Conectar
by Tom A. W. Schoufour, Linda Voogd, Kees L.M.C. Franken, Tom H.M. Ottenhoff, Ruud H.M. Wijdeven, Simone A. Joosten
Human leukocyte antigen E (HLA-E) communicates cellular health to natural killer (NK) cells through presentation of peptides derived from the leader sequence of classical major histocompatibility complex class I (MHC-I), inhibiting NK cell activation and lysis of healthy cells. Besides this canonical role, HLA-E can also present peptides from pathogens such as Mycobacterium tuberculosis (Mtb) to T cells and can inhibit phagocytosis by engaging with LILRB1/2. To identify additional HLA-E binding surface molecules, we utilized a CRISPR/Cas9 activation screen with HLA-E tetramers, which identified Stabilin (STAB)1 and STAB2 as novel interactors. This interaction depended on the nature of the peptide/HLA-E complex, whereby high affinity peptides did not permit the interaction while low affinity peptides did. Functionally, expression of STAB1 or STAB2 on THP-1 monocytes increased phagocytic uptake of HLA-E coated microbeads. These results provide the first evidence of an interaction between Stabilin receptors and specific HLA-E conformations.
by Andrea C. Aplasca, Peter B. Johantgen, Christopher Madden, Kilmer Soares, Randall E. Junge, Vanessa L. Hale, Mark Flint
Amphibian skin is integral to promoting normal physiological processes in the body and promotes both innate and adaptive immunity against pathogens. The amphibian skin microbiota is comprised of a complex assemblage of microbes and is shaped by internal host characteristics and external influences. Skin disease is a significant source of morbidity and mortality in amphibians, and increasing research has shown that the amphibian skin microbiota is an important component in host health. The Eastern hellbender (Cryptobranchus alleganiensis alleganiensis) is a giant salamander declining in many parts of its range, and captive-rearing programs are important to hellbender recovery efforts. Survival rates of juvenile hellbenders in captive-rearing programs are highly variable, and mortality rates are overall poorly understood. Deceased juvenile hellbenders often present with low body condition and skin abnormalities. To investigate potential links between the skin microbiota and body condition, we collected skin swab samples from 116 juvenile hellbenders and water samples from two holding tanks in a captive-rearing program. We used 16s rRNA gene sequencing to characterize the skin and water microbiota and observed significant differences in the skin microbiota by weight class and tank. The skin microbiota of hellbenders that were housed in tanks in close proximity were generally more similar than those housed physically distant. A single taxa, Parcubacteria, was differentially abundant by weight class only and observed in higher abundance in low weight hellbenders. These results suggest a specific association between this taxa and Low weight hellbenders. Additional research is needed to investigate how husbandry factors and potential pathogenic organisms, such as Parcubacteria, impact the skin microbiota of hellbenders and ultimately morbidity and mortality in the species.
by Michael Seid, David Bridgeland, Christine L. Schuler, David M. Hartley
Improving the healthcare system is a persistent and pressing challenge. Collaborative Learning Health Systems, or Learning Health Networks (LHNs), are a novel, replicable organizational form in healthcare delivery that show substantial promise for improving health outcomes. To realize that promise requires a scientific understanding that can serve LHNs’ improvement and scaling. We translated social and organizational theories of collaboration to a computational (agent-based) model to develop a computer simulation of an LHN and demonstrate the potential of this new tool for advancing the science of LHNs. Model sensitivity analysis showed a small number of parameters with outsized effect on outcomes. Contour plots of these influential parameters allow exploration of alternative strategies for maximizing model outcomes of interest. A simulated trial of two common health system interventions – pre-visit planning and use of a registry – suggested that the efficacy of these could depend on LHN current state. By translating heuristic theories of LHNs to a specifiable, reproducible, and explicit model, this research advances the scientific study of LHNs using tools available from complex systems science.
by Cheyenne R. Wagi, Renee McDowell, Anyssa Wright, Kathleen L. Egan, Christina S. Meade, April M. Young, Madison N. Enderle, Angela T. Estadt, Kathryn E. Lancaster
BackgroundHepatitis C virus (HCV) and injection drug use among young women are dramatically rising in the rural United States. From 2004 to 2017, heroin use among non-pregnant women increased 22.4% biennially, mirroring increases in HCV cases, especially among younger populations. Young women who inject drugs (YWID, ages 18–35) face elevated HCV risk due to biological, behavioral, and socio-cultural factors. Barriers to HCV testing and treatment services further delay diagnoses, fuel transmission, and limit access to harm reduction services. This study applies the Theoretical Domains Framework (TDF) to identify factors influencing HCV testing and treatment among YWID in rural Appalachia Ohio.
MethodsWe conducted in-depth interviews with YWID (n = 30) in 2023 to understand their HCV testing and treatment experiences in rural Appalachia Ohio. Interviews were transcribed, inductively coded, and analyzed using grounded theory. Identified themes were mapped onto the TDF domains.
ResultsKey TDF domains influencing HCV care included knowledge, beliefs about consequences, and intentions. While YWID knew where to get tested, they expressed uncertainty about treatment value and access while actively using drugs. Social influences, stigma, and mistreatment by healthcare providers created barriers to treatment. Environmental context and resources, such as transportation, also influenced access to care.
ConclusionsYWID in rural Appalachia face barriers to HCV care, such as gaps in knowledge about HCV treatment, which is compounded by gendered stigma, and logistical challenges. Rapidly changing treatment restrictions led to misinformation about treatment access. These gaps highlight the need for interventions specifically designed to address YWID lived experiences.
by Jordan Salomon, Haydee Montemayor, Cassandra Durden, Dorcas Abiara, Rachel E. Busselman, Gabriel L. Hamer, Sarah A. Hamer
Management of tick-borne disease necessitates an understanding of tick phenology, tick-host associations, and pathogen dynamics. In a recreational hotspot outside of one of the largest cities in the United States, we conducted a year of monthly standardized tick drag sampling and wildlife trapping in Sam Houston National Forest, a high use recreation site near Houston in east Texas, US. By sampling 150 wildlife hosts of 18 species, including rodents, meso-mammals, deer, reptiles, and amphibians, we collected 87 blood samples, 90 ear biopsies, and 861 ticks representing four species (Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis and Ixodes texanus). Drag sampling yielded 1,651 questing ticks of three species: A. americanum (921), D. variabilis (10), and I. scapularis (720). Off-host larval A. americanum abundance peaked in July, followed by peak infestations of wildlife, predominantly raccoons, in August. Off-host I. scapularis larvae abundance peaked in spring (March-May), while very few were removed from hosts and only a single I. scapularis nymph was found throughout the study via dragging in June. In contrast, both off-host and on-host adult I. scapularis occurred most frequently in the winter. Overall, tick infections included 25.3% (183/725) with Rickettsia buchneri, 15.5% (112/725) Rickettsia amblyommatis, 8.0% (58/725) Rickettsia tillamookensis, 0.8% (6/725) Rickettsia spp., and a single tick with a hard tick relapsing fever Borrelia spp.; no tick tested positive for Borrelia burgdorferi. Characterizing tick phenology, tick-host associations, and tick-borne bacteria fills important knowledge gaps for the risk of tick-borne diseases in pine-dominated forests of this region.
by Okkeun Jung, Angelene Soto, Andrew L. Wolfe, Shahana S. Mahajan
KRAS mutations, which induce proliferative signaling driving many human cancers, are detectable in a small subset of osteosarcoma patients. The recently developed pan-KRAS inhibitor daraxonrasib, also known as RMC-6236, is capable of targeting a wide array of KRAS mutations and shows promise against pancreatic and lung cancers. However, the efficacy and mechanisms of action of daraxonrasib in osteosarcoma (OS) remain unclear. We evaluated the effects of daraxonrasib on the viability, proliferation, and metastatic potential of wild-type and KRAS mutant OS cells. We assayed the effects of treatment on downstream targets using qPCR, immunoblotting, and activity assays to explore the underlying mechanism by which daraxonrasib selectively suppresses the metastatic potential of KRAS mutant osteosarcoma. Finally, we investigated how the increased prevalence of GTP-bound KRAS enhanced the sensitivity of KRAS wild-type osteosarcoma cells to daraxonrasib using siRNA targeting RASA1. Daraxonrasib selectively attenuated the proliferation and migratory ability of KRAS mutant HOS-143B cells without affecting KRAS wild-type controls. Additionally, daraxonrasib suppressed the expression of the matrix metalloproteases MMP9 and MMP1, which promote cell motility and metastasis. Daraxonrasib selectively inhibited the AKT/ETS1 pathway in HOS-143B cells, whereas no such effect was observed in HOS cells. HOS cells were sensitized to daraxonrasib by knocking down the GTPase-activating protein RASA1. In osteosarcoma, KRAS inhibition decreased MMP1, MMP9, and AKT/ETS1 signaling. Daraxonrasib is a promising agent for treating osteosarcoma with KRAS mutations.
by Vijeeth Guggilla, Jennifer A. Pacheco, Alexandre M. Carvalho, Grant R. Whitmer, Anna E. Pawlowski, Jodi L. Johnson, Catherine A. Gao, Chad J. Achenbach, Theresa L. Walunas
BackgroundAdults with immunosuppression are more likely to develop severe COVID-19 than adults without immunosuppression. Less is known about differences in outcomes for adults with immunosuppression who are hospitalized with COVID-19.
MethodsA retrospective cohort study of adults hospitalized with COVID-19 at Northwestern Medicine hospitals between 03/01/2020 and 05/31/2022 was performed. Regression analyses were performed comparing in-hospital mortality, intensive care unit (ICU) admission, oxygenation requirements, and hospital/ICU length of stay among patients without immunosuppression (n = 9079) and patients with immunosuppression (n = 873).
ResultsPatients with immunosuppression had significantly higher mortality than patients without immunosuppression (OR: 1.33, 95% CI: 1.11–1.60). This effect was even stronger when controlling for age at admission, diabetes, obesity, SARS-CoV-2 variant era, and COVID-19 medication use (adjusted OR: 1.78, 95% CI: 1.46–2.16). ICU admission (adjusted OR: 1.64, 95% CI: 1.41–1.90) and invasive ventilation (adjusted OR: 1.68, 95% CI: 1.36–2.06) were also significantly higher in patients with immunosuppression. Hospitalization length (median: 7 days) and ICU length of stay (median: 2.5 days) were longer in patients with immunosuppression compared to patients without immunosuppression (median: 5 days, adjusted p Conclusions
Patients with immunosuppression had worse outcomes than patients without immunosuppression. Subgroup analyses showed that patients with solid organ transplant had the worst outcomes overall. Patients with HIV had similar outcomes as patients without immunosuppression unless CD4 cell count was low.
by Melissa L. Woodward, Morgan W. Wolsey, Sophia Shalchy-Tabrizi, Jeffrey N. Bone, Tyler Black, Quynh Doan
BackgroundThe pediatric mental health crisis pre-dated the COVID 19 pandemic with rates of mental health visits to pediatric emergency departments steadily increasing for the last decade. The COVID-19 pandemic has profoundly impacted children and adolescents and understanding the trajectory of their psychosocial status is important for appropriate resource allocation and policy planning.
MethodsMyHEARTSMAP is a digital self-assessment mental health evaluation that examines four major psychosocial domains: psychiatry, social, function, and youth health. Children and adolescents throughout British Columbia, and their guardians, completed the baseline assessment between August 2020 and July 2021 (51.8% completed by guardian only, 40.2% youth and guardians, 7.9% youth only). Both children and their guardians repeated the MyHEARTSMAP evaluation three-months after their baseline. Patient demographics and psychosocial concerns were statistically described and compared between baseline and follow-up. A logistic regression model assessed the influence of baseline scores and demographic factors on follow-up severity.
Results241 of 424 participants (56.8%) completed both the baseline and three-month follow-up. The majority of participants reported no change overtime across the psychosocial domains. Both improvement and decline occurred in each domain, with a greater proportion of psychosocial states improving rather than worsening, for all domains. Higher severity of psychosocial concerns reported at baseline indicated a greater likelihood of psychosocial concerns at 3-month follow-up for psychiatric, social and function concerns. Demographic, pandemic, and support service variables were not associated with psychosocial trajectories.
ConclusionsThe severity of youth mental health concerns in British Columbia remained consistent through three-month follow up, despite the changing nature of the COVID-19 pandemic during this period. Greater persistence of psychosocial concerns with increased severity highlights the need for early intervention to prevent worsening mental health. Community support is needed for youth experiencing mental health concerns to address mild psychosocial concerns before presentation at the emergency department.
by Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson
Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via intracerebroventricular (ICV) injections and received 3, 30, or 200 μg rhGNS in 4 doses over 2 weeks or vehicle. Twenty-four hours after the final dose, HS in brain and CSF showed dose-dependent reductions, reaching carrier levels in the higher dose groups. Furthermore, the proteomic perturbations that we described were corrected by rhGNS treatment. Next, Gns KO or carrier adult mice were treated via ICV and received 3, 30 or 200 μg rhGNS or vehicle once every two weeks (Day 1, 15, 29, 43, 57, 71, 85) and were euthanized on day 91. Following treatment, total HS and MPS IIID-specific HS (GlcNAc6S) showed dose-dependent reductions in brain and CSF and markers of neuroinflammation were substantially reduced. ICV enzyme replacement therapy with rhGNS restores CNS pathology of adult MPS IIID mice even with treatment at 14-day intervals, demonstrating preclinical efficacy for MPS IIID.
by Florence L. Meier, Levy Jäger, Oliver Senn, Stefan Markun, Jakob M. Burgstaller
RegistrationProspero (CRD42024506727).
by Bisman Mangat, Luc Tremblay, Joyce L. Chen
BackgroundPriming the primary motor cortex (M1) with transcranial direct current stimulation (tDCS) prior to motor practice modulates post-synaptic activity, thereby impacting learning of a motor skill. This effect has been shown for the acquisition of simple motor skills. It is not clear whether priming tDCS can impact the learning/retention of a more naturalistic motor task.
Objective/HypothesisWe investigated the effects of priming M1 with tDCS on the performance on a golf putting task. We hypothesized that participants who receive tDCS with the cathode over M1 (C-M1) would show better skill acquisition and retention performance, relative to participants who receive tDCS with the anode over M1 (A-M1) or sham tDCS.
MethodsThirty-six participants were randomized into three groups: C-M1, A-M1, and sham tDCS. Participants received tDCS (1mA, 20 minutes) prior to practicing golf putting across two days. Performance (error) was measured for each putt. Participants returned on the third day for a retention test.
ResultsAfter accounting for baseline performance, the C-M1 group performed significantly better compared to A-M1 [p = 0.02] and sham tDCS [p = 0.01] at the retention test. There was no difference in retention performance between A-M1 and sham tDCS.
ConclusionOur findings partially support the Bienenstock-Cooper-Munro rule of metaplasticity. C-M1 tDCS priming enhanced motor learning, while A-M1 tDCS priming had no effect, relative to sham.
by Mayuko Takezaki, Biaoru Li, Hongyan Xu, Nikhil Patel, Rudolf Lucas, Ryan E. Cerbone, Sivanagireddy Koti, Clifford L. Hendrick, Louis H. Junker, Betty S. Pace
The most common hemoglobin disorder worldwide is sickle cell disease (SCD) caused by a point mutation in the adult β-globin gene. As a result, hemoglobin S production occurs leading to clinical symptoms including vaso-occlusive pain, organ damage, and a shortened lifespan. Hydroxyurea is the only FDA-approved fetal hemoglobin (HbF) inducer in the United States that ameliorates the clinical severity of SCD. Due to challenges with hydroxyurea, our study aimed to address the unmet need for the development of non-chemotherapeutic HbF inducers. We investigated the ability of CT-101, a Class 1 histone deacetylase inhibitor, to flip the γ-globin to β-globin switch in a humanized SCD mouse model. Pharmacokinetic parameters were assessed in CD-1 and Townes SCD mice after a single intraperitoneal drug dose. Similar drug uptake and half-life were observed in both animals. Subsequent studies in β-YAC mice expressing human γ-globin and β-globin genes established the optimal dose of CT-101 that induces HbF without peripheral blood toxicity. Subsequent confirmatory studies were conducted in the SCD mouse treated with intraperitoneal CT-101, demonstrating increases in F-cells, HbF, and γ-globin gene mRNA levels. Hydroxyurea combined with CT-101 significantly decreased spleen size and hemorrhagic infarcts and improved splenic extramedullary hematopoiesis. Our novel agent, CT-101, flipped the switch by activating γ-globin gene transcription and HbF protein synthesis in the preclinical SCD mouse model without significant toxicity in the peripheral blood. These findings support the development of an oral CT-101 formulation for clinical testing in SCD.
by Jaimee Cooper, Jeenu Mittal, Max Zalta, Nicholas DiStefano, Delany L. Klassen, Keelin McKenna, Dimitri A. Godur, Andrea Monterrubio, Moeed Moosa, Rahul Mittal, Adrien A. Eshraghi
Cochlear implantation is a surgical intervention to provide auditory rehabilitation to individuals with severe to profound hearing loss. Intraoperative electrocochleography (ECochG) has emerged as a promising tool for monitoring cochlear health during cochlear implant (CI) surgery. This systematic review aims to synthesize current evidence regarding the effectiveness of intraoperative ECochG in predicting postoperative residual hearing levels in CI recipients. A comprehensive literature search was conducted across major databases including PubMed, Embase, Web of Science, and SCOPUS. The protocol for this systematic review was registered in the PROSPERO database (registration number: CRD42023476617). The key outcomes assessed were the correlation between intraoperative ECochG patterns and postoperative residual hearing levels, as well as the influence of surgical techniques and electrode design on ECochG responses and hearing preservation. The Risk of Bias analysis was conducted using the Joanna Briggs Institute Critical Appraisal Tool. The review included a total of eighteen studies that met the inclusion and exclusion criteria. A significant correlation was reported between specific intraoperative ECochG response patterns and the preservation of residual hearing post-surgery. Studies highlighted that robust ECochG responses typically indicated a higher likelihood of postoperative hearing preservation. The review also identified factors influencing ECochG responses, including electrode design and insertion techniques. Several studies reported improved preservation of residual hearing with modifications in surgical approaches guided by ECochG feedback. Intraoperative ECochG monitoring emerges as a crucial tool in predicting and potentially enhancing postoperative residual hearing outcomes in implanted individuals. The review underscores the value of ECochG in guiding surgical technique adjustments, thereby maximizing hearing preservation. However, the heterogeneity in study designs and ECochG protocols suggests a need for standardization in this field. Future research should focus on large-scale, multicenter trials to establish definitive guidelines for integrating ECochG in CI surgeries, with an emphasis on long-term hearing outcomes.
by Kristina Devi Singh-Verdeflor, Michelle M. Kelly, Gregory P. DeMuri, Gemma Warner, Sabrina M. Butteris, Mary L. Ehlenbach, Barbara Katz, Joseph A. McBride, Shawn Koval, Ryan J. Coller
BackgroundCOVID-19 testing safeguards the health of children with medical complexity (CMC) through several key mechanisms, such as the implementation of clinical action plans and COVID-19-directed therapies. However, testing utility is limited by barriers to access and perceptions surrounding use. This study investigated associations between rurality and COVID-19 testing access, intent, motivators, and concerns for caregivers of CMC.
MethodsWe conducted a cross-sectional survey (April – June 2022) of English- and Spanish-speaking caregivers of children with at least one complex chronic condition between ages 5–17 at an academic medical center in the Midwestern USA. Rurality was dichotomized using Rural-Urban Commuting Area codes. Outcomes represented COVID-19 testing access, intent, motivators, and concerns. Covariates included demographic and clinical characteristics. Unadjusted and adjusted logistic regression analyses examined associations between rurality and each outcome.
ResultsAmong 1,432 responses (response rate 49%), 359 (25%) were classified as rural. Respondents had varied education, income, and insurance levels. In the multivariable models, rural and urban caregivers reported similarly high testing access, but rural caregivers had significantly less testing intent (adjusted Odds Ratio [95% CI]: 0.53, [0.40, 0.71]). Notably, rural caregivers were significantly more likely to indicate “It will be difficult to get needed healthcare if my child has it” (2.49 [1.19, 5.18]).
ConclusionsWhile rural and urban CMC caregivers reported generally high access and ease of COVID-19 testing, potentially modifiable factors exist to improve testing intention and decrease barriers, including communication regarding testing utility and timing as well as access to effective treatment response upon testing positive.
by Eugénie M. Kamabu, Justin L. Paluku, William P. Howlett, Abid M. Sadiq, Eliada B. Nziku, Doreen T. Eliah, Ibrahim Ali Ibrahim Muhina, Fuad H. Said, Tumaini E. Mirai, Elifuraha W. Mkwizu, Furaha S. Lyamuya, Elichilia R. Shao, Kajiru G. Kilonzo, Venance P. Maro, Sarah J. Urasa, Nyasatu G. Chamba
BackgroundAmong acute stroke patients (ASPs), diabetes mellitus (DM) is associated with a higher risk of death, functional dependency, and recurrence. This study aimed to determine the impact of DM on the 30-day mortality among admitted ASPs in northern Tanzania.
Materials and methodsThis was a hospital-based prospective cohort study performed among ASPs with and without DM who were admitted to Kilimanjaro Christian Medical Centre from November 2022 to May2023. ASPs were followed for 30 days after the onset of an acute stroke to identify the primary outcome, which was all-cause mortality. Descriptive statistics, logistic regression, and survival analysis were conducted,
ResultsOut of 213 ASP, 82 (38.5%) had DM. The overall crude mortality rate was 46.9%. ASPs with DM had a higher mortality rate of 53.7% compared with those without DM (42.7%). A higher proportion of acute stroke patients with DM (84.1%) had a poor outcome (mRS 3-6) (p = 0.038). DM was statistically non-significant for 30-day mortality (aHR 1.56; 95% CI: 0.73–3.32; p = 0.252). However, fever (p = 0.005), severe admission Glasgow coma scale (p = 0.005), severe stroke (p = 0.008), elevated serum creatinine (p = 0.008), and an abnormal respiratory pattern (p = 0.042), were predictors of 30-day mortality,
ConclusionThis study demonstrated a high mortality in ASPs. Although DM did not have a significant impact on 30-day mortality, other factors, such as altered mental state, stroke severity, fever, elevated creatinine, and abnormal respiration, need to be accounted for that may have a significant impact on the mortality in ASPs. These findings highlight the significant burden of DM in stroke patients and underscore the importance of early diagnosis and treatment of ASPs, in the hopes of improving clinical practice and guidelines and reducing morbidity and mortality in Tanzania.
by Jonathan Gwasupika, Davidson H. Hamer, Victor Daka, Ephraim Chikwanda, David Mwakazanga, Ruth L. Mfune, Choolwe Jacobs
BackgroundChildren with human immunodeficiency virus (HIV) infection are disproportionately susceptible to bacterial infections. There are a wide range of antibacterial agents available to manage HIV positive children with bacterial infections. However, administration of antibiotics in most children is empirical which could lead to antimicrobial resistance.
ObjectivesThis study aimed to determine commonly prescribed antibiotics and associated symptoms in children at Arthur Davison children’s hospital antiretroviral therapy clinic in Ndola, Zambia.
MethodsThis was a cross-sectional study that analysed the antibiotic prescribing patterns from routinely collected secondary data at Arthur Davison children’s hospital. Children diagnosed with HIV before the age of 5, actively attending antiretroviral therapy clinic identified by SmartCare software and who had taken antiretroviral therapy for at least 6 months were eligible. Data were collected from files of children who met the eligibility criteria. STATA software version 16 SE (STATA Corp., College Station, Texas, USA) was used for analysis. A p-value less than 0.05 was considered statistically significant at a confidence interval of 95%.
ResultsFrom a total of 132 children included in the study, 37.9% presented with symptoms with the most common symptoms being cough (70.0%) and diarrhoea (30.0%). A larger proportion of children (62.1%) were on arbacavir/lamivudine/dolutogravr combination of antiretroviral therapy while 8.2% were on the tenoforvir alafenamide/lamivudine/dolutobravir regimen. Children who were on abacavir/lamivudine/dolutegravir regimen presented with more symptoms (48.8%) compared to those on tenofovir alafenamide/lamivudine/dolutegravir (21.0%) and tenofovir disoproxil fumarate/lamivudine/dolutegravir (18.2%) (p = 0.006). Approximately 60.0% of children presenting with symptoms were prescribed antibiotics. Co-trimoxazole was the most commonly (38.0%) prescribed, while erythromycin (2.0%) and Cephalexin (2.0%) were the least.
ConclusionsRespiratory and gastrointestinal symptoms were the most common presentations suggestive of a suspected infection requiring antibiotic prescription in HIV-positive children on ART. Despite co-trimoxazole being the prophylactic drug among HIV-positive children, it was the most common antibiotic among children presenting with symptoms suggestive of an infection. This calls for the prudent use of co-trimoxazole to avoid its resistance.
by Melissa A. Hausburg, Kaysie L. Banton, Christopher D. Cassidy, Robert M. Madayag, Carlos H. Palacio, Jason S. Williams, Raphael Bar-Or, Rebecca J. Ryznar, David Bar-Or
Previous abdominal surgery (PAS) increases risk of small bowel obstruction (SBO) due to adhesions, and appendectomy (appy) is an independent risk factor for abdominal adhesion-related complications. Peritoneal inflammation, e.g., acute appendicitis (AA), causes formation of reactive ascitic fluid (rA) that activates peritoneum surface mesothelial cells (MCs) to form adhesions. Pathologic adhesions may arise if restoration of MC-regulated fibrinolysis and secretion of glycocalyx (GCX) are disrupted. Proteins affecting these processes may originate from peritoneal rA. This is a prospective observational IRB-approved study at three Level 1 trauma centers where rA is collected prior to surgical intervention for non-perforated AA or adhesiolysis for SBO. Samples from 48 appy and 15 SBO patients were used to treat human MCs and subjected to quantification of 85 inflammatory mediators. Results were compared between patients with surgically naïve abdomens (naïve) and patients with >1 PAS. Select rA caused MCs to form clusters of fibroblastic cells, extracellular matrix fibers (FIB), and secretion of GCX. PAS and naïve patient rA fluids were clustered into “fiber-GCX” (FIB-GCX) groups: highFIB-highGCX, highFIB-lowGCX, noFIB-highGCX, noFIB-lowGCX, and noFIB-noGCX. Between groups, 26 analytes were differentially abundant including innate immune response, wound healing, and mucosal defense proteins. Factors that contributed to the differences between groups were rA-induced highFIB and history of PAS. Overall, PAS patient rA showed a muted immune response compared to rA from naïve patients. Our data suggest that abdominal surgery may negatively impact future immune responses in the abdomen. Further, quantifying immunomodulators in peritoneal rA may lead to the development a personalized approach to post-surgical adhesion treatment and prevention.
by Féline E. V. Scheijmans, Roosmarijn van der Wal, Margot L. Zomers, Johannes J. M. van Delden, W. Ludo van der Pol, Ghislaine J. M. W. van Thiel
ObjectivesSolidarity-based healthcare systems are being challenged by the incremental costs of new and expensive medicines for cancer and rare diseases. To regulate reimbursement of such drugs, the Dutch government introduced a policy instrument known as the Coverage Lock (CL) in 2015. Little is known about the public opinion regarding such policy instruments and their consequences, i.e., reimbursement of some, but not all, expensive medicines. We aimed to identify the preferences of Dutch citizens regarding the reimbursement of expensive medicines, and to investigate the views of the public on the use of the CL as a healthcare policy instrument and their input for improvement.
MethodsWeb-based survey of a representative sample of 1999 Dutch citizens aged 18 years and older (panel of research company Kantar Public). Potential respondents were approached via e-mail. Several policy measures, real-life cases and statements related to the CL were presented in the survey to respondents. Their responses were analysed by tabulating descriptive statistics (proportions and percentages).
Results1179 individuals (response rate 59%) filled in the questionnaire. Although a majority considered the CL policy unjustified, they preferred it to the alternative policy measures that were presented. In four real-life case descriptions of patients in need of expensive medicines, respondents most often indicated effectiveness, lack of availability of alternative treatment and improved quality of life due to treatment as reasons for a positive reimbursement decision. An unfavourable cost-benefit ratio was their main reason to be against reimbursement. Some argued that withholding reimbursement was a way of informing manufacturers that extremely high prices are unacceptable.
ConclusionThere is public support for patients in need of expensive medicine. Many respondents supported the CL as a reimbursement policy. However, there is a wish to optimize the interpretation of the assessment criteria and the weight these are attributed in decision making about reimbursement of expensive innovative medicine for patients.
by Jasmine C. Mah, Olga Theou, Mario Ulises Perez-Zepeda, Jodie L. Penwarden, Judith Godin, Kenneth Rockwood, Melissa K. Andrew
BackgroundThe construct of social vulnerability attempts to understand social circumstances not merely as a descriptor, but as a predictor of adverse health events. It can be measured by aggregating social deficits in a social vulnerability index (SVI). We describe a standard procedure for constructing a multi-level SVI using two working examples.
MethodsFirst, we describe a six-step approach to constructing a SVI. Then, we conducted a secondary analysis of a clinical dataset (Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (SOS)) and a population-based dataset (Canadian Longitudinal Study on Aging (CLSA)). In both datasets, we construct SVIs, use descriptive statistics to report distributions by age and sex, and perform a multivariable linear regression of social vulnerability on frailty.
ResultsProcedures for drafting a list of candidate social items, selecting deficits for inclusion, and screening deficits to meet inclusion criteria were applied to yield a 18-deficit SVI for the SOS and 74-deficit SVI for the CLSA. Deficits in each SVI were re-scored between 0 and 1, where 1 indicates the greater risk. Finally, the sum of all deficits is calculated into an index. In the SOS, SVI was associated with age only for females and was weakly associated with frailty (r = 0.26, p Conclusion
We present a standard method of constructing a SVI by incorporating factors from multiple social domains and levels in a social-ecological model. This SVI can be used to improve our understanding of social vulnerability and its impacts on the health of communities and individuals.
by Irazú Contreras-Yáñez, Guillermo A. Guaracha-Basáñez, Diana Padilla-Ortiz, Laura L. Franco-Mejía, Laura V. Vargas-Sánchez, Julia G. Jiménez-Decle, Virginia Pascual-Ramos
IntroductionMany factors influence how doctors make treatment decisions. The study compares the outcomes of patients with rheumatic diseases and adequate control (AC) whose treating rheumatologists prescribed their first choice of treatment (FCHO) versus the second choice (SCHO) and the motivations behind them. It also investigates the motivations associated with FCHO.
Patients and methodsThe study was conducted at an outpatient clinic from February 2023 to February 2024. Patients with an RMD diagnosis were identified using systematic sampling (P-1). After their consultation, their rheumatologists detailed their treatment choice (FCHO vs. SCHO), the motivations behind it, and the outcomes. In a subsample of patients from P-1 and AC (SubP-1), treating rheumatologists repeated the assessment of outcomes at the next scheduled consultation. Descriptive statistics and multivariate regression analysis were used.
ResultsThere were 703 patients enrolled (P-1), 543 (77.2%) had AC, and 292 (Subp-1) underwent a follow-up evaluation. In P-1 and subP-1, FCHO was prescribed to 644 (91.5%) and 269 (92.1%) patients.Motivations related to evidence-based medicine and personal experience were more frequently referred to in FCHO. Concerns related to current or future drug shortages and a history of adverse events/intolerance were more frequent in SCHO.In SubP-1, a higher proportion of patients remained in AC and experienced remission/ improved disease activity with FCHO. Patients who received FCHO experienced a greater risk for favorable outcomes.The following motivations were associated with FCHO: “It aligns with guidelines”; “solid scientific evidence supporting the treatment effectiveness”; “I am concerned that the shortage of the drug may hinder the continuation of the treatment” and “history of adverse events or intolerance”.
ConclusionsPatients with AC of their underlying RMD, whose rheumatologists prescribed their FCHO, had better outcomes than those who were prescribed SCHO. Evidence-based motivations, rheumatologists´ concern of medication shortage, and patient-related motivations were associated with FCHO.
FreshRSS