Adult Asian Patients Research Articles

Quality of Life and Burden of Moderate-to-Severe Atopic Dermatitis in Adult Patients Within the Asia-Pacific Region: A Cross-sectional Survey.

The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs. Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory. Median age of enrolled patients (N = 1103) was 41.0years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2%) and oral steroids (58.7%) were frequently prescribed to manage AD. Common atopic comorbidities were allergic urticaria (64.2%), allergic rhinitis (61.8%), and allergic conjunctivitis (51.5%). Median DLQI score was 13.0 (IQR11.0), while median EQ-5D-5L (based on China value set) score was 0.8 (IQR0.4); 87.2% and 77.2% of patients reported pain/discomfort and anxiety/depression on the EQ-5D-5L domains, respectively. Median total annual costs associated with AD were USD10,128.52 (IQR12,963.26) per patient, with indirect costs being the largest component. Findings from WPAI indicated that presenteeism is a major contributor to productivity loss. This multinational survey study showed that AD is associated with substantial QoL impairment and economic burden among Asian adult patients with moderate-to-severe AD. To alleviate burden of AD, clinicians should be more proactive in managing other concomitant conditions including psychological issues, and advocate for increased reimbursement for AD treatments.

Narrative Review of Brivaracetam: Preclinical Profile and Clinical Benefits in the Treatment of Patients with Epilepsy.

One third of patients with epilepsy will continue to have uncontrolled seizures despite treatment with antiseizure medications (ASMs). There is therefore a need to develop novel ASMs. Brivaracetam (BRV) is an ASM that was developed in a major drug discovery program aimed at identifying selective, high-affinity synaptic vesicle protein 2A (SV2A) ligands, the target molecule of levetiracetam. BRV binds to SV2A with 15- to 30-fold higher affinity and greater selectivity than levetiracetam. BRV has broad-spectrum antiseizure activity in animal models of epilepsy, a favorable pharmacokinetic profile, few clinically relevant drug-drug interactions, and rapid brain penetration. BRV is available in oral and intravenous formulations and can be initiated at target dose without titration. Efficacy and safety of adjunctive BRV (50-200mg/day) treatment of focal-onset seizures was demonstrated in three pivotal phase III trials (NCT00490035/NCT00464269/NCT01261325), including in patients who had previously failed levetiracetam. Efficacy and safety of adjunctive BRV were also demonstrated in adult Asian patients with focal-onset seizures (NCT03083665). In several open-label trials (NCT00150800/NCT00175916/NCT01339559), long-term safety and tolerability of adjunctive BRV was established, with efficacy maintained for up to 14years, with high retention rates. Evidence from daily clinical practice highlights BRV effectiveness and tolerability in specific epilepsy patient populations with high unmet needs: the elderly (≥ 65years of age), children (< 16years of age), patients with cognitive impairment, patients with psychiatric comorbid conditions, and patients with acquired epilepsy of specific etiologies (post-stroke epilepsy/brain tumor related epilepsy/traumatic brain injury-related epilepsy). Here, we review the preclinical profile and clinical benefits of BRV from pivotal trials and recently published evidence from daily clinical practice.

Long-term effects of adjunctive eslicarbazepine acetate in adult Asian patients with refractory focal seizures: Post hoc analysis of a phase III trial.

A post hoc analysis of data from Asian patients included in the study BIA-2093-304 was conducted to evaluate the long-term safety/tolerability and efficacy of adjunctive eslicarbazepine acetate (ESL) in adult Asian patients with refractory focal seizures. Part I was a randomized controlled trial, in which patients received ESL (800 or 1200 mg once daily [QD]) or placebo, assessed over a 12-week maintenance period. Patients completing Part I could enter two open-label extension periods (Part II, 1 year; Part III, ≥2 years), during which all received ESL (400-1600 mg QD). Safety/tolerability was assessed by evaluating treatment-emergent adverse events (TEAEs). Efficacy assessments included responder and seizure freedom rates. The safety population included 125, 92, and 23 Asian patients in Parts I, II, and III, respectively. Incidence of ESL-related TEAEs was 61.3%, 45.7%, and 17.4% during Parts I, II, and III, respectively. ESL-related TEAEs (most commonly, dizziness, somnolence, and headache) were consistent with ESL's known safety profile. During Part I, responder rates were higher with ESL 800 (41.7%) and 1200 mg QD (44.4%) versus placebo (32.6%), although not statistically significant. Seizure freedom rates with ESL 800 (5.5%) and 1200 mg QD (11.1%) were also higher versus placebo (0%) (p < 0.05 for ESL 1200 mg QD versus placebo). At the end of Part II, responder and seizure freedom rates were 60.3% and 14.7%, respectively. In summary, adult Asian patients with refractory focal seizures were responsive to treatment with ESL as adjunctive therapy and generally showed treatment tolerance well for up to 3 years. No new/unexpected safety findings were observed.

Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial.

Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS). Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs. In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p < 0.0001) with BRV 50 mg/day and 200 mg/day, respectively, 50% responder rate was 19.0%, 41.1%, and 49.3% with placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p < 0.0001 for both BRV groups vs. placebo). Median percent reduction in FOS frequency from baseline was 21.3%/38.9%/46.7% in patients on placebo/BRV 50 mg/BRV 200 mg/day, respectively. Overall, 0, 7 (4.6%), and 10 (6.8%) patients were classified as seizure-free during the treatment period on placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p = 0.0146/p = 0.0017 for BRV 50 mg/200 mg/day vs. placebo, respectively). TEAE incidences were similar between patients on placebo (58.4%) and all patients receiving BRV (58.5%); TEAE incidences for BRV 50 mg/day and BRV 200 mg/day were 57.0% and 60.1%, respectively. Overall, 0.7% of patients on placebo and 2.0% of all patients on BRV reported serious TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 1.3% and 2.7%, respectively), 20.1% of patients on placebo and 33.1% of all patients on BRV reported drug-related TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 26.5% and 39.9%, respectively), and 4.7% of patients on placebo and 3.0% of all patients on BRV discontinued due to TEAEs (discontinuation incidences for BRV 50 mg/day and BRV 200 mg/day were 2.6% and 3.4%, respectively). Adjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non-Asian populations. Brivaracetam is used to treat partial or focal seizures in people with epilepsy. Most studies with brivaracetam tablets have involved people from non-Asian racial backgrounds. In this study, 449 Asian adults with epilepsy took part. One third took 50 mg of brivaracetam, one third took 200 mg of brivaracetam, and one third took a placebo each day for 12 weeks. On average, those who took brivaracetam had fewer seizures than those given the placebo. Most of the side effects were mild and the number and type of side effects seen were as expected for this medication.

Evaluation of a creatinine clearance correction equation based on body fat mass in older Japanese patients with diabetes.

The estimation of creatinine clearance (CCr) in older adult patients with diabetes is subject to deviations from the results of actual measurements because of changes in body composition. In the present study, we aimed to create a correction for the equation used for the estimation of CCr in older adult Asian patients with diabetes using body composition parameters. We enrolled 50 older Japanese patients with diabetes in whom the measured values of CCr were compared with values estimated using the Cockcroft-Gault equation. The relationships between the error in the estimated CCr and body composition parameters were investigated, and the Cockcroft-Gault equation was corrected using the appropriate parameters. To evaluate the generalizability of the corrected equation, the utility of the Cockcroft-Gault equation, which was corrected on the basis of body composition measured using a household body composition meter, was also investigated. Body fat mass (BFM) was closely correlated with the error in the estimated CCr. The BFM-corrected Cockcroft-Gault equation was more accurate than the original equation. Similarly, the error became smaller using BFM measured with a household body composition meter. The BFM-corrected Cockcroft-Gault equation may provide an accurate method of estimating CCr that can be used in general practice.

Modified physiologic criteria for the field triage scheme: Efficacy of major trauma recognition in different age groups in Asia

BackgroundMajor trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear. MethodsWe conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups. ResultsThe sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups. ConclusionssFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients.

Racial Distribution and Associated Outcomes for Patients With and Without Severe-Isolated Traumatic Brain Injuries Following Venous Thromboembolism Prophylaxis.

Disparities in venous thromboembolism (VTE) incidence and prophylaxis have been observed across racial groups. This study investigates the relationship between race, injury type, and the timing of VTE prophylaxis in severe trauma patients, both with and without isolated traumatic brain injuries. The primary goal is to analyze how these factors interact and their potential impact on clinical outcomes. A retrospective cohort study of the American College of Surgeons Trauma Quality Program Participant Use File (ACS-TQIP-PUF) from 2018 to 2021. Patient demographics, injury categories, VTE prophylaxis timing, injury severity, and in-hospital complications were collected. Multivariable regression models explored associations between race, injury type, VTE prophylaxis, and in-hospital mortality. Groups were analyzed by injury profile (isolated TBI vs non-TBI) and then by VTE prophylaxis timing (early ≤24hours, late >24hours). Of 68,504 trauma patients analyzed, the majority were non-Hispanic or Latino (83.3%), White (71.2%), and male (69.6%). Patients receiving late VTE prophylaxis had higher rates of DVT and PE across race groups than patients with early prophylaxis. Logistic regression showed Asian patients with TBI receiving early prophylaxis were significantly more likely to have in-hospital mortality (OR 16.27, CI = 1.11-237.43, P = .04) than other races. Patients who received late prophylaxis had higher VTE rates than early prophylaxis, independent of injury pattern or race. Additionally, assessing the implications of race in early VTE prophylaxis for isolated TBI showed that adult Asian patients had 16 times higher odds of in-hospital mortality compared to other races.

The association of P-terminal force value and increased risk for ischemic stroke among admitted patients in a tertiary hospital: a retrospective case-control study

Abstract Funding Acknowledgements Type of funding sources: None. Background Cerebrovascular disease is the second leading cause of mortality in the Philippines, with prevalence of 0.9 to 2.6%.³ However, recent researches show that left atrial abnormality, even without atrial fibrillation, increases risk for ischemic stroke. Purpose This study aims to determine the association of P-terminal force value in V1 (PTFV1) and ischemic stroke. Secondary objectives are to elucidate the relationships of PTFV1 and dilated left atrium (LA), and dilated LA and ischemic stroke. Methods This is a retrospective case-control study which included adult Asian patients managed as first-time ischemic stroke, with an age-, gender- and co-morbidity-matched control group. A total of 290 patients were evaluated. Binary logistic regression was used in the analysis of the primary outcome, while independent T-test and chi-square test were utilized for the secondary outcomes. Results PTFV1 and ischemic stroke had a statistically significant positive association. Every 1 unit change of PTFV1 confers 1.7% increased risk for ischemic stroke. Furthermore, a higher PTFV1 was significantly correlated with dilated LA. However, there was no significant association between dilated LA and ischemic stroke. Conclusion PTFV1 confers an easier way to diagnose patients with left atrial abnormality, and stratify those with increased risk for ischemic stroke.

Discriminant ability of the shock index, modified shock index, and reverse shock index multiplied by the Glasgow coma scale on mortality in adult trauma patients: a PATOS retrospective cohort study.

The shock index (SI) predicts short-term mortality in trauma patients. Other shock indices have been developed to improve discriminant accuracy. The authors examined the discriminant ability of the SI, modified SI (MSI), and reverse SI multiplied by the Glasgow Coma Scale (rSIG) on short-term mortality and functional outcomes. The authors evaluated a cohort of adult trauma patients transported to emergency departments. The first vital signs were used to calculate the SI, MSI, and rSIG. The areas under the receiver operating characteristic curves and test results were used to compare the discriminant performance of the indices on short-term mortality and poor functional outcomes. A subgroup analysis of geriatric patients with traumatic brain injury, penetrating injury, and nonpenetrating injury was performed. A total of 105641 patients (49±20 years, 62% male) met the inclusion criteria. The rSIG had the highest areas under the receiver operating characteristic curve for short-term mortality (0.800, CI: 0.791-0.809) and poor functional outcome (0.596, CI: 0.590-0.602). The cutoff for rSIG was 18 for short-term mortality and poor functional outcomes with sensitivities of 0.668 and 0.371 and specificities of 0.805 and 0.813, respectively. The positive predictive values were 9.57% and 22.31%, and the negative predictive values were 98.74% and 89.97%. rSIG also had better discriminant ability in geriatrics, traumatic brain injury, and nonpenetrating injury. The rSIG with a cutoff of 18 was accurate for short-term mortality in Asian adult trauma patients. Moreover, rSIG discriminates poor functional outcomes better than the commonly used SI and MSI.

Non-germinal center B-cell subtype of pediatric diffuse large B-cell lymphoma in Japan: A retrospective cohort study.

Diffuse large B-cell lymphoma (DLBCL) is classified into two molecular subtypes according to its cell of origin: germinal center B-cell (GCB) subtype and activated B-cell/non-GCB subtype. This latter subtype shows a poorer prognosis in adults. However, in pediatric DLBCL, the prognostic impact of the subtype is yet to be clarified. This study sought to compare the prognosis between GCB and non-GCB DLBCL in a large number of cases in children and adolescents. In addition, this study intended to describe the clinical, immunohistochemical, and cytogenetic characteristics of these two molecular subtypes of DLBCL, and consider differences in the biology, frequency, and prognosis of GCB and non-GCB subtypes in pediatric versus adult DLBCL or in Japanese versus Western pediatric DLBCL patients. We selected mature B-cell lymphoma/leukemia patients for whom specimens had been submitted to the central pathology review in Japan between June 2005 and November 2019. We referred the past studies on Asian adult patients and Western pediatric patients to compare with our results. Data were obtained from 199 DLBCL patients. The median age of all patients was 10years, with 125 patients (62.8%) in the GCB group and 49 (24.6%) in the non-GCB group other than 25 cases whose immunohistochemical data were insufficient. Overall, the percentage of translocation of MYC (1.4%) and BCL6 (6.3%) was lower than in adult and Western pediatric DLBCL cases. The non-GCB group showed a significantly higher proportion of females (44.9%), a higher incidence of stage III disease (38.8%), and B-cell lymphoma 2 (BCL2)-positivity in immunohistochemistry (79.6%) compared to the GCB group; however, no BCL2 rearrangement was observed in both GCB and non-GCB groups. The prognosis did not differ significantly between the GCB and non-GCB groups. This study including a large number of non-GCB patients showed the same prognosis between GCB and non-GCB groups and suggested a difference in the biology of pediatric and adolescent DLBCL compared to adult DLBCL as well as between Asian and Western DLBCL.

Waiting-List and early posttransplant prognosis among ethnoracial groups: Data from the organ procurement and transplantation network.

Racial/ethnic disparity in waiting-list mortality among candidates listed for kidney transplantation (KT) in the United States remains unclear. We aimed to assess racial/ethnic disparity in waiting-list prognosis among patients listed for KT in the United States in the current era. We compared waiting-list and early posttransplant in-hospital mortality or primary nonfunction (PNF) among adult (age ≥18 years) white, black, Hispanic, and Asian patients listed for only KT in the United States between July 1, 2004 and March 31, 2020. Of the 516,451 participants, 45.6%, 29.8%, 17.5%, and 7.1% were white, black, Hispanic, and Asian, respectively. Mortality on the 3-year waiting list (including patients who were removed for deterioration) was 23.2%, 16.6%, 16.2%, and 13.8% in white, black, Hispanic, and Asian patients, respectively. The cumulative incidence of posttransplant in-hospital death or PNF after KT was 3.3%, 2.5%, 2.4%, and 2.2% in black, white, Hispanic, and Asian patients,respectively. White candidates had the highest mortality risk on the waiting list or of becoming too sick for a transplant, while black (adjusted hazard ratio, [95% confidence interval, CI], 0.67 [0.66-0.68]), Hispanic (0.59 [0.58-0.60]), and Asian (0.54 [0.52-0.55]) candidates had a lower risk. Black KT recipients (odds ratio, [95% CI] 1.29 [1.21-1.38]) had a higher risk of PNF or death before discharge than white patients. After controlling confounders, black recipients (0.99 [0.92-1.07]) had a similar higher risk of posttransplant in-hospital mortality or PNF as white patients than Hispanic and Asian counterparts. Despite having a better socioeconomic status and being allocated better kidneys, white patients had the worst prognosis during the waiting periods. Black recipients and white recipients have higher posttransplant in-hospital mortality or PNF.

Validation of the PICC length prediction formula based on anteroposterior chest radiographs for bedside ultrasound-guided placement.

This study aimed to validate the accuracy of the peripherally inserted central catheter (PICC) length prediction formula using only anteroposterior chest radiographs (AP-CXR) and the technical feasibility of bedside ultrasound-guided PICC placement. This study included 156 Asian adult patients who underwent bedside PICC placement at three hospitals from September 2021 to March 2022. The shortest straight-line distance from the cubital crease to the puncture point (CP) was measured first. Using the formula of a previous study, the CP + estimated PICC length (eCL) was calculated with the parameters measured on AP-CXR. The formula was as follows: 19.409 + 0.424 × (MHTD, maximal horizontal thoracic diameter) + 0.287 × (CL, clavicle length) + 0.203 × (DTV, distance of thoracic vertebrae) + (2VBUs, two vertebral body units below the carina inferior border) (if from the left, 3.063cm was added; if female, 0.997cm was subtracted). Catheters were pretrimmed according to calculated eCL prior to the procedure. Technical success was evaluated, and the validation success of catheter length prediction was classified according to the catheter tip position as follows: optimal position or suboptimal position. Technical success was achieved in 153 cases (98.1%). Evaluation of validation success revealed that the position was "optimal" in 108 cases (70.6%) and "suboptimal" in 45 cases (29.4%). There was no validation failure. There was no case where the catheter was inserted too deep as to wedge into the right atrial wall. In conclusion, the PICC could be positioned accurately using the formula based on only AP-CXR. Furthermore, this bedside procedure was technically feasible.

32316 Five-year cancer-specific survival for melanoma in LEP: An analysis of the SEER database

Limited English Proficient (LEP) patients have been shown to have barriers to health care access. LEP is concentrated amongst Asian and Hispanic White populations. There is little known about cancer specific health outcomes for LEP melanoma patients. We hypothesized that there would be a statistically greater 5-year Cancer Specific Survival (CSS) in low LEP counties compared with high LEP counties. We performed a retrospective cross-sectional study on Asian and Hispanic White melanoma patients from the Surveillance, Epidemiology, and End Results database (SEER, 2018, 18 Reg.). 5-year CSS was compared between low LEP (0-12% LEP population) vs high LEP counties (≥12% LEP population) using a Kaplan-Meier analysis. A Cox proportional hazards regression was performed to investigate the effects of age of diagnosis, and county LEP status on 5-year CSS. A total of 8490 adult Asian and Hispanic White melanoma patients were identified, of whom 660 were in high LEP counties (7.8%). Mean age of diagnosis in high LEP counties (60.3 ± 17.7yo) was later than in low LEP counties (58.1 ± 16.9 yo, P = .002). 5-year melanoma CSS was marginally lower among patients in high LEP counties (P < .15). County LEP status did not confer a significant hazard (P = .334). 5-year melanoma CSS decreased with age of diagnosis (HR 1.01 per year, 95% CI [1.01-1.02]). Our results indicate that once diagnosed LEP does not affect a patient’s 5 year Cancer specific survival indicating the importance of melanoma screen in high LEP counties for early detection of melanoma. A limitation to this study is that it uses county level LEP data.

RetinoblastomainAdults: Clinical Features, Gene Mutations and Treatment Outcomes: A Study of Six Cases.

PurposeTo report six Asian adult patients with retinoblastoma (RB).DesignRetrospective and observational small case series.ParticipantsSix patients with a white dome-shaped tumor of the retina were evaluated from May 10, 1995, to September 10, 2021.Main Outcome MeasuresInitial tumor and associated fundus features, pathology, gene mutation, treatment, tumor course on follow-up, and salvage globe outcome.ResultsThe six affected Asian patients consisted of three men and three women. The mean age at the time of diagnosis was 36.5 years (median: 31 years, range: 20-55 years). All patients were unilateral. In all cases, the tumors were white, dome-shaped, with full-thickness retinal involvement, and mushroom-like protrusions into the vitreous cavity. The mean tumor thickness measured by ultrasonography was 4.5 mm (median: 3.2 mm, range: 3.2-6.8 mm). Associated characteristic symptoms included dilated retinal feeding artery and draining vein (100%), surrounding subretinal infiltration (83%), exudative retinal detachment (83%), and vitreous seeds (67%). Local tumor resection was performed in three patients, I-125 plaque brachytherapy combined with transpupillary thermotherapy (TTT) and intravitreous injection of melphalan (combination treatment) in one patient, I-125 plaque brachytherapy in two patients, and enucleation in one (20%) patient. RB1 gene testing was carried out on four patients and pathological diagnosis on five patients. Genetic analysis revealed that the RB1 mutation was a mosaic c.709dupG (p.Glu237GlyfsTer4) duplication in one patient, a mosaic c.763C>T(p.Arg255Ter) mutation in another patient, while the remaining two patients were RB1 negative. At the end of the follow-up, none of the patients had developed tumor-related metastasis or died. The findings were consistent in all patients who had an adequate follow-up. This study focused on this rare lesion to distinguish it from other intraocular white lesions in adults, including choroidal osteoma, vitreoretinal lymphoma, and retinal capillary hemangioma, all of which are different clinical entities.ConclusionIn adults, RB is typically a white, full-thickness retinal mass that is unilateral, often combining with retinal feeding vessels, subretinal infiltration, and vitreous seeds. Genetic studies on adult-onset RB are essential and still require elucidation. Despite RB being a malignant tumor, patient survival was minimally affected.

The effect of oral diabetes medications on glycated haemoglobin (HbA1c) in Asians in primary care: a retrospective cohort real-world data study

BackgroundClinical trials have demonstrated that initiating oral anti-diabetic drugs (OADs) significantly reduce glycated hemoglobin (HbA1c) levels. However, variability in lifestyle modifications and OAD adherence impact on their actual effect on glycemic control. Furthermore, evidence on dose adjustments and discontinuation of OAD on HbA1c is lacking. This study aims to use real-world data to determine the effect of OAD initiation, up-titration, down-titration, and discontinuation on HbA1c levels, among Asian patients managed in primary care.MethodsA retrospective cohort study over a 5-year period, from Jan 2015 to Dec 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of type 2 diabetes mellitus (T2DM) managed by a network of primary care clinics in Singapore. Nine OADs from five different classes (biguanides, sulphonyurea, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 [SGLT-2] inhibitors, and alpha-glucosidase inhibitors) were evaluated. Patients were grouped into “No OAD”, “Non-titrators,” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the various OAD titrations were identified. Subsequently, a descriptive analysis of HbA1c values before and after each titration was performed to compute a mean difference for each unique titration identified.ResultsAmong the cohort of 57,910 patients, 43,338 of them had at least one OAD titration, with a total of 76,990 pairs of HbA1c values associated with an OAD titration. There were a total of 206 unique OAD titrations. Overall, initiation of OADs resulted in a reduction of HbA1c by 3 to 12 mmol/mol (0.3 to 1.1%), respectively. These results were slightly lower than those reported in clinical trials of 6 to 14 mmol/mol (0.5 to 1.25%). The change of HbA1c levels due to up-titration, down-titration, and discontinuation were −1 to −8 mmol/mol (−0.1 to −0.7%), +1 to 7 mmol/mol (+0.1 to +0.6%), and +2 to 11 mmol/mol (+0.2 to +1.0%), respectively. The HbA1c lowering effect of initiating newer OADs, namely DPP-4 inhibitors and SGLT-2 inhibitors was 8 to 11 mmol/mol (0.7 to 0.9%) and 7 to 11 mmol/mol (0.6 to 1.0%), respectively.ConclusionThe real-world data on Asians with T2DM in this study show that the magnitudes of OAD initiation and dose titration are marginally lower than the results from clinical trials. During shared decision-making in selecting treatment options, the results enable physicians to communicate realistic expectation of the effect of oral medications on the glycemic control of their patients in primary care.

Moyamoya Disease Associated with Hyperhomocysteinemia: A Rare Cause of Stroke in Sub-Saharan Africa

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by progressive bilateral occlusion of the supraclinoid internal carotid artery (ICA) and its main branches, associated with the development of fine collateral networks, especially adjacent to the site of occlusion in the deep areas of the brain. MMD frequently occurs in East Asian populations, including pediatric and adult patients, and may lead to ischemic or hemorrhagic stroke, headache, epilepsy or transient ischemic attack. The majority is presumed to be of genetic origin and few cases of thrombophilia have been reported in MMD. We report a case of MMD in a young sub-Saharan African woman associated with Hyperhomocysteninemia (HHCys). Observation: A 33-year-old female was seen for aphasia, which had suddenly appeared fourteen days before, and was associated with memory impairment. She mentioned chronic headaches during the 10 previous years, of frontal seat, without migraine criteria. She had no history of hypertension, no obesity, no known dyslipidemia, and there was no family history of stroke. Neurological examination noted Wernicke’s aphasia, with discreet right central facial palsy, associated with memory impairment. The brain MRI revealed semi recent infarct in the left parietal lobe, sequelae in the left temporo-occipital and right frontal with lacunar ischemic lesions, associated with several foci of sub- cortical demyelination. MRA showed stenosis of the supraclinoid carotid arteries and their division branches. In addition, there was a stenosis of the posterior cerebral arteries, with a network of anastomosis at the level of the base of the skull. An investigation of thrombophilia showed hyperhomocysteinemia (HHCys). The diagnosis of moyamoya disease associated with hyperhomocysteinemia was mentioned. She was treated by Aspirin combined to folic acid. After a 3-year setback the patient was asymptomatic. Conclusion: MMD is a rare cause of stroke in sub-Saharan Africa. MRA should be performed whenever possible, as well as investigation for thrombophilia when it’s available. Combined antiplatelet agent with folic acid for ischemic stroke prevention is effective.

Sildenafil for adult Asian patients with pulmonary arterial hypertension: a systematic review and meta-analysis.

The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was beneficial, but the dose varies greatly. In this study, we aimed to evaluate the safety and effectiveness of sildenafil [dose: 20 mg/three times a day (TID)] for adult Asian PAH patients. Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane Library, CBM, CNKI, and Wanfang Data) were searched from their inception to January 2022. We recruited all randomized controlled trials and non-randomized studies of interventions that compared sildenafil (20 mg/TID) versus placebo or symptomatic treatment for adult Asian PAH patients. A total of 10 studies involving 480 participants were included. Compared to symptomatic treatment, sildenafil-treated patients were more likely to walk 57.68 meters further in six-minute walk distance [mean difference (MD) =57.68 m, 95% confidence interval (CI): 41.55 to 73.81], achieve an improvement in systemic arterial oxygen saturation (MD =2.48%, 95% CI: 1.26 to 3.71), and increase the score of the Borg scale for dyspnea (MD =-0.99 points, 95% CI: -1.45 to -0.53). The total number of patients with World Health Organization class III and IV also exhibited a downtrend. Compared to the placebo, sildenafil was associated with a reduction in the mean pulmonary artery pressure (MD =-4.13 mmHg, 95% CI: -6.52 to -1.74) and the level of brain natriuretic peptide (MD =-86.16 pg/mL, 95% CI: -103.39 to -68.93). The most common adverse events were headache, flushing, dyspepsia, and diarrhea, which were relatively mild. Sildenafil at a dose of 20 mg/TID is well tolerated in adult Asian PAH patients, and is associated with statistically significant improvements in exercise capacity, cardio-pulmonary function, and haemodynamic indices. The long-term prognosis still needs to be evaluated and confirmed by further trials.

Integrated care teams in primary care improve clinical outcomes and care processes in patients with non-communicable diseases.

Primary care physicians face the increasing burden of managing multimorbidities in an ageing population. Implementing an integrated care team (ICT) with defined roles and accountability to share consultation tasks is an emerging care model to address this issue. This study compared outcomes with ICT versus usual care for patients with multimorbidities in primary care. Data was retrospectively extracted from the electronic medical records (EMRs) of consecutive adult Asian patients empanelled to ICT and those in UC at a typical primary care clinic (polyclinic) in eastern Singapore in 2018. The study population had hypertension, and/or hyperlipidaemia and/or type 2 diabetes mellitus (T2DM). Clinical outcomes included the proportion of patients (ICT vs. UC) who attained their treatment goals after 12 months. Process outcomes included the proportion of patients who completed annual diabetic eye and foot screenings, where applicable. Data from 3,302 EMRs (ICT = 1,723, UC = 1,579) from January 2016 to September 2017 was analysed. The ICT cohort was more likely to achieve treatment goals for systolic blood pressure (SBP) (adjusted odds ratio [AOR] = 1.52, 95% confidence interval [CI] = 1.38-1.68), low-density lipoprotein cholesterol (AOR = 1.72, 95% CI = 1.49-1.99), and glycated haemoglobin (AOR = 1.28, 95% CI = 1.09-1.51). The ICT group had higher uptake of diabetic retinal screening (89.1% vs. 83.0%, P < 0.001) and foot screening (85.2% vs. 77.9%, P < 0.001). The ICT model yielded better clinical and process outcomes than UC, with more patients attaining treatment goals.

Intensive Immunosupressive Therapy Combining with Eltrombopag for Adult Chinese Patients with Severe Aplastic Anemia

In sight of different pharmacokinetics between races, the recommended dose is 75mg/d for Asian using eltrombopag [1]. However, the efficacy and safety of antithymocyte immunoglobulin (ATG) and cyclosporin A (CsA) with eltrombopag are still largely unknown for adult Asian patients with severe aplastic anemia (SAA).From May 2014 to March 2021, 121 Chinese adult patients with SAA were treated with IST (r-ATG, 3.5mg/kg/d × 5d and CsA 3-5 mg/kg/d) or in conjunction with eltrombopag (75mg/d, from day 1 to 6 months) prospectively and non-randomly. The adverse events (≥3 grades) referring to Common Terminology Criteria for Adverse Events version (CTCAE) 5.0 within 6 months.In pretreatment evaluation of clinical and laboratory characteristics. Median age (39 years and 40 years) was comparable. The complete blood count with differential and quantification of CD4/CD8 T-cell subsets were similar in both groups, but median time from diagnosis to treatment (16 d and 28 d, P=0.038) was different significantly (Table 1).The Chi-Squared test was used to compare the efficacy. The overall response rates (ORR) of IST alone or in combination with eltrombopag in the 1st, 3rd, 6th and 12th month after IST were 12% vs 35% (P=0.002), 44% vs 64% (P=0.028), 61% vs 85% (P=0.006) and 73% vs 91% (P=0.031), respectively. The complete response (CR) rates in the 3rd, 6th and 12th month after IST are 7% vs 17% (P=0.069), 14% vs 27% (P=0.11) and 33% vs 32% (P=0.92) (Table 2).We analyzed factors associated with the efficacy at 6 months by the Binary-Logistic regression model. Elements would be listed in multivariate analysis whether the factors might impact on the efficacy or had P value lower than 0.2 in univariate analysis. It was suggested that ORR was significantly related with the use of eltrombopag (P=0.011, OR=3.600, 95%CI 1.345-9.638) (Table 3).The overall survival (OS) and factors related to survival were analyzed by Kaplan-Meier method and Cox regression model. The OS in IST combined with eltrombopag group was 98% compared to 88% for IST alone (P=0.078). No significant intergroup differences were noted in multivariate analysis of OS.The nonhematologic adverse events (≥3 grades) were infrequent, occurring in 16% patients. 8 in IST plus E-PAG cohort and 11 in IST alone cohort (15% vs 16%, P=0.80). Hepatic injury was prevalent complication (6% vs 8%, P=0.96), relatively. But none showed significant difference between two groups.DiscussionIt has been reported that eltropopag promoted the response of megakaryocytic or even three lineages in refractory SAA [2]. The 6th month CR rate and ORR of our study are lower than the results of Townsley's research with 35% and 94% in the cohort of IST plus eltrombopag [1]. But the CR rate ORR is comparable to De Latour's results with 21.9% and 59.4% in the 3rd month [3]. Median age and dosage of eltrombopag needs to be considered with caution between different researchs, whist the efficacy of horse ATG (hATG) and rATG remained a subject of some debate [4]. Townsley et al. had reported that hepatic impairment (≥3 grades) was 18% [1], but our research showed lower rate of liver impairment with 6%. We should increase the sample volume to analyze the adverse events.Reference[1] Townsley DM, et al. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia [J]. N Engl J Med, 2017, 376 (16): 1540-1550.[2] Desmond R, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug [J]. Blood, 2014, 123 (12): 1818-1825.[3] De Latour, RP, et al. Results of the EBMT SAAWP Phase III Prospective Randomized Multicenter RACE Study of Horse ATG and Ciclosporin with or without Eltrombopag in naive SAA patients. EBMT 2020 abstract O018.[4] Vallejo, C., et al., Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis. Annals of Hematology, 2015. 94(6): p. 947-954. [Display omitted] DisclosuresHe: F. Hoffmann-La Roche Ltd.: Consultancy; LongBio Pharma: Consultancy, Research Funding.

Segmental Maxillomandibular Rotational Advancement (SMMRA) in the Treatment of Adult Patients with Severe Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) occurs as an increased collapsibility of the upper airway during sleep, which threatens health and quality of life. Asian men with greater severity of OSA presents less obese and are connected with craniofacial abnormalities. Although the traditional maxillomandibular advancement (MMA) had the comparable effectiveness to the continuous positive airway pressure therapy, the midfacial esthetics might be compromised in Asian individuals. The modified MMA procedure was proposed to balance the esthetic demands and improvement of OSA symptoms. The case report showed a 25-year-old man presented with a diagnosis of severe OSA. The pretreatment Apnea Hypopnea Index (AHI) score was 100 events/h. He exhibited skeletal Class II hyperdivergent facial pattern with mandibular retrognathism. To correct dentofacial deformities and improve sleep function, the modified surgical-orthodontic procedure was undertaken. The surgery-first approach was adopted for early improvement of OSA. The surgical procedures of SMMRA comprise the maxillary LeFort I segmental osteotomy, bilateral sagittal split osteotomy and genioglossus-genioplasty osteotomy. The counterclockwise rotation of maxillomandibular complex was further done to maximize mandibular advancement. The total treatment duration was 13 months. The well-aligned dentitions and solid dental occlusion were achieved. The subjective perception of sleep quality was improved. The patient was satisfied with the post-treatment facial appearance. Following the skeletal movement, the dimension of pharyngeal airway space was increased. The post-treatment AHI score was reduced to 12.1 events/h; the nadir oxygen saturation increased from 74% to 86%. The case report demonstrated the SMMRA procedure effectively improved adult Asian patients with severe OSA without deterioration of facial attractiveness and dental occlusion.