Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Discriminative capacity of the Spanish version of the Inventory of Depression and Anxiety Symptoms-II (IDAS-II) for detecting DMS-5 specific disorders and poor quality of life in a clinical sample.

BACKGROUND: Emotional problems can be evaluated using categorical approaches to guide treatment choices focused on targeting specific disorders, or dimensional approaches to reduce symptom severity. Moreover, recent evidence points out the need to intervene in patients' quality of life (QoL), which often remains low even after the remission of emotional problems. Thus, assessment instruments are needed to provide information on diagnosis, symptom severity, and QoL. The present study aimed to provide diagnostic and QoL cutoffs for the Inventory of Depression and Anxiety Symptoms-II (IDAS-II). METHODS: 273 patients recruited from mental health services in Huelva (Spain) completed the IDAS-II, Mini International Neuropsychiatric Interview, and Short Form-36 Health Survey. Receiver operating characteristic curve analyses were used to establish cutoff values. Diagnostic, balanced, and screening cutoffs were provided for each IDAS-II scale to detect corresponding diagnoses and poor QoL. RESULTS: The specific IDAS-II scales Suicidality, Panic, Social Anxiety, Claustrophobia, and Traumatic Intrusions showed adequate discrimination values for their corresponding diagnoses (suicidal behavior disorder, panic disorder, social anxiety disorder, agoraphobia, and post-traumatic stress disorder, respectively). Both the General Depression and Dysphoria scales showed adequate ability to detect major depressive disorder. The IDAS-II scales showed a higher discrimination ability for Mental Health-related QoL, than for General Health-related QoL. CONCLUSIONS: The diagnostic and QoL cutoffs expand the clinical utility of the IDAS-II in clinical practice and research, making it a comprehensive, detailed, and versatile self-report tool. The IDAS-II allows for the assessment of emotional problems consistent with the dimensional, categorical, transdiagnostic, and QoL approaches.

NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

Examining Profiles and Treatment Outcomes in Dual Diagnosis: Comparison of Coordinated Treatment With Mental Health Services Versus Addiction Center Alone. A Real-World Data Analysis.

OBJECTIVE: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. METHODS: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. RESULTS: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. CONCLUSIONS: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.

Clinical and economic outcomes of a systematic same-day discharge programme after pulmonary vein isolation: comparison between cryoballoon vs. radiofrequency ablation.

AIMS: Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme. METHODS AND RESULTS: We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8). CONCLUSION: In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.

Coordinated treatment between addiction and mental health services vs. uncoordinated treatment for patients with dual diagnosis: higher dropout rates but lower impairement of functional disability.

Dual pathology is often found in addiction and mental health centers. Although there are integrated services for these patients, most countries have developed joint action protocols between addiction and mental health centers. The objective is to analyze the progress of patients diagnosed with dual pathology, comparing the therapeutic outcomes of those who exclusively attend either addiction or mental health centers with those patients who follow a program in which the two services are coordinated. It is hypothesized that patients assisted in coordinate manner will present a better evolution on psychopathological symptomatology, drug use and functional impairment.

The Role of Anxiety in Patients With Persistent Atrial Fibrillation Undergoing Elective Cardioversion: An Observational Study.

OBJECTIVE: Anxiety is often present among patients with atrial fibrillation (AF). This condition has been associated with greater symptom severity and worse quality of life in these patients. However, the influence of anxiety on the risk of AF recurrence is not well known. We aimed to define the level of anxiety in patients with persistent AF undergoing elective cardioversion (EC) and determine whether there is an association between anxiety and the risk of early AF recurrence after EC. METHODS: Anxiety was measured before EC using the State-Trait Anxiety Inventory. Early AF recurrence was assessed with a control electrocardiogram at 30-day follow-up. RESULTS: We included 107 patients undergoing effective EC. Early AF recurrence was diagnosed in 40 patients (37.4%). Compared with those who remained in sinus rhythm, individuals with early AF recurrence had significantly higher levels of trait anxiety (23.1 [10.4] versus 17.9 [9.5]; p = .013) and larger left atrial volume index (45.8 [12.3] versus 37.9 [13.3] ml/m; p = .004). Both variables remained independently associated with early AF recurrence after multivariate analysis. A predictive model including trait anxiety score >20 and left atrial volume index >41 ml/m showed acceptable accuracy for the diagnosis of early AF recurrence (area under the curve = 0.733; 95% confidence interval = 0.634-0.832; p < .001). CONCLUSIONS: Our study shows that trait anxiety is an independent risk factor for early AF recurrence after EC. Further studies are warranted to assess the beneficial role of anxiety-reducing strategies on the outcomes of patients with AF.

Adaptive biokinetic modelling of iodine-131 in thyroid cancer treatments: implications on individualised internal dosimetry.

Nowadays therapies involving radioiodine (I-131) represent 84% of the total metabolic treatments in Europe, according to the last report of the European Association of Nuclear Medicine in relation to treatment planning for molecular radiotherapy. Last recommendations of the European Council, i.e. 2013/59/Euroatom, mandates that metabolic treatments should be planned according to the radiation doses delivered to individual patients, analogous to external beam radiotherapy. In this work, we present a novel biokinetic model for I-131 that allows on to obtain realistic activity distributions for particular patients with thyroid cancer in absence of metastasis. Other models existing in the literature present either a too simple metabolic description to obtain realistic results or a too complex one for adapting the model to individual patients, and many of these models are not indicated for metabolic treatments. The individualisation of activity distribution is obtained by an optimisation method that adjusts our model to a set of experimental measurements. Significant differences in terms of absorbed doses are observed between our model and the standard generalist models, especially in terms of red marrow absorbed dose.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.

Most eukaryotes require oxygen for their survival and, with increasing multicellular complexity, oxygen availability and delivery rates vary across the tissues of complex organisms. In humans, healthy tissues have markedly different oxygen gradients, ranging from the hypoxic environment of the bone marrow (where our haematopoietic stem cells reside) to the lungs and their alveoli, which are among the most oxygenated areas of the body. Immune cells are therefore required to adapt to varying oxygen availability as they move from the bone marrow to peripheral organs to mediate their effector functions. These changing oxygen gradients are exaggerated during inflammation, where oxygenation is often depleted owing to alterations in tissue perfusion and increased cellular activity. As such, it is important to consider the effects of oxygenation on shaping the immune response during tissue homeostasis and disease conditions. In this Review, we address the relevance of both physiological oxygenation (physioxia) and disease-associated hypoxia (where cellular oxygen demand outstrips supply) for immune cell functions, discussing the relevance of hypoxia for immune responses in the settings of tissue homeostasis, inflammation, infection, cancer and disease immunotherapy.

Multidimensional Analysis of Quality of Life in Patients with Chronic Non-Cancer Pain and Short- and Long-Term Intrathecal Analgesic Therapy.

Background: Intrathecal drug delivery (IDD) is part of the fourth analgesic step. Evidence on the quality of life of patients with refractory chronic non-cancer pain (CNCP) using these devices and their long-term outcomes is scarce. This study aims to evaluate patients with IDD to assess their HRQoL. Additionally, the study seeks to understand the patients' satisfaction with the treatment and changes in pain magnitude over time. Methods: Adult patients with CNCP and intrathecal drug delivery systems (IDDS) were included. The study population was divided into two groups: less than and more than 15 years of treatment. HRQoL was analyzed using validated questionnaires. Pain reduction was assessed using the visual analog scale (VAS), and treatment satisfaction was evaluated using the Patient Global Impression of Improvement scale. Results: The results indicate a poor HRQoL in IDD patients, with better scores in the group with ≥15 years of treatment. Pain reduction was similar in both groups, and patients reported a positive satisfaction level with the treatment. Conclusions: HRQoL in CNCP patients is severely affected. Long-term IDD patients have a similar or even better HRQoL in some respects compared to those with shorter follow-ups. IDD patients experienced pain reduction, with most feeling better or much better.

Outcomes of a 24/7 service for urgent permanent pacemaker implantation.

INTRODUCTION AND OBJECTIVES: Most of the complications associated with acute and symptomatic bradyarrhythmia (ASB) occur in the time from diagnosis to permanent pacemaker implantation (PPI). We aimed to evaluate the outcomes of an urgent 24/7 PPI service (PPI-24/7) for patients with ASB. METHODS: A total of 664 patients undergoing first-time PPI for ASB were prospectively assessed during 2 periods of identical length (18 months): 341 patients who underwent the procedure during working hours only (PPI-WH), and 323 patients who underwent the procedure after the implementation of the PPI-24/7 service. The primary safety endpoint was established as the cumulative 180-day incidence of complications related to the index arrhythmia and device implant. The primary efficacy endpoint was determined as the average number of hospital stays per patient. RESULTS: The PPI-24/7 period was associated with a significant shortening of the time from diagnosis to implantation (median [interquartile range]): 3hours [2-6] vs 16 [5-21]). The cumulative incidence of patients with complications at 180 days was lower in the PPI-24/7 period: 9% vs 17% (adjusted odds ratio, 0.5; P=.002), due to a significant reduction in preimplant complications: 2.5% vs 12% (P <.001). The average number of hospital stays was reduced by 2 per patient in the PPI-24/7 period (nonparametric P <.001). PPI-24/7 implants performed outside working hours (n=178) were safe, with a 180-day cumulative incidence in procedure-related complications of 3.9%. CONCLUSIONS: Among patients with ASB, PPI-24/7 was associated with a significant reduction in patient morbidity and efficient hospital resource use.

The theory of planned behavior and alcohol protective behavioral strategies: a prospective study examining the role of habit and gender invariance.

OBJECTIVES: Alcohol Protective Behavioral Strategies (PBS) have consistently shown to be effective in reducing alcohol use and its associated consequences. We aimed to examine the explanatory value of the Theory of Planned Behavior (TPB) for using five PBS, studying the role of habit, and its potential variation across genders. METHODS: Targeted sampling was used to recruit 339 young adults in the community (women = 50.7%; mean age = 2.21[SD = 2.21]), who completed baseline and 2-month follow-up questionnaires. RESULTS: The explained variance of the TPB ranged from 58-68% for intention to use PBS, and 18-50% for behavior. The inclusion of habit produced increases of 17-26% in explained variance in intention, while explained variance in behavior remained similar. Habit was the strongest predictor of intention to use PBS, followed by attitude. Except for one behavior (drinking slowly), habits did not moderate the intention-behavior relationship, and the explanatory value of the TPB did not differ across genders. CONCLUSIONS: Our findings support the utility of the TPB as an explanatory model of alcohol PBS, along with the need to include habits within the framework of dual-process models. Interventions aimed at promoting alcohol PBS could be optimized by targeting attitudes towards PBS and habits.

Comparison of Different Sexual Behaviors According to Sexual Orientation and the Mediating Role of Attitudes toward Sexual Behaviors between Sexual Orientation and Sexual Behaviors in Young Adults.

Objectives: To explore the relationship between sexual orientation and specific sexual and risk behaviors, compare the number of sexual behaviors and attitudes among people of different sexual orientations, and test the mediating effect of attitudes toward sexual behaviors in the relationship between sexual orientation and the number of sexual behaviors. Methods: A total of 2288 participants completed a checklist of sexual behaviors, indicators of sexual risk behaviors, and a scale of attitudes toward sexual behaviors. Results: Bisexual women engaged in a greater number of sexual behaviors and had more positive attitudes toward sexual behaviors than heterosexual women. Homosexual men engaged in a greater number of sexual behaviors than heterosexual men, and homosexual and bisexual men had more positive attitudes toward sexual behaviors than heterosexuals. Finally, we show the mediating role of attitudes toward sexual behaviors in the relationship between sexual orientation and the number of sexual behaviors engaged in. Conclusions: The importance of considering sexual orientation when analyzing sexual behaviors and attitudes is highlighted.

Operational definitions and measurement of externalizing behavior problems: An integrative review including research models and clinical diagnostic systems.

Measurement of externalizing disorders such as antisocial disorders, attention-deficit/hyperactivity disorder or borderline disorder have relevant implications for the daily lives of people with these disorders. While the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD) have provided the diagnostic framework for decades, recent dimensional frameworks question the categorical approach of psychopathology, inherent in traditional nosotaxies. Tests and instruments develop under the DSM or ICD framework preferentially adopt this categorical approach, providing diagnostic labels. In contrast, dimensional measurement instruments provide an individualized profile for the domains that comprise the externalizing spectrum, but are less widely used in practice. Current paper aims to review the operational definitions of externalizing disorders defined under these different frameworks, revise the different measurement alternatives existing, and provide an integrative operational definition. First, an analysis of the operational definition of externalizing disorders among the DSM/ICD diagnostic systems and the recent Hierarchical Taxonomy of Psychopathology (HiTOP) model is carried out. Then, in order to analyze the coverage of operational definitions found, a description of measurement instruments among each conceptualization is provided. Three phases in the development of the ICD and DSM diagnosis systems can be observed with direct implications for measurement. ICD and DSM versions have progressively introduced systematicity, providing more detailed descriptions of diagnostic criteria and categories that ease the measurement instrument development. However, it is questioned whether the DSM/ICD systems adequately modelize externalizing disorders, and therefore their measurement. More recent theoretical approaches, such as the HiTOP model seek to overcome some of the criticism raised towards the classification systems. Nevertheless, several issues concerning this model raise mesasurement challenges. A revision of the instruments underneath each approach shows incomplete coverage of externalizing disorders among the existing instruments. Efforts to bring nosotaxies together with other theoretical models of psychopathology and personality are still needed. The integrative operational definition of externalizing disorders provided may help to gather clinical practice and research.

Spontaneous Variation of Ventriculo-Atrial Interval after Tachycardia Induction: Determinants and Usefulness in the Diagnosis of Supraventricular Tachycardias with Long Ventriculoatrial Interval.

Background: Determining the mechanism of supraventricular tachycardias with prolongedP ventriculoatrial (VA) intervals is sometimes a challenge. Our objective is to analyse the determinants, time course and diagnostic accuracy (atypical atrioventricular nodal reentrant tachycardias [AVNRT] versus orthodromic reentrant tachycardias through an accessory pathway [ORT]) of spontaneous VA intervals variation in patients with narrow QRS tachycardias and prolonged VA. Methods: A total of 156 induced tachycardias were studied (44 with atypical AVNRT and 112 with ORT). Two sets of 10 measurements were performed for each patient­after tachycardia induction and one minute later. VA and VV intervals were determined. Results: The difference between the longest and the shortest VA interval (Dif-VA) correlates significantly with the diagnosis of atypical AVNRT (C coefficient = 0.95 and 0.85 after induction and at one minute, respectively; p < 0.001). A Dif-VA ≥ 15 ms presents a sensitivity and specificity for atypical AVNRT of 50% and 99%, respectively after induction, and of 27% and 100% one minute later. We found a robust and significant correlation between the fluctuations of VV and VA intervals in atypical AVNRTs (Coefficient Rho: 0.56 and 0.76, after induction and at one minute, respectively; p < 0.001 for both) but not in ORTs. Conclusions: The analysis of VA interval variability after induction and one minute later correctly discriminates atypical AVNRT from ORT in almost all cases.

Psychometric properties of the Spanish adaptation of the Externalizing Spectrum Inventory-Brief Form (ESI-BF).

The Externalizing Spectrum Inventory-Brief Form (ESI-BF) measures tendencies toward disinhibition, lack of control, aggression, and substance use. This study adapts the ESI-BF to the Spanish population and assesses its psychometric properties. The study included 742 community adults obtained by stratified random sampling with proportional allocation according to gender, age, and geographical area of the Spanish territory and a clinical sample consisting of 333 patients. All participants completed the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (PID-5) and the Alcohol Substance Dependence Severity Scale, in addition to the Spanish version of the ESI-BF. Reliability was quantified using McDonald's omega and Cronbach's α reliability coefficients. Validity evidences were studied applying confirmatory factor analysis (CFA) and correlations. Results indicated adequate reliability of scores on the ESI-BF's general factors and most of its facets. Regarding internal structure, and in line with previous studies, both symmetric and S-1 hierarchical two-subfactor (bifactor) emerged as the best-fitting models. Considering both criticisms of symmetric models and parsimony, the S-1 bifactor model, which showed configural invariance across gender and samples, was retained. Validity evidence based on the relationship with other measures of personality and alcohol consumption show correlations values theoretically expected in both clinical and community samples. Findings suggest that the Spanish adaptation of the ESI-BF shows functional near-equivalence to the original version. Its effective psychometric properties make it useful instrument for further research related to the externalizing spectrum. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Differential roles for the oxygen sensing enzymes PHD1 and PHD3 in the regulation of neutrophil metabolism and function.

Background: Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised to be more diverse and malleable than was previously appreciated. Hypoxic signalling pathways are known to regulate important neutrophil behaviours and, as such, are potential therapeutic targets for regulating neutrophil antimicrobial and inflammatory responses. Methods: We used a combination of in vivo and ex vivo models, utilising neutrophil and myeloid specific PHD1 or PHD3 deficient mouse lines to investigate the roles of oxygen sensing prolyl hydroxylase enzymes in the regulation of neutrophilic inflammation and immunity. Mass spectrometry and Seahorse metabolic flux assays were used to analyse the role of metabolic shifts in driving the downstream phenotypes. Results: We found that PHD1 deficiency drives alterations in neutrophil metabolism and recruitment, in an oxygen dependent fashion. Despite this, PHD1 deficiency did not significantly alter ex vivo neutrophil phenotypes or in vivo outcomes in mouse models of inflammation. Conversely, PHD3 deficiency was found to enhance neutrophil antibacterial properties without excessive inflammatory responses. This was not linked to changes in the abundance of core metabolites but was associated with increased oxygen consumption and increased mitochondrial reactive oxygen species (mROS) production. Conclusions: PHD3 deficiency drives a favourable neutrophil phenotype in infection and, as such, is an important potential therapeutic target.

Concepts and methods for the dosimetry of radioembolisation of the liver with Y-90-loaded microspheres.

This article aims at presenting in a didactic way, dosimetry concepts and methods that are relevant for radio-embolization of the liver with 90Y-microspheres. The application of the medical internal radiation dose formalism to radio-embolization is introduced. This formalism enables a simplified dosimetry, where the absorbed dose in a given tissue depends on only its mass and initial activity. This is applied in the single-compartment method, partition model, for the liver, tumour and lung dosimetry, and multi-compartment method, allowing identification of multiple tumours. Voxel-based dosimetry approaches are also discussed. This allows taking into account the non-uniform uptake within a compartment, which translates into a non-uniform dose distribution, represented as a dose-volume histogram. For this purpose, dose-kernel convolution allows propagating the energy deposition around voxel-sources in a computationally efficient manner. Alternatively, local-energy deposition is preferable when the spatial resolution is comparable or larger than the beta-particle path. Statistical tools may be relevant in establishing dose-effect relationships in a given population. These include tools such as the logistic regression or receiver operator characteristic analysis. Examples are given for illustration purpose. Moreover, tumour control probability modelling can be assessed through the linear-quadratic model of Lea and Catcheside and its counterpart, the normal-tissue complication probability model of Lyman, which is suitable to the parallel structure of the liver. The selectivity of microsphere administration allows tissue sparing, which can be considered with the concept of equivalent uniform dose, for which examples are also given. The implication of microscopic deposition of microspheres is also illustrated through a liver toxicity model, even though it is not clinically validated. Finally, we propose a reflection around the concept of therapeutic index (TI), which could help tailor treatment planning by determining the treatment safety through the evaluation of TI based on treatment-specific parameters.