METHODS: In this systematic review, meta-analysis, and modelling study, we searched PubMed, Ovid, and Web of Science for articles published from database inception until Sept 26, 2022, for prospective and retrospective cross-sectional studies that addressed serological chikungunya virus infection in any geographical region, age group, and population subgroup and for longitudinal prospective and retrospective cohort studies with data on chronic chikungunya or hospital admissions in people with chikungunya. We did a systematic review of studies on chikungunya seroprevalence and fitted catalytic models to each survey to estimate location-specific FOI (ie, the rate at which susceptible individuals acquire chikungunya infection). We performed a meta-analysis to estimate the proportion of symptomatic patients with laboratory-confirmed chikungunya who had chronic chikungunya or were admitted to hospital following infection. We used a random-effects model to assess the relationship between chronic sequelae and follow-up length using linear regression. The systematic review protocol is registered online on PROSPERO, CRD42022363102.
FINDINGS: We identified 60 studies with data on seroprevalence and chronic chikungunya symptoms done across 76 locations in 38 countries, and classified 17 (22%) of 76 locations as endemic settings and 59 (78%) as epidemic settings. The global long-term median annual FOI was 0·007 (95% uncertainty interval [UI] 0·003-0·010) and varied from 0·0001 (0·00004-0·0002) to 0·113 (0·07-0·20). The highest estimated median seroprevalence at age 10 years was in south Asia (8·0% [95% UI 6·5-9·6]), followed by Latin America and the Caribbean (7·8% [4·9-14·6]), whereas median seroprevalence was lowest in the Middle East (1·0% [0·5-1·9]). We estimated that 51% (95% CI 45-58) of people with laboratory-confirmed symptomatic chikungunya had chronic disability after infection and 4% (3-5) were admitted to hospital following infection.
INTERPRETATION: We inferred subnational heterogeneity in long-term average annual FOI and transmission dynamics and identified both endemic and epidemic settings across different countries. Brazil, Ethiopia, Malaysia, and India included both endemic and epidemic settings. Long-term average annual FOI was higher in epidemic settings than endemic settings. However, long-term cumulative incidence of chikungunya can be similar between large outbreaks in epidemic settings with a high FOI and endemic settings with a relatively low FOI.
FUNDING: International Vaccine Institute.
METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study.
RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p
METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.
METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
METHODS: The study involved conducting intradermal injections on four cadavers and participants using a 2 mm length, 34-gauge needle (N-Finders, Inc., South Korea). During the cadaveric study, the polynucleotide prefilled syringe was dyed green, and an anatomist performed dissections, removing only the skin layer. Ultrasonographic observations were carried out to ensure accurate intradermal injection placement.
RESULTS: In all four cadavers, the facial injections at the anterior cheek region were precisely administered intradermally at a 30-degree injection angle. However, the 90-degree injection was found just below the dermal layer upon skin layer removal.
DISCUSSION: The findings suggest that using a 2 mm needle length allows for easy and convenient intradermal injections.
METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety.
RESULTS: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively.
CONCLUSIONS: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile.
OBJECTIVES: This study aimed to provide a personalized surgical recommendation that enables more confidence in advising patients to pursue surgical treatment.
METHODS: We enrolled 328 patients with uPA harboring KCNJ5 mutations (n = 158) or not (n = 170) who had undergone adrenalectomy. Eighty-seven features were collected, including demographics, various blood and urine test results, and clinical comorbidities. We designed 2 versions of the prediction model: one for institutes with complete blood tests (full version), and the other for institutes that may not be equipped with comprehensive testing facilities (condensed version).
RESULTS: The results show that in the full version, the Light Gradient Boosting Machine outperformed other classifiers, achieving area under the curve and accuracy values of 0.905 and 0.864, respectively. The Light Gradient Boosting Machine also showed excellent performance in the condensed version, achieving area under the curve and accuracy values of 0.867 and 0.803, respectively.
CONCLUSIONS: We simplified the preoperative diagnosis of KCNJ5 mutations successfully using machine learning. The proposed lightweight tool that requires only baseline characteristics and blood/urine test results can be widely applied and can aid personalized prediction during preoperative counseling for patients with uPA.
SUMMARY ANSWER: Age, ethnicity, obesity (BMI ≥ 30 kg/m2), and polycystic ovarian syndrome (PCOS) significantly impacted serum AMH levels, with the rate of decrease accelerating as age increased; a concentration of 4.0 ng/ml was the optimal cut-off for diagnosis of PCOS.
WHAT IS KNOWN ALREADY: There are significant differences in ovarian reserve among women from different races and ethnicities, and Asian women often have poorer reproductive outcomes during assisted reproductive treatment cycles.
STUDY DESIGN, SIZE, DURATION: A population-based multi-nation, multi-centre, multi-ethnicity prospective cohort study of 4613 women was conducted from January 2020 to May 2021. Infertile women of 20-43 years of age were enrolled. The exclusion criteria included: age <20 or >43, non-Asian ethnicity, and missing critical data.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were Asian women of Chinese, Japanese, Korean, Thai, Vietnamese, Malay, Indian, and Indonesian ethnicities from 12 IVF centres across Asia. These women were all naïve to ovarian stimulation cycles and attended IVF centres for fertility assessment. The AMH measurement was performed using an AMH automated assay on a clinically validated platform.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4556 infertile Asian women were included in the final analyses. The mean ± SD for serum AMH concentrations (ng/ml) across specific age groups were: overall, 3.44 ± 2.93; age <30, 4.58 ± 3.16; 30-31, 4.23 ± 3.23; 32-33, 3.90 ± 3.06; 34-35, 3.21 ± 2.65; 36-37, 2.74 ± 2.44; 38-39, 2.30 ± 1.91; 40 and above, 1.67 ± 2.00. The rate of AMH decrease was ∼0.13 ng/ml/year in patients aged 25-33 and 0.31 ng/ml/year in women aged 33-43. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%). Age (P
METHODS: This cross-sectional study recruited adult PWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using Patient Health Questionnaire-9 and SU using Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Factors associated with mean QoL and disability scores were analysed using linear regression.
RESULTS: Of 864 PWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PWH reporting previous trauma/stress (difference = 2.7, 95% confidence interval [CI] 1.5-3.9, P
METHODS AND RESULTS: Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination.
CONCLUSION: In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.