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Precise and efficient performance in remote robotic teleoperation relies on intuitive interaction. This requires both accurate control actions and complete perception (vision, haptic, and other sensory feedback) of the remote environment. Especially in immersive remote teleoperation, the complete perception of remote environments in 3D allows operators to gain improved situational awareness. Color and Depth (RGB-D) cameras capture remote environments as dense 3D point clouds for real-time visualization. However, providing enough situational awareness needs fast, high-quality data transmission from acquisition to virtual reality rendering. Unfortunately, dense point-cloud data can suffer from network delays and limits, impacting the teleoperator’s situational awareness. Understanding how the human eye works can help mitigate these challenges. This paper introduces a solution by implementing foveation, mimicking the human eye’s focus by smartly sampling and rendering dense point clouds for an intuitive remote teleoperation interface. This provides high resolution in the user’s central field, which gradually reduces toward the edges. However, this systematic visualization approach in the peripheral vision may benefit or risk losing information and burdening the user’s cognitive load. This work investigates these advantages and drawbacks through an experimental study and describes the overall system, with its software, hardware, and communication framework. This will show significant enhancements in both latency and throughput, surpassing 60% and 40% improvements in both aspects when compared with state-of-the-art research works. A user study reveals that the framework has minimal impact on the user’s visual quality of experience while helping to reduce the error rate significantly. Further, a 50% reduction in task execution time highlights the benefits of the proposed framework in immersive remote telerobotics applications.
Most of the Ross Sea has been designated a marine protected area (MPA), proposed ‘to protect ecosystem structure and function’. To assess effectiveness, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) selected Adélie (Pygoscelis adeliae) and emperor (Aptenodytes forsteri) penguins, Weddell seals (Leptonychotes weddellii) and Antarctic toothfish (Dissostichus mawsoni) as ecosystem change ‘indicator species’. Stable for decades, penguin and seal populations increased during 1998–2018 to surpass historical levels, indicating that change in ecosystem structure and function is underway. We review historical impacts to population trends, decadal datasets of ocean climate and fishing pressure on toothfish. Statistical modelling for Adélie penguins and Weddell seals indicates that variability in climate factors and cumulative extraction of adult toothfish may explain these trends. These mesopredators, and adult toothfish, all prey heavily on Antarctic silverfish (Pleuragramma antarcticum). Toothfish removal may be altering intraguild predation dynamics, leading to competitive release of silverfish and contributing to penguin and seal population changes. Despite decades of ocean/weather change, increases in indicator species numbers around Ross Island only began once the toothfish fishery commenced. The rational-use, ecosystem-based viewpoint promoted by CCAMLR regarding toothfish management needs re-evaluation, including in the context of the Ross Sea Region MPA.
In 2022, highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b became enzootic and caused mass mortality in Sandwich Tern Thalasseus sandvicensis and other seabird species across north-western Europe. We present data on the characteristics of the spread of the virus between and within breeding colonies and the number of dead adult Sandwich Terns recorded at breeding sites throughout north-western Europe. Within two months of the first reported mortalities, 20,531 adult Sandwich Terns were found dead, which is >17% of the total north-western European breeding population. This is probably an under-representation of total mortality, as many carcasses are likely to have gone unnoticed and unreported. Within affected colonies, almost all chicks died. After the peak of the outbreak, in a colony established by late breeders, 25.7% of tested adults showed immunity to HPAI subtype H5. Removal of carcasses was associated with lower levels of mortality at affected colonies. More research on the sources and modes of transmission, incubation times, effective containment, and immunity is urgently needed to combat this major threat for colonial seabirds.
Individuals living with HIV may experience cognitive difficulties or marked declines known as HIV-Associated Neurocognitive Disorder (HAND). Cognitive difficulties have been associated with worse outcomes for people living with HIV, therefore, accurate cognitive screening and identification is critical. One potentially sensitive marker of cognitive impairment which has been underutilized, is intra-individual variability (IIV). Cognitive IIV is the dispersion of scores across tasks in neuropsychological assessment. In individuals living with HIV, greater cognitive IIV has been associated with cortical atrophy, poorer cognitive functioning, with more rapid declines, and greater difficulties in daily functioning. Studies examining the use of IIV in clinical neuropsychological testing are limited, and few have examined IIV in the context of a single neuropsychological battery designed for culturally diverse or at-risk populations. To address these gaps, this study aimed to examine IIV profiles of individuals living with HIV and who inject drugs, utilizing the Neuropsi, a standardized neuropsychological instrument for Spanish speaking populations.
Participants and Methods:
Spanish speaking adults residing in Puerto Rico (n=90) who are HIV positive and who inject drugs (HIV+I), HIV negative and who inject drugs (HIV-I), HIV positive who do not inject drugs (HIV+), or healthy controls (HC) completed the Neuropsi battery as part of a larger research protocol. The Neuropsi produces 3 index scores representing cognitive domains of memory, attention/memory, and attention/executive functioning. Total battery and within index IIV were calculated by dividing the standard deviation of T-scores by mean performance, resulting in a coefficient of variance (CoV). Group differences on overall test battery mean CoV (OTBMCoV) were investigated. To examine unique profiles of index specific IIV, a cluster analysis was performed for each group.
Results:
Results of a one-way ANOVA indicated significant between group differences on OTBMCoV (F[3,86]=6.54, p<.001). Post-hoc analyses revealed that HIV+I (M=.55, SE=.07, p=.003), HIV-I (M=.50, SE=.03, p=.001), and HIV+ (M=.48, SE=.02, p=.002) had greater OTBMCoV than the HC group (M=.30, SE=.02). To better understand sources of IIV within each group, cluster analysis of index specific IIV was conducted. For the HIV+ group, 3 distinct clusters were extracted: 1. High IIV in attention/memory and attention/executive functioning (n=3, 8%); 2. Elevated memory IIV (n=21, 52%); 3. Low IIV across all indices (n=16, 40%). For the HIV-I group, 2 distinct clusters were extracted: 1. High IIV across all 3 indices (n=7, 24%) and 2. Low IIV across all 3 indices (n=22, 76%). For the HC group, 3 distinct clusters were extracted: 1. Very low IIV across all 3 indices (n=5, 36%); 2. Elevated memory IIV (n=6, 43%); 3. Elevated attention/executive functioning IIV with very low attention/memory and memory IIV (n=3, 21%). Sample size of the HIV+I group was insufficient to extract clusters.
Conclusions:
Current findings support IIV in the Neuropsi test battery as clinically sensitive marker for cognitive impairment in Spanish speaking individuals living with HIV or who inject drugs. Furthermore, the distinct IIV cluster types identified between groups can help to better understand specific sources of variability. Implications for clinical assessment in prognosis and etiological considerations are discussed.
Injection drug use is a significant public health crisis with adverse health outcomes, including increased risk of human immunodeficiency virus (HIV) infection. Comorbidity of HIV and injection drug use is highly prevalent in the United States and disproportionately elevated in surrounding territories such as Puerto Rico. While both HIV status and injection drug use are independently known to be associated with cognitive deficits, the interaction of these effects remains largely unknown. The aim of this study was to determine how HIV status and injection drug use are related to cognitive functioning in a group of Puerto Rican participants. Additionally, we investigated the degree to which type and frequency of substance use predict cognitive abilities.
Participants and Methods:
96 Puerto Rican adults completed the Neuropsi Attention and Memory-3rd Edition battery for Spanish-speaking participants. Injection substance use over the previous 12 months was also obtained via clinical interview. Participants were categorized into four groups based on HIV status and injection substance use in the last 30 days (HIV+/injector, HIV+/non-injector, HIV/injector, HIV-/non-injector). One-way analysis of variance (ANOVA) was conducted to determine differences between groups on each index of the Neuropsi battery (Attention and Executive Function; Memory; Attention and Memory). Multiple linear regression was used to determine whether type and frequency of substance use predicted performance on these indices while considering HIV status.
Results:
The one-way ANOVAs revealed significant differences (p’s < 0.01) between the healthy control group and all other groups across all indices. No significant differences were observed between the other groups. Injection drug use, regardless of the substance, was associated with lower combined attention and memory performance compared to those who inject less than monthly (Monthly: p = 0.04; 2-3x daily: p < 0.01; 4-7x daily: p = 0.02; 8+ times daily: p < 0.01). Both minimal and heavy daily use predicted poorer memory performance (p = 0.02 and p = 0.01, respectively). Heavy heroin use predicted poorer attention and executive functioning (p = 0.04). Heroin use also predicted lower performance on tests of memory when used monthly (p = 0.049), and daily or almost daily (2-6x weekly: p = 0.04; 4-7x daily: p = 0.04). Finally, moderate injection of heroin predicted lower scores on attention and memory (Weekly: p = 0.04; 2-6x weekly: p = 0.048). Heavy combined heroin and cocaine use predicted worse memory performance (p = 0.03) and combined attention and memory (p = 0.046). HIV status was not a moderating factor in any circumstance.
Conclusions:
As predicted, residents of Puerto Rico who do not inject substances and are HIVnegative performed better in domains of memory, attention, and executive function than those living with HIV and/or inject substances. There was no significant difference among the affected groups in cognitive ability. As expected, daily injection of substances predicted worse performance on tasks of memory. Heavy heroin use predicted worse performance on executive function and memory tasks, while heroin-only and combined heroin and cocaine use predicted worse memory performance. Overall, the type and frequency of substance is more predictive of cognitive functioning than HIV status.
As the scale of cosmological surveys increases, so does the complexity in the analyses. This complexity can often make it difficult to derive the underlying principles, necessitating statistically rigorous testing to ensure the results of an analysis are consistent and reasonable. This is particularly important in multi-probe cosmological analyses like those used in the Dark Energy Survey (DES) and the upcoming Legacy Survey of Space and Time, where accurate uncertainties are vital. In this paper, we present a statistically rigorous method to test the consistency of contours produced in these analyses and apply this method to the Pippin cosmological pipeline used for type Ia supernova cosmology with the DES. We make use of the Neyman construction, a frequentist methodology that leverages extensive simulations to calculate confidence intervals, to perform this consistency check. A true Neyman construction is too computationally expensive for supernova cosmology, so we develop a method for approximating a Neyman construction with far fewer simulations. We find that for a simulated dataset, the 68% contour reported by the Pippin pipeline and the 68% confidence region produced by our approximate Neyman construction differ by less than a percent near the input cosmology; however, they show more significant differences far from the input cosmology, with a maximal difference of 0.05 in $\Omega_{M}$ and 0.07 in w. This divergence is most impactful for analyses of cosmological tensions, but its impact is mitigated when combining supernovae with other cross-cutting cosmological probes, such as the cosmic microwave background.
Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.
Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics.
Methods
Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report.
Results
After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed.
Conclusions
There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.
Despite the fact that 95% of all <5 years of age children with developmental disabilities including Autism Spectrum Disorders (ASD) live in low- and middle-income countries (LAMI), to date there is an information gap in LAMI studies including Republic of Georgia.
Objectives
To estimate the prevalence and describe the clinical characteristics of ASDs among the third-grade school students using a total population approach.
Methods
The target population (N=27,336) included all 3rd grade students of schools of five main cities of Georgia. The study was conducted in four steps: phase I screening, sampling of screen positive students, phase II confirmative diagnostic assessment, and best-estimate diagnosis. Parents and teachers completed two screening questionnaires in phase I: 27-item Autism Spectrum Screening Questionnaire (ASSQ) and 25-item Strengths and Difficulties Questionnaire (SDQ). In phase II, screen-positive children were evaluated using standardized diagnostic assessments.
Results
Overall, 16,654 students (82%) were assessed by either parent and/or teacher. Students whose ASSQ and/or SDQ scores were in the top 10th percentile were considered as screened positive for diagnostic assessment (N=1976). Of 300 students completed diagnostic assessment 53 were diagnosed ASD. Crude prevalence of ASDs was estimated to be 4.5%. 75% of cases of ASD were first diagnosed. Efforts are currently underway to compute adjusted prevalence, which will be available for the Conference presentation.
Conclusions
The prevalence data of ASD is important to assess the burden of the disorder and facilitate better understanding of specifics of the disorder in different part of the world.
Numerous factors are considered to impact on the rate of complications during salvage total laryngectomy procedures. Neck dissection could be one of these factors. This study analysed the pattern of lymph node metastasis and rate of occult neck disease during salvage total laryngectomy as well as the impact of neck dissection on survival and complication rates.
Method
This was a retrospective analysis of a prospectively maintained laryngectomy database in two large tertiary teaching hospitals.
Results
The rate of occult neck disease was 11.1 per cent. Most cases with occult neck disease had rT4 disease. Patients with complications, advanced tumour stage and positive margins had a significant decrease in overall survival. Patients receiving elective neck dissection did not have any survival benefit. Positron emission tomography-computed tomography showed a very high specificity and negative predictive value.
Conclusion
According to the low risk of occult neck disease when using contemporary imaging techniques as well as the lack of impact on survival, conservative management of the neck should be considered for crT1-T3 recurrence.
Psychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Here, we asked whether a technology-enhanced approach to relapse prevention could reduce days spent in a hospital after discharge.
Methods
The Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between 26 February 2013 and 17 April 2015 at 10 different sites in the USA in an outpatient setting. Patients were between 18 and 60 years old with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified. Patients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge. The health technology program included in-person, individualized relapse prevention planning with treatments delivered via smartphones and computers, as well as a web-based prescriber decision support program. The main outcome measure was days spent in a psychiatric hospital during 6 months after discharge.
Results
The study included 462 patients, of which 438 had complete baseline data and were thus used for propensity matching and analysis. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention followed by 349 participants (128 females) who received technology-enhanced relapse prevention. During 6-month follow-up, 43% of control and 24% of intervention participants were hospitalized (χ2 = 11.76, p<0.001). Days of hospitalization were reduced by 5 days (mean days: b = −4.58, 95% CI −9.03 to −0.13, p = 0.044) in the intervention condition compared to control.
Conclusions
These results suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.
We present the most sensitive and detailed view of the neutral hydrogen (${\rm H\small I}$) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ($1.6\,\mathrm{mJy\ beam}^{-1}$) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ (${\sim}10\,\mathrm{pc}$). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.
In this era of spatially resolved observations of planet-forming disks with Atacama Large Millimeter Array (ALMA) and large ground-based telescopes such as the Very Large Telescope (VLT), Keck, and Subaru, we still lack statistically relevant information on the quantity and composition of the material that is building the planets, such as the total disk gas mass, the ice content of dust, and the state of water in planetesimals. SPace Infrared telescope for Cosmology and Astrophysics (SPICA) is an infrared space mission concept developed jointly by Japan Aerospace Exploration Agency (JAXA) and European Space Agency (ESA) to address these questions. The key unique capabilities of SPICA that enable this research are (1) the wide spectral coverage $10{-}220\,\mu\mathrm{m}$, (2) the high line detection sensitivity of $(1{-}2) \times 10^{-19}\,\mathrm{W\,m}^{-2}$ with $R \sim 2\,000{-}5\,000$ in the far-IR (SAFARI), and $10^{-20}\,\mathrm{W\,m}^{-2}$ with $R \sim 29\,000$ in the mid-IR (SPICA Mid-infrared Instrument (SMI), spectrally resolving line profiles), (3) the high far-IR continuum sensitivity of 0.45 mJy (SAFARI), and (4) the observing efficiency for point source surveys. This paper details how mid- to far-IR infrared spectra will be unique in measuring the gas masses and water/ice content of disks and how these quantities evolve during the planet-forming period. These observations will clarify the crucial transition when disks exhaust their primordial gas and further planet formation requires secondary gas produced from planetesimals. The high spectral resolution mid-IR is also unique for determining the location of the snowline dividing the rocky and icy mass reservoirs within the disk and how the divide evolves during the build-up of planetary systems. Infrared spectroscopy (mid- to far-IR) of key solid-state bands is crucial for assessing whether extensive radial mixing, which is part of our Solar System history, is a general process occurring in most planetary systems and whether extrasolar planetesimals are similar to our Solar System comets/asteroids. We demonstrate that the SPICA mission concept would allow us to achieve the above ambitious science goals through large surveys of several hundred disks within $\sim\!2.5$ months of observing time.
To investigate the association between parity and the risk of incident dementia in women.
Methods
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Results
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Conclusions
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.
We deposit films of tin–calcium sulfide by atomic layer deposition (ALD) and demonstrate the metastability of this material. Rough and spiky films are obtained by using Sn and Ca precursors with different ligands, whereas compact and smooth films are obtained when the two metal sources share the same ligands. Compositional and quartz crystal microbalance results indicate that part of the underlaying SnS film is replaced and/or removed during the CaS ALD cycle during the ternary film deposition, possibly via a temperature-dependent cation exchange mechanism. The crystal structure transforms from orthorhombic to cubic as the calcium content increases. Furthermore, resistivity increases with calcium content in the alloy films, whereas optical band gap only depends weakly on Ca content. After annealing at 400 °C in an H2S environment, the cubic alloy film undergoes a phase transition into the orthorhombic phase and its resistivity also decreases. Both phenomena could be explained by phase separation of the metastable alloy.
Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.
Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).
This study evaluated the annual prevalence of anogenital warts (AGW) caused by human papillomavirus (HPV) and analysed the trend in annual per cent changes (APC) by using national claims data from the Health Insurance Review and Assessment of Korea, 2007–2015. We also estimated the socio-economic burden and co-morbidities of AGW. All analyses were performed based on data for primary A63.0, the specific diagnosis code for AGW. The socio-economic cost of AGW was calculated based on the direct medical cost, direct non-medical cost and indirect cost. The overall AGW prevalence and socio-economic burden has increased during the last 9 years. However, the prevalence of AGW differed significantly by sex. The female prevalence increased until 2012, and decreased thereafter (APC + 3·6%). It would fall after the introduction of routine HPV vaccination, principally for females, in Korea. The male prevalence increased continuously over time (APC + 11·6%), especially in those aged 20–49 years. Referring to the increasing AGW prevalence and its disease burden, active HPV infection control surveillance and prevention in males are worth consideration.