Dengue virus infection and neurological manifestations: an update.

Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100-400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms, such as acute transverse myelitis, acute cerebellitis and myositis. The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antivirals and vaccines against the dengue virus. In this article, we discuss the recent findings of different spectrums of neurological manifestations in dengue infection and provide an update on antiviral and vaccine development and their challenges.

Evaluation of the impact of weak end feedback on the SBS threshold in high-power narrow-linewidth fiber amplifiers.

In this work, we quantitatively investigate the SBS threshold in high-power narrow-linewidth fiber amplifiers seeded with phase-modulated single-frequency lasers in presence of weak end feedback. The impacts of the end feedback and spectral linewidths on the SBS threshold are demonstrated in detail through comparative experiments and numerical simulations, respectively. In the experiment, we have pointed out a practical method to estimate the end reflectivity in high-power fiber amplifiers. Based on this estimation, the SBS threshold characters of the high-power narrow-linewidth fiber amplifiers with different end reflectivity and seed linewidths are investigated. By reducing the end reflectivity, a 2.85 times SBS threshold enhancement has been achieved at the most susceptible linewidth (16.8 GHz). Furthermore, we propose a spectral evolution model to investigate the SBS threshold in high-power narrow-linewidth fiber amplifiers, which is even capable for calculating SBS thresholds of the systems with tens of GHz linewidth while weak end reflection is considered. The simulation results demonstrate that end reflection will obviously affect the SBS threshold when the linewidth of the seed laser is broadened beyond 5 GHz, especially for the spectral linewidth of seed lasers nearing the Brillouin frequency shift. Besides, when the end reflectivity is set to be stronger than -65 dB, the SBS threshold performs a tendency to decline and then rise with the growth of seed linewidth. The experiment and simulation results provide a new optimization sight for the SBS effect suppression in high-power narrow-linewidth fiber amplifiers.

Patient Welfare Implications of Indication-Specific Value-Based Pricing of Multi-Indication Drugs.

OBJECTIVES: Indication-specific value-based pricing (ISVBP) is a mechanism that allows the prices of multi-indication drugs to vary across indications by aligning the drug prices with value. However, the overall impact of ISVBP on patients across indications is uncertain. This study examines the theoretical welfare effects of ISVBP for multi-indication drugs and compares consumer surplus under ISVBP and single pricing, the latter of which is based on the weighted average value. METHODS: We considered a healthcare system with government-negotiated drug prices based on the value of drugs. We assumed a drug with 2 indications and 1 relevant comparator for each indication. The value of the drug was uniformly distributed among the patients of each indication in the base case. We also considered alternative scenarios with exponentially and Pareto distributed drug values. Numerical simulations were conducted to explore potential settings where ISVBP was welfare-improving for patients compared with single pricing. RESULTS: The theoretical analysis showed that the consumer surplus change was strictly non-positive from single pricing to ISVBP. Therefore, it was not welfare-improving for patients in the settings of interest. Numerical simulations confirmed this result across various scenarios of value distributions. CONCLUSIONS: This study provides insights into the patient welfare implications of ISVBP for multi-indication drugs. We did not identify conditions under which ISVBP can enhance overall patient well-being, suggesting that it should be implemented cautiously. Future research should examine dynamic welfare implications related to innovation incentives because they may significantly affect population health in the future.

The effect of 20-minute mindful breathing exercise on psychological well-being in epilepsy: A pilot randomized controlled trial.

INTRODUCTION: Depression and anxiety are prevalent in epilepsy patients, but psychiatric or psychological services may not be accessible to all patients. This study aimed to determine the effectiveness of the 20-minute mindful breathing on the psychological well-being of PWE using an instructional video. METHOD: This was a pilot, assessor-blinded, randomized controlled trial. The intervention group received a guided video and was briefed to perform the exercise twice a week for two weeks while the waitlist control group only received the video upon completion of the study. The subjects were assessed at three-time points (T0: Baseline, T1: 2 weeks after the intervention, T2: 4 weeks after intervention), using the Neurological Disorders Depression Index (NDDI-E), General Anxiety Disorder (GAD-7), Quality of Life in Epilepsy Inventory (QOLIE-31) and Mindfulness Attention Awareness Scale (MAAS). RESULTS: Twenty patients were recruited, with 10 in the intervention and waitlist-control groups. Compared with the waitlist-control group, participants in the intervention group showed significant improvement in NDDI-E at T1 (p = 0.022) but not at T2 (p = 0.056) and greater improvement in GAD-7 at T1 and T2 but not statistically significant. The QOLIE-31 overall score in the intervention group has significantly improved at T1 (p = 0.036) and T2 (p = 0.031) compared to the waitlist-control group. For MAAS, the intervention group also had an increased score at T2 (p = 0.025). CONCLUSION: The 20-minute mindfulness breathing exercise has an immediate effect in improving depression and quality of life among people with epilepsy.

Observer-Based Adaptive Sliding Mode Compensation Position-Tracking Control for Drilling Tool Attitude Adjustment.

This study develops an adaptive sliding mode control approach for a drilling tool attitude adjustment system, aiming at solving the problems of model uncertainties and insufficient ability of disturbance suppression during the regulation behavior. To further improve the performance of the position-tracking loop in terms of response time, tracking accuracy, and robustness, a state observer based on an improved radial basis function is designed to approximate the model uncertainties, a valve dead-zone compensate controller is used to reduce control deviation, an adaptive sliding mode controller is designed to improve the position-tracking precision and attenuate sliding mode chattering. Finally, simulation and experimental results are carried out to verify the observability of the model uncertainties and position-tracking errors of the drilling tool attitude adjustment system, which can effectively improve the position-tracking performance and robustness of the drilling tool attitude adjustment system.

Cost-Effectiveness of a Household Salt Substitution Intervention: Findings From 20 995 Participants of the Salt Substitute and Stroke Study.

BACKGROUND: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. METHODS: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. RESULTS: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. CONCLUSIONS: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.

Confined-doped fiber enabled kilowatt-level all-fiber laser with 1.28†GHz linewidth.

In this manuscript, a narrow linewidth fiber amplifier based on confined-doped fiber is established, and the power scaling and beam quality maintaining capabilities of this amplifier are investigated. Benefitted from the large mode area of the confined-doped fiber and precisely controlling the Yb-doped region in the fiber core, the stimulated Brillouin scattering (SBS) and transverse mode instability (TMI) effects are effectively balanced. As a result, a 1007 W signal laser with just 1.28 GHz linewidth is obtained by combining the advantages of confined-doped fiber, near-rectangular spectral injection, and 915 nm pump manner. As far as we know, this result is the first beyond kilowatt-level demonstration of all-fiber lasers with GHz-level linewidth, which could provide a well reference for simultaneously controlling spectral linewidth, suppressing the SBS and TMI effects in high-power, narrow-linewidth fiber lasers.

Affordability of newer antiseizure medications in Asian resource-limited countries.

OBJECTIVE: One of the objectives of the Intersectoral Global Action Plan on epilepsy and other neurological disorders for 2022 to 2031 is to ensure at least 80% of people with epilepsy (PWE) will have access to appropriate, affordable, and safe antiseizure medications (ASMs) by 2031. However, ASM affordability is a significant issue in low- and middle-income countries, preventing PWE from accessing optimal treatment. This study aimed to determine the affordability of the newer (second and third generation) ASMs in resource-limited countries in Asia. METHODS: We conducted a cross-sectional survey by contacting country representatives in lower-middle-income countries (LMICs) in Asia, including Indonesia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Vietnam, India, Bangladesh, and Pakistan, and the upper-middle-income country Malaysia, from March 2022 to April 2022. The affordability of each ASM was calculated by dividing the 30-day ASM cost by the daily wage of the lowest paid unskilled laborers. Treatment costing 1 day's wage or less for a 30-day supply of chronic disease is considered affordable. RESULTS: Eight LMICs and one upper-middle-income country were included in this study. Lao PDR had no newer ASM, and Vietnam had only three newer ASMs. The most frequently available ASMs were levetiracetam, topiramate, and lamotrigine, and the least frequently available was lacosamide. The majority of the newer ASMs were unaffordable, with the median number of days' wages for a 30-day supply ranging from 5.6 to 14.8 days. SIGNIFICANCE: All new generation ASMs, whether original or generic brands, were unaffordable in most Asian LMICs.

Integrating real-world data in cost-effectiveness analysis of universal HLA-B*15:02 screening in Malaysia.

AIMS: Despite the availability of newer antiseizure medications, carbamazepine (CBZ) remains the gold standard. However, patients of Asian ancestry are susceptible to CBZ-related severe cutaneous adverse reactions. Universal HLA-B*15:02 screening is a promising intervention to address this. With the increasing recognition of integrating real-world evidence in economic evaluations, the cost-effectiveness of universal HLA-B*15:02 screening was assessed using available real-world data in Malaysia. METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate 3 strategies for treating newly diagnosed epilepsy among adults: (i) CBZ initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to CBZ initiation; and (iii) alternative prescribing without HLA-B*15:02 screening. The model was populated with real-world inputs derived from the Malaysian population. From a societal perspective, base-case analysis and sensitivity analyses estimated the costs and outcomes over a lifetime. Incremental cost-effectiveness ratios were calculated. RESULTS: In the base-cases analysis, universal HLA-B*15:02 screening yielded the lowest total costs and the highest total quality-adjusted life years (QALYs) gained. Compared with current practice, universal screening was less costly by USD100 and more effective by QALYs increase of 0.1306, while alternative prescribing resulted in 0.1383 QALYs loss at additional costs of USD332. The highest seizure remission rate (56%) was estimated for universal HLA-B*15:02 screening vs. current practice (54%) and alternative prescribing (48%). CONCLUSION: Our study suggests that universal HLA-B*15:02 screening is a cost-effective intervention in Malaysia. With the demonstrated value of real-world evidence in economic evaluations, more relevant standardization efforts should be emphasized to better inform decision-making.

Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study.

INTRODUCTION: The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China. METHODS: For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2-6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer's perspective. The equivalence margin for cost and effectiveness was set at USD 691 and -0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior. RESULTS: While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: -1,000-1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415-509) and 410 (95% CI: 363-457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: -0.016-0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group. CONCLUSIONS: This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.

A case of limb shaking transient ischaemic attack due to internal carotid artery dissection: an unusual presentation of fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) has a high prevalence of associated nontraumatic carotid artery dissection, which could further result in transient ischaemic attack (TIA) or stroke. Limb shaking TIA is an unusual form of TIA that is commonly discribed in elderly patients with atherosclerotic backgrounds, while there are limited data about it in patients with FMD. Furthermore, discussions of limb shaking TIA in nonelderly patients are scarce. CASE PRESENTATION: An Asian 47-year-old female presented with intermittent involuntary movement of the left upper limb accompanied by neck torsion. The episode stopped soon after changing to the supine position. On native source images of time-of-flight magnetic resonance angiography (TOF-MRA), the right internal carotid artery showed a "dual lumen sign" with an intimal flap. On contrast-enhanced magnetic resonance angiography and sagittal black-blood T1WI, an intravascular haematoma with irregular lumen stenosis was observed, which overall indicated right internal carotid artery dissection. Digital subtraction angiography showed the characteristic "string-of-beads" appearance in the left internal carotid artery, and the presence of this sign pointed to the diagnosis of FMD. The patient was finally diagnosed with limb shaking TIA due to internal carotid dissection with fibromuscular dysplasia. The patient was prescribed dual anti-platelet therapy. The limb shaking vanished soon after admission with no reoccurrence in the three-month follow-up. CONCLUSIONS: This case demonstrates that limb shaking TIA can present in patients with FMD. Limb shaking TIA in nonelderly patients can be caused by multiple diseases, and more detailed patient guidance is required in clinical practice.

Temporal trends in inequalities of the burden of cardiovascular disease across 186 countries and territories.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. The extent to which CVD affects the population's health varies across countries. Moreover, quantitative estimates of the trend of inequalities in CVD burden remain unclear. The objective of our study was to assess the socioeconomic inequalities and temporal trends of CVD burden across 186 countries and territories from 2000 to 2019. METHODS: We extracted data from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019, and conducted a cross-national time-series analysis. Age-standardized disability-adjusted life-year (DALY) rates were used to measure the burden of CVDs, and gross national income (GNI) per capita was used to approximate the socioeconomic development. Concentration curves and concentration indexes (CIs) were generated to evaluate the cross-national socioeconomic inequality of CVD burden. A joinpoint regression analysis was used to quantify the changes in trends in socioeconomic inequality of CVD burden from 2000 to 2019. RESULTS: The age-standardized DALY rates of CVDs decreased in 170 (91%) of 186 countries from 2000 to 2019. The concentration curves of the age-standardized DALY rates of CVDs were above the equality line from 2000 to 2019, indicating a disproportional distribution of CVD burden in low-income countries. The CIs declined from - 0.091 (95% CI: -0.128 to - 0.054) in 2000 to - 0.151 (95% CI: -0.190 to - 0.112) in 2019, indicating worsened pro-poor inequality distributions of CVD burden worldwide. A four-phase trend of changes in the CIs of age-standardized DALY rates for CVD was observed from 2000 to 2019, with an average annual percentage change (AAPC) of - 2.7% (95% CI: -3.0 to - 2.4). Decreasing trends in CIs were observed in all CVD subcategories but endocarditis, with AAPC ranging from - 6.6% (95% CI: -7.3 to - 5.9) for ischemic heart disease to - 0.2% (95% CI: -0.4 to - 0.1) for hypertensive heart disease. CONCLUSIONS: Globally, the burden of CVD has decreased in more than 90% of countries over the past two decades, accompanied by an increasing trend of cross-country inequalities. Moreover, the overall burden of CVD continues to fall primarily on low-income countries.

Caregiver burden for adults with epilepsy in Malaysian families: A qualitative study.

BACKGROUND: Caregivers of adults with epilepsy (AWE) play an important role in the healthcare pathway of AWE and are described as the "co-client." Being caregivers can be stressful and the negative impacts might accumulate over time, affecting their quality of life and well-being. OBJECTIVES: This qualitative study aimed to explore the lived experience of caregivers of AWE in Malaysian families and understand their caregiving challenges. Individual semi-structured interviews were held with 12 primary caregivers of AWE. Interpretative Phenomenological Approach (IPA) was used. The interview transcripts were analyzed using NVivo12 software. RESULTS: Primary caregivers of AWE were parents or siblings, with ages ranging from 56 to 80 years old and years of caregiving from 24 to 40 years. Most AWE (58%) were intellectually disabled and fully dependent on ADL needs. Two categories of themes emerged, including four themes on caregiver burden, i.e., physical, emotional, and social burdens, and challenges in future planning of care, and two themes on coping strategies (problem- or emotional-focused). In future planning of care, most caregivers especially parents carried a burden of responsibility and were reluctant to depend on others or institutional services. CONCLUSION: The caregiving burden among caregivers for adult AWE was not confined to current burdens only but also challenges in future planning. A better understanding of the caregiving burden for AWE and coping strategies is needed to provide tailored psychoeducation or psychosocial intervention to support this population.

Feasibility of psychological screening in a tertiary epilepsy clinic.

OBJECTIVE: People with epilepsy (PWE) have a high prevalence of developing depression and anxiety. The objective is to determine the feasibility of brief screening tools to screen for depression and anxiety in epilepsy, and the predictive factors. METHOD: This is a cross-sectional study in the neurology clinic in a tertiary teaching hospital in Kuala Lumpur. The screening tools used were the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the General Anxiety Disorder Form (GAD-7). RESULTS: Five hundred and eighty-five patients were recruited in this study, and 50.8% of them were male, predominantly Chinese (46.7%), with a mean age of seizure onset of 21.8 ± 16.1 years. The majority had focal seizures (75.0%), and 41.9% had seizure remission. There were 15.5% who scored ≥15 in the NDDI-E, and 17.0% had moderate or severe anxiety (scored ≥10 in the GAD-7). In a regression model to predict the NDDI-E score, the age of seizure onset recorded a higher beta value (ß = -0.265, p =< 0.001), followed by the duration of epilepsy (ß = -0.213, p =< 0.001), use of levetiracetam (LEV) (ß = 0.147, p = 0.002), clonazepam (CLZ) (ß = 0.127, p = 0.011), and lamotrigine (LTG) (ß = 0.125, p = 0.011), number of current antiseizure medications (ß = -0.124, p = 0.049), seizure remission for ≥1 year (ß = -0.108, p = 0.011), and female (ß = 0.082, p = 0.049). For the GAD-7 score, the predictors included current age (ß = -0.152, p = 0.001), the use of LEV (ß = 0.122, p = 0.011), Indian ethnicity (ß = 0.114, p = 0.006), and the use of carbamazepine (ß = -0.090, p = 0.043). CONCLUSION: Implementation of simple psychological screening using self-administered questionnaires was feasible in a busy tertiary epilepsy clinic.

Induced abortions among Chinese adolescent girls.

BACKGROUND: Induced abortion among adolescent girls is a global public health issue and a serious challenge in China, but still remains under-examined. We aimed to examine the overall trend and characteristics of induced abortions among Chinese adolescent girls and to investigate the factors associated with induced abortion. STUDY DESIGN: Based on the 2017 China Fertility Survey, this study examined the trend and characteristics of induced abortions among adolescent girls with statistical analysis and multiple indicators of descriptive statistics from period and cohort perspectives, including induced abortion proportion and rate, age-specific cumulative proportion, and age-specific cumulative number of induced abortions in adolescent girls. RESULTS: Between 1996 and 2016, the proportion and rate of adolescent induced abortions first increased and then decreased, and the mean age at the time of induced abortions among adolescent girls declined. The cumulative proportion of women who had experienced induced abortion at the age of 15-19 in a cohort is less than 2.5% but shows an upward trend. Over 70% of all adolescent induced abortions are premarital. The proportion of women with unintended pregnancy experiences increased and is higher among rural, less educated, and ethnic minority women. Similarly, the prevalence of induced abortion is higher among adolescent girls who live in rural areas, are less educated, and come from ethnic minorities. The cumulative number of induced abortions and premarital abortions increased with later cohorts. CONCLUSIONS: This study shows an upward trend in adolescent-induced abortion and a decline in the age at the time of the induced abortion. Women in later birth cohort have a higher proportion of having experienced adolescent induced abortion. Adolescent girls who live in rural areas, who are less educated, or who are from ethnic minorities, are more likely to undergo induced abortions at the age of 15-19. More appropriate educational efforts and interventions are urgently needed to reduce the incidence of adolescent induced abortions.

Temporal trends in inequalities of the burden of HIV/AIDS across 186 countries and territories.

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) has reported that HIV/AIDS continues to take a disproportionate toll on global health. However, the trends in global inequality of HIV/AIDS burden have remained ambiguous over the past two decades. The objectives of our study were to assess the socioeconomic inequalities, and temporal trends of HIV/AIDS across 186 countries and territories from 2000 to 2019. METHODS: We extracted data from the GBD 2019, and conducted a cross-national time-series analysis. Age-standardized disability-adjusted life-year (DALY) rates were used to measure the global burden of HIV/AIDS. Gross national income (GNI) per capita was used to approximate the national socioeconomic status. Linear regression analysis was conducted to investigate the relationship between age-standardized DALY rates due to HIV/AIDS and GNI per capita. The concentration curve and concentration index (CI) were generated to evaluate the cross-national socioeconomic inequality of HIV/AIDS burden. A joinpoint regression analysis was used to quantify the changes in trends in socioeconomic inequality of HIV/AIDS burden from 2000 to 2019. RESULTS: A decrease in age-standardized DALY rates for HIV/AIDS occurred in 132 (71%) of 186 countries/territories from 2000 to 2019, of which 52 (39%) countries/territories achieved a decrease in DALYs of more than 50%, and 27 (52%) of the 52 were from sub-Saharan Africa. The concentration curves of the age-standardized DALY rates of HIV/AIDS were above the equality line from 2000 to 2019. The CI rose from - 0.4625 (95% confidence interval - 0.6220 to -0.2629) in 2000 to -0.4122 (95% confidence interval - 0.6008 to -0.2235) in 2019. A four-phase trend of changes in the CIs of age-standardized DALY rates for HIV/AIDS was observed across 2000 to 2019, with an average increase of 0.6% (95% confidence interval 0.4 to 0.8, P < 0.001). CONCLUSIONS: Globally, the burden of HIV/AIDS has decreased over the past two decades, accompanied by a trend of narrowing cross-country inequalities of HIV/AIDS burden. Moreover, the burden of HIV/AIDS continues to fall primarily in low-income countries.

Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia. METHODS: A microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort's ranges of ages. RESULTS: Sixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective. CONCLUSIONS: HCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.

[Effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of prostate cancer cells by regulating E2F5 expression].

OBJECTIVE: To analyze the effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of PCa cells by regulating the expression of E2F5. METHODS: Using real time fluorescence RT-PCR, we detected the expressions of lncRNA SNHG12 and E2F5, constructed the PC3 cells inhibiting the lncRNA SNHG12 expression. After transfection of the PC3 cells, we divided them into an NC, a si-NC, a si-SNHG12, a si-E2F5, a si-SNHG12+OE-si-NC, and a si-SNHG12+OE-E2F5 group, followed by examination of the proliferation, apoptosis, migration and invasiveness of the cells in different groups. RESULTS: The expressions of lncRNA SNHG12 and E2F5 were significantly up-regulated in the PCa tissue compared with those in the adjacent tissue (P < 0.05), remarkably higher in the DU145, LNCaP and PC3 groups than in the RWPE-1 group, the highest in the PC3 group (P < 0.05). The expression of SNHG12 was markedly down-regulated in the si-SNHG12 group (P < 0.05) in comparison with that in the si-NC group, indicating the successful construction of a PC3 cell line interfering with the lncRNA SNHG12 expression. Compared with the si-NC group, the si-SNHG12 group showed significant decreases in the values of CyclinD1, MMP-9 and OD and the numbers of migrating and invading cells, and an increase in apoptotic cells (P < 0.05), while the si-E2F5 group exhibited a remarkably down-regulated expression of E2F5 (P < 0.05), reduced values of CyclinD1, MMP-9 and OD, decreased numbers of migrating and invading cells and an increased number of apoptotic cells (P < 0.05). The dual luciferase report test showed that E2F5 reduced the luciferase activity of SNHG12 (P < 0.05 and had an insignificant impact on the luciferase activity of MUT-SNHG12 (P > 0.05). Inhibiting the expression of lncRNA SNHG12 resulted in significant decreases in the expression of E2F5, values of CyclinD1, MMP-9 and OD and numbers of migrating and invading cells, but an increase in apoptotic cells (P < 0.05). The E2F5 expression, the CyclinD1, MMP-9 and OD values and the numbers of migrating and invading cells were markedly increased while the number of apoptotic cells decreased in the si-SNHG12+OE-E2F5 group compared with those in the si-SNHG12+OE-si-NC group (P < 0.05). CONCLUSION: Interfering with the expression of lncRNA SNHG12 can regulate that of E2F5, inhibit the proliferation, migration and invasiveness of PCa cells and promote their apoptosis.

694 W sub-GHz polarization-maintained tapered fiber amplifier based on spectral and pump wavelength optimization.

The comprehensive suppression of the stimulated Brillouin scattering (SBS) and transverse mode instability (TMI) is a critical issue for the power scaling of fiber laser with sub-GHz spectral linewidth. In this manuscript, a narrow linewidth and polarization-maintained (PM) fiber amplifier based on tapered Yb-doped fiber (T-YDF) is established, and the effects of spectral linewidth, spectral shape and pump wavelength on the SBS and/or TMI thresholds are investigated. Up to 694 W polarization-maintained fiber laser with just ∼790 MHz linewidth is obtained by combining the advantages of tapered Yb-doped fiber, near-rectangular spectral injection and 915 nm pump manner. This work could provide a well reference solution for the realization of high-power ultra-narrow linewidth fiber lasers.

Confined-doped active fiber enabled all-fiber high-power single-frequency laser.

In this paper, we investigate the performances of an in-house fabricated confined-doped active fiber in the applications of all-fiber high-power single-frequency amplifiers. A 210-W single-frequency single-mode fiber laser is obtained directly, which confirms the excellent performance of the confined-doped active fiber for high-power single-mode operation. To further demonstrate the power scalability of the fiber amplifier, the strategy of applying a temperature gradient along the active fiber is investigated numerically and experimentally, and an up to ∼75% enhancement of the stimulated Brillouin scattering (SBS) threshold is achieved. As a result, a 368-W single-frequency fiber laser is obtained with the beam quality factor of Mx2 = 1.19, My2 = 1.26. Overall, the technique of the confined-doped active fiber provides a promising approach to scale the output power of single-frequency single-mode fiber lasers.