BACKGROUND: In 2017, the Food and Drug Administration approved pembrolizumab for treatment of any mismatch repair-deficient (dMMR) tumor making MMR immunohistochemistry (IHC) testing beneficial for all tumor types. For the first time, MMR IHC was not performed exclusively to screen for Lynch syndrome (LS).
METHODS: In this study, all MMR IHC reports issued between 2017 and 2021 at an academic hospital were reviewed and completion of genetic testing was determined through chart review. Colorectal cancers (CRCs), endometrial cancers (ECs), and noncancerous lesions were excluded.
RESULTS: Between 2017 and 2021, MMR IHC was completed in 1939 patients with a malignancy other than CRC or EC. Absent or weak staining for at least one MMR protein was detected in 115 (5.9%) patients and 59 (51%) of those completed germline genetic testing. Overall, the identification rate of LS in this cohort was 0.72%, which is similar to the rate in our previously reported CRC and EC universal screening cohort. A diagnosis of LS was most commonly made in patients with dMMR brain (18.75%) and small intestinal cancers (10.20%). Five additional patients were found to carry a pathogenic variant in a non-LS gene.
CONCLUSIONS: Pan-cancer MMR testing for pembrolizumab consideration can identify LS cases at a rate similar to universal CRC and EC screening programs. A persistent challenge is subsequent uptake of genetic testing. MMR testing should be prioritized in brain and small intestinal tumors, and multigene panel testing is recommended in patients with dMMR, as unexpected pathogenic variants in non-LS genes were found as frequently as LS gene variants.

OBJECTIVE: We aimed to evaluate the influence of easing COVID-19 preventive measures following its downgrading to a common infectious disease on COVID-19 occurrence among hospitalized patients.
METHODS: Nosocomial occurrence of COVID-19 was compared between periods with national infectious disease category 5 versus the preceding category 2 equivalent. Changes in the revised manual included a shorter duration of work restrictions for infected health care practitioners (HCPs); no work restriction for HCPs exposed to SARS-CoV-2 with a negative test on days 1, 3 and 5; discontinuation of universal pre-admission screening; and pre-emptive isolation of patients without screening. Wearing an N95 mask and face shield was required in procedure/care with moderate-to high-risk contact.
RESULTS: Although the mean monthly number of infected HCPs increased from 8.1 to 12.7 in the category 5 period (p = 0.034) and that of pre-admission screening decreased to one-fourth, the COVID-19 incidence in hospitalized patients remained similar between the two study periods (1.60 ± 5.59/month versus 1.40 ± 2.63/month, p = 0.358). Clusters, defined as ≥3 COVID-19 patients on the ward, were experienced twice in the preceding period and only once in the category 5 period. The index cases causing nosocomial SARS-CoV-2 transmission mostly involved rehabilitation therapists in the preceding period; five of six index cases were patients in the category 5 period. Following the expanded indication for N95 masks, neither SARS-CoV-2 transmission to patients nor transmission from infected patients was observed in HCPs for 1 year.
CONCLUSIONS: With sustained, enhanced standard precautions, easing prevention strategies could limit nosocomial SARS-CoV-2 infections.

Childhood represents a critical window for the emergence and treatment of mental health disorders, yet many are not being identified, or are identified too late to receive adequate intervention. This systematic review (Prospero registration: CRD42022299560) aimed to determine the effectiveness and acceptability of parent reported universal mental health screening (UMHS) to improve the early identification of children at-risk of mental health difficulties, and to identify barriers and enablers that may influence parental engagement. Six databases were searched in February 2022 for peer-reviewed, primary research. Studies conducted in targeted populations, evaluating psychometric properties, or focused on screening non-psychological problems were excluded. Ten studies examined parent reported (n = 3,464 parents) UMHS for children from birth to 18 years, suggesting an overall scarcity of research. Findings are presented in a table of study characteristics and a narrative summary of acceptability, effectiveness, barriers, and enablers. Quantitative findings indicated that parents generally support and accept UMHS. Research assessing effectiveness was limited, although two studies indicated increased referrals and referral adherence following positive screens. Confidentiality and stigma were commonly identified barriers. Quality assessment using the Mixed Methods Appraisal Tool indicated that studies varied in quality, meeting four to seven of the seven quality criteria. Understanding and addressing parent attitudes to UMHS across settings is necessary for the successful implementation of screening and improvement of child mental health outcomes. More high-quality research studies, including randomized controlled trials are therefore needed to examine the acceptability and effectiveness of UMHS for parents and their children.

BACKGROUND: Alcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS.
METHODS: This retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction.
RESULTS: There were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006).
CONCLUSIONS: Protocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits in US children. To inform patient management, it is important to define whether central nervous system (CNS) manifestations are present at birth. This study characterized neuroimaging findings in infants with cCMV identified by a universal screening study in Minnesota during February 2016 - December 2022.
METHODS: Newborns with cCMV infection (confirmed by urine CMV PCR following a positive screening saliva and/or dried blood spot result) underwent diagnostic evaluation, including cranial ultrasound (cUS), laboratory studies, ophthalmological, and audiological evaluation. Neuroimaging findings and cCMV disease classification were interpreted based on international consensus guidelines.
RESULTS: Among 87 newborns with confirmed cCMV, 76 underwent cUS. Of these, 53/76 (70%) had normal examinations, while 23/76 (30%) exhibited cUS findings: for 5 infants, these were clearly cCMV disease-defining, while for 18 infants, there were findings of uncertain significance. Magnetic resonance imaging (MRI) results (n=10 infants) aligned with cUS cCMV-disease defining findings in 2 infants, while cCMV-specific abnormalities were noted by MRI in 2 of 6 infants with nondiagnostic/incidental cUS findings. Of 9 infants who had both cUS and MRI examination, the average time interval between studies was 220 days (range, 2 to 1061). Excluding infants with cCMV CNS disease-defining cUS abnormalities, incidental findings were observed more commonly in infants with clinical/laboratory features described in cCMV disease classification guidelines (9/13) than in newborns with completely asymptomatic infections (9/58; p<0.0001).
CONCLUSIONS: Among infants with cCMV identified in a universal screening study, the majority had a normal cUS. CNS disease-defining abnormalities were present in 7%, while 24% had findings of uncertain significance. We propose that many cUS findings are incidental, and not diagnostic of symptomatic cCMV infection. Although insufficient to define symptomatic disease, incidental findings were more common in infants with other manifestations of cCMV infection.

Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy.
We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables.
We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22-0.84), with significantly higher rates (2.1%, 95% CI 0.58-5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31-4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23-37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83).
For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

Limited awareness, social stigma, and access to mental health professionals hinder early detection and intervention of internet gaming disorder (IGD), which has emerged as a significant concern among young individuals. Prevalence estimates vary between 0.7% and 15.6%, and its recognition in the International Classification of Diseases, 11th Revision and Diagnostic and Statistical Manual of Mental Disorders, 5th Edition underscores its impact on academic functioning, social isolation, and mental health challenges.
This study aimed to uncover digital phenotypes for the early detection of IGD among adolescents in learning settings. By leveraging sensor data collected from student tablets, the overarching objective is to incorporate these digital indicators into daily school activities to establish these markers as a mental health screening tool, facilitating the early identification and intervention for IGD cases.
A total of 168 voluntary participants were engaged, consisting of 85 students with IGD and 83 students without IGD. There were 53% (89/168) female and 47% (79/168) male individuals, all within the age range of 13-14 years. The individual students learned their Korean literature and mathematics lessons on their personal tablets, with sensor data being automatically collected. Multiple regression with bootstrapping and multivariate ANOVA were used, prioritizing interpretability over predictability, for cross-validation purposes.
A negative correlation between IGD Scale (IGDS) scores and learning outcomes emerged (r166=-0.15; P=.047), suggesting that higher IGDS scores were associated with lower learning outcomes. Multiple regression identified 5 key indicators linked to IGD, explaining 23% of the IGDS score variance: stroke acceleration (β=.33; P<.001), time interval between keys (β=-0.26; P=.01), word spacing (β=-0.25; P<.001), deletion (β=-0.24; P<.001), and horizontal length of strokes (β=0.21; P=.02). Multivariate ANOVA cross-validated these findings, revealing significant differences in digital phenotypes between potential IGD and non-IGD groups. The average effect size, measured by Cohen d, across the indicators was 0.40, indicating a moderate effect. Notable distinctions included faster stroke acceleration (Cohen d=0.68; P=<.001), reduced word spacing (Cohen d=.57; P=<.001), decreased deletion behavior (Cohen d=0.33; P=.04), and longer horizontal strokes (Cohen d=0.34; P=.03) in students with potential IGD compared to their counterparts without IGD.
The aggregated findings show a negative correlation between IGD and learning performance, highlighting the effectiveness of digital markers in detecting IGD. This underscores the importance of digital phenotyping in advancing mental health care within educational settings. As schools adopt a 1-device-per-student framework, digital phenotyping emerges as a promising early detection method for IGD. This shift could transform clinical approaches from reactive to proactive measures.

UNASSIGNED: Diabetes in pregnancy (DIP) is associated with adverse fetal and maternal outcomes. DIP is classified as either pre-existing or new-onset diabetes mellitus (DM), which is classified into gestational DM (GDM) and newly detected type 2 (N-T2D). All pregnant women in Qatar who are not known to have pre-existing DM are offered screening for DIP during the first antenatal care visit and after 24 weeks gestation. The study aims to report the DIP screening rates, the prevalence of DIP, and the impact of the universal screening program on adverse pregnancy outcomes.
UNASSIGNED: This retrospective study included all women who gave birth in Hamad Medical Corporation (HMC) hospitals between 2019 and 2022. New-onset DIP was defined using the WHO-2013 criteria. The primary outcomes were the screening rates and the prevalence of DIP in Qatar. The secondary outcomes were the difference in preterm delivery, C-section, macrosomia, large for gestational age (LGA), small for gestational age (SGA), and intra-uterine fetal death (IUFD) between women with or without GDM.
UNASSIGNED: We included 94,422 women who gave birth to 96,017 neonates (85.7%) out of 112,080 neonates born nationwide. The number of women with pre-existing diabetes was 2496 women. Of 91,926 eligible women, 77,372 (84.2%) were screened for DIP. The prevalence of GDM is 31.6% (95% CI: 31.3-32.0%); N-T2D is 2.2% (95% CI: 2.1-2.3%), and pre-existing Type 2 DM and Type 1 DM was 2.6% (95% CI: 0.8-3.0%) and 0.2% (0.19-0.25), respectively. Compared to the non-GDM group, women with GDM were older (30.8 ± 5.3 versus 29.7 ± 5.2 years, p < 0.001). After adjusting for age, women with GDM had lower risk of IUFD and SGA (0.63 [95% CI 0.50-0.80, p < 0.001], 0.88 [95% CI 0.84-0.92, p < 0.001] respectively) but higher risk of C-section and LFD (1.07 [95% CI 1.04-1.10, p < 0.001], 1.09 [95% CI 1.01-1.15, p = 0.01], respectively, compared to women with no-GDM.
UNASSIGNED: Of the women eligible for screening, 84.2% were screened by the DIP program in Qatar. The prevalence of DIP in Qatar is 36.9%. Integrated care is critical for the screening and management of diabetes during pregnancy.
UNASSIGNED: The authors did not receive any funding for this project.

BACKGROUND: The purpose of this study was to evaluate the management and results of our standarized protocol for preoperative identification of MRSA colonisation in patients undergoing primary total hip and knee replacement procedures.
METHODS: Following hospital protocol, between January 2016 and June 2019 37,745 patients awaiting elective joint replacement underwent a standardized questionnaire to assess the risk of MRSA infection, identifying patients requiring preoperative MRSA screening. An evaluation of the questionnaire identified effective questions for identifying infected patients. Furthermore, an analysis evaluated the impact of comorbidities or Charlson Comorbidity Index scores on positive MRSA colonization. Additionally, we evaluated the cost savings of targeted testing compared to testing all surgery patients.
RESULTS: Of the 37,745 patients, 8.057 (21.3%) were swabbed, with a total of 65 (0.81%) positive tests. From this group 27 (36.48%) who were treated were negative before surgery. Some of the questionnaire results were consistently associated with a higher chance of colonization, including hospitalization during the past year (47,7%), previous history of MRSA (44,6%), and agriculture or cattle farming related work (15,4%). By selectively testing high-risk patients identified through the questionnaire, we achieved a 79% reduction in costs compared to universal MRSA screening.
CONCLUSIONS: Our results suggest that the simple and standardized questionnaire is a valuable tool for preoperative screening, effectively identifying high-risk patients prone to MRSA colonisation. The risk of periprosthetic joint infection (PJI) and its associated sequelae may be reduced by this approach.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection, resulting from non-primary maternal infection or reactivation during pregnancy, can cause serious fetal abnormalities, complications in the immediate neonatal period, and severe sequelae later in childhood. Maternal non-primary cytomegalovirus infection in pregnancy is transmitted to the fetus in 0.5-2% of cases (1).
METHODS: An African full term male newbornwas delivered by emergency caesarean section. Due to signs of asphyxia at birth and clinical moderate encephalopathy, he underwent therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 h, however, soon after rewarming, he presented refractory status epilepticus due to an intracranial hemorrhage, related to severe thrombocytopenia. The patient also presented signs of sepsis (hypotension and signs of reduced perfusions). An echocardiography revealed severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. Research for CMV DNA Polymerase Chain Reaction (PCR) on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions was positive.The mother had positive CMV IgG with negative IgM shortly before pregnancy. Serology for CMV was therefore not repeated during pregnancy, but CMV DNA performed on the Guthrie bloodspot taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. The baby was discharged in good general condition and follow up showed a normal neurodevelopmental outcome at 9 months.
CONCLUSIONS: Although uncommon, congenital cytomegalovirus infection should be included in the differential diagnosis of intraventricular hemorrhage and cardiomyopathy. Furthermore, this case highlights the possible severity of congenital cytomegalovirus infection, even in cases of previous maternal immunity.