gestational trophoblastic neoplasia (GTN) patients with liver and brain metastases. Design A retrospective review of data from a national gestational trophoblastic disease centre. Setting The Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China. Sample Total of 298 GTN patients recruited from January 2014 to December 2017. Main outcome measures The CR rate and drug-resistance rate after initial treatment of ultra-high-risk GTN patients with liver or brain metastases. Methods The clinical characteristics and treatment and prognosis outcomes in 11 ultra-high-risk GTN patients with liver or brain metastases were performed by descriptive analyses. The prognostic factors for death in all GTN patients were identified by Cox proportional hazards regression. Survival analysis were used to analyze survival time between GTN patients stratified according to liver or brain metastases. Results. The CR rate and drug-resistance rate after initial treatment of ultra-high-risk GTN patients with liver or brain metastases was 0% and 90.9% respectively, but the 5-year OS rate was 81.8% (n=11). Liver metastases (hazard ratio [HR]: 34.05; 95% confidence interval [CI]: 1.65–703.7; P=0.02) and brain metastases (HR: 49.19; 95% CI: 5.6–432.1; P<0.01) were independently significant risk factors for death in all GTN patients. Conclusions. Liver and brain metastases were found to be independently significant risk factors for death in all GTN patients. The drug-resistance rate with initial treatment was 90.9% in ultra-high-risk GTN patients with liver or brain metastases.

Monkeypox virus (MPXV) is a zoonotic disease endemic in the rain forest countries of Central and West Africa. Understanding the immune response in zoonosis is fundamental to prevent and contrast viral spreading. MPXV is a close relative of the Variola (smallpox) virus and vaccination with vaccinia virus give an 85% protection against MPXV. With the emergence of the recent MPXV outbreak, Jynneos vaccine has been proposed to individuals at high-risk of exposure. Comparative data on MPXV immune response in vaccinated or infected subjects is still scarce. Here we described the differences between a group of infected patients in comparison to smallpox or Jynneos vaccinated subjects. The patients’ response is stronger and faster, while the Jynneos vaccinated controls need more time to develop a good immunity. Interestingly, the historic smallpox-vaccinated controls retain a degree of protection, even after years from vaccination, which is most visible in the T-cellular memory that is comparable to the newly vaccinated subjects.

A document by Alaa Khedr. Click on the document to view its contents.

A document by Ranjit Sah. Click on the document to view its contents.

Objectives: We aimed to evaluate the trend of HPV infection status in oropharyngeal squamous cell carcinoma (OPSCC) according to various epidemiologic factors in the United States. Design: Retrospective cohort study. Setting: Surveillance, Epidemiology, and End Results (SEER) 2010-2016 database. Participants: A total of 13081 patients with OPSCC were enrolled. Patients were diagnosed with OPSCC primarily in the base of tongue, posterior pharyngeal wall, soft palate, and tonsil between 2010 and 2016 and were tested for HPV infection status. Main outcome measures: We analyzed how the number of OPSCC patients changed according to various demographic factors from 2010 to 2016. Additionally, we forecasted and confirmed the number of HPV (+) and (-) patients with OPSCC using the autoregressive integrated moving average (ARIMA) model. Results: The number of HPV (+) patients with OPSCC has increased over the past 7 years, but the degree of increase varied greatly according to the age, sex, and subsites. The number of HPV (-) patients increased until 2015 in all age groups for each site but did not change or decrease since then. Appropriate ARIMA models were applied to forecast HPV (+) and (-) patients, and the predicted data matched the actual data well. Conclusions: This large population-based study suggests that HPV (+) patients with OPSCC has increased and will continue to increase. However, the trends in HPV infection status in patients differed greatly according to various demographic factors. These results present a direction for establishing appropriate preventive measures to deal with HPV-related OPSCC in more detail.

Pakistan struggles to eliminate poliomyelitis. There are some principal tasks to deal with, including ending transmission in central reservoirs, enduring pressure to exploit the quality of Supplemental Immunization Activity [SIA], handling in critical Community Based Vaccination [CBV] and mobile team areas, and covering high-risk mobile residents to avoid additional spread. Due to the discovery and availability of vaccinations, polio is currently considered almost eliminated. Positive effects include continual reviews of communication, observation, and control mechanisms, enhanced coordination between the Polio Eradication Initiative [PEI] and the Expanded Program on Immunization [EPI], and a stronger emphasis on strengthening relationships with other service workers in high-risk regions. To eradicate polio, politicians, community mobilizers, government, public health specialists, and education departments must collaborate to better grasp the issue and operate more effectively. The high-level political leadership and promise detailing Pakistan’s response to COVID-19 is the best practical strategy to achieve PEI’s fundamental goals.

Objective This study aimed to determine the correlation between interpregnancy interval (IPI) and neurodevelopmental delay in infants and to explore the potential mediating role of maternal-fetal glucose metabolism. Design Population based cohort study. Setting China Participants A total of 2559 mother-infant pairs between 2018 and 2022. Methods The prospective birth cohort study included 2559 mother-infant pairs. The IPI is calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Maternal fasting venous blood collection at 24-28 weeks and cord blood collection at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Main outcome measures Neurodevelopmental outcomes at 12 months in offspring were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Results In our cohort, 14.0% had an IPI <12 months. IPI <12 months increased the failure of the communication domain, fine motor domain, and personal social domain of the ASQ [relative risks (RRs) with 95% confidence interval (CI): 1.75(1.13, 2.72); 1.77(1.13, 2.77); 1.51(1.01, 2.28)]. Maternal homeostasis model assessment of insulin resistance (HOMA-IR) and cord blood C-peptide was significantly associated with failure in the communication domain [RRs with 95% CI: 1.15(1.02, 1.31); 2.15(1.26, 3.67)]. The proportion of the association between IPI and failure of the communication domain risk mediated by maternal HOMA-IR and cord blood C-peptide was 14.4%. Conclusions IPI <12 months was associated with failing the communication domain in offspring. Maternal-fetal glucose metabolism abnormality may partially explain the neurodevelopmental delay caused by short IPI.

Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic co-administration. By diminishing gut bacteria β-glucuronidase activity, oral antibiotics seem to prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, is advised.