Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Spatial Distribution of Plasmodium falciparum and Plasmodium vivax in Northern Ethiopia by Microscopic, Rapid Diagnostic Test, Laboratory Antibody, and Antigen Data.

BACKGROUND: Determining malaria transmission within regions of low, heterogenous prevalence is difficult. A variety of malaria tests exist and range from identification of diagnostic infection to testing for prior exposure. This study describes the concordance of multiple malaria tests using data from a 2015 household survey conducted in Ethiopia. METHODS: Blood samples (n=2279) from 3 regions in northern Ethiopia were assessed for Plasmodium falciparum and Plasmodium vivax by means of microscopy, rapid diagnostic test, multiplex antigen assay, and multiplex assay for immunoglobulin G (IgG) antibodies. Geospatial analysis was conducted with spatial scan statistics and kernel density estimation to identify malaria hot spots by different test results. RESULTS: The prevalence of malaria infection was low (1.4% by rapid diagnostic test, 1.0% by microscopy, and 1.8% by laboratory antigen assay). For P. falciparum, overlapping spatial clusters for all tests and an additional 5 unique IgG clusters were identified. For P. vivax, clusters identified with bead antigen assay, microscopy, and IgG partially overlapped. CONCLUSIONS: Assessing the spatial distribution of malaria exposure using multiple metrics can improve the understanding of malaria transmission dynamics in a region. The relative abundance of antibody clusters indicates that in areas of low transmission, IgG antibodies are a more useful marker to assess malaria exposure.

Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015.

BACKGROUND: Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting. METHODS: The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual's RDT results. Dose-response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey. RESULTS: Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively). CONCLUSIONS: There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings.

An update on the distribution, bionomics, and insecticide susceptibility of Anopheles stephensi in Ethiopia, 2018-2020.

BACKGROUND: Anopheles stephensi, an invasive malaria vector, was first detected in Africa nearly 10 years ago. After the initial finding in Djibouti, it has subsequently been found in Ethiopia, Sudan and Somalia. To better inform policies and vector control decisions, it is important to understand the distribution, bionomics, insecticide susceptibility, and transmission potential of An. stephensi. These aspects were studied as part of routine entomological monitoring in Ethiopia between 2018 and 2020. METHODS: Adult mosquitoes were collected using human landing collections, pyrethrum spray catches, CDC light traps, animal-baited tent traps, resting boxes, and manual aspiration from animal shelters. Larvae were collected using hand-held dippers. The source of blood in blood-fed mosquitoes and the presence of sporozoites was assessed through enzyme-linked immunosorbent assays (ELISA). Insecticide susceptibility was assessed for pyrethroids, organophosphates and carbamates. RESULTS: Adult An. stephensi were collected with aspiration, black resting boxes, and animal-baited traps collecting the highest numbers of mosquitoes. Although sampling efforts were geographically widespread, An. stephensi larvae were collected in urban and rural sites in eastern Ethiopia, but An. stephensi larvae were not found in western Ethiopian sites. Blood-meal analysis revealed a high proportion of blood meals that were taken from goats, and only a small proportion from humans. Plasmodium vivax was detected in wild-collected An. stephensi. High levels of insecticide resistance were detected to pyrethroids, carbamates and organophosphates. Pre-exposure to piperonyl butoxide increased susceptibility to pyrethroids. Larvae were found to be susceptible to temephos. CONCLUSIONS: Understanding the bionomics, insecticide susceptibility and distribution of An. stephensi will improve the quality of a national response in Ethiopia and provide additional information on populations of this invasive species in Africa. Further work is needed to understand the role that An. stephensi will have in Plasmodium transmission and malaria case incidence. While additional data are being collected, national programmes can use the available data to formulate and operationalize national strategies against the threat of An. stephensi.

Independent risk factors for prolonged postoperative ileus development.

BACKGROUND: Postoperative ileus (POI) has a significant impact on patient wellbeing, and with a 15% incidence in colectomy patients costs US hospitals >$1.3 billion per year. Although some causative mechanisms have been identified, little is known about what places patients at risk for ileus. We aimed to identify factors that independently influence the development of POI. MATERIALS AND METHODS: Patients who underwent elective surgery between 2011 and 2012 were identified from the colectomy-specific American College of Surgeons National Surgical Quality Improvement Program database. Descriptive statistics were calculated, and demographics, comorbidities, preoperative treatments, and operative characteristics were evaluated as risk factors using multivariate analyses. RESULTS: A total of 9734 patients were included in this analysis; 1364 (14%) were found to have POI. Patients who developed an ileus were more likely to develop any postoperative complication, to be readmitted, and require reoperation compared with patients without POI. In addition, we identified 13 independent risk factors for POI. CONCLUSIONS: Five modifiable risk factors for development of POI were identified as follows: smoking, weight loss, preoperative oral antibiotics, mechanical bowel preparation, and surgical approach. These identifications provide insight into possible targets for preoperative modification, which may lead to improvements in patients' quality of life and influence outcomes such as postoperative complications, readmission, and reoperation.

Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

Determining the Number of Bariatric Beds Needed in a U.S. Acute Care Hospital.

AIM: This project used historical hospital data to forecast demand for specialized bariatric beds. Models were evaluated that determined the relationship between the number of bariatric beds owned and service level for patients of size requiring these beds. A calculator was developed for minimizing the equipment costs of meeting demand. BACKGROUND: Failing to provide enough bariatric beds may negatively affect outcomes for patients of size and healthcare workers, whereas owning more bariatric beds than required to meet demand means unnecessary cost. With rising rates of obesity increasing care costs, minimizing equipment costs is increasingly important. METHOD: One year of hospital admissions data were used to determine arrival rates and lengths of stay for patients of size. Two subsequent years verified the consistency of these rates. Simulations modeled the flow of patients of size through the hospital and the service level associated with the number of beds owned. A minimization function determined the optimal number of bariatric beds to be provided. A simplified, generalizable model was compared to the simulation. RESULTS: The simplified model produced similar results to more complex simulation. The optimization was robust, or insensitive to small changes in inputs, and identified substantial opportunity for savings if demand for beds was substantially over- or underestimated. CONCLUSIONS: The simplified model and cost optimization could be used in many situations to prevent costly errors in equipment planning. However, hospitals should consider customized simulation to estimate demand for high-cost equipment or unique circumstances not fitting the assumptions of these models.

Mauling of the "Celtic Tiger": clinical characteristics and outcome of first-episode depression secondary to the economic recession in Ireland.

BACKGROUND: There is a dearth of studies describing clinical characteristics and outcome of patients who present with mood disorders related to economic recession. AIMS: To describe a cohort of patients admitted with first-episode depression related to the Irish economic recession and compare this cohort with all other first-episode depressives admitted during the same time period (2009-2010). METHODS: A cohort of 137 patients admitted with first-episode depression to an independent university teaching hospital was prospectively identified and followed up from admission over 2 years (mean follow-up 430 days, s.d. 176 days). The cohort was divided into "Celtic Tiger" (patients with first-episode depression secondary to the economic recession) and non-Celtic Tiger control patients (other first-episode depressed patients). Both groups were compared in terms of clinical characteristics at baseline and outcome over follow-up. RESULTS: The number of admissions due to first depressive episodes were higher in recession years 2009/10 than in pre-recession years 2008/9. Celtic Tiger patients were predominantly male and more severely depressed with more marked suicidal ideation (χ(2), p<0.001) than control patients. They were more likely to recover (χ(2), p=0.013), less likely to recur (χ(2), p<0.001) and had faster time to recovery (log rank, p<0.001) and slower time to full recurrence (log rank, p=0.001). The Celtic Tiger patients spent more time asymptomatic and less time at full and subthreshold depression levels over follow-up. LIMITATIONS: Study setting of centre specializing in affective disorders treatment, retrospective nature of follow-up after initial prospective interview and lack of patient follow-up interview. CONCLUSION: The study describes a subgroup of patients with severe depression associated with economic recession with likely high suicide risk but very favourable outcome.