Evaluation of the VioOne HIV profile supplemental assay.

HIV is an ongoing global epidemic with estimates of more than a million new infections occurring annually. To combat viral spread, continuous innovations in areas including testing and treatment are necessary. In the United States, the Centers for Disease Control and Prevention recommend that laboratories follow an HIV testing algorithm that first uses a US Food and Drug Administration approved immunoassay to detect antibodies to HIV-1 or HIV-2 as well as HIV-1 p24 antigen in serum or plasma samples. An initially reactive specimen is tested by a supplemental assay for confirmation and to differentiate antibodies to HIV-1 or HIV-2. There are few Food and Drug Administration (FDA)-approved supplemental differentiation tests currently available. A multicenter investigation was conducted to determine the clinical performance for two independent versions of the Avioq VioOne HIV Profile Supplemental Assay (Avioq, Inc., Research Triangle Park, NC). The performance of both assay versions compared favorably with the performance parameters for the Geenius HIV 1/2 Supplemental Assay as published in that assay package insert (Bio-Rad Laboratories, Hercules, CA), the current gold standard for HIV supplemental testing. When comparing the two VioOne assays, version 2 (lacking HIV-2 p27 antibody detection) demonstrated improved reproducibility, specificity, and sensitivity as compared to its predecessor. IMPORTANCE We evaluated the reproducibility, sensitivity, and specificity data for two versions of the VioOne HIV Profile Supplemental Assay and compared these results back to similar results for the Geenius HIV 1/2 Supplemental Assay that are publicly available. Our study concluded that the VioOne HIV Profile Supplemental Assay compared favorably with the Geenius HIV 1/2 Supplemental Assay, thus providing an additional option for clinical laboratories to improve and expand their HIV testing capabilities.

The roots of polarization in the individual reward system.

Polarization raises concerns for democracy and society, which have expanded in the internet era where (mis)information has become ubiquitous, its transmission faster than ever, and the freedom and means of opinion expressions are expanding. The origin of polarization however remains unclear, with multiple social and emotional factors and individual reasoning biases likely to explain its current forms. In the present work, we adopt a principled approach and show that polarization tendencies can take root in biased reward processing of new information in favour of choice confirmatory evidence. Through agent-based simulations, we show that confirmation bias in individual learning is an independent mechanism and could be sufficient for creating polarization at group level independently of any additional assumptions about the opinions themselves, a priori beliefs about them, information transmission mechanisms or the structure of social relationship between individuals. This generative process can interact with polarization mechanisms described elsewhere, but constitutes an entrenched biological tendency that helps explain the extraordinary resilience of polarization against mitigating efforts such as dramatic informational change in the environment.

Indirect reciprocity with abductive reasoning.

Indirect reciprocity is a reputational mechanism through which cooperative behavior can be promoted amongst a group of individuals. However, in order for this mechanism to effectively do so, cheating must be appropriately punished and cooperating appropriately rewarded. Errors in assessments and actions can hinder this process. In such a setting, individuals might try to reason about evidence to assign reputations given the possibility of errors. Here, we consider a well-established theory of reasoning used to combine evidence, abductive reasoning, as a possible means by which such errors can be circumvented. Specifically, we use Dempster-Shafer theory to model individuals who account for possible errors by combining information about their beliefs about the status of the population and the errors rates and then choose the simplest scenario that could explain their observations in the context of these beliefs. We investigate the effectiveness of abductive reasoning at promoting cooperation for five social norms: Scoring, Shunning, Simple Standing, Staying, and Stern Judging. We find that, generally, abductive reasoning can outperform non-reasoning models at ameliorating the effects of the aforementioned challenges and promote higher levels of cooperation under low-error conditions. However, for high-error conditions, we find that abductive reasoning can undermine cooperation. Furthermore, we also find that a degree of bias towards believing previously held reputations can help sustain cooperation.

Higher rates of laboratory-confirmed cases of syphilis in Western Canadian blood donors compared with Eastern Canadian blood donors following a period of societal re-opening.

BACKGROUND AND OBJECTIVES: There is a growing infectious syphilis outbreak in Western Canada. Although blood donors are screened for syphilis risks, some blood donors will still be confirmed test-positive for syphilis. This study compares the characteristics of confirmed test-positive syphilis donations in both Western Canada and Eastern Canada, November 2022-August 2023. MATERIALS AND METHODS: Donors were defined as Western or Eastern Canadian. Blood donations were tested for syphilis using the PK-TP assay (Beckman Coulter PK7300 Automated Microplate System). Confirmatory Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR) assays were performed by one of two reference laboratories. An RPR titre ≥1:8 was used as a proxy for possible infectious syphilis. RESULTS: Rates of laboratory-confirmed syphilis were higher in Western (n = 43, 13.4/100,000 donations) versus Eastern donors (n = 19, 4.7/100,000 donations; Fisher's exact test, two-sided, p ≤ 0.0001). Most syphilis confirmations were in first-time donors (Western Canada n = 31/43, 72.1%, Eastern Canada 12/19, 63.2%). CONCLUSION: Although rates of laboratory-confirmed syphilis were higher in Western versus Eastern donors, Western donors did not have higher rates of infectious syphilis. Further studies might assess whether donors with laboratory-confirmed syphilis understood pre-donation screening questions or were completely unaware of a past infection.

Self-Correcting Method for Highly Effective Office-Based Helicobacter pylori Therapy Using Cumulative Test of Cure Data.

BACKGROUND AND AIM: Helicobacter pylori infections have become resistant to many previously highly effective antimicrobial regimens resulting in clarithromycin, metronidazole, or fluoroquinolone-containing therapies becoming unsuccessful. Pretreatment susceptibility testing is only widely available in the United States but is still rarely done. Here, we propose a framework to monitor H. pylori eradication in small clinical settings by routinely assessing the effectiveness of therapy. METHODS: Because of the small sample size in individual practice's, we assume an acceptable cure rate of ≥80% (preferred cure rate ≥85%) in adherent patients, with a dichotomous outcome (cured vs. failed) and consecutive patient enrollment. To obtain results (feedback) in a timely manner, for individual practices, cure rates can be estimated after 10 patients. Large practices which acquire patients more rapidly can delay analysis until a total of 104 H. pylori-infected patients, assuming a baseline cure rate of at least 85% with the preferred regimen. RESULTS: We show how data from individual practices can be utilized to improve the effectiveness of H. pylori treatment decisions. The method consists of recording and accumulating the confirmation of cure data for successive small groups of patients. These data are then analyzed as binary outcomes (pass-fail) and serve as the basis for studying and improving the effectiveness of H. pylori treatment decisions. CONCLUSION: A simple actuarial method can serve outpatient clinics to ensure a reliable test-to-cure method and avoid futile Hp regimens.

Blind measurements did not confirm effects of forest fragmentation on fluctuating asymmetry of a tropical butterfly Morpho helenor.

Re-evaluation of photographs of the tropical butterfly Morpho helenor from a previous study (Pignataro et al. 2023) revealed that its conclusion regarding increased wing fluctuating asymmetry in forest edge habitats compared to forest interior habitats could not be replicated. This discrepancy likely arises from (i) original measurements not being conducted blindly, (ii) insufficient photograph quality hindering accurate landmark selection, and (iii) a lack of detailed description of the measurement protocol. The likelihood of false positive discoveries within the published data concerning the impacts of environmental stress on the fluctuating asymmetry of plants and animals is probably higher than previously assumed.

Isolation of Caribbean Ciguatoxin-5 (C-CTX5) and confirmation of its structure by NMR spectroscopy.

Ciguatera poisoning occurs throughout subtropical and tropical regions globally. The Virgin Islands in the Caribbean Sea is a known hyperendemic region for ciguatera and has been associated with Caribbean ciguatoxin (C-CTX) contamination in fish. An algal C-CTX (C-CTX5) was identified in Gambierdiscus silvae and G. caribeaus isolated from benthic algal samples collected in waters south St. Thomas, US Virgin Islands. The highest CTX-producing isolate, G. silvae 1602 SH-6, was grown at large-scale to isolate sufficient C-CTX5 for structural confirmation by NMR spectroscopy. A series of orthogonal extraction and fractionation procedures resulted in purification of approximately 40 µg of C-CTX5, as estimated by quantitative NMR. A suite of 1D and 2D NMR experiments were acquired that verified the structure originally proposed for C-CTX5. The structural confirmation and successful isolation of C-CTX5 opens the way for work on the stability, toxicology and biotransformation of C-CTXs, as well as for the production of quantitative reference materials for analytical method development and validation. The strategies developed for purification of C-CTX5 may also apply to isolation and purification of CTXs from the Pacific Ocean and other regions.

First Insight into the Phylogenetic Diversity of Bovicola caprae Infesting Goats of Different Agro-climatic Locations in India.

Bovicola caprae is an important obligate ectoparasite of goats worldwide including India. The present study aimed at the molecular confirmation, phylogenetics and population structure analyses of B. caprae infesting goats of three different agro-climatic locations in India, by targeting the mitochondrial cytochrome C oxidase subunit 1 (cox1) genetic marker. The phylogenetic tree exhibited the presence of two different lineages of B. caprae. The sequences generated herein clustered in lineage 2 along with the GenBank™ archived sequences from China and Iran. The sequences generated herein also showed the circulation of sub-lineages of B. caprae in India based on the analysis of pairwise genetic distances between sequences and median-joining haplotype network. The population structure analyses revealed low nucleotide (0.00353 ± 0.00291 and 0.02694 ± 0.00363) and high haplotype (0.667 ± 0.314 and 0.618 ± 0.104) diversities for the present study isolates as well as for the complete dataset, respectively, which evinced a recent demographic expansion. High genetic differentiation (FST value = 0.97826) and low gene flow (Nm = 0.00556) were also recorded in the different lineages/populations. In conclusion, the present study addressed the research gap and provided the first insight into the phylogenetics of the goat louse B. caprae and highlighted the circulation of sub-lineages of the ectoparasite in India.

Modality-specific sensory and decisional carryover effects in duration perception.

BACKGROUND: The brain uses recent history when forming perceptual decisions. This results in carryover effects in perception. Although separate sensory and decisional carryover effects have been shown in many perceptual tasks, their existence and nature in temporal processing are unclear. Here, we investigated whether and how previous stimuli and previous choices affect subsequent duration perception, in vision and audition. RESULTS: In a series of three experiments, participants were asked to classify visual or auditory stimuli into "shorter" or "longer" duration categories. In experiment 1, visual and auditory stimuli were presented in separate blocks. Results showed that current duration estimates were repelled away from the previous trial's stimulus duration, but attracted towards the previous choice, in both vision and audition. In experiment 2, visual and auditory stimuli were pseudorandomly presented in one block. We found that sensory and decisional carryover effects occurred only when previous and current stimuli were from the same modality. Experiment 3 further investigated the stimulus dependence of carryover effects within each modality. In this experiment, visual stimuli with different shape topologies (or auditory stimuli with different audio frequencies) were pseudorandomly presented in one visual (or auditory) block. Results demonstrated sensory carryover (within each modality) despite task-irrelevant differences in visual shape topology or audio frequency. By contrast, decisional carryover was reduced (but still present) across different visual topologies and completely absent across different audio frequencies. CONCLUSIONS: These results suggest that serial dependence in duration perception is modality-specific. Moreover, repulsive sensory carryover effects generalize within each modality, whereas attractive decisional carryover effects are contingent on contextual details.

Pragmatism and Experimental Bioethics.

Pragmatism gained considerable attention in bioethical discussions in the early 21st century. However, some dimensions and contributions of pragmatism to bioethics remain underexplored in both research and practice. It is argued that pragmatism can make a distinctive contribution to bioethics through its concept, developed by Charles S. Peirce and John Dewey, that ethical issues can be resolved through experimental inquiry. Dewey's proposal that policies can be confirmed or disconfirmed through experimentation is developed by comparing it to the confirmation of scientific hypotheses, with a focus on the objection that the consequences of following a moral view or policy do not provide guidance on choosing among competing ethical perspectives. As confirmation of scientific hypotheses typically relies on evidence gathered from observation, the possibility of ethically relevant observation is then explored based on Peirce's views on feelings as emotional interpretants. Finally, the connection between Dewey's experimental ethics and democracy is outlined and compared to unfettered ethical progressivism.

Efficient Integration of Rate-Adaptive Reconciliation with Syndrome-Based Error Estimation and Subblock Confirmation for Quantum Key Distribution.

An effective post-processing algorithm is essential for achieving high rates of secret key generation in quantum key distribution. This work introduces an approach to quantum key distribution post-processing by integrating the three main steps into a unified procedure: syndrome-based error estimation, rate-adaptive reconciliation, and subblock confirmation. The proposed scheme employs low-density parity-check codes to estimate the quantum bit error rate using the syndrome information, and to optimize the channel coding rates based on the Slepian-Wolf coding scheme for the rate-adaptive method. Additionally, this scheme incorporates polynomial-based hash verification in the subblock confirmation process. The numerical results show that the syndrome-based estimation significantly enhances the accuracy and consistency of the estimated quantum bit error rate, enabling effective code rate optimization for rate-adaptive reconciliation. The unified approach, which integrates rate-adaptive reconciliation with syndrome-based estimation and subblock confirmation, exhibits superior efficiency, minimizes practical information leakage, reduces communication rounds, and guarantees convergence to the identical key. Furthermore, the simulations indicate that the secret key throughput of this approach achieves the theoretical limit in the context of a BB84 quantum key distribution system.

Bronchiolitis, Regardless of Its Etiology and Severity, Is Associated With Increased Risk of Asthma: A Population-Based Study.

An association exists between severe respiratory syncytial virus (RSV)-bronchiolitis and a subsequent increased risk of recurrent wheezing (RW) and asthma. However, a causal relationship remains unproven. Using a retrospective population-based cohort study (339 814 children), bronchiolitis during the first 2 years of life (regardless of etiology and severity) was associated with at least a 3-fold increased risk of RW/asthma at 2-4 years and an increased prevalence of asthma at ≥5 years of age. The risk was similar in children with mild bronchiolitis as in those with hospitalized RSV-bronchiolitis and was higher in children with hospitalized non-RSV-bronchiolitis. The rate of RW/asthma was higher when bronchiolitis occurred after the first 6 months of life. Our results seem to support the hypothesis of a shared predisposition to bronchiolitis (irrespective of etiology) and RW/asthma. However, 60% of hospitalized bronchiolitis cases in our setting are due to RSV, which should be paramount in decision-making on imminent RSV prevention strategies.

Predictivism and avoidance of ad hoc-ness: An empirical study.

Predictivism is the thesis that evidence successfully predicted by a scientific theory counts more (or ought to count more) in the confirmation of that theory than already known evidence would. One rationale that has been proposed for predictivism is that predictive success guards against ad hoc hypotheses. Despite the intuitive attraction of predictivism, there is historical evidence that speaks against it. As valuable as the historical evidence may be, however, it is largely indirect evidence for the epistemic attitudes of individual - albeit prominent - scientists. This paper presents the results of an empirical study of scientists' attitudes toward predictivism and ad hoc-ness (n = 492), which will put the debate on a more robust empirical footing. The paper also draws attention to a tension between the ad hoc-ness avoidance rationale of predictivism and the ways philosophers have spelled out the notion of ad hoc-ness.

Confirmation by Robustness Analysis: A Bayesian Account.

Some authors claim that minimal models have limited epistemic value (Fumagalli, 2016; Grüne-Yanoff, 2009a). Others defend the epistemic benefits of modelling by invoking the role of robustness analysis for hypothesis confirmation (see, e.g., Levins, 1966; Kuorikoski et al., 2010) but such arguments find much resistance (see, e.g., Odenbaugh & Alexandrova, 2011). In this paper, we offer a Bayesian rationalization and defence of the view that robustness analysis can play a confirmatory role, and thereby shed light on the potential of minimal models for hypothesis confirmation. We illustrate our argument by reference to a case study from macroeconomics. At the same time, we also show that there are cases in which robustness analysis is detrimental to confirmation. We characterize these cases and link them to recent investigations on evidential variety (Landes, 2020b, 2021; Osimani and Landes, forthcoming). We conclude that robustness analysis over minimal models can confirm, but its confirmatory value depends on concrete circumstances.

Functional inhibition of c-Myc using novel inhibitors identified through "hot spot" targeting.

Protein-protein interactions drive various biological processes in healthy as well as disease states. The transcription factor c-Myc plays a crucial role in maintaining cellular homeostasis, and its deregulated expression is linked to various human cancers; therefore, it can be considered a viable target for cancer therapeutics. However, the structural heterogeneity of c-Myc due to its disordered nature poses a major challenge to drug discovery. In the present study, we used an in silico alanine scanning mutagenesis approach to identify "hot spot" residues within the c-Myc/Myc-associated factor X interface, which is highly disordered and has not yet been systematically analyzed for potential small molecule binding sites. We then used the information gained from this analysis to screen potential inhibitors using a conformation ensemble approach. The fluorescence-based biophysical experiments showed that the identified hit molecules displayed noncovalent interactions with these hot spot residues, and further cell-based experiments showed substantial in vitro potency against diverse c-Myc-expressing cancer/stem cells by deregulating c-Myc activity. These biophysical and computational studies demonstrated stable binding of the hit compounds with the disordered c-Myc protein. Collectively, our data indicated effective drug targeting of the disordered c-Myc protein via the determination of hot spot residues in the c-Myc/Myc-associated factor X heterodimer.

Are Confirmatory Assays Reliable for HIV-1/HIV-2 Infection Differentiation? A Multicenter Study.

Immunoblots remain the gold standard for HIV-1/HIV-2 infection confirmation. However, their ability to differentiate HIV-1 from HIV-2 infection on an antigenically diversified HIV-1 and HIV-2 panel remain uncommon. We performed a multicenter study on 116 serum samples accounting for most of the diversity of HIV-1 (9 different subtypes in group M, 17 circulating recombinant forms (CRFs), and 3 group O) and HIV-2 (groups A and B), evaluating seven confirmatory assays (six commercially available assays and one in-house assay) with genotyping as the reference. The assays were INNO-LIA HIV I/II score, HIV-2 blot 1.2, HIV blot 2.2, New Lav blot I and II, Geenius, and an in-house serotyping enzyme-linked immunosorbent assay (ELISA). Among the HIV-1 samples, INNO-LIA, HIV blot 2.2, New Lav blot I, Geenius, and serotyping had comparable high sensitivities, from 98% to 100%, whereas HIV-2 blot 1.2 and New Lav blot II had high rates of "undetermined" results (85% and 95%, respectively). HIV-2 blot 1.2 and New Lav blot II misclassified 7% and 5% of HIV-1 samples as HIV-2, respectively, and HIV-2 blot 1.2 had an 8% false-negative rate. Among the HIV-2 samples, INNO-LIA, New Lav blot II, HIV-2 blot 1.2, and serotyping had high sensitivities, from 96% to 100%. HIV blot 2.2 misclassified 17% of HIV-2 samples as HIV-1/HIV-2 dual infections. New Lav blot I misclassified 19% of HIV-2 samples as HIV-1 with a high (81%) undetermined rate, and Geenius misclassified 2% as HIV-1 and 7% as untypeable HIV positive. For HIV-1/HIV-2 dual infection, the results were less sensitive, with at most 87.5% for INNO-LIA and Geenius and 75% for HIV blot 2.2 and serotyping. Overall, confirmatory assays remain useful for most cases, with the exception of HIV-1/HIV-2 dual-infection suspicion.

Incidence and trends of 17 notifiable bacterial infectious diseases in China, 2004-2019.

BACKGROUND: Certain bacterial infectious diseases are categorized as notifiable infectious diseases in China. Understanding the time-varying epidemiology of bacterial infections diseases can provide scientific evidence to inform prevention and control measures. METHODS: Yearly incidence data for all 17 major notifiable bacterial infectious diseases (BIDs) at the province level were obtained from the National Notifiable Infectious Disease Reporting Information System in China between 2004 and 2019. Of them 16 BIDs are divided into four categories, respiratory transmitted diseases (RTDs, 6 diseases), direct contact/fecal-oral transmitted diseases (DCFTDs, 3 diseases), blood-borne/sexually transmitted diseases (BSTDs, 2 diseases), and zoonotic and vector-borne diseases (ZVDs, 5 diseases), and neonatal tetanus is excluded in the analysis. We characterized the demographic, temporal, and geographical features of the BIDs and examined their changing trends using a joinpoint regression analysis. RESULTS: During 2004‒2019, 28 779 thousand cases of BIDs were reported, with an annualized incidence rate of 134.00 per 100 000. RTDs were the most commonly reported BIDs, accounting for 57.02% of the cases (16 410 639/28 779 000). Average annual percent changes (AAPC) in incidence were - 1.98% for RTDs, - 11.66% for DCFTDs, 4.74% for BSTDs, and 4.46% for ZVDs. Females had a higher incidence of syphilis than males, and other BIDs were more commonly reported in males. Among 0-5-year-olds, the diseases with the largest increases in incidence were pertussis (15.17% AAPC) and scarlet fever (12.05%). Children and students had the highest incidence rates of scarlet fever, pertussis, meningococcal meningitis, and bacillary dysentery. Northwest China had the highest incidence of RTDs, while South and East China had the highest incidences of BSTDs. Laboratory confirmation of BIDs increased from 43.80 to 64.04% during the study period. CONCLUSIONS: RTDs and DCFTDs decreased from 2004 to 2019 in China, while BSTDs and ZVDs increased during the same period. Great attention should be paid to BSTDs and ZVDs, active surveillance should be strengthened, and timely control measures should be adopted to reduce the incidence.

Confirmatory reinforcement learning changes with age during adolescence.

Understanding how learning changes during human development has been one of the long-standing objectives of developmental science. Recently, advances in computational biology have demonstrated that humans display a bias when learning to navigate novel environments through rewards and punishments: they learn more from outcomes that confirm their expectations than from outcomes that disconfirm them. Here, we ask whether confirmatory learning is stable across development, or whether it might be attenuated in developmental stages in which exploration is beneficial, such as in adolescence. In a reinforcement learning (RL) task, 77 participants aged 11-32 years (four men, mean age = 16.26) attempted to maximize monetary rewards by repeatedly sampling different pairs of novel options, which varied in their reward/punishment probabilities. Mixed-effect models showed an age-related increase in accuracy as long as learning contingencies remained stable across trials, but less so when they reversed halfway through the trials. Age was also associated with a greater tendency to stay with an option that had just delivered a reward, more than to switch away from an option that had just delivered a punishment. At the computational level, a confirmation model provided increasingly better fit with age. This model showed that age differences are captured by decreases in noise or exploration, rather than in the magnitude of the confirmation bias. These findings provide new insights into how learning changes during development and could help better tailor learning environments to people of different ages. RESEARCH HIGHLIGHTS: Reinforcement learning shows age-related improvement during adolescence, but more in stable learning environments compared with volatile learning environments. People tend to stay with an option after a win more than they shift from an option after a loss, and this asymmetry increases with age during adolescence. Computationally, these changes are captured by a developing confirmatory learning style, in which people learn more from outcomes that confirm rather than disconfirm their choices. Age-related differences in confirmatory learning are explained by decreases in stochasticity, rather than changes in the magnitude of the confirmation bias.

Factors influencing loyalty to online health consultation platform: a cross-strait cultural perspective.

BACKGROUND: The geographical, cultural, and linguistic proximity between Taiwan and Mainland China has facilitated rapid growth of cross-strait interactions. Both countries have developed online health consultation platforms on the Internet for the public to access healthcare related information. This study examines factors that influence loyalty to a specific online health consultation platform (OHCP) from a cross-strait perspective. METHODS: Based on the Expectation Confirmation Theory and the combined Trust, Perceived Health Risks and Culture, we examine factors that influence loyalty to OHCPs among cross-strait users by investigating the roles of trust, perceived health risks, and culture. Data was collected through a questionnaire survey. RESULTS: The research models used provide a high-power explanation of loyalty to OHCPs. Results generally align with those of previous studies, with the exception of the relationships between Perceived Health Risks and Perceived Usefulness, Perceived Usefulness and Loyalty, Confirmation and Satisfaction, and Trust and Loyalty. In other words, culture may have moderated these relationships. CONCLUSIONS: Findings can help promote OHCPs among cross-strait users to make things easier for patients, and further reduce the load on the emergency department, especially in view of the still ongoing issues related to global outbreak of Coronavirus disease by facilitating early detection of potential cases.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.