Disparities in time to treatment initiation for rectal cancer patients: an analysis of demographic and socioeconomic factors.

Background: This study investigated demographic and socioeconomic factors contributing to disparities in the time to treatment for rectal cancer. Subgroup analysis based on age < 50 and ≥ 50 was performed to identify differences in time to treatment among young adults (age < 50) compared to older adults with rectal cancer. Methods: An analysis was performed using data from the National Cancer Database, spanning from 2004 to 2019. The study encompassed 281,849 patients diagnosed with rectal cancer. We compared time intervals from diagnosis to surgery, radiation, and chemotherapy, considering age, sex, race, and socioeconomic variables. Analyses were performed for the entire cohort and for two subgroups based on age (< 50 and ≥ 50). Results: Overall, Hispanic patients experienced longer times to surgery, radiation, and chemotherapy compared to non-Hispanic patients (surgery: 94.2 vs. 79.1 days, radiation: 65.0 vs. 55.6 days, chemotherapy: 56.4 vs. 47.8 days, all p < 0.001). Patients with private insurance had shorter times to any treatment (32.5 days) compared to those with government insurance or no insurance (30.6 and 32.5 days, respectively, p < 0.001). Black patients experienced longer wait times for both radiation (63.4 days) and chemotherapy (55.2 days) compared to White patients (54.9 days for radiation and 47.3 days for chemotherapy, both p < 0.001). Interestingly, patients treated at academic facilities had longer times to treatment in surgery, radiation, and chemotherapy compared to those treated at comprehensive and community facilities. When analyzed by age, many of the overall differences persisted despite the age stratification, suggesting that these disparities were driven more by demographic and socioeconomic variables rather than by age. Conclusion: Significant differences in the time to treatment for rectal cancer have been identified. Hispanic patients, individuals lacking private insurance, Black patients, and patients receiving care at academic facilities had the longest times to treatment. However, these differences were largely unaffected by the age (< 50 and ≥ 50) subgroup analysis. Further investigation into the causes of these disparities is warranted to develop effective strategies for reducing treatment gaps and enhancing overall care for rectal cancer patients.

Liposomal Phenylephrine Nanoparticles Enhance the Antitumor Activity of Intratumoral Chemotherapy in a Preclinical Model of Melanoma.

Intratumoral injection of anticancer agents has limited efficacy and is not routinely used for most cancers. In this study, we aimed to improve the efficacy of intratumoral chemotherapy using a novel approach comprising peri-tumoral injection of sustained-release liposomal nanoparticles containing phenylephrine, which is a potent vasoconstrictor. Using a preclinical model of melanoma, we have previously shown that systemically administered (intravenous) phenylephrine could transiently shunt blood flow to the tumor at the time of drug delivery, which in turn improved antitumor responses. This approach was called dynamic control of tumor-associated vessels. Herein, we used liposomal phenylephrine nanoparticles as a "local" dynamic control strategy for the B16 melanoma. Local dynamic control was shown to increase the retention and exposure time of tumors to intratumorally injected chemotherapy (melphalan). C57BL/6 mice bearing B16 tumors were treated with intratumoral melphalan and peri-tumoral injection of sustained-release liposomal phenylephrine nanoparticles (i.e., the local dynamic control protocol). These mice had statistically significantly improved antitumor responses compared to melphalan alone (p = 0.0011), whereby 58.3% obtained long-term complete clinical response. Our novel approach of local dynamic control demonstrated significantly enhanced antitumor efficacy and is the subject of future clinical trials being designed by our group.

Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

Women, water and access: inscribing gender power in and through a place.

This paper explores the socio-cultural and gender-based dynamics associated with place values, and their implications for women's access to water through case studies of upland and riverine communities in southern Nigeria. We used a range of fieldwork methods including public meetings, focus group discussions, in-depth interviews, keen observations, key informants and other secondary sources. Our findings show that drinking water sources are a part of the many forms of visible material structures that embody and generate automatic reproduction of gender-based beliefs, attitudes, feelings and practices. The outcome of such practices affects men and women differently in relation to access, workload and capacity for hygiene and other socio-economic practices. In discussing access to essential public goods, social and economic capacities take priority focus over the impact of 'place values' either as standalone or intersectional elements. Research should be expanded to incorporate these elements and their intersectional perspectives in shaping access to water.

Assessing urogenital schistosomiasis and female genital schistosomiasis (FGS) among adolescents in Anaocha, Anambra State, Nigeria: implications for ongoing control efforts.

BACKGROUND: Urogenital schistosomiasis (UgS) remains a persistent health challenge among adolescents in Anambra State, Nigeria, despite ongoing control efforts. Mass praziquantel treatment programs, initiated in 2013, primarily target primary school-aged children (5-14 years old), leaving adolescents (10-19 years old) enrolled in secondary schools vulnerable to urogenital schistosomiaisis. Additionally, the extent of female genital schistosomiasis (FGS), a neglected gynaecological manifestation of UgS remains unclear. METHODOLOGY: To address these gaps, a cross-sectional study was conducted in Anaocha Local Government Area from February to May 2023. Four hundred and seventy consenting adolescents aged 10-19 years were enrolled. Urinalysis including urine filtration was employed to confirm haematuria and detect urogenital schistosomiasis (UGS) among the participants. For females with heavy infections (≥ 50 eggs/10 ml urine), a gynaecologist performed colposcopy examinations, complemented by acetic acid and Lugol's iodine staining to assess for female genital schistosomiasis (FGS) lesions or other related reproductive health conditions. Socio-demographic data, including information on potential risk factors, were systematically collected using the Kobo ToolBox software, following gender-sensitive data collection guidelines. Data were analysed using SPSS version 25, incorporating descriptive statistics, multinomial logistic regression, odds ratios, and significance testing. RESULTS: Among the 470 adolescents (52.8% females, 47.2% males) examined, an overall UgS prevalence of 14.5% was observed, with an average of 5.25 eggs per 10 ml of urine. Females had a slightly higher prevalence (16.1%), and 7.5% had heavy infections. Although gender differences in infection rates were not statistically significant, males had slightly higher odds of infection (OR: 1.332; 95% CI: 0.791-2.244; p-value: 0.280). Adolescents aged 10-14 had the highest prevalence, with significantly increased odds of infection (OR: 1.720; 95% CI: 1.012-2.923; p-value: 0.045). Colposcopy examinations of females with heavy infections revealed FGS lesions and co-infections with Trichomonas vaginalis. Haematuria, though prevalent (24.6%), was not the sole indicator, as those without it faced significantly higher odds of infection (OR: 2.924; 95% CI: 1.731-4.941; p-value: 0.000). Dysuria and genital itching/burning sensation were other UgS and FGS associated symptoms. Direct water contact was associated with higher infection odds (OR: 2.601; 95% CI: 1.007-6.716; p-value: 0.048). Various risk factors were associated with UgS. CONCLUSION: The study highlights the need for a comprehensive Urogenital Schistosomiasis (UGS) control strategy that includes secondary school adolescents, emphasizes risk factor management, promotes safe water practices, and raises awareness about UGS and Female Genital Schistosomiasis (FGS) among adolescents, thus improving control efforts and mitigating this health challenge in the region.

Growth and Fruit morphometric characteristics of local avocado germplasm (Persea americana Mill.) grown in northern Tanzania.

Tanzania has a diverse agroecological area suitable for growing tropical fruits, including avocados. In Northern Tanzania, avocados have been growing under variable soil and altitudinal characteristics for over 100 years, allowing the naturalisation of this crop in this region. However, the region's avocado germplasm is uncharacterised, thus impeding the selection of elite genotypes for increased value and breeding programmes. This study examined the growth and fruit morphometric characteristics of avocado populations grown under variable soil pH and altitude in six districts in the Tanga, Kilimanjaro and Arusha regions. Variations in growth and fruit morphometric characteristics were compared using a one-way analysis of variance (ANOVA). Pearson product-moment correlations (r) were used to evaluate the relationship between studied growth and fruit morphometric traits. A linear mixed-effects model (LMM) was used to assess the influence of the soil pH, altitude, tree height, canopy diameter, and trunk diameter on fruit length, fruit diameter, pulp thickness, and seed diameter. Principal Component Analysis (PCA) was used to depict the extent of the racial admixtures in the avocado germplasm in the Northern regions of Tanzania. The results revealed a significant variation in growth and fruit morphometric characteristics (p < 0.05). The Korogwe population had the highest tree height, while the Karatu had the lowest. Tree height was positively correlated with the trunk diameter (r = 0.63, p < 0.001. There was a positive correlation between fruit length and pulp thickness (r = 0.51, p < 0.001), fruit diameter and pulp thickness (r = 0.47, p < 0.001), and fruit length and fruit diameter (r = 0.36, p < 0.001). The fruit diameter was positively correlated with the seed diameter (r = 0.61, p < 0.001). There was a significant but weak association between fruit length and trunk diameter (-0.01), fruit length and canopy diameter (0.15), and between seed diameter and tree height (2.95e-2). These findings highlight the influence of individual tree genetic makeup on the variation in growth and fruit morphometric characteristics. The morphometric trait correlations may prove valuable in field measurements, especially when resources are limited. The study further indicates the presence of all avocado races within the local germplasm, highlighting its high diversity. Remarkably, the observed admixture of variant races implies gene flow among studied avocado populations, possibly facilitated by sharing seedlings among farmers or seed disposal through avocado fruit trading. Further study is needed, particularly in quantifying the above-ground biomass of local avocados in northern Tanzania, potentially contributing to carbon credit initiatives for fruit crops..

Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.

BACKGROUND: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients. METHOD: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results. RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance. CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma.

In this study, we tested a novel approach of "repurposing" a biomarker typically associated with breast cancer for use in melanoma. HER2/neu is a well characterized biomarker in breast cancer for which effective anti-HER2/neu therapies are readily available. We constructed a lentivirus encoding c-erb-B2 (the animal homolog to HER2/neu). This was used to transfect B16 melanoma in vitro for use in an orthotopic preclinical mouse model, which resulted in expression of c-erb-B2 as a neoantigen target for anti-c-erb-B2 monoclonal antibody (7.16.4). The c-erb-B2-expressing melanoma was designated B16/neu. 7.16.4 produced statistically significant in vivo anti-tumor responses against B16/neu. This effect was mediated by NK-cell antibody-dependent cell-mediated cytotoxicity. To further model human melanoma (which expresses <5% HER2/neu), our c-erb-B2 encoding lentivirus was used to inoculate naïve (wild-type) B16 tumors in vivo, resulting in successful c-erb-B2 expression. When combined with 7.16.4, anti-tumor responses were again demonstrated where approximately 40% of mice treated with c-erb-B2 lentivirus and 7.16.4 achieved complete clinical response and long-term survival. For the first time, we demonstrated a novel strategy to repurpose c-erb-B2 as a neoantigen target for melanoma. Our findings are particularly significant in the contemporary setting where newer anti-HER2/neu antibody-drug candidates have shown increased efficacy.

The Practicality of Preparing Skim Breast Milk at Home for Treatment of Infants Requiring Low Fat Diets.

Introduction: The benefits of breast milk (BM) for infants have long been established. However, for health-compromised infants with difficulty processing long-chain triglycerides, BM is often discontinued, and skimmed breast milk (SBM) is used as a dietary treatment. SBM is usually produced for inpatients in a hospital laboratory. The aim of this study was to determine the viability of skimming BM at home. Case Report: A female infant was diagnosed with congenital lipomatous asymmetric overgrowth, vascular malformations, epidermal nevi, and skeletal and spinal anomalies (CLOVES) syndrome, with symptoms of lymphatic malformation, chylothorax, and pleural effusion. The patient's family produced SBM at home after discharge; the SBM met the dietary treatment requirements and kept symptoms under control. Methods: A nonrefrigerated benchtop centrifuge was used to produce SBM at the patient's home. The optimal setting for the centrifuge was determined and then used to process BM samples from the infant's mother. The samples were randomly selected from each 10-day period over 6 months, and 18 samples were processed in total. The hospital laboratory processed the same samples of BM and analyzed the macronutrients with a comparison of the home-produced SBM to the hospital-produced SBM. Results: The home-produced SBM met the dietary treatment requirement of <1.0 g/dL of fat content. Fat was significantly lower, proteins were significantly higher, and carbohydrates and calories were not significantly different compared to hospital-produced SBM. Conclusions: It is viable to consistently produce SBM at home that meets the dietary treatment requirements of health-compromised infants.

Medical Home Care and Educational Services for Children and Youth on the Autism Spectrum: A Scoping Review.

This scoping review examined current evidence on medical home care and its association with educational services for children and youth on the autism spectrum. We searched five databases and grey literature resulting in 328 publications. Publications meeting inclusion criteria were mapped to medical home care component(s) addressed, type(s) of educational services and their strength and type of association. The Andersen Behavioral Model of Health Services Use was used to summarize predisposing, enabling, and need factors considered. Eighteen publications were reviewed, including eight practice/policy reports and ten original research publications. Medical home care components most addressed included family-centered care (n = 10), referrals (n = 16), and effective care coordination (n = 13). Seven publications also addressed multiple educational service types. Two of the five publications that established a significant association between medical home care components and educational services had mixed results, with one publication reporting a negative association and the other publication reporting a positive association. Challenges to medical home care and educational services were most categorized as enabling factors. Results suggest three areas for further investigation: (1) limited evidence on the strength and type of association between medical home care components and educational services; (2) limited use of population data sources; and (3) the need to consider a broader range of factors when examining their association.

Carboxymethyl hydroxypropyl guar gum physicochemical properties in dilute aqueous media.

We investigate carboxymethyl hydroxypropyl guar gum (CMHPG) solution properties in water and NaCl, KCl, and CaCl2 aqueous solutions. The Huggins, Kraemer, and Rao models were applied by fitting specific and relative viscosity of CMHPG/water and CMHPG/salt/water to determine the intrinsic viscosity [η]. The Rao models yielded better results (R2 = 0.779-0.999) than Huggins and Kraemer equations. [η] decreased up to 84% in salt solution over the range 0.9-100 mM compared to water. Salt effects screened the CMHPG charged side groups chains leading to a compacted structure. In 0.9 mM NaCl(aq), the hydrodynamic coil radius (Rcoil) was 28% smaller and 45% smaller in 100 mM NaCl solution relative to water. Similar decreases were seen in KCl and CaCl2 solutions. KCl and CaCl2 were more effective than NaCl. CMHPG is salt-tolerant and shows comparatively less viscosity change than native guar gum, with modest reduced viscosity increases with CMHPG dilution at all salt concentrations. The electrostatic interactions were effective up to 100 mM salt. The activation energy of viscous flow for CMHPG solutions was computed and compared to measured xanthan gum and several literature values. These data show that the barrier to CMHPG flow is higher than for xanthan gum.

Disparities in Time-to-treatment for Patients With Melanoma.

BACKGROUND/AIM: This study aimed to investigate the demographic and socioeconomic factors associated with disparities in the time-to-treatment for melanoma. PATIENTS AND METHODS: We conducted an analysis of patients with melanoma from 2004 to 2019 using the National Cancer Database. Time intervals from diagnosis to surgery, radiation, and chemotherapy were compared based on age, sex, race, and socioeconomic status. RESULTS: A total of 647,273 patients with melanoma were included. Overall, Hispanic patients had the longest times to surgery, radiation, and chemotherapy compared to non-Hispanic patients (surgery 38.52 vs. 31.90 days, radiation 130.12 vs. 99.67 days, chemotherapy 93.66 vs. 83.72 days, all p<0.01). Similarly, black patients and those who were uninsured had the longest times-to-treatment. CONCLUSION: We identified significant disparities in time-to-treatment, related to both race and socioeconomic factors. It is increasingly imperative to conduct further investigations into the root causes of these disparities to effectively address and rectify the inequities present in breast cancer care.

Changes in the Seroprevalence of Tick-Borne Rickettsia and Ehrlichia Among Soldiers-Fort Liberty, North Carolina, 1991-2019.

We obtained samples from the Department of Defense Serum Repository from soldiers who were stationed at Fort Liberty, North Carolina, between 1991 and 2019 to assess temporal trends in tick-borne rickettsiosis and ehrlichiosis. Serological evidence of infection was common, with nearly 1 in 5 (18.9%) demonstrating antibodies. We observed significant decreases in Rickettsia seroprevalence (adjusted odds ratio [aOR], 0.42 [95% CI, .27-.65], P = .0001) while over the same period Ehrlichia seroprevalence, albeit less common, nearly doubled (aOR, 3.61 [95% CI, 1.10-13.99], P = .048). The increase in Ehrlichia seroprevalence likely reflects increased transmission resulting from the expanding geographic range of the lone star tick.

High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Prognostic evaluation of quick sequential organ failure assessment score in ICU patients with sepsis across different income settings.

BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p < 0.001) and UMIC (p < 0.001) and not HIC (p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC (p < 0.001) and UMIC (p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions (p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00-1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. CONCLUSIONS: qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions.

The Need for Children's Surgical Care Prioritisation in National Surgical Care Policies: A Systematic Review of National Surgical Obstetric and Anaesthetic Plans (NSOAPs) in Sub-Saharan Africa.

BACKGROUND: Children born in Sub-Saharan Africa (SSA) have an 85 % risk of requiring surgical care by the age of 15 [1,2]. Yet, children's surgery has been largely neglected by global health policies. National Surgical Obstetric and Anaesthetic Plans' (NSOAPs) reflect countries' strategic health priorities, policies, and targets related to surgical care. This study assessed the prioritisation of children's surgical care in national surgical care policies in SSA. METHODS: This systematic review of national surgical care policies in SSA conducted in December 2022, analysed NSOAPs developed in SSA electronically for search terms "child∗", "pediatric∗", "paediatric∗" and evaluated manually for children's surgical care in relation to the NSOAP domains, health system building blocks, and surgical care. Policies were evaluated for collaboration. RESULTS: Eight policies met the inclusion criteria. In the 797 (M = 99.63; SD = 34.83) text-containing pages analysed, there were 258 (15.5; 0-164) mentions of children's surgery search terms. Twenty-five percent (n = 2) of the NSOAPs dedicated sections to children's surgical care, 62.5 % (n = 5) mentioned children's surgery, and 12.5 % (n = 1) did not mention children's surgery. Children's surgery received citations in 25 % (n = 2) of backgrounds, 37.5 % (n = 3) of situational analyses, 87.5 % (n = 7) of strategic frameworks, 37.5 % (n = 3) of monitoring and evaluation, and 25 % (n = 2) of the costing sections. Overall, 62.5 % (n = 5) of countries included a children's surgery stakeholder. CONCLUSION: NSOAPs are a pragmatic measure of national surgical care priorities. Our findings suggest children's surgery is not widely recognised even where commitments to improving surgical care exist. Greater prioritisation of children's surgery is needed in surgical policy development.

Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study. APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.

Valorization of the essential oil from Drypetes gossweileri S. Moore (Putranjivaceae): in vitro, in vivo, and in silico nematicidal activity.

The chemical composition, insect antifeedant, in vtro/in vivo nematicidal activity, phytotoxicity, and in silico nematicidal activity of the essential oil (EO) of the African medicinal plant Drypetes gossweileri were studied. Chemical analysis using GC/MS indicated that benzyl isothiocyanate (96.23%) was the major compound, followed by benzyl cyanide (1.38%). The biocidal effects of this oil were tested against insect pests and root-knot nematodes. All the insect species tested were significantly affected by the oil according to their feeding adaptations (Spodoptera littoralis and Myzus persicae were less affected than Rhopalosiphum padi) with efficient doses (EC50) of 29.4 8.3 µg/cm2, 14.744 8.3 µg/cm2, and 8.3 µg/cm2, respectively. The oil was highly effective against juveniles J2 of the nematode Meloidogyne javanica, with LC50-LC90 values of 0.007 mg/mL-0.0113 mg/mL. D. gossweileri EO at minimum lethal concentrations (MLC) and below strongly inhibited egg hatching in vitro, whereas soil treatment caused a strong suppression of nematode population, infection frequency, and multiplication rate. The EO inhibited ryegrass (Lolium perenne) germination at 0.4 mg/mL, while at 0.1 mg/mL, its effects on germination, root and leaf growth were moderate (32.4%, 8.4%, and 18.3%, respectively). The tomato (Solanum lycopersicum) germination was not affected by the EO, but the root growth was reduced (56% at 0.1 mg/mL) at a dose 10 times higher than the LD50 calculated for M. javanica J2 mortality. Molecular docking of the nematicidal effects of the oil using PyRx revealed a strong interaction between potassium chloride transporting KCC3 (PDB ID: 7D90) and benzyl cyanide at a distance of 2.20 A° with GLN C:350, followed by benzyl isothiocyanate at a distance of 2.78 A° with ARG B:294. The in vivo nematicidal effects of D. gossweileri EO on M. javanica penetration and reproduction in tomato roots further support the potential of this EO as a nematicidal agent with insect antifeedant effects, which could be used by local farmers for crop protection.

Acute soft head syndrome in a teenager with sickle cell anemia: A case report.

Key Clinical Message: Sickle cell disease (SCD) rarely presents with acute soft head syndrome (ASHS) often posing a diagnostic dilemma. Recovery is typically spontaneous, however, in the context of lack of awareness and limited brain imaging it could potentially lead to poor outcome. Abstract: ASHS is a rare complication of SCD, invariably occurring near puberty with hitherto elusive pathogenic mechanisms. ASHS often resolves spontaneously on conservative management, however, lack of awareness in the context of limited access to brain imaging could pose diagnostic challenges resulting in inappropriate management and untoward outcome. We present a case of a teenager who presented with subtle symptoms for which the diagnosis of sickle cell anemia (SCA) was delayed until he developed ASHS. LTM was a 16 years old boy with a history of recurrent joints pain since the age of 6 years, with a family history of SCA, but had initial negative sickling test. He presented with episodes of multiple joints pain, unprovoked scalp and left orbital swelling, low-grade fever and mild headache without any evidence for bleeding diathesis. The diagnosis of SCA was confirmed by hemoglobin electrophoresis. Computed tomography (CT) scan of the head revealed subgaleal heamatoma (SGH) and intraorbital haematoma without intracranial hemorrhage (ICH). He was managed conservatively with analgesics and hydration together with antibiotics for associated sepsis with complete resolution of clinical symptoms within 2 weeks. This case represents a rare scenario for a relatively mild SCA phenotype presenting with ASHS whose diagnosis poses an enigma in the resource-limited contex. It is therefore, prudent to recognize ASHS to avoid judicious interventions which could potentially result in untoward clinical outcome.