Assessing public health sector performance in Bangladesh: Implications for health systems strengthening and universal health coverage - A secondary data analysis.

The Ministry of Health and Family Welfare has established a health systems strengthening initiative for measuring the performance of public sector health facilities in Bangladesh. The objective of the performance management initiative is to establish routine systems for measuring and scoring health facility performance and promote best practices in public health service management. The performance initiative includes a set of assessments conducted across the four tiers of the public health sector. The findings of assessments demonstrate improvements in the quality of health services and a sharp increase in the utilisation of services across all tiers during the period 2017-2019. The performance management initiative has also identified areas for improvement in the supply-side health system readiness, including ensuring an adequate supply of human resources, essential medicines, and functioning medical equipment and technologies. This initiative outlines the need to systematically address the issue of high health workforce vacancy rates through effective human resource planning and management strategies. The reporting of these ongoing health systems successes and challenges through the performance management initiative in Bangladesh provides an opportunity to develop evidence-based policy reforms for strengthening supply-side health systems. The initiative results, particularly in the context of growing public demand for services, also justifies a monitoring and evaluation mechanism focusing on the quality and coverage of frontline health facilities and the development of more integrated health systems. The performance management initiative will facilitate the maintenance of essential health services while addressing emergency health needs and tracking progress towards achieving the Universal Health Coverage goal.

An analysis of the gender and social determinants of health in urban poor areas of the most populated cities of Pakistan.

BACKGROUND: Recent surveys, studies and reviews in urban areas of Pakistan have highlighted the impacts of social inequities on access of women and children to health services for women and children in Pakistan. OBJECTIVES: The Urban Slum Profiles and coverage surveys were conducted between 2017 and 2019. The objective of the profiles was to obtain an updated listing of slums and other underserved areas, and to better understand current vaccination and health service coverage in these areas. Utilising findings from these studies, this paper aims to better understand the gender and social determinants of health that are giving rise to health inequalities in the slums. METHODS: The Urban Slum Profiles adopted a mixed methods approach combining both qualitative and quantitative methods. The study was comprised of two main survey approaches of Urban Slum Profiles and Immunisation Coverage Survey in 4431 urban poor areas of the 10 most highly populated cities of Pakistan. RESULTS: Findings are classified into six analytic categories of (1) access to health services, (2) female workforce participation, (3) gender-friendly health services, (4) access to schools and literacy, (5) social connections, and (6) autonomy of decision making. Out of a national sample of 14,531 children in urban poor areas of 10 cities, the studies found that just over half of the children are fully immunised (54%) and 14% of children had received zero doses of vaccine. There are large shortages of health facilities and female health workforce in the slums, with significant gaps in the quality of health infrastructure, which all serve to limit both demand for, and supply of, health services for women and children. Results demonstrate low availability of schools, low levels of female literacy and autonomy over decision making, limited knowledge of the benefits of vaccination, and few social connections outside the home. All these factors interact and reinforce existing gender norms and low levels of health literacy and service access. CONCLUSION: The Urban Slum profiles and coverage studies provide an opportunity to introduce gender transformative strategies that include expansion of a female health workforce, development of costed urban health action plans, and an enabling policy environment to support community organisation and more equitable health service delivery access.

Technology-based support for stroke caregiving: A rapid review of evidence.

AIM: This rapid review examines the technology-based interventions for caregivers of stroke proposed in the literature while also identifying the acceptance, effectiveness and satisfaction of the implemented approaches. BACKGROUND: The increasing burden of supporting stroke survivors has resulted in caregivers searching for innovative solutions, such as technology-based interventions, to provide better care. Hence, its potential to support caregivers throughout the disease trajectory needs to be assessed. EVALUATION: Five electronic databases were systematically searched for articles related to stroke caregiving technologies based on well-defined inclusion and exclusion criteria. KEY ISSUE(S): Fifteen articles met the inclusion criteria that focused on supporting caregivers through functionalities such as education, therapy and support, remote consultations, health assessments and logs and reminders using different devices. The majority of interventions demonstrated positive conclusions for caregiving impact, acceptance, effectiveness and satisfaction. CONCLUSION: Findings highlight the influences of technology in improving stroke caregiving and the need to include user-centred design principles to create a meaningful, actionable and feasible system for caregivers. IMPLICATIONS FOR NURSING MANAGEMENT: Technology can educate and support stroke caregivers, thereby minimizing uncertainty and ensuring better care for the survivor.

A large scale analysis of mHealth app user reviews.

The global mHealth app market is rapidly expanding, especially since the COVID-19 pandemic. However, many of these mHealth apps have serious issues, as reported in their user reviews. Better understanding their key user concerns would help app developers improve their apps' quality and uptake. While app reviews have been used to study user feedback in many prior studies, many are limited in scope, size and/or analysis. In this paper, we introduce a very large-scale study and analysis of mHealth app reviews. We extracted and translated over 5 million user reviews for 278 mHealth apps. These reviews were then classified into 14 different aspects/categories of issues reported. Several mHealth app subcategories were examined to reveal differences in significant areas of user concerns, and to investigate the impact of different aspects of mhealth apps on their ratings. Based on our findings, women's health apps had the highest satisfaction ratings. Fitness activity tracking apps received the lowest and most unfavourable ratings from users. Over half of users who reported troubles leading them to uninstall mHealth apps gave a 1-star rating. Half of users gave the account and logging aspect only one star due to faults and issues encountered while registering or logging in. Over a third of users who expressed privacy concerns gave the app a 1-star rating. However, only 6% of users gave apps a one-star rating due to UI/UX concerns. 20% of users reported issues with handling of user requests and internationalisation concerns. We validated our findings by manually analysing a sample of 1,000 user reviews from each investigated aspect/category. We developed a list of recommendations for mHealth apps developers based on our user review analysis.

mHealth applications to support caregiver needs and engagement during stroke recovery: A content review.

Caregiving in stroke results in severe physical, psychological, and social impacts on the caregiver. Over the past few years, researchers have explored the use of mHealth technologies to support healthcare-related activities due to their ability to provide real-time care at any given place or time. The purpose of this content review is to investigate mHealth apps in supporting stroke caregiving engagement based on three aspects: motivation, value, and satisfaction. We searched app stores and repositories for apps related to stroke caregiving published up to September 2020. Extracted apps were reviewed and filtered using inclusion criteria, and then downloaded onto compatible devices to determine eligibility. Results were compared with evidence-based frameworks to identify the ability of these apps in engaging and supporting the caregiver. Forty-seven apps were included in this review that enabled caregivers to support their needs, such as adjustment to new roles and relationships, involvement in care and caring for oneself using several different functionalities. These functionalities include information resources, risk assessment, remote monitoring, data sharing, reminders and so on. However, no single app was identified that focuses on all aspects of stroke caregiving. We also identified several challenges faced by users through their reviews and the factors associated with value and satisfaction. Our findings can add to the knowledge of existing mHealth technologies and their functionalities to support stroke caregiving needs, and the importance of considering user engagement in the design. They can be used by developers and researchers looking to design better mHealth apps for stroke caregiving.

Bilingualism modifies disengagement of attention networks across the scalp: A multivariate ERP investigation of the IOR paradigm.

A recent approach to explaining the domain-general cognitive outcomes of bilingualism is to consider the role of disengagement of attention, rather than the engagement of focused attention or inhibition as typical in most accounts. The present study pursues this approach by examining the neurophysiological changes associated with disengagement of attention in young adults performing an inhibition of return (IOR) paradigm while EEG was recorded. Participants were drawn from a diverse community and varied widely in their bilingual experience. There were three main findings. First, dividing the sample into dichotomous groups based on language proficiency did not lead to reliable group differences on the task. Second, using instead continuous measures of bilingualism across the sample indicated that greater bilingual experience and proficiency were associated with the magnitude of the IOR effect, with more bilingual individuals showing larger and earlier IOR effects. Finally, a network of processes that are temporally and spatially distinct were found to work together to produce facilitation, disengagement of attention, and inhibition of return. These findings contribute to debates regarding the electrophysiological correlates of the IOR effect and provide additional evidence for how bilingualism affects domain-general cognition.

Health service delivery and workforce in northern Australia: a scoping review.

INTRODUCTION: Delivering health services and improving health outcomes of the 1.3 million people residing in northern Australia, a region spanning 3 million km2 across the three jurisdictions of Western Australia, Northern Territory and Queensland, presents specific challenges. This review addresses a need for systems level analysis of the issues influencing the coverage, quality and responsiveness of health services across this region by examining the available published literature and identifying key policy-relevant gaps. METHODS: A scoping review design was adopted with searches incorporating both peer-reviewed and grey literature (eg strategy documents, annual reports and budgets). Grey literature was predominantly sourced from websites of key organisations in the three northern jurisdictions, with peer-reviewed literature sourced from electronic database searches and reference lists. Key articles and documents were also contributed by health sector experts. Findings were synthesised and reported narratively using the WHO health system 'building blocks' to categorise the data. RESULTS: From the total of 324 documents and data sources included in the review following screening and eligibility assessment, 197 were peer-reviewed journal articles and 127 were grey literature. Numerous health sector actors across the north - comprising planning bodies, universities and training organisations, peak bodies and providers - deliver primary, secondary and tertiary healthcare and workforce education and training in highly diverse contexts of care. Despite many exemplar health service and workforce models in the north, this synthesis describes a highly fragmented sector with many and disjointed stakeholders and funding sources. While the many strengths of the northern health system include expertise in training and supporting a fit-for-purpose health workforce, health systems in the north are struggling to meet the health needs of highly distributed populations with poorly targeted resources and ill-suited funding models. Ageing of the population and rising rates of chronic disease and mental health issues, underpinned by complex social, cultural and environmental determinants of health, continue to compound these challenges. CONCLUSION: Policy goals about developing northern Australia economically need to build from a foundation of a healthy and productive population. Improving health outcomes in the north requires political commitment, local leadership and targeted investment to improve health service delivery, workforce stability and evidence-based strengthening of community-led comprehensive primary health care. This requires intersectoral collaboration across many organisations and the three jurisdictions, drawing from previous collaborative experiences. Further evaluative research, linking structure to process and outcomes, and responding to changes in the healthcare landscape such as the rapid emergence of digital technologies, is needed across a range of policy areas to support these efforts.

The relation between brain signal complexity and task difficulty on an executive function task.

On a daily basis, we constantly deal with changing environmental cues and perceptual conflicts and as such, our brains must flexibly adapt to current demands in order to act appropriately. Brains become more efficient and are able to switch states more readily by increasing the complexity of their neural networks. However, it is unclear how brain signal complexity relates to behavior in young adults performing cognitively demanding executive function tasks. Here we used multiscale entropy analysis and multivariate statistics on EEG data while participants performed a bivalency effect task-switching paradigm to show that brain signal complexity in young adults increases as task demands increase, that increases in brain signal complexity are associated with both speed gains and losses depending on scalp location, and that more difficult tasks are associated with more circumscribed complexity across the scalp. Overall, these findings highlight a critical role for brain signal complexity in predicting behavior on an executive function task among young adults.

Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial.

PURPOSE: This phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH). METHODS: 61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 µg twice daily. Dosage was then up-titrated as tolerated over the course of the 9-week dose-titration period, to a maximum total daily dose of 600 µg (300 µg twice daily). The primary efficacy end-point was the absolute change in pulmonary vascular resistance (PVR) from baseline to week 22. Additional end-points included percentage change in PVR from baseline, other haemodynamic parameters, 6-min walk distance (6MWD) and safety and tolerability. RESULTS: Ralinepag significantly decreased PVR by 163.9 dyn·s·cm-5 compared to an increase of 0.7 dyn·s·cm-5 with placebo (p=0.02); the least-squares mean change from baseline PVR was -29.8% compared with placebo (p=0.03). 6MWD increased from baseline by 36.2 m with ralinepag and 29.4 m with placebo (p=0.90). Serious adverse events occurred in 10% of ralinepag patients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepag patients and 10% of placebo patients. SUMMARY: Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.

Effects of bilingualism on white matter integrity in older adults.

Bilingualism can delay the onset of dementia symptoms and has thus been characterized as a mechanism for cognitive or brain reserve, although the origin of this reserve is unknown. Studies with young adults generally show that bilingualism is associated with a strengthening of white matter, but there is conflicting evidence for how bilingualism affects white matter in older age. Given that bilingualism has been shown to help stave off the symptoms of dementia by up to four years, it is crucial that we clarify the mechanism underlying this reserve. The current study uses diffusion tensor imaging (DTI) to compare monolinguals and bilinguals while carefully controlling for potential confounds (e.g., I.Q., MMSE, and demographic variables). We show that group differences in Fractional Anisotropy (FA) and Radial Diffusivity (RD) arise from multivariable interactions not adequately controlled for by sequential bivariate testing. After matching and statistically controlling for confounds, bilinguals still had greater axial diffusivity (AD) in the left superior longitudinal fasciculus than monolingual peers, supporting a neural reserve account for healthy older bilinguals.

Safety, tolerability, and antiviral effect of RG-101 in patients with chronic hepatitis C: a phase 1B, double-blind, randomised controlled trial.

BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1). We enrolled men and postmenopausal or hysterectomised women (aged 18-65 years) with chronic HCV genotype 1, 3, or 4 infection diagnosed at least 24 weeks before screening who were either treatment naive to or relapsed after interferon-α based therapy. Patients with co-infection (hepatitis B virus or HIV infection), evidence of decompensated liver disease, or a history of hepatocellular carcinoma were excluded. Randomisation was done by an independent, unblinded, statistician using the SAS procedure Proc Plan. The first cohort received one subcutaneous injection of 2 mg/kg RG-101 or placebo; the second cohort received one subcutaneous injection of 4 mg/kg or placebo. Patients were followed up for 8 weeks (all patients) and up to 76 weeks (patients with no viral rebound and excluding those who were randomised to the placebo group) after randomisation. The primary objective was safety and tolerability of RG-101. This trial was registered with EudraCT, number 2013-002978-49. FINDINGS: Between June 4, 2014, and Oct 27, 2014, we enrolled 32 patients with chronic HCV genotype 1 (n=16), 3 (n=10), or 4 (n=6) infections. In the first cohort, 14 patients were randomly assigned to receive 2 mg/kg RG-101 and two patients were randomly assigned to receive placebo, and in the second cohort, 14 patients were randomly assigned to receive 4 mg/kg RG-101 and two patients were randomly assigned to receive placebo. Overall, 26 of the 28 patients dosed with RG-101 reported at least one treatment-related adverse event. At week 4, the median viral load reduction from baseline was 4·42 (IQR 3·23-5·00) and 5·07 (4·19-5·35) log10 IU/mL in patients dosed with 2 mg/kg RG-101 or 4 mg/kg RG-101. Three patients had undetectable HCV RNA levels 76 weeks after a single dose of RG-101. Viral rebound at or before week 12 was associated with the appearance of resistance associated substitutions in miR-122 binding regions in the 5' UTR of the HCV genome. INTERPRETATION: This study showed that one administration of 2 mg/kg or 4 mg/kg RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated anti-miR-122 oligonucleotide, was well tolerated and resulted in substantial viral load reduction in all treated patients within 4 weeks, and sustained virological response in three patients for 76 weeks. FUNDING: Regulus Therapeutics, Inc.

Monolinguals and bilinguals disengage attention differently following conflict and errors: Evidence from ERPs.

Monolingual and bilingual young adults performed a task-switching experiment while EEG was recorded to investigate how bilingualism affects cognitive control following conflict. Participants were given pure blocks composed of three intermixed tasks, each consisting of univalent trials in which they responded to one feature of the stimulus - color, shape, or size. In the crucial conflict block, an irrelevant feature was added to one of the tasks, creating bivalent trials that included conflict. Behaviorally, all participants slowed responses to univalent trials that followed conflict, reflecting the post-conflict slowing effect. Electrophysiologically, monolinguals displayed longer-lasting post-conflict ERP effects and showed larger ERN amplitudes following responses than bilinguals, amplitudes that were associated with adjustments in response times. The interpretation is that bilinguals disengage attention following conflict from misleading stimuli or error responses more rapidly than do monolinguals.

Bilinguals have more complex EEG brain signals in occipital regions than monolinguals.

Brain signal complexity increases with development and is associated with better cognitive outcomes in older age. Research has also shown that bilinguals are able to stave off cognitive decline for longer periods of time than monolinguals, but no studies to date have examined whether bilinguals have more complex brain signals than monolinguals. Here we explored the hypothesis that bilingualism leads to greater brain signal complexity by examining multiscale entropy (MSE) in monolingual and bilingual young adults while EEG was recorded during a task-switching paradigm. Results revealed that bilinguals had greater brain signal complexity than monolinguals in occipital regions. Furthermore, bilinguals performed better with increasing occipital brain signal complexity, whereas monolinguals relied on coupling with frontal regions to demonstrate gains in performance. These findings are discussed in terms of how a lifetime of experience with a second language leads to more automatic and efficient processing of stimuli and how these adaptations could contribute to the prevention of cognitive decline in older age.

Post-conflict slowing effects in monolingual and bilingual children.

Previous research has shown that bilingual children outperform their monolingual peers on a wide variety of tasks measuring executive functions (EF). However, recent failures to replicate this finding have cast doubt on the idea that the bilingual experience leads to domain-general cognitive benefits. The present study explored the role of disengagement of attention as an explanation for why some studies fail to produce this result. Eighty children (40 monolingual, 40 bilingual) who were 7 years old performed a task-switching experiment. In the pure blocks, three simple non-conflict tasks were performed in which children responded by pressing one of two response keys. In the conflict block, occasional bivalent stimuli appeared and created conflict because the irrelevant dimension was mapped to the incorrect response key. The results showed that these bivalent stimuli affected subsequent performance in the conflict block. For monolinguals, the effect of conflict was found for up to 12 trials after the appearance of the bivalent stimulus, but for bilinguals the effect disappeared after only two trials. The results are interpreted as evidence for faster disengagement of attention by bilingual children. Most studies examining EF in monolingual and bilingual children do not examine trial-by-trial adjustments following conflict, but these are essential considerations because relevant processing differences are masked when analyses are applied to data averaged across entire blocks.

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PURPOSE: The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. METHODS: In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. RESULTS: In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. CONCLUSIONS: Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

The Effectiveness of Simulator Motion in the Transfer of Performance on a Tracking Task Is Influenced by Vision and Motion Disturbance Cues.

OBJECTIVE: To examine the importance of platform motion to the transfer of performance in motion simulators. BACKGROUND: The importance of platform motion in simulators for pilot training is strongly debated. We hypothesized that the type of motion (e.g., disturbance) contributes significantly to performance differences. METHODS: Participants used a joystick to perform a target tracking task in a pod on top of a MOOG Stewart motion platform. Five conditions compared training without motion, with correlated motion, with disturbance motion, with disturbance motion isolated to the visual display, and with both correlated and disturbance motion. The test condition involved the full motion model with both correlated and disturbance motion. We analyzed speed and accuracy across training and test as well as strategic differences in joystick control. RESULTS: Training with disturbance cues produced critical behavioral differences compared to training without disturbance; motion itself was less important. CONCLUSION: Incorporation of disturbance cues is a potentially important source of variance between studies that do or do not show a benefit of motion platforms in the transfer of performance in simulators. APPLICATION: Potential applications of this research include the assessment of the importance of motion platforms in flight simulators, with a focus on the efficacy of incorporating disturbance cues during training.

Public Health and International Partnerships in the Democratic People's Republic of Korea.

David Hipgrave and colleagues argue that sustained collaboration is required to improve population health and health services in North Korea.

Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates.

Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer of SMN2 exon 7 inclusion and SMN protein expression, and improves function and survival of mild and severe SMA mouse models. Here, we demonstrate that ISIS 396443 is the most potent ASO in central nervous system (CNS) tissues of adult mice, compared with several other chemically modified ASOs. We evaluated methods of ISIS 396443 delivery to the CNS and characterized its pharmacokinetics and pharmacodynamics in rodents and nonhuman primates (NHPs). Intracerebroventricular bolus injection is a more efficient method of delivering ISIS 396443 to the CNS of rodents, compared with i.c.v. infusion. For both methods of delivery, the duration of ISIS 396443-mediated SMN2 splicing correction is long lasting, with maximal effects still observed 6 months after treatment discontinuation. Administration of ISIS 396443 to the CNS of NHPs by a single intrathecal bolus injection results in widespread distribution throughout the spinal cord. Based upon these preclinical studies, we have advanced ISIS 396443 into clinical development.

Lack of clinical pharmacodynamic and pharmacokinetic drug-drug interactions between warfarin and the antisense oligonucleotide mipomersen.

Mipomersen is a second-generation antisense oligonucleotide indicated as an adjunct therapy for homozygous familial hypercholesterolemia (HoFH). Warfarin is commonly prescribed for a variety of cardiac disorders in homozygous familial hypercholesterolemia population, and concurrent use of warfarin and mipomersen is likely. This open-label, single-sequence 2-period phase 1 study in healthy subjects evaluated the potential drug-drug interactions between mipomersen and warfarin. The subjects received a single oral 25 mg dose of warfarin alone on day 1, and after a 7-day washout period, received 200 mg mipomersen alone subcutaneously every other day on days 8-12, and received both concurrently on day 14. Coadministration of mipomersen did not change the pharmacodynamics (international normalized ratio, prothrombin time, and activated partial thromboplastin time) and pharmacokinetics (PK) of warfarin. There were no clinically significant changes in the PK of mipomersen with concurrent administration of warfarin. There were no events indicative of an increase in bleeding tendency when warfarin was coadministered with mipomersen, and the adverse event profile of mipomersen did not appear to be altered in combination with warfarin, as compared with that of the respective reference treatment. The combination of these 2 medications appeared to be safe and well tolerated. These results suggest that the dosage adjustment of warfarin or mipomersen is not expected to be necessary with coadministration.