Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such ...crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010–12) and Syria (2009–11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015–17) and Jordan (2016–17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers.
Abstract
The induction of self-tolerance and regulation of inflammatory immune responses is critical during early life when a myriad of primary antigenic challenges are encountered. Regulatory T ...Cells (Tregs) promote self-tolerance and function to modulate immune responses utilizing a variety of immunosuppressive mechanisms. Tregs are known to be disproportionately more abundant during early life, suggesting an essential role during immune development. We performed bulk RNA sequencing and multi-parameter flow cytometry on Tregs isolated from adult and pediatric (1 – 3 years of age) tissue (tonsils) and blood to discern the defining characteristics of early life Tregs. Early life Tregs were found to have an increased expression of genes associated with cell cycle (Ki67), effector and suppressive function (ICOS/CTLA4/IL10/GZMB/GZMA) and chemokine signaling (CCR5/CCR9) compared to adults. Importantly, distinctions in canonical effector function genes were apparent across all early life Tregs and not restricted to tissue site. Interestingly, CCR9, essential in gut-specific homing, was upregulated in both tissue and blood early life Tregs, suggesting a biasing towards intestinal immune homeostasis during childhood. We further explored the upregulation of genes related to cell cycle and found that early life Tregs exhibit higher proliferative capacity compared to both adult Tregs and early life CD4 conventional T cells, revealing a potential effector mechanism unique to early life. Early life Tregs are defined by a signature of augmented effector functionality enhancing their ability to respond to the abundant immunological challenges of infancy and childhood.
Background
CT-P13 subcutaneous (SC)—the first and only SC version of infliximab—is approved by the European Medicines Agency for the treatment of rheumatoid arthritis (RA). This new mode of ...infliximab administration will allow patients to self-inject at home, significantly reducing the number of outpatient visits and costs of intravenous (IV) administration. This paper describes the economic impact of introducing CT-P13 SC to the market from the UK societal perspective.
Objective
The budget impact analysis was conducted to assess the financial impact of the adoption of CT-P13 SC over a 5-year period.
Methods
A prevalence-based budget impact model was developed incorporating epidemiological data, administration cost data, and market share data. The analysis compared a “world with” CT-P13 SC scenario to a “world without” CT-P13 SC. A sensitivity analysis included dose escalation up to 4.1 mg/kg to reflect the real-world care delivery setting.
Results
Compared to the “world without” scenario, the introduction of CT-P13 SC resulted in cost savings of ₤69.3 million in the UK over a 5-year period. In the scenario analysis, the saving increased to ₤173.5 million over 5 years.
Conclusion
Use of CT-P13 SC may lead to substantial cost savings for the UK society.
Pre-mRNA splicing is regulated through the combinatorial activity of RNA motifs, including splice sites and splicing regulatory elements. Here we show that the activity of the G-run (polyguanine ...sequence) class of splicing enhancer elements is approximately 4-fold higher when adjacent to intermediate strength 5' splice sites (ss) than when adjacent to weak 5' ss, and approximately 1.3-fold higher relative to strong 5' ss. We observed this dependence on 5' ss strength in both splicing reporters and in global microarray and mRNA-Seq analyses of splicing changes following RNA interference against heterogeneous nuclear ribonucleoprotein (hnRNP) H, which cross-linked to G-runs adjacent to many regulated exons. An exon's responsiveness to changes in hnRNP H levels therefore depends in a complex way on G-run abundance and 5' ss strength. This pattern of activity enables G-runs and hnRNP H to buffer the effects of 5' ss mutations, augmenting both the frequency of 5' ss polymorphism and the evolution of new splicing patterns. Certain other splicing factors may function similarly.
Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more ...susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied.
This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women.
Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood.
Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy.
Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.
Unilateral vocal cord paralysis (UVCP) in infants may be managed medically or surgically, with the latter including injection laryngoplasty (IL). However, there is limited information regarding ...injection laryngoplasty in infants. We therefore proposed a survey of American Society of Pediatric Otolaryngology (ASPO) members to elucidate current practices, outcomes, and complications.
An online survey was distributed to all 548 ASPO members via email. The survey was closed for data analysis 2 months after initial distribution. Statistical analysis was deferred due to the primarily descriptive nature of the data and lack of comparative studies.
We received 113 responses for a response rate of 20.6%. Only 31% of the respondents (n = 36) reported performing IL in infants 12 months old or younger. The most commonly cited reasons for not injecting in this age group were preference for non-surgical management and concern for increased risk of airway obstruction. IL was most commonly performed to treat persistent aspiration despite attempts at medical management. The majority (66%) reported no complications, while the remainder noted stridor requiring intensive care unit observation. Re-intubation due to airway obstruction occurred in 6% (n = 2 of 33). Carboxymethylcellulose gel (Prolaryn Gel) was the most commonly used injectable material, but a variety of other materials were used as well. Two respondents noted they perform reinnervation procedures in children, but not in infants, as they require at least a 12 month period of observation for possible spontaneous recovery before considering the option.
There is limited data regarding management of UVCP in infants with IL, and considerable variation among those who do perform the procedure. While adverse events are rare, multi-institutional studies should be considered to help determine best practices.
Endoscopic laryngeal tracheal reconstruction was performed on a child with glottic stenosis and pulmonary arterial hypertension. The surgical repair was performed while delivering inhaled nitric ...oxide via the ventilating port of a suspension laryngoscope with the patient maintaining spontaneous respirations. The surgery was accomplished without complications.
Objectives:
Evaluate the educational and exposure opportunities provided to students by national otolaryngology organizations.
Methods:
Twenty-four otolaryngology organizations and subspecialty ...societies were reviewed for medical student involvement opportunities, educational and enrichment opportunities, costs of involvement, and available research and travel scholarships.
Results:
Nine organizations (37.5%) offered membership; 6 charged a membership fee, averaging $73 ± $30 (mean ± SD). Membership was limited to associate status for 7 organizations (77.8%; 7/9). Three organizations (12.5%) provided service opportunities, 4 (16.7%) allowed students to vote, and 1 (4.2%) allowed students to endorse others for membership. Most organizations allowed students to attend conferences (95.8%), and 19 (79.2%) allowed students to present research. Twenty-one (87.5%) organizations charged a conference registration fee ($366 ± $300). Seven organizations (29.2%) offered research scholarships, and 5 (20.8%) offered travel awards.
Conclusions:
Opportunities exist for medical students to attend conferences and present research; however, educational and enrichment activities in other areas were limited. Future efforts may be warranted to increase the number and type of opportunities for students.
Patients with limited English language proficiency have indicated that they believe post-operative instructions written in their native language will improve comprehension over verbal translation ...alone, but the effect of this has not been previously studied. We hypothesize that providing written discharge instructions in Spanish for native Spanish speakers will improve comprehension regarding post-operative care after routine otolaryngologic procedures when compared to instructions written in English.
This prospective randomized controlled trial enrolled subjects who met criteria from June 2016 to November 2016. Subjects were Spanish-speaking parents and legal guardians of children undergoing tympanostomy tube insertion, adenoidectomy, and/or tonsillectomy. Subjects were given written discharge instructions in either English or Spanish. Both cohorts received standard verbal counseling in Spanish as well. Primary outcome was score on a standardized quiz assessing comprehension of discharge instructions. Patient satisfaction and preferences were secondary outcomes assessed through a survey. Participants underwent follow up one month after initial enrollment.
Twenty subjects were enrolled, with ten receiving written discharge instructions in Spanish and ten receiving instructions written in English. There was no significant difference in comprehension scores between the two groups. Eleven participants completed the survey on patient satisfaction and preferences. Most subjects (91%, 10/11, p<0.01) preferred written instructions in their native language and subjectively felt this would improve their comprehension. However, there was no significant effect on patient satisfaction.
Spanish-speaking patients indicate a strong preference for written discharge instructions in their native language, although there was no significant difference in short-term comprehension of instructions written in English vs. Spanish on objective evaluation. Accommodating these preferences may improve long-term comprehension and patient satisfaction, and ultimately build invaluable rapport between providers and patients.
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