Improving Medication Adherence Levels in Inflammatory Bowel Disease (IBD) Patients: A Narrative Evidence-Based Review.

Inflammatory bowel disease (IBD) management is typified by a long-term medication regimen which can comprise multiple medications prescribed in different combinations, doses, frequencies, and with various administration routes. This complexity can make medication adherence (MA) - patients taking their medications per the prescription - for patients with IBD a challenge. The research corpus contains diverse interventions aimed at improving MA in patients with IBD. Therefore, to condense the evidenced strategies for ease of reference, this narrative evidence-based review broadly outlines the patient-level interventions reported. The interventions are grouped as educational, behavioural, cognitive-behavioural, and multicomponent. They, however, present mixed results as to their efficacy at improving MA, with those employing combined approaches being the most promising. This reflects the reality that MA is impacted by multiple factors encompassing those pertaining to the patient, disease, therapy, patients' socioeconomic status, and health system. Hence, the most ideal interventions would likely be multifaceted patient-level interventions alongside policy/system-level strategies, to maximise the potential for successfully improving patients' MA. These findings might have been impacted by the heterogeneity of the studies in terms of the method of MA assessment, duration of interventions, and more besides.

Medication adherence to inflammatory bowel disease medications in Aotearoa New Zealand and correlation with health outcomes: A nationwide database analysis.

AIMS: Inflammatory bowel disease (IBD) management entails long-term medication therapy. Worse disease outcomes and reduced quality of life might arise from poor medication adherence (MA). This study is the first to investigate patients with IBD's adherence across Aotearoa New Zealand and its relationship with disease outcomes. METHODS: Dispensing claims data (Pharmaceutical Collection) were used to calculate (3- and 5-year) adherence, using daily polypharmacy possession ratio. Using hospitalization data (National Minimum Dataset), the relationship between adherence and the numbers of hospitalizations and corticosteroid dispensings was investigated. RESULTS: In total, 4654 patients (53% female; 55% Crohn's disease [CD], 45% ulcerative colitis [UC]; median age-at-first-dispensing, 43 years) and 3148 patients (54% female; 55% CD, 44% UC; median age-at-first-dispensing, 44 years) were in the 3- and 5-year cohorts, respectively. The 3- and 5-year cohorts had mean 4.6 and 4.2 IBD-related hospitalizations and 6.9 and 9.2 corticosteroid dispensings, respectively. Average adherence estimates were 77.4% (95% confidence interval: 76.9-78.0%) and 74.9% (95% confidence interval: 74.1-75.6%; 3 and 5 years), while 54% and 51% of patients, respectively, had good adherence (MA ≥ 80%). There was no correlation between adherence and the numbers of hospitalizations (Pearson's R = -.0007; P = .65 and R = -.04; P = .02 [3 and 5 years]) and corticosteroid dispensings (R = .08; P = <.0001 and R = .08; P = <.0001, respectively). CONCLUSION: MA of Aotearoa New Zealand patients with IBD is moderately high but just over half of patients meet the adherent threshold. There was no correlation between adherence and hospitalizations or corticosteroid dispensings; hence, research into longitudinal adherence patterns and associated factors is needed.

Charting the Course of Targeted α Therapy With First-in-Human, Postadministration Image-Guided Dosimetry and Response Assessment of 212 Pb-VMT-α-NET in Metastatic Neuroendocrine Tumors.

ABSTRACT: 212 Pb emerges as a compelling in vivo α-particle generator for targeted α therapy due to its favorable half-life ( t1/2 = 10.6 hours) aligning with the biological half-lives of small peptides and its potent α-particle emissions within the decay series. However, one of the challenges with 212 Pb is to perform appropriate image-guided dosimetry. To date, all the data have been extrapolated from its imaging analog, 203 Pb. We present the first-in-human posttherapy image-guided dosimetric estimates of a single cycle of 212 Pb VMT-α-peptide, administered in a 41-year-old woman with an advanced grade 2 NET. The patient also demonstrated partial response on treatment.

Towards Effective Targeted Alpha Therapy for Neuroendocrine Tumours: A Review.

This review article explores the evolving landscape of Molecular Radiotherapy (MRT), emphasizing Peptide Receptor Radionuclide Therapy (PRRT) for neuroendocrine tumours (NETs). The primary focus is on the transition from ß-emitting radiopharmaceuticals to α-emitting agents in PRRT, offering a critical analysis of the radiobiological basis, clinical applications, and ongoing developments in Targeted Alpha Therapy (TAT). Through an extensive literature review, the article delves into the mechanisms and effectiveness of PRRT in targeting somatostatin subtype 2 receptors, highlighting both its successes and limitations. The discussion extends to the emerging paradigm of TAT, underlining its higher potency and specificity with α-particle emissions, which promise enhanced therapeutic efficacy and reduced toxicity. The review critically evaluates preclinical and clinical data, emphasizing the need for standardised dosimetry and a deeper understanding of the dose-response relationship in TAT. The review concludes by underscoring the significant potential of TAT in treating SSTR2-overexpressing cancers, especially in patients refractory to ß-PRRT, while also acknowledging the current challenges and the necessity for further research to optimize treatment protocols.

Using electronic health records in analysing medication adherence in southern New Zealand patients with inflammatory bowel diseases.

AIMS: Electronic health records (EHRs) are widely used in medication adherence (MA) assessment. Poor adherence in patients with inflammatory bowel diseases (IBD) can lead to worse disease outcomes and increased health costs. This study explores the suitability of southern New Zealand EHRs for estimating adherence, and the relationship between adherence and corticosteroid dispensings (indicating negative disease outcomes). METHODS: Medication dispensing EHR data of former Southern District Health Board IBD patients were analysed to estimate 3-year adherence, using daily polypharmacy possession ratio. The correlation with the number of corticosteroid dispensings was investigated. RESULTS: Of 248/1,290 (19%) consenting patients, only 108/248 (44%) had sufficient data available (46%/54% Crohn's disease/ulcerative colitis; 57% female; 89.8%/0.9% NZ European/Maori; mean 5.1 corticosteroid dispensings). Mean adherence was 83.2% (95% confidence interval [CI] 80.0-86.4; standard deviation [SD]:16.7), with 69% of patients having MA ≥80% (good adherence). Median adherence was 13% higher for males versus females (96% vs 83%; p=0.0001). There was no correlation between adherence and the number of corticosteroid dispensings (Pearson's r=0.11; p>0.05). These findings should be considered with caution as the data were not obtained from all pharmacies and the quantum/nature of missing data is unknown. CONCLUSIONS: The patients' adherence seems high, with no correlation with corticosteroid dispensings demonstrated. Useful EHR data are available but need optimisation for adherence assessments.

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. MATERIALS AND METHODS: Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). RESULTS: On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. CONCLUSION: TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.

Pre-clinical evaluation of biomarkers for the early detection of nephrotoxicity following alpha-particle radioligand therapy.

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Some differences between social work, spiritual care, and psychology: Content variance in end-of-life conversations.

OBJECTIVES: Within the multidisciplinary team, there can sometimes be lack of clarity as to the specific different contributions of each of the psycho-social-spiritual professionals: social workers, psychologist, and spiritual caregivers. This study examined the content of their end-of-life conversations with patients. METHODS: A total of 180 patients with terminal cancer received standard multidisciplinary care, including conversations with a social worker, psychologist, and spiritual caregiver. After each patient's death, these professionals reported using a structured tool which content areas had arisen in their conversations with that patient. RESULTS: Across all content areas, there were significant differences between social work and spiritual care. The difference between social work and psychology was slightly smaller but still quite large. Psychology and spiritual care were the most similar, though they still significantly differed in half the content areas. The differences persisted even among patients who spoke with more than 1 kind of professional. The 6 content areas examined proved to subdivide into 2 linked groups, where patients speaking about 1 were more likely to speak about the others. One group, "reflective" topics (inner and transpersonal resources, interpersonal relationships, one's past, and end of life), included all those topics which arose more often with spiritual caregivers or psychologists. The second group, "decision-making" topics (medical coping and life changes), was comprised of those topics which arose most commonly with social workers, bridging between the medical and personal aspects of care and helping patients navigate their new physical, psychological, and social worlds. SIGNIFICANCE OF RESULTS: These findings help shed light on the differences, in practice, between patients' conversations with social workers, psychologists, and spiritual caregivers and the roles these professionals are playing; can aid in formulating individualized care plans; and strengthen the working assumption that all 3 professions contribute in unique, complementary ways to improving patients' and families' well-being.

Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors.

PURPOSE: The lead-203 (203Pb)/lead-212 (212Pb) elementally identical radionuclide pair has gained significant interest in the field of image-guided targeted alpha-particle therapy for cancer. Emerging evidence suggests that 212Pb-labeled peptide-based radiopharmaceuticals targeting somatostatin receptor subtype 2 (SSTR2) may provide improved effectiveness compared to beta-particle-based therapies for neuroendocrine tumors (NETs). This study aims to improve the performance of SSTR2-targeted radionuclide imaging and therapy through structural modifications to Tyr3-octreotide (TOC)-based radiopharmaceuticals. METHODS: New SSTR2-targeted peptides were designed and synthesized with the goal of optimizing the incorporation of Pb isotopes through the use of a modified cyclization technique; the introduction of a Pb-specific chelator (PSC); and the insertion of polyethylene glycol (PEG) linkers. The binding affinity of the peptides and the cellular uptake of 203Pb-labeled peptides were evaluated using pancreatic AR42J (SSTR2+) tumor cells and the biodistribution and imaging of the 203Pb-labeled peptides were assessed in an AR42J tumor xenograft mouse model. A lead peptide was identified (i.e., PSC-PEG2-TOC), which was then further evaluated for efficacy in 212Pb therapy studies. RESULTS: The lead radiopeptide drug conjugate (RPDC) - [203Pb]Pb-PSC-PEG2-TOC - significantly improved the tumor-targeting properties, including receptor binding and tumor accumulation and retention as compared to [203Pb]Pb-DOTA0-Tyr3-octreotide (DOTATOC). Additionally, the modified RPDC exhibited faster renal clearance than the DOTATOC counterpart. These advantageous characteristics of [212Pb]Pb-PSC-PEG2-TOC resulted in a dose-dependent therapeutic effect with minimal signs of toxicity in the AR42J xenograft model. Fractionated administrations of 3.7 MBq [212Pb]Pb-PSC-PEG2-TOC over three doses further improved anti-tumor effectiveness, resulting in 80% survival (70% complete response) over 120 days in the mouse model. CONCLUSION: Structural modifications to chelator and linker compositions improved tumor targeting and pharmacokinetics (PK) of 203/212Pb peptide-based radiopharmaceuticals for NET theranostics. These findings suggest that PSC-PEG2-TOC is a promising candidate for Pb-based targeted radionuclide therapy for NETs and other types of cancers that express SSTR2.

212Pb-Pretargeted Theranostics for Pancreatic Cancer.

Although pancreatic ductal adenocarcinoma (PDAC) is associated with limited treatment options and poor patient outcomes, targeted α-particle therapy (TAT) represents a promising development in the field. TAT shows potential in treating metastatic cancers, including those that have become resistant to conventional treatments. Among the most auspicious radionuclides stands the in vivo α-generator 212Pb. Combined with the imaging-compatible radionuclide 203Pb, this theranostic match is a promising modality rapidly translating into the clinic. Methods: Using the pretargeting approach between a radiolabeled 1,2,4,5-tetrazine (Tz) tracer and a trans-cyclooctene (TCO) modified antibody, imaging and therapy with radiolead were performed on a PDAC tumor xenograft mouse model. For therapy, 3 cohorts received a single administration of 1.1, 2.2, or 3.7 MBq of the pretargeting agent, [212Pb]Pb-DO3A-PEG7-Tz, whereby administered activity levels were guided by dosimetric analysis. Results: The treated mice were holistically evaluated; minimal-to-mild renal tubular necrosis was observed. At the same time, median survival doubled for the highest-dose cohort (10.7 wk) compared with the control cohort (5.1 wk). Conclusion: This foundational study demonstrated the feasibility and safety of pretargeted TAT with 212Pb in PDAC while considering dose limitations and potential adverse effects.

"It's just like putting your socks on": patients' perspectives on inflammatory bowel disease medication adherence.

Background: A careful, often life-long, medication regimen is central to therapy for Inflammatory Bowel Disease (IBD) - a chronic gut disorder. Hence, medication adherence (MA) - patients taking medications in line with prescription - is important. Previous research indicates that a third of patients with IBD in southern New Zealand have poor medication adherence (MA). Objective: This study investigated these patients' experiences to determine factors that influence their MA, for the first time. Methods: Two focus group discussions (FGDs) were held with IBD patients in Otago, New Zealand. Reflexive thematic analysis from a 'direct realist' viewpoint was used to analyse the data. Results: Data were analysed in three segments: perceptions, experiences and support. Participants perceived MA as a "duty" that was very important to their wellbeing. The participants' MA was centred around a routine requiring proactivity to maintain. MA was negatively impacted by side effects and regimen factors including (high) pill numbers/dose frequency, and getting refills was framed as challenging; whilst healthcare professionals were presented as major MA facilitators. Lastly, the support structures identified included family, friends and colleagues as well as targeted health system factors e.g. medication subsidies. Conclusions: Factors spanning those related to the patients, their socioeconomic status, the disease, IBD therapy and the health system were presented as influencing IBD patients' MA in southern NZ. Thus, multifaceted interventions are needed across the health system to overcome the inhibiting and promote the facilitating elements.

Influence of the Molar Activity of 203/212Pb-PSC-PEG2-TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake.

(1) Background: In neuroendocrine tumors (NETs), somatostatin receptor subtype 2 is highly expressed, which can be targeted by a radioactive ligand such as [177Lu]Lu-1,4,7,10-tetraazacyclododecane-N,N',N″,N‴,-tetraacetic acid-[Tyr3,Thr8]-octreotide (177Lu-DOTA-TOC) and, more recently, by a lead specific chelator (PSC) containing 203/212Pb-PSC-PEG2-TOC (PSC-TOC). The molar activity (AM) can play a crucial role in tumor uptake, especially in receptor-mediated uptake, such as in NETs. Therefore, an investigation of the influence of different molar activities of 203/212Pb-PSC-TOC on cell uptake was investigated. (2) Methods: Optimized radiolabeling of 203/212Pb-PSC-TOC was performed with 50 µg of precursor in a NaAc/AcOH buffer at pH 5.3-5.5 within 15-45 min at 95° C. Cell uptake was studied in AR42 J, HEK293 sst2, and ZR75-1 cells. (3) Results: 203/212Pb-PSC-TOC was radiolabeled with high radiochemical purity >95% and high radiochemical yield >95%, with AM ranging from 0.2 to 61.6 MBq/nmol. The cell uptake of 203Pb-PSC-TOC (AM = 38 MBq/nmol) was highest in AR42 J (17.9%), moderate in HEK293 sstr (9.1%) and lowest in ZR75-1 (0.6%). Cell uptake increased with the level of AM. (4) Conclusions: A moderate AM of 15-40 MBq/nmol showed the highest cell uptake. No uptake limitation was found in the first 24-48 h. Further escalation experiments with even higher AM should be performed in the future. It was shown that AM plays an important role because of its direct dependence on the cellular uptake levels, possibly due to less receptor saturation with non-radioactive ligands at higher AM.

Activity induced worsening of a tuberculous process in the vertebral column of a Late Bronze Age female from Liushui, Xinjiang (China)?

The partial skeleton of a 22-24-year old female from Liushui, Southern Silk Road, Xinjiang (China) was analyzed using morphological and biochemical methods. The most striking finding in this individual of a Late Bronze Age mounted nomadic population was the complete ossification of the caudal vertebral column including parts of the ligaments of this region due to chronic tuberculosis (Pott's disease). The morphological diagnosis is definitely confirmed by the results of the proteomic analysis. The bacterial protein Ag85 and, for the first time in archaeological skeletal remains, also ESAT-6 was detected, which are typical for Mycobacterium tuberculosis. Extremely intense physical stress aggravated the pathological kyphosis primarily caused by the tuberculous process and promoted dislocation of the caudal thoracic versus the lumbar vertebrae. The fate of this young female suffering from tuberculosis and the consequences of this extreme physical stress characterize the harsh living conditions of typical prehistoric population of mounted nomadic pastoralists.

Pre-clinical Evaluation of Biomarkers for Early Detection of Nephrotoxicity Following Alpha-particle Radioligand Therapy.

Purpose: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLTs nephrotoxicity. Methods: A bifunctional cyclic peptide, melanocortin ligand-1(MC1L), labeled with [ 203 Pb]Pb-MC1L, was used for [ 212 Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [ 212 Pb]Pb-MC1L in a dose escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. Results: Biodistribution analysis identified [ 212 Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [ 212 Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary Neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [ 212 Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. Conclusion: urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Biochemical evidence that the whole compartment activity behavior of GAPDH differs between the cytoplasm and nucleus.

Some metabolic enzymes normally occur in the nucleus and cytoplasm. These compartments differ in molecular composition. Since post-translational modification and interaction with allosteric effectors can tune enzyme activity, it follows that the behavior of an enzyme as a catalyst may differ between the cytoplasm and nucleus. We explored this possibility for the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Homogenates of pristine nuclei and cytoplasms isolated from Xenopus laevis oocytes were used for whole compartment activity profiling in a near-physiological buffer. Titrations of NAD+ revealed similar whole compartment activity profiles for GAPDH in nuclear and cytoplasmic homogenates. Surprisingly however GAPDH in these compartments did not have the same behavior in assays of the dependence of initial velocity (v0) on G3P concentration. First, the peak v0 for nuclear GAPDH was up to 2.5-fold higher than the peak for cytoplasmic GAPDH. Second, while Michaelis Menten-like behavior was observed in all assays of cytoplasm, the v0 versus [G3P] plots for nuclear GAPDH typically exhibited a non-Michaelis Menten (sigmoidal) profile. Apparent Km and Vmax (G3P) values for nuclear GAPDH activity were highly variable, even between replicates of the same sample. Possible sources of this variability include in vitro processing of a metabolite that allosterically regulates GAPDH, turnover of a post-translational modification of the enzyme, and fluctuation of the state of interaction of GAPDH with other proteins. Collectively these findings are consistent with the hypothesis that the environment of the nucleus is distinct from the environment of the cytoplasm with regard to GAPDH activity and its modulation. This finding warrants further comparison of the regulation of nuclear and cytoplasmic GAPDH, as well as whole compartment activity profiling of other enzymes of metabolism with cytosolic and nuclear pools.

Optimized Methods for the Production of High-Purity 203Pb Using Electroplated Thallium Targets.

203Pb is a surrogate imaging match for 212Pb. This elementally matched pair is emerging as a suitable pair for imaging and targeted radionuclide therapy in cancer care. Because of the half-life (51.9 h) and low-energy γ-rays emitted, 203Pb is suitable for the development of diagnostic radiopharmaceuticals. The aim of this work was to optimize the production and separation of high-specific-activity 203Pb using electroplated thallium targets. We further investigated the radiochemistry optimization using a suitable chelator, tetraazacyclododecane-1,4,7-triacetic acid (DO3A), and targeting vector, VMT-α-NET (lead-specific chelator conjugated to tyr3-octreotide via a polyethylene glycol linker). Methods: Targets were prepared by electroplating of natural or enriched (205Tl) thallium metal. Scanning electron microscopy was performed to determine the structure and elemental composition of electroplated targets. Targets were irradiated with 24-MeV protons with varying current and beam time to investigate target durability. 203Pb was purified from the thallium target material using an extraction resin (lead resin) column followed by a second column using a weak cation-exchange resin to elute the lead isotope as [203Pb]PbCl2 Inductively coupled plasma mass spectrometry studies were used to further characterize the separation for trace metal contaminants. Radiolabeling efficiency was also investigated for DO3A chelator and VMT-α-NET (a peptide-based targeting conjugate). Results: Electroplated targets were prepared at a high plating density of 76-114 mg/cm2 using a plating time of 5 h. A reproducible separation method was established with a final elution in HCl (400 µL, 1 M) suitable for radiolabeling. Greater than 90% recovery yields were achieved, with an average specific activity of 37.7 ± 5.4 GBq/µmol (1.1 ± 0.1 Ci/µmol). Conclusion: An efficient electroplating method was developed to prepare thallium targets suitable for cyclotron irradiation. A simple and fast separation method was developed for routine 203Pb production with high recovery yields and purity.

Constraints on medication-based inflammatory bowel disease therapy in Aotearoa New Zealand-why medication adherence is important.

The therapeutic landscape for treating Inflammatory Bowel Disease (IBD) in Aotearoa New Zealand had remained largely unchanged for about a decade; however, just this year, two further biologic medications became available. In an international context, these medications are not exactly new, and several other highly efficacious, modern medications and treatment paradigms are available overseas but not in New Zealand. Medication adherence (MA), alongside factors including (relaxation of) medicines funding criteria, specialist availability, IBD awareness in primary healthcare etc., contributes to good patient care. Hence, we contend that MA remains of particular importance for New Zealand patients with IBD to derive maximum benefits from the limited therapeutic options available. Moreover, increased research and interventions for promoting MA, in IBD especially, are crucial.

Associations Between Psycho-Social-Spiritual Interventions, Fewer Aggressive End-of-Life Measures, and Increased Time After Final Oncologic Treatment.

BACKGROUND: Little is known about the impact of spiritual caregivers, psychologists, and social workers on desired end-of-life (EoL) medical outcomes, such as reduced use of aggressive care in the final 2 weeks of life, having more time between the last active oncological treatment and death, and increased hospice use. PATIENTS AND METHODS: We conducted a prospective study of 180 patients with cancer and their families, their interactions with social work, psychology, and spiritual care, and the above three treatment outcomes. RESULTS: We found that having one or more spiritual care visits (adjusted odds ratio (AOR) = 2.02; P = .04), having more quality visits with the psychologist (P = .01), and speaking with someone about one's inner resources (AOR = 2.25; P = .03) all correlated with reduced EoL aggressive care. The key interventions correlating with increased time after final treatment were more visits with the spiritual caregiver or the social worker (AOR = 1.30; P < .001), and speaking about the medical treatment (AOR = 1.54; P < .001) and about interpersonal relationships (AOR = 2.28; P < .001). A subjectively good-quality connection with the spiritual caregiver correlated with increased hospice use (AOR = 10.00; P = .01). CONCLUSIONS: Patients with cancer who availed themselves of the spiritual care, psychology, and social work services, each profession in distinct ways, had significantly different outcomes in their EoL medical treatment, including undergoing fewer futile aggressive measures, having more time after their last active treatment, and using hospice services more. These outcomes directly bear on improved quality of life and reduced costs.