Attitude and concerns of Chinese couples enrolled in the pre-implantation genetic diagnosis program in Hong Kong

Background and Objectives: Pre-implantation Genetic Diagnosis (PGD) is an established alternative to prenatal diagnosis to select genetically disease-free embryos in vitro before they are transferred back to the mother, and it has gained acceptance for couples at risk of passing on monogenic diseases and chromosomal abnormalities around the world. More PGD cycles in conjunction with in vitro fertilization (IVF) have been offered to the Asian couples in Hong Kong who are carriers of genetic diseases or chromosomal abnormalities. This study evaluates the attitude and moral concerns towards PGD of the enrolled couples, and their knowledge of their underlying genetic conditions. Methods: This cross-sectional survey was carried out between June2013 and March 2014. All the couples enrolled in the PGD program at the Queen Mary Hospital were invited to join the study. Total 47 couples and 2 women, whose male partners declined to respond, were recruited. Self-reported structured questionnaires were completed by participating subjects. Statistical analysis was performed to study the attitude and concerns related to different PGD stages, genetic conditions, experience of past pregnancies and sex of the surveyed participants. Results and discussion: Ninety-six completed questionnaires were analysed with 36.5%from the Pre-PGD group, 31.2%from the PGD Treatment group and 32.5% from the Post-PGD group. There was a trend of increase in psychological stress and concerns related to the IVF/PGD related procedures when couples proceeded from the pre-PGD to the post-PGD stage. A good acceptability of PGD related procedures and similar moral value about the embryo fate, comparable to overseas studies, were observed, except we had a lower percentage of subjects (25%) who expressed no concern about repeated IVF cycles. The worries about the transfer of carrier embryos were high (33%)among couples who are thalassemia carriers. While 15% of the subjects disagreed with termination of pregnancy for a genetically confirmed abnormal IVF/PGD fetus,18% of the subjects could not decide at the time of the study. So counselling support to the couples when they face the above two difficult situations is important. We also found majority of the subjects (76%) optedto tell their children later about their conception. Support for parents to access counseling advice at their preferred time of disclosure is therefore worth considering. Regarding the knowledge of the couples on their underlying genetic conditions, most subjects (95%)knew their carrier status well. Most subjects (89%) with single gene disorder knew their recurrent risk of having an affected baby but only 32% could tell the inheritance pattern. Estimation of recurrent risk is more difficult for the group with balanced chromosomal translocation. Significance: This first study in Hong Kong on the Chinese couples enrolled in the PGD program highlights the specific concerns of the couples with different underlying genetic conditions at the different stages of PGD. The findings could serve as local reference to guide future studies and the development of PGD counseling services and follow-up for the couples seeking such intervention in the future.published_or_final_versionPaediatrics and Adolescent MedicineMasterMaster of Medical Science

Selective Dorsal Rhizotomy in Hong Kong: Multidimensional Outcome Measures

We prospectively case series study evaluated the short-term effectiveness of selective dorsal rhizotomy plus physiotherapy. Twenty children with spastic cerebral palsy, selected for selective dorsal rhizotomy (mean age, 8.57 years; range, 5.96-11.18 years), were assessed before, and 6 and 12 months after, selective dorsal rhizotomy. Main outcome measures included the Modified Ashworth Scale, passive range of joint movement, the Gross Motor Function Measure, the Pediatric Evaluation of Disability Inventory, the Canadian Occupational Performance Measure, and three-dimensional gait analysis. The results confirmed that selective dorsal rhizotomy plus physiotherapy provided a statistically significant reduction of spasticity, functional improvements in mobility and self-care performance, and increased participation in social situations in our study group (85% exhibited normal intelligence, and 90% belonged to Gross Motor Function Classification System levels I-III). The Gross Motor Function Measure proved to be sensitive in documenting motor functional changes, except for children at Gross Motor Function Classification System level I. Instrumental three-dimensional gait analysis with kinematics and kinetics data analysis confirmed gait improvements in children of higher motor function. The Canadian Occupational Performance Measure indicated improvements in social participation. © 2008 Elsevier Inc. All rights reserved.Link_to_subscribed_fulltex

Hesitancy, reactogenicity and immunogenicity of the mRNA and whole-virus inactivated Covid-19 vaccines in pediatric neuromuscular diseases

The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two widely used COVID-19 vaccines that confer immune protection to healthy individuals. However, hesitancy toward COVID-19 vaccination appeared to be common for patients with neuromuscular diseases (NMDs) due to the paucity of data on the safety and efficacy in this high-risk patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for NMDs and assessed the reactogenicity and immunogenicity of these two vaccines. Patients aged 8–18 years with no cognitive delay were invited to complete surveys in January and April 2022. Patients aged 2–21 years were enrolled for COVID-19 vaccination between June 2021 and April 2022, and they recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before and within 49 days after vaccination to measure serological antibody responses compared to healthy children and adolescents. Forty-one patients completed vaccine hesitancy surveys for both timepoints, while 22 joined the reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81–75.1, p = .010). Pain at the injection site, fatigue, and myalgia were the commonest ARs. Most ARs were mild (75.5%, n = 71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of either vaccine, similar to 280 healthy counterparts. There was lower neutralization against the Omicron BA.1 variant. BNT162b2 and CoronaVac were safe and immunogenic for patients with NMDs, even in those on low-dose corticosteroids

Parental restriction reduces the harmful effects of in-bedroom electronic devices

Objective: To investigate whether school readiness could be affected by placing electronic devices (EDs) in children’s bedroom and whether the relationship was moderated by parental restriction and family socioeconomic status (SES). Design: This is a cross-sectional study with bedroom ED placement and parental restriction reported by parents. Multiple linear regressions were used to test the relationship between school readiness and ED placement. Multiple regression with interaction terms were used to test whether the effect was consistent with and without parental restriction. Setting: Kindergartens randomly selected from two districts of different socioeconomic backgrounds in Hong Kong, China. Patients: 556 young children attending the third year of kindergarten. Main outcome measures: Children’s school readiness was rated by teachers using the Chinese Early Development Instrument. Results: 556 preschoolers (mean age 5.46; 51.8% girls) from 20 kindergartens participated in this study. About 30% of parents placed at least one ED in their children’s bedroom. After controlling for sex and SES, the placement of television in the bedroom was associated with lower overall school readiness (β −1.11, 95% CI −1.80 to −0.42) and the placement of game console was associated with lower social competence (β−0.94, 95% CI −1.74 to −0.15). Such harmful effect was more prominent among lower SES families and could be partially alleviated with parental restriction. Conclusion: ED placement in children’s bedroom was associated with lower school readiness, particularly among lower SES families. Parental restriction might help to alleviate the harm

Neurocognitive function, performance status, and quality of life in pediatric intracranial germ cell tumor survivors

Background: Intracranial germ cell tumors (GCT) are more common in Asia than in the West, accounting for about 15% of brain tumors in Asian children. The survival rate for intracranial GCT is excellent, but there are concerns about the effects of radiotherapy on neuropsychological function and quality of life of patients. Methods: Intracranial germ cell tumors (GCT) are more common in Asia than in the West, accounting for about 15% of brain tumors in Asian children. The survival rate for intracranial GCT is excellent, but there are concerns about the effects of radiotherapy on neuropsychological function and quality of life of patients. Intracranial GCT survivors in Hong Kong aged ≥ 6 years who received cranial irradiation in the past 15 years were recruited. Neurocognitive function and performance status were assessed by the Hong Kong Wechsler Intelligence scale and Karnofsky/Lansky performance scales (KPS), respectively. Quality of life was assessed using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales. A chart review was performed for tumor characteristics and complications related to the tumor and its treatment. Results: Twenty-five intracranial GCT survivors were recruited. Longer length of time since treatment was associated with lower IQ scores. Larger tumor size was associated with lower KPS scores. Hemiparesis, poor manual dexterity, and complications with multi-organ involvement were associated with significantly lower KPS scores. Higher irradiation dosage was associated with lower PedsQL physical scores. Conclusions: The majority of GCT survivors had average intellectual functioning, satisfactory performance status and relatively good quality of life, except in the physical aspect. Comprehensive evaluation and long-term follow-up of GCT survivors are essential to provide timely support and improve long-term outcomes

International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

<p>Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barre syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination.</p><p>Methods: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach.</p><p>Results: We found a relative incidence of GBS of 2.42(95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09(95% CI 1.28-3.42) using the meta-analytic approach.</p><p>Conclusions: This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines. (C) 2013 Elsevier Ltd. All rights reserved.</p>

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

International audienceBACKGROUND Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2: 1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (>= 3 points), an outcome that indicates improvement in at least two motor skills. RESULTS In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P< 0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P< 0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials. gov number, NCT02292537.