The use of once-daily LCP-Tacrolimus with adolescent and young adult solid organ transplant recipients.

BACKGROUND: Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once-daily formulation of tacrolimus, LCP-tacrolimus (LCPT), on medication adherence for AYA SOT patients. METHODS: A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single-center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). RESULTS: Twenty-nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate-acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p = .140) and MLVI (40.0% vs. 71.4%, p = .276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. CONCLUSIONS: LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients.

Diagnosis and Classification of Fistula from Inflammatory Bowel Disease and Inflammatory Bowel Disease-Related Surgery.

Fistula in inflammatory bowel disease (IBD) is a well-known yet poorly understood phenotype. Pathophysiology is largely based on the activation of the epithelial-mesenchymal transition (EMT); however, interactions with the microbiome, genetics, mechanical stress and the presence of stricturing disease, and surgical complications play a role. Perianal penetrating disease represents a more severe phenotype in IBD. Pouch-associated fistula can arise as a result of an anastomotic leak, surgical complications, or Crohn's disease (CD) of the pouch. Classification is site-dependent, includes a range of severity, and informs management. It is important to determine associated symptoms and recognize the complex interplay of underlying etiologies to form the basis of appropriate care.

Medical student's perception of the COVID-19 pandemic effect on their education and well-being: a cross-sectional survey in the United States.

BACKGROUND: The effects of drastic curricular changes necessitated by the COVID-19 pandemic on medical students' education and wellbeing have remained largely unstudied. Out study aimed to characterize how medical students were affected by the pandemic, specifically how limitations introduced by the pandemic may have affected the quality, delivery, and experience of medical education. METHODS: Three hundred students from 5 U.S. allopathic medical schools were surveyed to determine students' perceptions about their quality of medical education, professional development, and mental health during the COVID-19 pandemic (October 2020-December 2020). RESULTS: A large majority of students report that while lecture-based learning has not been significantly affected by the pandemic, small-group and clinical learning have greatly declined in quality. Students also reported higher levels of depression, anxiety, and uncertainty with regards to their futures as physicians. CONCLUSIONS: The COVID-19 pandemic has greatly affected the medical student education and wellbeing. Although medical schools have implemented measures to continue to train medical students as effectively as they can, further strategies must be devised to ensure the well-being of students in the present and for future national emergencies.

Characterization and clinical course of 1000 patients with COVID-19 in New York: retrospective case series.

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results: Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. DESIGN: Retrospective manual medical record review. SETTING: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. PARTICIPANTS: The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. MAIN OUTCOME MEASURES: Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. RESULTS: Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. CONCLUSIONS: Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.

Maternal perceptions of father involvement among refugee and disadvantaged families in Beirut, Lebanon.

The role of fathers in (co-)parenting their children among refugee and disadvantaged families in low and middle-income countries (LMICs) remains poorly understood. This study sought to examine the associations among mothers' perceptions of their husband's involvement (hereafter referred to as paternal involvement), and her perceptions of her own well-being and a number of other variables, as well as observed mother-child interactions in families living in refugee and disadvantaged communities in Beirut, Lebanon. We analyzed baseline data from 104 mother-child dyads (mean age of children = 4.34 years; range = 2.05 to 7.93 years of age) who participated in a randomized controlled trial aimed at evaluating the impact of the Mother-Child Education Program in Beirut. In addition to the mother's perception of paternal involvement and the videotaped mother-child interactions, data were collected concerning the mother's well-being and her level of social support, as well as her level of stress as a parent and the way her children were disciplined in the family. Mother-child pairs were videotaped while completing a puzzle together and dyadic interactions were coded. Path analysis showed that paternal involvement was significantly associated with a higher level of maternal well-being and lower distress levels. In addition, higher levels of maternal distress were associated with higher levels of harsh discipline and parenting stress. Correlation analysis showed that higher perceptions of paternal involvement were associated with more positive affect displayed by the child, more positive regard for the child, and better mother-child synchrony during the dyadic interactions. Limitations include the cross-sectional design and the modest sample size, which hinder causal inferences and generalizability of the findings. These preliminary findings suggest that higher levels of paternal involvement may have an impact on markers of maternal mental health and positive mother-child interactions in families living in disadvantaged communities or humanitarian settings. Paternal involvement should be considered when designing and implementing parenting programs in LMICs.

Effects of the Mother-Child Education Program on Parenting Stress and Disciplinary Practices Among Refugee and Other Marginalized Communities in Lebanon: A Pilot Randomized Controlled Trial.

OBJECTIVE: Few randomized controlled trials (RCTs) have explored the implementation and impact of early childhood parenting education programs in very fragile contexts and humanitarian settings. We tested the effects of a group-based intervention, the Mother-Child Education Program (MOCEP), on parenting stress and practices among two refugee communities and one other marginalized community in Beirut, Lebanon. METHOD: A pilot wait-list RCT was conducted to assess the program's impact on maternal, child (average age: 4 years), and dyadic outcomes. A total of 106 mother-child dyads were randomly assigned to either the intervention group (n = 53) or the wait-list control group (n = 53). Analysis was conducted by modified intention-to-treat and supplemental analyses through multiple imputation of missing post-intervention data. RESULTS: Forty families (38%) withdrew early from the study. After completing the program, mothers in the intervention group showed a reduction in their harsh parenting practices, as indexed by the Disciplinary Style Questionnaire (Cohen's d = -0.76, 95% CI = -1.24, -0.27) and in their level of parenting stress, as indexed by the Parenting Stress Index-Short Form (PSI-SF; Cohen's d = -0.90, 95% CI = -1.39, -0.40). Exploratory but underpowered analyses of dyadic interactions revealed reductions in the PSI were associated with a reduction in harsh parenting after the intervention. However, we did not detect any positive impact on behavioral or emotional outcomes among the children. CONCLUSION: Our analyses suggest that MOCEP had a positive impact on disciplinary practices and parenting stress in a context of high fragility, but that broader effects on maternal and child outcomes may be dependent on program attendance and the availability of other services. We discuss implications of this pilot study for practice and research of a largely unexplored area of program evaluation. CLINICAL TRIAL REGISTRATION INFORMATION: Mother and Child Education Program in Palestinian Refugee Camps; https://clinicaltrials.gov; NCT02402556.

Zika virus causes testicular atrophy.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1-/- mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males.

Zika virus productively infects primary human placenta-specific macrophages.

The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus-associated pregnancy complications.