Vantage View (United States)

The low- and middle-income countries (LMICs) are characterised by the highest burden of diseases and resource constraints. Thus, reforms imperative for responsive healthcare systems must be supported by context-appropriate evidence. However, lacunae persist with respect to the gap in terms of knowledge related to the level, barriers and inequities associated with effective healthcare coverage. The study was, thus, conducted to identify, describe, appraise and synthesise various bottlenecks impeding the trajectory towards effective coverage in LMICs. The study employed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A search of published articles was conducted on six electronic databases along with a manual and bibliographic search of grey literature. A gamut of peer-reviewed articles and technical reports evaluating the measure of—and barriers to—effective coverage in LMICs was included using an exhaustive set of inclusion criteria. A quality assessment of included studies was conducted using a standardised checklist adopted from the Joanna Briggs Institute. Further, selected studies were transcribed using data extraction and assessment templates adapted from the Cochrane Review Group, and a content analysis was performed within the Tanahashi framework of effective coverage. The search strategy retrieved 736 articles from the database, out of which 65 met the eligibility criterion. The majority of studies were characterised by cross-sectional and quantitative design, maternal and child health (MCH) interventions and availability/accessibility barriers. Analogously, most of the studies were conducted in the Sub-Saharan African region and were representative at the multi-country/national level. Conversely, the evidence on socio-economic determinants associated with effective health coverage was exiguous. The literature underscores supply-side constraints such as health workforce shortage, suboptimal structural quality and inefficient fund allocation as the most pronounced bottlenecks. Demand-side barriers, such as negative attitudes towards providers, lack of knowledge and community engagement, were also unravelled to exert an adverse impact on coverage. The study divulged that most of the literature on effective health coverage is underpinned by skewed representation. An evidence gap was found with respect to the studies from South-East Asian, Latin American and Caribbean LMICs and disaggregated administrative levels. Methodological deficiencies were also found in measurement metrics with respect to the assessment of a comprehensive package of services, equity, quality and robustness checks.

It is well established that Cutibacterium acnes (C. acnes) is a common skin commensal microorganism that has been linked to acne. In acne flare-ups, C. acnes can be found in abundant levels within the inflammatory lesions (called comedones) associated with the skin disease. Recently, it was reported that 3D reconstructed human epidermis (RHE) treated with viable cultures of C. acnes can elicit β-defensin antimicrobial peptide responses in the skin and can weaken the skin barrier of the RHE after three days of exposure to C. acnes. Employing a modification of this in vitro assay, RHE was pretreated with C. acnes for 48 hours, then further treated with a mixture of water-soluble polysaccharides (STRATAPHIX™ POLY, "Polysaccharide Blend") previously shown to reduce inflammasome-mediated inflammatory responses in normal human epidermal keratinocytes (NHEK). Two inflammasome-mediated inflammation markers were tested, including caspase-1, a potent protease enzyme activated by NOD-like receptor protein (NLRP)-induced inflammasome activation, and interleukin-1β (IL-1β), a cytokine which is activated from inactive pro-IL-1β by caspase-1. The treatment of the RHE tissues with C. acnes for 48 hours elicited an inflammatory response measured with both markers compared against untreated tissues. Treatment of the tissues with 1% and 2% salicylic acid for 24hours after C. acnes treatment increased the inflammatory response measured with both markers. Application of the water-soluble polysaccharides in combination with 1% and 2% of salicylic acid significantly reduces expression of both active caspase-1 and IL-1β compared against the tissues treated with C. acnes and salicylic acid alone. The results lend further support to previously reported work which was done on NHEKs treated with ultraviolet B (UVB) light and adenosine triphosphate (ATP) and demonstrate that the same mixture of polysaccharides can have a modulating effect against bacterial and chemical induced inflammation in RHE.

Recent work examined the influence of topically applied just-add-water creams containing Lactobacillus plantarum probiotic cultures on to reconstructed human epidermis (RHE). The ability to blend various quiescent probiotic powders in topical systems allows for the examination of these powders on RHEs employing various individual quiescent probiotics using human gene microarrays. Four topical Just-Add-Water powders (STRATABIOSYS™ Technologies) were prepared containing the following: (1) Lactobacillus plantarum Lp90 [200 M CFU/g]; (2) Saccharomyces cerevisiae [200 M CFU/g]; (3) Streptococcus thermophilus [200 M CFU/g]; and (4) Lactococcus Lactis LLa61 [200 M CFU/g]. A powder without probiotics was used as a placebo control. The creams were prepared by taking 3% of each powder and dissolving it into sterile water. A 15 μL sample of each cream was applied to a RHE tissue that presented approximately 90 K CFU/g of each microorganism on the tissue. The RHE was treated for 24 h with the creams whereupon the residual cream was rinsed off, and the tissues were analysed using Agilent human gene microarrays containing 19 217 individual genes from which a smaller subset of 244 genes pertinent to skin were culled. The following probiotic specific gene responses were found: (1) Lactobacillus plantarum upregulated 4.9% of the skin-relevant gene set; (2) Saccharomyces cerevisiae upregulated 7.8% of the skin relevant gene set; Streptococcus thermophilus upregulated 6.1% of the skin relevant gene set; Lactococcus lactis upregulated 7.0% of the skin relevant gene set. A method to examine topical probiotics on RHE has been described that involves converting the powders to preservative-free creams.

RECISTv1.1 (Response Evaluation Criteria In Solid Tumors) is the most commonly used response grading criteria in early oncology trials. In this perspective, we argue that RECISTv1.1 is ambiguous regarding lesion-to-lesion variation that can introduce bias in decision making. We show theoretical examples of how lesion-to-lesion variability causes bias in RECISTv1.1, leading to misclassification of patient response. Next, we review immune checkpoint inhibitor (ICI) clinical trial data and find that lesion-to-lesion heterogeneity is widespread in ICI-treated patients. We illustrate the implications of ignoring lesion-to-lesion heterogeneity in interpreting biomarker data, selecting treatments for patients with progressive disease, and go/no-go decisions in drug development. Further, we propose that Quantitative Systems Pharmacology (QSP) models can aid in developing better metrics of patient response and treatment efficacy by capturing patient responses robustly by considering lesion-to-lesion heterogeneity. Overall, we believe patient response evaluation with an appreciation of lesion-to-lesion heterogeneity can potentially improve decision-making at the early stage of oncology drug development and benefit patient care.

ABSTRACTThe purpose of this study is to describe our experience using expandable spherical hydrogel implants and injectable hydrogel pellets for orbital volume augmentation in cases of post-enucleation socket syndrome after acquired anophthalmia or phthisis bulbi. We retrospectively reviewed the clinical records of all adult patients who received an expandable hydrogel implant for orbital volume loss following enucleation or phthisis bulbi at the Emory Eye Center between 2004 and January 2007 and the Yale Eye Center between 2009 and 2011. The study included 9 women and 5 men with a mean age of 51.2 years old (range 35-76 years old). Follow-up spanned 6 to 71 months (median of 18.5 months). Four patients received spherical hydrogel implants and 10 patients received hydrogel pellet injections. On average, nine pellets (range 5-16) were placed in each patient over an average of 1.7 injections (range 1-3). Most commonly, five pellets were injected per session, as was the case for 13 of the 17 treatment sessions. Post-operative complications included 2 cases of pellet migration, one subcutaneously and one anteriorly due to insufficiently posterior implant placement, and 1 hospital admission for pain after injection of 10 pellets in one visit. All patients experienced an overall subjective improvement in cosmesis. Self-expandable hydrogel implants appear to offer several advantages over other existing options for orbital volume augmentation, as they are easy to place, generally well-tolerated, volume-titratable, and to the extent that our follow-up shows, may be a safe and durable means of treating orbital volume loss in patients with acquired anophthalmia and phthisis bulbi.

The present work describes use of a water-equivalent radio-fluorogenic gel dosimeter for measurement of a depth dose distribution from a medical linear accelerator. Relative depth dose distributions for a 6 MV photon beam were measured with a novel radio-fluorogenic gel comprised of aqueous gelatin and coumarin-3-carboxylic acid. Agreement was within 3 % of published values in most areas of electronic equilibrium. Results support continued development of radio-fluorogenic gel dosimetry systems for quality assurance of clinical photon beams.

Hormone ablation therapy is a mainstay in the treatment of breast and prostate cancers. However, aromatase inhibitors (AIs) used in postmenopausal women with breast cancer and androgen-deprivation therapy (ADT) used in men with prostate cancer contribute to substantial bone loss, thereby increasing the risk of osteoporotic fractures. Evidence-based guidelines, therefore, urge oncology practices to screen these patients for bone loss and, if needed, provide treatment to maintain bone health. In addition to lifestyle modification and calcium or vitamin D supplementation, bone protection strategies include treatment with bisphosphonates and denosumab, a monoclonal antibody against RANK ligand. Identification of patients at greater risk for bone loss and fracture and proper interventions can reduce fracture rates. Oncology nurses can play an important role in screening these patients. The purpose of this article is to inform oncology nurses about the effects of cancer treatment on bone health, review current prevention and treatment options for cancer treatment-induced bone loss, and discuss recommendations for identifying high-risk individuals.

In the more developed Western economies, foods that have historically been thought of as “poor people's foods,” such as pulses, sorghum, quinoa, and even potatoes, have recently gained in popularity. However, pulse product development remains underexplored, and there are a number of challenges and opportunities related to pulses to be considered. Pulses are superb rotational crops because they contribute nitrogen to the soil and grow well in areas where weed pressure is low, making them highly sustainable. Global production of edible pulses has increased to nearly 60 million tonnes. Two important nutritional drivers behind consumption of pulses are their roles as primary sources of dietary protein and high-value nutrients. Pulses can also function as substitutes for common allergenic food ingredients (e.g., wheat and soybeans). There are technical obstacles to future pulse development, however, that will require significant R&D investment. In addition, although some individual regional organizations have ...