Adaptation and psychometric testing of the end-of-life professional caregiver survey in Jamaica.

BACKGROUND: Using a validated instrument to measure palliative care (PC) educational needs of health professionals is an important step in understanding how best to educate a well-versed PC workforce within a national health system. The End-of-life Professional Caregiver Survey (EPCS) was developed to measure U.S. interprofessional PC educational needs and has been validated for use in Brazil and China. As part of a larger research project, this study aimed to culturally adapt and psychometrically test the EPCS among physicians, nurses, and social workers practicing in Jamaica. METHODS: Face validation involved expert review of the EPCS with recommendations for linguistic item modifications. Content validation was carried out by six Jamaica-based experts who completed a formal content validity index (CVI) for each EPCS item to ascertain relevancy. Health professionals practicing in Jamaica (n = 180) were recruited using convenience and snowball sampling to complete the updated 25-item EPCS (EPCS-J). Internal consistency reliability was assessed using Cronbach's [Formula: see text] coefficient and McDonald's [Formula: see text]. Construct validity was examined through confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). RESULTS: Content validation led to elimination of three EPCS items based on a CVI < 0.78. Cronbach's [Formula: see text] ranged from 0.83 to 0.91 and McDonald's [Formula: see text] ranged from 0.73 to 0.85 across EPCS-J subscales indicating good internal consistency reliability. The corrected item-total correlation for each EPCS-J item was > 0.30 suggesting good reliability. The CFA demonstrated a three-factor model with acceptable fit indices (RMSEA = 0.08, CFI = 0.88, SRMR = 0.06). The EFA determined a three-factor model had the best model fit, with four items moved into the effective patient care subscale from the other two EPCS-J subscales based on factor loading. CONCLUSIONS: The psychometric properties of the EPCS-J resulted in acceptable levels of reliability and validity indicating that this instrument is suitable for use in measuring interprofessional PC educational needs in Jamaica.

Palliative care integration: a critical review of nurse migration effect in Jamaica.

BACKGROUND: Provision of palliative care to individuals with late-stage serious illnesses is critical to reduce suffering. Palliative care is slowly gaining momentum in Jamaica but requires a highly skilled workforce, including nurses. Out-migration of nurses to wealthier countries negatively impacts the delivery of health care services and may impede palliative care capacity-building. This critical review aimed to explore the evidence pertaining to the nurse migration effect on the integration of palliative care services in Jamaica and to formulate hypotheses about potential mitigating strategies. METHODS: A comprehensive search in the PubMed, CINAHL, and ProQuest PAIS databases aimed to identify articles pertinent to nurse migration in the Caribbean context. Grant and Booth's methodologic framework for critical reviews was used to evaluate the literature. This methodology uses a narrative, chronologic synthesis and was guided by the World Health Organization (WHO) Public Health Model and the Model of Sustainability in Global Nursing. RESULTS: Data from 14 articles were extracted and mapped. Poorer patient outcomes were in part attributed to the out-migration of the most skilled nurses. 'Push-factors' such as aggressive recruitment by wealthier countries, lack of continuing educational opportunities, disparate wages, and a lack of professional autonomy and respect were clear contributors. Gender inequalities negatively impacted females and children left behind. Poor working conditions were not necessarily a primary reason for nurse migration. Four main themes were identified across articles: (a) globalization creating opportunities for migration, (b) recruitment of skilled professionals from CARICOM by high income countries, (c) imbalance and inequities resulting from migration, and (d) mitigation strategies. Thirteen articles suggested education, partnerships, policy, and incentives as mitigation strategies. Those strategies directly align with the WHO Public Health Model drivers to palliative care integration. CONCLUSION: Emerged evidence supports that nurse migration is an ongoing phenomenon that strains health systems in Caribbean Community and Common Market (CARICOM) countries, with Jamaica being deeply impacted. This critical review demonstrates the importance of strategically addressing nurse migration as part of palliative care integration efforts in Jamaica. Future studies should include targeted migration mitigation interventions and should be guided by the three working hypotheses derived from this review.

A model operationalizing sustainability in global nursing.

BACKGROUND: The concept of sustainability has received growing attention since the adoption of the United Nations' (UN) Sustainable Development agenda. Yet, in the context of sweeping changes regarding the status and profile of global nursing, sustainability has not been fully conceptualized. PURPOSE: To explore the concept of sustainability in global nursing in order to develop an operational definition and model. METHODS: Concept analysis using Rodger's Evolutionary method to explicate the term "sustainability" in a global nursing context. FINDINGS: Key features of sustainability were described. Existing models of global nursing focus on partnerships and lack a clear conceptualization and integration of sustainability. An operational definition and model of sustainability in global nursing were developed. DISCUSSION: Evolutionary review and analysis led to clarity in operationalizing sustainability in global nursing. The definition and model compliment existing models and provide a road map for global nursing to contribute toward the UN Sustainable Development agenda.

The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites.

The spice turmeric, with its active polyphenol curcumin, has been used as anti-inflammatory remedy in traditional Asian medicine for centuries. Many cellular targets of curcumin have been identified, but how such a wide range of targets can be affected by a single compound is unclear. Here, we identified curcumin as a pro-drug that requires oxidative activation into reactive metabolites to exert anti-inflammatory activities. Synthetic curcumin analogs that undergo oxidative transformation potently inhibited the pro-inflammatory transcription factor nuclear factor κB (NF-κB), whereas stable, non-oxidizable analogs were less active, with a correlation coefficient (R2) of IC50versus log of autoxidation rate of 0.75. Inhibition of glutathione biosynthesis, which protects cells from reactive metabolites, increased the potency of curcumin and decreased the amount of curcumin-glutathione adducts in cells. Oxidative metabolites of curcumin adducted to and inhibited the inhibitor of NF-κB kinase subunit ß (IKKß), an activating kinase upstream of NF-κB. An unstable, alkynyl-tagged curcumin analog yielded abundant adducts with cellular protein that were decreased by pretreatment with curcumin or an unstable analog but not by a stable analog. Bioactivation of curcumin occurred readily in vitro, which may explain the wide range of cellular targets, but if bioactivation is insufficient in vivo, it may also help explain the inconclusive results in human studies with curcumin so far. We conclude that the paradigm of metabolic bioactivation uncovered here should be considered for the evaluation and design of clinical trials of curcumin and other polyphenols of medicinal interest.

Stability and anti-inflammatory activity of the reduction-resistant curcumin analog, 2,6-dimethyl-curcumin.

The efficacy of the curry spice compound curcumin as a natural anti-inflammatory agent is limited by its rapid reductive metabolism in vivo. A recent report described a novel synthetic derivative, 2,6-dimethyl-curcumin, with increased stability against reduction in vitro and in vivo. It is also known that curcumin is unstable at physiological pH in vitro and undergoes rapid autoxidative transformation. Since the oxidation products may contribute to the biological effects of curcumin, we tested oxidative stability of 2,6-dimethyl-curcumin in buffer (pH 7.5). The rate of degradation was similar to curcumin. The degradation products were identified as a one-carbon chain-shortened alcohol, vanillin, and two isomeric epoxides that underwent cleavage to vanillin and a corresponding hydroxylated cleavage product. 2,6-Dimethyl-curcumin was more potent than curcumin in inhibiting NF-κB activity but less potent in inhibiting expression of cyclooxygenase-2 in LPS-activated RAW264.7 cells. 2,6-Dimethyl-curcumin and some of its degradation products covalently bound to a peptide that contains the redox-sensitive cysteine of IKKß kinase, the activating kinase upstream of NF-κB, providing a mechanism for the anti-inflammatory activity. In RAW264.7 cells vanillin, the chain-shortened alcohol, and reduced 2,6-dimethyl-curcumin were detected as major metabolites. These studies provide new insight into the oxidative transformation mechanism of curcumin and related compounds. The products resulting from oxidative transformation contribute to the anti-inflammatory activity of 2,6-dimethyl-curcumin in addition to its enhanced resistance against enzymatic reduction.

Compound heterozygotes and beta-thalassemia: top-down mass spectrometry for detection of hemoglobinopathies.

We have shown previously that liquid extraction surface analysis of dried blood spots coupled to high resolution top-down MS may be applied for the diagnosis of hemoglobin (Hb) variants FS, FAS, FC, FAC, FAD in newborn samples. The objective of the current work was to determine whether the structural variant HbE, compound heterozygote variants FSC and FSD, and ß-thalassemia were amenable to diagnosis by this approach. Anonymized residual neonatal dried blood spot samples, taken as part of the routine newborn screening program, were analyzed by liquid extraction surface analysis coupled to high resolution MS/MS. The samples had been previously screened and were known to be FAE, FSC, FSD, or ß-thalassemia. Manual analysis of the mass spectra revealed that, in all cases, the variants may be confirmed. Direct surface sampling MS should be considered as an alternative to current screening techniques for the diagnosis of Hb variants.

Next generation multiplexing for digital PCR using a novel melt-based hairpin probe design.

Digital PCR (dPCR) is a powerful tool for research and diagnostic applications that require absolute quantification of target molecules or detection of rare events, but the number of nucleic acid targets that can be distinguished within an assay has limited its usefulness. For most dPCR systems, one target is detected per optical channel and the total number of targets is limited by the number of optical channels on the platform. Higher-order multiplexing has the potential to dramatically increase the usefulness of dPCR, especially in scenarios with limited sample. Other potential benefits of multiplexing include lower cost, additional information generated by more probes, and higher throughput. To address this unmet need, we developed a novel melt-based hairpin probe design to provide a robust option for multiplexing digital PCR. A prototype multiplex digital PCR (mdPCR) assay using three melt-based hairpin probes per optical channel in a 16-well microfluidic digital PCR platform accurately distinguished and quantified 12 nucleic acid targets per well. For samples with 10,000 human genome equivalents, the probe-specific ranges for limit of blank were 0.00%-0.13%, and those for analytical limit of detection were 0.00%-0.20%. Inter-laboratory reproducibility was excellent (r 2 = 0.997). Importantly, this novel melt-based hairpin probe design has potential to achieve multiplexing beyond the 12 targets/well of this prototype assay. This easy-to-use mdPCR technology with excellent performance characteristics has the potential to revolutionize the use of digital PCR in research and diagnostic settings.

Development of Objectives to Inform a National Standardized Primary Palliative Care Curriculum for Health Professions Students.

Introduction: Despite recent educational advances, the need for a national standardized primary palliative care curriculum for health professions students remains evident. Methods: An interprofessional leadership team developed a set of core learning objectives built on previously published competencies. A survey was then sent to palliative care experts for feedback and consensus. Results: Twenty-eight of 31 objectives met a 75% consensus threshold, 2 were combined with others, and 12 were refined based on survey feedback. Discussion: With interprofessional input at all stages, we finalized a comprehensive list of 26 learning objectives for a primary palliative care curriculum targeting health professions students. These objectives will be widely available through an online course but can also be adopted for use by individual educators across health professions institutions. These objectives and related curriculum are critical to producing practice-ready clinicians who are prepared to care for the burgeoning population of seriously ill patients.

Cell-free DNA as a solid-organ transplant biomarker: technologies and approaches.

High-quality biomarkers that detect emergent graft damage and/or rejection after solid-organ transplantation offer new opportunities to improve post-transplant monitoring, allow early therapeutic intervention and facilitate personalized patient management. Donor-derived cell-free DNA (DD-cfDNA) is a particularly exciting minimally invasive biomarker because it has the potential to be quantitative, time-sensitive and cost-effective. Increased DD-cfDNA has been associated with graft damage and rejection episodes. Efforts are underway to further improve sensitivity and specificity. This review summarizes the procedures used to process and detect DD-cfDNA, measurement of DD-cfDNA in clinical transplantation, approaches for improving sensitivity and specificity and long-term prospects as a transplant biomarker to supplement traditional organ monitoring and invasive biopsies.

Hemoglobin variant analysis via direct surface sampling of dried blood spots coupled with high-resolution mass spectrometry.

Hemoglobinopathies are the most common inherited disorders. Newborn blood screening for clinically significant hemoglobin variants, including sickle (HbS), HbC, and HbD, has been adopted in many countries as it is widely acknowledged that early detection improves the outcome. We present a method for determination of Hb variants by direct surface sampling of dried blood spots by use of an Advion Triversa Nanomate automated electrospray system coupled to a high-resolution mass spectrometer. The method involves no sample preparation. It is possible to unambiguously identify homozygous and heterozygous HbS, HbC, and HbD variants in <10 min without the need for additional confirmation. The method allows for repeated analysis of a single blood spot over a prolonged time period and is tolerant of blood spot storage conditions.

Mechanistic Differences in the Inhibition of NF-κB by Turmeric and Its Curcuminoid Constituents.

Turmeric extract, a mixture of curcumin and its demethoxy (DMC) and bisdemethoxy (BDMC) isomers, is used as an anti-inflammatory preparation in traditional Asian medicine. Curcumin is considered to be the major bioactive compound in turmeric but less is known about the relative anti-inflammatory potency and mechanism of the other components, their mixture, or the reduced in vivo metabolites. We quantified inhibition of the NF-κB pathway in cells, adduction to a peptide mimicking IκB kinase ß, and the role of cellular glutathione as a scavenger of electrophilic curcuminoid oxidation products, suggested to be the active metabolites. Turmeric extracts (IC50 14.5 ± 2.9 µM), DMC (IC50 12.1 ± 7.2 µM), and BDMC (IC50 8.3 ± 1.6 µM), but not reduced curcumin, inhibited NF-κB similar to curcumin (IC50 18.2 ± 3.9 µM). Peptide adduction was formed with turmeric and DMC but not with BDMC, and this correlated with their oxidative degradation. Inhibition of glutathione biosynthesis enhanced the activity of DMC but not BDMC in the cellular assay. These findings suggest that NF-κB inhibition by curcumin and DMC involves their oxidation to reactive electrophiles, whereas BDMC does not require oxidation. Because it has not been established whether curcumin undergoes oxidative transformation in vivo, oxidation-independent BDMC may be a promising alternative to test in clinical trials.

Afatinib Therapy: Practical Management of Adverse Events With an Oral Agent for Non-Small Cell Lung Cancer Treatment.

BACKGROUND: Afatinib is an oral, irreversible ErbB family blocker indicated for first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with non-resistant epidermal growth factor receptor (EGFR) mutations. Afatinib is also approved for the treatment of metastatic squamous NSCLC following progression on platinum-based chemotherapy. Common afatinib-associated toxicities include gastrointestinal and dermatologic events, which can be dose limiting. OBJECTIVES: In this review, the authors describe clinical trial experiences with afatinib, as well as best practices and practical approaches to the management of afatinib-associated adverse events in EGFR mutation-positive NSCLC. METHODS: Safety and tolerability data from phase 3 trials of afatinib were reviewed, together with real-life experiences from the authors' clinical practices. FINDINGS: Patient education, combined with early assessment and effective management of afatinib-related adverse events as well as dose- reduction strategies, allows patients to continue treatment and maximize the clinical benefits of afatinib.

Cancer and Palliative Care in the United States, Turkey, and Malawi: Developing Global Collaborations.

As the global cancer burden grows, so too will global inequities in access to cancer and palliative care increase. This paper will describe the cancer and palliative care landscape relative to nursing practice, education, and research, and emerging global collaborations in the United States (U.S.), Turkey, and Malawi. It is imperative that nurses lead efforts to advance health and strengthen education in these high-need areas. Leaders within the University of Alabama at Birmingham School of Nursing, through a Pan American Health Organization/World Health Organization Nursing Collaborating Center, have initiated collaborative projects in cancer and palliative care between the U.S., Turkey, and Malawi to strengthen initiatives that can ultimately transform practice. These collaborations will lay a foundation to empower nurses to lead efforts to reduce the global inequities for those with cancer and other serious and life-limiting illnesses.

Degradation of Curcumin: From Mechanism to Biological Implications.

Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as a dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, the formation of which has only recently been appreciated. This paper discusses how the degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. It is suggested that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin.

Native Liquid Extraction Surface Analysis Mass Spectrometry: Analysis of Noncovalent Protein Complexes Directly from Dried Substrates.

Liquid extraction surface analysis (LESA) mass spectrometry is a promising tool for the analysis of intact proteins from biological substrates. Here, we demonstrate native LESA mass spectrometry of noncovalent protein complexes of myoglobin and hemoglobin from a range of surfaces. Holomyoglobin, in which apomyoglobin is noncovalently bound to the prosthetic heme group, was observed following LESA mass spectrometry of myoglobin dried onto glass and polyvinylidene fluoride surfaces. Tetrameric hemoglobin [(αß)2(4H)] was observed following LESA mass spectrometry of hemoglobin dried onto glass and polyvinylidene fluoride (PVDF) surfaces, and from dried blood spots (DBS) on filter paper. Heme-bound dimers and monomers were also observed. The 'contact' LESA approach was particularly suitable for the analysis of hemoglobin tetramers from DBS.

Hemoglobin variant analysis of whole blood and dried blood spots by MS.

MS allows for the unequivocal diagnosis of hemoglobin variants, or hemoglobinopathies. Hemoglobinopathies are the most common inherited disorder and there is a need for rapid detection of clinically significant variants, such as sickle hemoglobin, which is responsible for sickle cell disease. In this review, we describe the development of MS approaches for the determination of hemoglobin variants from both whole blood samples and dried blood spots. MS approaches that are suitable for population screening are discussed, as are recent advances in direct surface analysis of dried blood spots.

Top-down proteomics and direct surface sampling of neonatal dried blood spots: diagnosis of unknown hemoglobin variants.

We have previously shown that liquid microjunction surface sampling of dried blood spots coupled with high resolution top-down mass spectrometry may be used for screening of common hemoglobin variants HbS, HbC, and HbD. In order to test the robustness of the approach, we have applied the approach to unknown hemoglobin variants. Six neonatal dried blood spot samples that had been identified as variants, but which could not be diagnosed by current screening methods, were analyzed by direct surface sampling top-down mass spectrometry. Both collision-induced dissociation and electron transfer dissociation mass spectrometry were employed. Four of the samples were identified as ß-chain variants: two were heterozygous Hb D-Iran, one was heterozygous Hb Headington, and one was heterozygous Hb J-Baltimore. The fifth sample was identified as the α-chain variant heterozygous Hb Phnom Penh. Analysis of the sixth sample suggested that it did not in fact contain a variant. Adoption of the approach in the clinic would require speed in both data collection and interpretation. To address that issue, we have compared manual data analysis with freely available data analysis software (ProsightPTM). The results demonstrate the power of top-down proteomics for hemoglobin variant analysis in newborn samples.