Subcutaneous Injection Site Pain of Formulation Matrices.

PURPOSE: The objective of this work was to systematically evaluate the effects of formulation composition on subcutaneous injection site pain (ISP) using matrices comprising of common pharmaceutical excipients. METHODS: Two randomized, blinded, crossover studies in healthy subjects were conducted at a single site, where subjects received 1 mL SC injections of the buffer matrices. ISP intensity was measured using a 100 mm visual analogue scale (VAS), which was then analyzed via heatmap, categorical grouping, subgroup analysis, and paired delta analysis. RESULTS: Buffer type, buffer concentration and tonicity agent showed a substantial impact on ISP. Citrate buffer demonstrated a higher ISP than acetate buffer or saline). The 20 mM citrate buffer was more painful than 10 or 5 mM citrate buffers. NaCl and propylene glycol were significantly more painful than sugar alcohols (mannitol, sucrose, trehalose or glycerol). Histidine buffers exhibited ISP in the descending order of 150 mM > 75 mM > 25 mM > 0 mM NaCl, while histidine buffers containing Arginine-HCl at 0, 50, or 150 mM all showed very low ISP. Histidine buffer at pH 6.5 showed a lower ISP than pH 5.7. CONCLUSIONS: This systematic study via orthogonal analyses demonstrated that subcutaneous ISP is significantly influenced by solution composition.

The etemic model of Gypsy Roma Traveller community vulnerability: is it time to rethink our understanding of vulnerability?

AIMS AND OBJECTIVES: To present a new etemic model of vulnerability. BACKGROUND: Despite vulnerability being identified as a core consequence of health and health experiences, there has been little research exploring the meaning of vulnerability as a concept. Yet, being vulnerable is known to have dire physical/mental health consequences. It is therefore a fundamental issue for nurses to address. To date, the meaning of the term vulnerability has been influenced by the work of Spiers (Journal of Advanced Nursing, 31, 2000, 715, The Essential Concepts of Nursing: Building Blocks for Practice, 2005, Elsevier, London). Spiers identified two aspects of vulnerability: the etic (external judgment of another persons' vulnerability) and the emic (internal lived experience of vulnerability). This approach has led to a plethora of research which has explored the etic (external judgment) of vulnerability and rendered the internal lived (or emic) experience invisible. Consequences of this, for marginalised communities such as Gypsy Roma Travellers include a lack of culturally sensitive services compounding health inequalities. DESIGN: Position paper. METHOD: Drawing upon a qualitative phenomenological research study exploring the lived experience of vulnerability from a Gypsy Roma Travelling community (published previously), this paper presents a new model of vulnerability. This etemic model of vulnerability values both external and internal dimensions of vulnerability and argues for a fusion of these two opposing perspectives. CONCLUSIONS: If nurses and other health- and social care professionals wish to develop practice that is successful in engaging with Gypsy Roma Travellers, then there is a need to both understand and respect their community. This can be achieved through an etemic approach to understanding their vulnerability achieved by eliciting lived experience alongside the appreciation of epidemiological studies. RELEVANCE TO CLINICAL PRACTICE: If nurses and health practitioners used this etemic approach to practice then it would enable both the development and delivery of culturally sensitive services facilitating health access to this community. Only then, will their poor health status be successfully addressed.

Lived experience of vulnerability from a Gypsy Roma Traveller perspective.

AIMS AND OBJECTIVES: To describe the lived experience of vulnerability of individuals within a Gypsy Roma Travelling community. BACKGROUND: People experience vulnerability whenever their health or usual functioning is compromised. This may increase when they enter unfamiliar surroundings, situations or relationships. One's experience of vulnerability can also be heightened through interactions between the individual and the society within which they live. Gypsy Roma Travellers are often identified as vulnerable owing to increased morbidity and mortality as well as their marginalised status within society. Yet little is known of the experiences of vulnerability by the individuals themselves. Without their stories and experiences, health professionals cannot effectively develop services that meet their needs. DESIGN: This descriptive phenomenological study sought to explore the lived experience of vulnerability in a Gypsy Roma Travelling community. METHODS: Seventeen Gypsy Roma Travellers were interviewed in 2013-2014 about their experiences of feeling vulnerable. This paper reports on the findings from the depth phase in which 13 individuals were interviewed. The interviews were conducted and analysed using Giorgi's descriptive phenomenological approach. FINDINGS: Six constituents of the phenomenon of vulnerability were identified as feeling: defined and homogenised as a group; pressurised to conform to live in a particular way; split in one's identity; a loss of one's heritage; discriminated, persecuted and threatened; and powerlessness. RELEVANCE TO CLINICAL PRACTICE: There is a wealth of evidence that Gypsy Roma Travellers experience high levels of morbidity and mortality, which has led to them being identified by health professionals and policy makers as a vulnerable community. Exploring their lived experience of vulnerability presents a different perspective regarding this concept and can help explain why they may experience poorer levels of physical and mental health.

Quantification of 21 metabolites of methylnaphthalenes and polycyclic aromatic hydrocarbons in human urine.

Polycyclic aromatic hydrocarbons (PAHs) and their alkylated derivatives, such as methylnaphthalenes (MeNs), are harmful pollutants ubiquitously present in the environment. Exposure to PAHs has been linked to a variety of adverse health effects and outcomes, including cancer. Alkyl PAHs have been proposed as petrogenic source indicators because of their relatively high abundance in unburned petroleum products. We report a method to quantify 11 urinary methylnaphthols (Me-OHNs), metabolites of 1- and 2-methylnaphthalenes, and 10 monohydroxy PAH metabolites (OH-PAHs), using automated liquid-liquid extraction and isotope dilution gas chromatography tandem mass spectrometry (GC-MS/MS). After spiking urine (1 mL) with (13)C-labeled internal standards, the conjugated target analytes were hydrolyzed enzymatically in the presence of ascorbic acid. Then, their free species were preconcentrated into 20 % toluene in pentane, derivatized and quantified by GC-MS/MS. The 11 Me-OHNs eluted as 6 distinct chromatographic peaks, each representing 1 - 3 isomers. Method detection limits were 1.0- 41 pg/mL and the coefficients of variation in quality control materials were 4.7 - 19 %. The method was used to analyze two National Institute of Standards and Technology's Standard Reference Materials® and samples from 30 smokers and 30 non-smokers. Geometric mean concentrations were on average 37 (Me-OHNs) and 9.0 (OH-PAHs) fold higher in smokers than in non-smokers. These findings support the usefulness of Me-OHNs as potential biomarkers of non-occupational exposure to MeNs and sources containing MeNs.

Navigating the Complexity of a Bipolar Pregnant Patient With Multiple Comorbidities.

Bipolar disorder I (BDI) is a psychiatric disorder characterized by the occurrence of at least one manic episode. Within the scope of neurological disorders, epilepsy and psychogenic nonepileptic seizures (PNES) share clinical features and can be differentiated using electroencephalogram (EEG). Substance use disorder is a condition defined by impaired control, risky use, social impairment, and addictive behaviors. We present the case of a 20-year-old pregnant woman with BDI associated with a history of epilepsy, PNES, and polyvalent substance use. The patient presented to the emergency department via the Baker Act involuntary hold multiple times throughout her pregnancy. Recognizing that the welfare of the mother and child was at risk, the court ordered a two-month commitment of inpatient psychiatric treatment at 30 weeks' gestation to ensure safe delivery. Comprehensive inpatient treatment, including risperidone, levetiracetam, lacosamide, haloperidol, diphenhydramine, lorazepam, and later clozapine, and a discharge plan for both the mother and the child are described in detail. Our goal is to contribute to the growing body of knowledge on the management of complex pregnant patients with psychiatric conditions in order to optimize outcomes for maternal and fetal health.

Primary Intraocular Lymphoma: Rad-Path and Ophthalmologic Correlation.

Primary intraocular lymphoma (PIOL) is a rare form of primary central nervous system lymphoma that poses diagnostic challenges due to its nonspecific clinical features and complex imaging characteristics. This paper presents a focus case and two companion cases, highlighting the complexities in identifying and treating PIOL. In the focus case, A 66-year-old male experienced gradual painless vision loss with choroidal thickening on funduscopic exam and subsequent follow-up MRI. Trans-vitreal biopsy confirmed PIOL, and the patient was treated with intravitreal steroids and systemic rituximab without recurrence. The companion case 1 involved a 66-year-old woman with vision changes and choroidal thickening with episcleral extension on MRI suggestive of intraocular lymphoma and ultimately treated with radiation with this presumed diagnosis of PIOL. In the companion case 2, a 63-year-old man with ocular symptoms was diagnosed with chronic lymphocytic leukemia along with vitreoretinal Richter's transformation. Enucleation was performed due to a lack of visual potential and failure of chemotherapy, which confirmed PIOL. Distinguishing PIOL from other ocular conditions is crucial, given its potential for CNS involvement. Imaging plays a vital role in corroborating clinical findings. While cytology remains the gold standard for diagnosis, supplementary tests, including cytokine analysis, immunohistochemistry, and flow cytometry, provide additional insights. PIOL treatment strategies are tailored to disease extent, ranging from locoregional chemotherapy to invasive enucleation. CNS involvement carries a poor prognosis and must evaluated and surveilled with MRI. In conclusion, this case series reviews the clinical and radiological features of PIOL, emphasizing the significance of diagnostic imaging in determining disease extent and guiding treatments.ABBREVIATIONS: CLL: chronic lymphocytic leukemia; CNS: central nervous system; FFA: fundus fluorescein angiography; IHC: cytometric immunohistochemistry; OCT: optical coherence tomography; FDG-PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomography; PIOL: Primary intraocular lymphoma; PCNSL: primary central nervous system lymphoma; UBM: ultrasound biomicroscopy.

Managing a Complex Case of Bipolar Disorder in a Patient With Recurrent Hospitalizations.

Bipolar disorder type 1 (BD-1) is a complex psychiatric disorder characterized by recurrent episodes of mania and depression. While manic episodes typically present with classic symptoms such as impulsivity, elevated mood, and increased energy, atypical presentations are not as common and when encountered may pose diagnostic challenges. In addition, multiple previous hospitalizations can prove for a more nuanced case with a potentially worse prognosis. This clinical case study explores the atypical clinical presentation of a 22-year-old Hispanic male with BD-1 and discusses the challenges associated with the correct diagnosis and recognition of this disorder. Typical BD-1 symptoms consist of depressive and manic episodes. The mania can encompass elevated mood, increased energy, racing thoughts, decreased need for sleep, grandiosity, and impulsivity. The typical depressive episodes consist of fatigue, low mood, loss of motivation, changes in appetite or weight, and even suicidal thoughts. Atypical symptoms consist of a mixture of both mania and depression at once, psychosis, present with seasonal patterns, anxious distress, catatonia, and rapid cycling of mood. The patient, with a medical history of BD-1, anxiety, polysubstance abuse, and multiple inpatient psychiatric hospitalizations presented to the emergency department via involuntary hold due to threats of suicidal behavior. Upon arrival, he presented with a myriad of typical and atypical acute manic symptoms including severe agitation, disorganization, anxiety, pressured speech, and rapid mood cycling. Throughout his admission he demonstrated extreme episodes of agitation, making threats of physical violence towards staff, attempting self-injury, behaving violently towards others, and displaying impulsivity as well as grandiosity despite receiving his long-acting injectable neuroleptic medication just three weeks prior to his hospitalization. Scheduled medication treatment during his inpatient hospitalization included a combination of risperidone, thorazine, divalproex sodium, mirtazapine, clonazepam, and temazepam. This clinical case underscores the importance of recognizing both typical and atypical presentations of manic episodes in BD-1 as well as the challenges involved in the treatment of a patient with severe and refractory symptoms requiring frequent hospitalizations.

Treatment of Psychogenic Polydipsia and Hyponatremia: A Case Report.

Psychogenic polydipsia occurs during water or fluid intoxication and can lead to electrolyte disturbances, such as hyponatremia. Hyponatremia can give rise to signs and symptoms, including lethargy, psychosis, seizures, or death. Psychogenic, or primary polydipsia, can be compared to other medical conditions that cause excessive thirst. This case report will focus on the symptoms, disease, and treatment involved in the care and hospitalization of a 30-year-old male patient who reported ingesting up to 40 liters of water a day for the last three years. This patient with psychogenic polydipsia, chronic schizophrenia, and active psychosis was diagnosed with metabolic encephalopathy secondary to severe hyponatremia (day one sodium level: 108 mEq/L). The management goal was to stabilize electrolytes and increase sodium levels without causing osmotic demyelination syndrome. During subsequent hospitalization, the psychiatry team worked towards the normalization of sodium levels and managed behavioral patterns contributing to water consumption. The patient achieved a normal sodium level on day 21 of inpatient psychiatric treatment with the following medication regimen: acetazolamide, candesartan, olanzapine, sodium chloride, and trazodone.

Catatonia in a Patient With Bipolar Affective Disorder and Hypothyroidism: A Diagnostic and Therapeutic Challenge.

This case report presents the clinical course of a 33-year-old female with a history of bipolar affective disorder (BAD) who presented to the psychiatric emergency department with sudden-onset altered behavior, along with features indicative of catatonia. Before hospitalization, the patient had not been adherent to psychiatric medications for BAD for a period of several months, likely a contributing factor to the patient's presenting symptoms. Over a two-week period before hospitalization, the patient exhibited progressive withdrawal, psychomotor retardation, disorganized behavior, and a lack of response to external stimuli. Initial labs upon admission had findings consistent with a diagnosis of hypothyroidism. The patient had no prior history of thyroid disease and further endocrinology workup was deferred by the hospitalist to outpatient care upon discharge. While initially in the emergency department, the patient received intramuscular lorazepam for immediate symptom relief, the initial response to the Ativan challenge was not fully documented. Upon evaluation by the inpatient team the next morning, a Bush-Francis Catatonia Rating Scale score of 22 highlighted the severity of catatonia, which may have been further exacerbated by concurrent hypothyroidism. As such, thyroid hormone replacement therapy (levothyroxine) was indicated to normalize thyroid function. Combination treatment initially with lorazepam and levothyroxine was administered for the patient's catatonia and olanzapine was chosen as the anti-psychotic. Over the subsequent days, the patient's catatonic symptoms demonstrated positive responses to treatment, prompting adjustments in pharmacotherapy. The patient eventually returned to baseline functioning, with substantial improvements in catatonia as well as mood symptoms. This case underscores the complex interplay between catatonia, bipolar affective disorder, and thyroid dysfunction. The timely identification and management of hypothyroidism in the context of catatonia showcase the potential for favorable outcomes with targeted interventions.

Bupropion Treatment for Stimulant Withdrawal in a Patient With Substance Use Disorder and Unspecified Bipolar Disorder.

Patients presenting with comorbid stimulant use disorder is a common occurrence in nearly all medical specialties. New clinical strategies to care for patients experiencing stimulant withdrawal should be considered as an effort to improve clinical outcomes. Our patient, a woman in her early 20s with a history of substance use disorder and unspecified bipolar and related disorder, presented with acute psychosis with symptoms including agitation, auditory hallucinations, and delusions in the context of chronic mental illness and cocaine abuse. She was subsequently admitted to the inpatient psychiatry unit. Notable symptoms included mood swings, erratic behavior, anger, and agitation. Mood and psychotic symptoms were treated with olanzapine. She also received medications, including haloperidol, lorazepam, and diphenhydramine, as needed for agitation, which were given as an emergency treat option (ETO) injection. The patient continuously exhibited irritability and endorsed that she was undergoing cocaine withdrawal symptoms, for which she was started on bupropion. Within days of taking this medication, she reported significant improvement in her psychotic and mood symptoms. The patient continued this treatment during the remainder of her stay until the resolution of her symptoms and was discharged with both bupropion and olanzapine to continue while awaiting an outpatient psychiatry appointment in one week.

Searching for Peptide Inhibitors of T Regulatory Cell Activity by Targeting Specific Domains of FOXP3 Transcription Factor.

(1) Background: The ability of cancer cells to evade the immune system is due in part to their capacity to induce and recruit T regulatory cells (Tregs) to the tumor microenvironment. Strategies proposed to improve antitumor immunity by depleting Tregs generally lack specificity and raise the possibility of autoimmunity. Therefore, we propose to control Tregs by their functional inactivation rather than depletion. Tregs are characterized by the expression of the Forkhead box protein 3 (FOXP3) transcription factor, which is considered their "master regulator". Its interaction with DNA is assisted primarily by its interaction with other proteins in the so-called "Foxp3 interactome", which elicits much of the characteristic Treg cell transcriptional signature. We speculated that the disruption of such a protein complex by using synthetic peptides able to bind Foxp3 might have an impact on the functionality of Treg cells and thus have a therapeutic potential in cancer treatment. (2) Methods: By using a phage-displayed peptide library, or short synthetic peptides encompassing Foxp3 fragments, or by studying the crystal structure of the Foxp3:NFAT complex, we have identified a series of peptides that are able to bind Foxp3 and inhibit Treg activity. (3) Results: We identified some peptides encompassing fragments of the leuzin zipper or the C terminal domain of Foxp3 with the capacity to inhibit Treg activity in vitro. The acetylation/amidation of linear peptides, head-to-tail cyclization, the incorporation of non-natural aminoacids, or the incorporation of cell-penetrating peptide motifs increased in some cases the Foxp3 binding capacity and Treg inhibitory activity of the identified peptides. Some of them have shown antitumoral activity in vivo. (4) Conclusions: Synthetic peptides constitute an alternative to inhibit Foxp3 protein-protein interactions intracellularly and impair Treg immunosuppressive activity. These peptides might be considered as potential hit compounds on the design of new immunotherapeutic approaches against cancer.

Use of Warfarin or Direct Oral Anticoagulants and Risk of Prostate Cancer in PCBaSe: A Nationwide Case-Control Study.

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014-2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88-0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13-1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.

Manufacture and Performance of Welds in Creep Strength Enhanced Ferritic Steels.

Welding is a vital process required in the fabrication of 'fracture critical' components which operate under creep conditions. However, often the procedures used are based on 'least initial cost'. Thus, it is not surprising that in many high energy applications, welds are the weakest link, i.e., damage is first found at welds. In the worst case, weld cracks reported have had catastrophic consequences. Comprehensive Electric Power Research Institute (EPRI) research has identified and quantified the factors affecting the high temperature performance of advanced steels working under creep conditions. This knowledge has then been used to underpin recommendations for improved fabrication and control of creep strength enhanced ferritic steel components. This review paper reports background from this work. The main body of the review summarizes the evidence used to establish a 'well engineered' practice for the manufacture of welds in tempered martensitic steels. Many of these alternative methods can be applied in repair applications without the need for post-weld heat treatment. This seminal work thus offers major benefits to all stakeholders in the global energy sector.

Francis Biley 1958-2012.

Francis (Fran) Biley, who has died at the age of 54, was an enthusiastic champion of health and wellbeing in nursing and mental health.

Effect of a titration polysomnogram on treatment success with a mandibular repositioning appliance.

STUDY OBJECTIVES: Mandibular repositioning appliance (MRA) therapy is a treatment option for patients with mild to moderate sleep apnea and for patients who do not tolerate continuous positive airway pressure. Titration of MRAs consists of sequential mandibular advancement guided by symptom improvement. The goal of the study was to determine if patients with an elevated apnea hypopnea index (AHI), despite the use of a subjectively optimized MRA, could achieve better results with additional titration during polysomnography (PSG). METHODS: Patients were enrolled if they had an AHI > or = 15/h and were referred for MRA therapy. The MRAwas advanced until symptoms improved. During the PSG, the technologist monitored the patient's sleep and increased mandibular protrusion until the AHI was improved. RESULTS: There was a significant improvement in AHI, minimum oxygen saturation, and total sleep time with the MRA before further advancement. At the final PSG, 65.2% of patients had an AHI < or = 10 associated with at least a 50% reduction in AHI. The incomplete responders had their appliance further titrated, and this improved the results of MRA therapy by 30.4% to a total success rate of 95.6%. CONCLUSIONS: This study shows that it is possible to improve the results of MRA therapy by further advancing the appliance during a titration PSG in patients with an incomplete response. The titration night improved the results of the usual clinical advancement of the MRA with substantially more patients achieving a successful outcome.

Exploring community nurses' perceptions of life review in palliative care.

AIMS AND OBJECTIVES: This exploratory study aimed to identify community nurses' understanding of life review as a therapeutic intervention for younger people requiring palliative care. The objectives set out to: (i) Describe the participants' understanding of reminiscence and life review (ii) Detail their current ideas regarding a structured approach to using life review in the community setting. (iii) Outline their understanding of the possible advantages and limitations of life review in relation to palliative care. (iv) Identify future training requirements. BACKGROUND: The literature review illustrated how the eighth developmental stage of Erikson's theory, ego-integrity vs. despair, is a 'crisis' often faced by older people entering the final stage of life. Life review is considered a useful therapeutic intervention in the resolution of this crisis. Younger terminally ill people in the palliative stage of an illness may face the same final crises due to their reduced lifespan. Therefore, this study explored the benefits and limitations of life review as an intervention in palliative care. METHOD: The study used a purposive sample of community nurses responsible for delivering generic and specialist palliative care. A qualitative method of data collection in the form of three focus group interviews was used. Subsequent data were manually analysed, categorized and coded with associations between the themes identified. RESULTS: The findings suggested that community nurses have limited knowledge pertaining to the use of life review and tend to confuse the intervention with reminiscence. Furthermore, they believed that life review could potentially cause harm to practitioners engaged in listening to another person's life story. However, the participants concur that with appropriate training they would find life review a useful intervention to use in palliative care. CONCLUSIONS: The results led to the identification of a number of key recommendations: Community nurses require specific education in the technicalities of life review and additional interpersonal skills training. The need for formalized support through clinical supervision is also recognized and discussed. Finally, suggestions are offered regarding the need to generate wider evidence and how, possibly, to integrate life review into existing palliative care services. RELEVANCE TO CLINICAL PRACTICE: This study has demonstrated that community nurses are keen to extend the support offered to younger terminally ill people who are in the palliative stage of their illness. Despite having limited knowledge of life the main components and underpinning theory pertaining to life review participants could appreciate the potential of life review as a therapeutic intervention in palliative care and were keen to learn more about its use and gain the necessary knowledge and skills.