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Structural proteins of Getah virus isolates from Japan and Malaysia

Srivastava AK, Igarashi A

Acta Virol., 1986 Mar;30(2):126-30.
PMID: 2873729

Purified preparations of Getah virus strains have been analysed by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE) to reveal their structural proteins. Two envelope proteins (E1 and E2) and core protein (C) were found with the prototype AMM2021 strain both under reducing and nonreducing conditions, while separation of E1 and E2 was observed only under nonreducing conditions for 3 strains isolated in Japan. Limited digestion by Staphylococcus aureus V8 protease revealed difference in the peptide patterns of E1 between AMM2021 and Japanese isolates. Mobility of E1 and E2 was slower for the virus grown in BHK21 cells compared with the virus grown in Aedes albopictus cells, indicating host-controlled modification on the envelope glycoproteins.
Management of haemophilia in the developing world

Srivastava A, Chuansumrit A, Chandy M, Duraiswamy G, Karagus C

Haemophilia, 1998 Jul;4(4):474-80.
PMID: 9873777

The problems with management of haemophilia in developing countries are poor awareness, inadequate diagnostic facilities and scarce factor concentrates for therapy. The priorities in establishing services for haemophilia include training care providers, setting up care centres, initiating a registry, educating affected people and their families about the condition, providing low-cost factor concentrates, improving social awareness and developing a comprehensive care team. A coagulation laboratory capable of reliably performing clotting times with correction studies using normal pooled, FVIII and FIX deficient patient plasma and factor assay is most essential for diagnosis. More advanced centralized laboratories are also needed. Molecular biology techniques for mutation detection and gene tracking should be established in each country for accurate carrier detection and antenatal diagnosis. Different models of haemophilia care exists. In India, there is no support from the government. Services, including import of factor concentrates, are organized by the Haemophilia Federation of India, with support from other institutions. Haemophilia is managed with minimal replacement therapy (about 2000 i.u./PWH/year). In Malaysia, where the system is fully supported by the government, facilities are available at all public hospitals and moderate levels of factor concentrates are available 'on-demand' (about 11,000 i.u./PWH/year) at the hospitals. Haemophilia care in South Africa is provided through major public hospitals. Intermediate purity factor concentrates are locally produced (about 12,000 i.u./PWH/year) at low cost. The combined experience in the developing world in providing haemophilia services should be used to define standards for care and set achievable goals.
Animacy-Based Accessibility and Competition in Relative Clause Production in Hindi and Malayalam

Perera CK, Srivastava AK

J Psycholinguist Res, 2016 Aug;45(4):915-30.
PMID: 26108301 DOI: 10.1007/s10936-015-9384-0

Two studies investigated interaction of animacy-based accessibility and competition processes with language specific constraints in shaping production preferences. Relative clause elicitation tasks (Gennari et al. in Cogn Psychol 65:141-176, 2012) were performed by two groups with 40 participants in each. Significantly more passives were produced with animate question/focus and assigned subject function to them in Malayalam, while the difference was insignificant in Hindi with animacy not equating with grammatical function assignment. Both languages produced active objects with OSV order significantly more with animate question/focus. This indicates animacy effect on word order. Animacy also influenced the expression of the agent phase in both languages as a tendency was found to omit the agent by-phase or to delay its appearance, when the two animate nouns entering into the structure are highly similar. The results point to language specific constraints in relative clause production and variability in the role of animacy-based retrieval order across languages.
Fulltext Dendrimer entrapped microsponge gel of dithranol for effective topical treatment

Tripathi PK, Gorain B, Choudhury H, Srivastava A, Kesharwani P

Heliyon, 2019 Mar;5(3):e01343.
PMID: 30957038 DOI: 10.1016/j.heliyon.2019.e01343

Dithranol is one of the important topical agents for the treatment of psoriasis, a chronic inflammatory skin disease with aberrant differentiation of keratinocytes. However, its application is troublesome and inconvenient because of its associated side effects, including staining, burning sensation, irritation, and necrotizing effect on the diseased cells as well as on the normal cells. The purpose of the current investigation was to explore the potential of poly(amido) amine (PAMAM) dendrimers in the topical delivery of dithranol through a novel microsponge based gel. Generation-4 (G4) dendrimers were incorporated into the microsponge based gel formulation by quasi-emulsion solvent diffusion method with varying concentration of polymers, and evaluated for the morphology of the formulation, encapsulation efficiency and skin irritation potential. Percentage yield of the formulation was found to be 66.28%, whereas encapsulation efficiency was ranged between 71.33% to 49.21%, and an average particle size was ranged between 28 ± 1.12 μm to 130 ± 1.01 μm. Surface morphology of developed microsponge was confirmed by scanning electron microscopy, revealed micro-porous nature. The optimized microsponge formulation was found to be stable and recorded non-irritant during cutaneous application of the experimental animals. Further, the pharmacokinetic outcomes of study were showed prolong penetration of the drug through the skin, equivalent to the marketed formulation of dithranol. Therefore, it could be conferred that the microsponge formulation of the PAMAM entrapped dithranol can produce prolonged efficacy without producing toxicities to the skin, and thus can effectively be projected in the treatment of diseases like psoriasis.
Hemophilia treatment in developing countries: products and protocols

Srivastava A, You SK, Ayob Y, Chuansumrit A, de Bosch N, Perez Bianco R, et al.

Semin Thromb Hemost, 2005 Nov;31(5):495-500.
PMID: 16276456

The most important aspect of management of hemophilia is to provide adequate replacement of safe clotting factor concentrates to prevent or treat bleeding episodes. There has been considerable progress in many countries in the developing world with regard to this aspect of care. However, very little data are available in the literature on the types of products being used for factor replacement and the doses being administered for control or treatment of bleeding in different countries. These data are important to document because only then can data from different centers be compared. This article provides data from seven countries: Korea, Malaysia, Thailand, Venezuela, Argentina, Iran, and India. It shows that there is wide variability not only in the types of products used (plasma to recombinant factor concentrates) but also in the doses administered (minimal to very high) for similar indications. Prospective documentation of data on musculoskeletal outcome at these centers and correlation with dose of factor replacement could help identify different models of care. Comparing such data and collating the experience in different countries could be useful for optimizing care and establishing cost-effective models. The combined experience in the developing world in providing hemophilia services should be used to define standards of care that are practical and to set achievable goals.
Randomized comparison of W.A.R.A. (Wiring Affect with ReAttach) versus distraction: A pilot study assessing the efficacy of an ultrafast transdiagnostic intervention

Weerkamp-Bartholomeus P, Marazziti D, Chan E, Srivastava A, van Amelsvoort T

Heliyon, 2020 Aug;6(8):e04660.
PMID: 32802985 DOI: 10.1016/j.heliyon.2020.e04660

Background: Generally, neuropsychiatric patients share different symptoms across nosological categories, such as, amongst other, psychological distress, mood alterations, anxiety, and self-regulation disturbances.ReAttach is a novel psychological intervention with its key elements being external affect and arousal regulation, stimulation of multiple sensory processing, conceptualization, affective mentalization, and associative memory processing. ReAttach has been hypothesized to be effective in reducing symptom severity in different psychiatric conditions. Given the limited information currently available, the present study aimed to investigate the effect of main ReAttach elements called "Wiring Affect with ReAttach" (W.A.R.A.) on negative affect (N.A.), and to compare it with "Distraction," another well-established affect-regulating strategy.
Methods: We used a single-blind, randomized controlled crossover equivalence design to compare the efficacy on N.A. regulation of W.A.R.A. versus Distraction in 101 patients with different neuropsychiatric disorders.
Results: The results showed a significant difference (p < 0.001) in response to W.A.R.A. vs. Distraction, with W.A.R.A. being significantly more effective in regulating N.A., with a large effect size (dRMpooled = 2.38) and a high probability (95%) of success.
Limitations: The heterogeneity of the study population makes generalization and clear recommendations for specific patient groups difficult. The Numeric Rating Scale might have prevented detection of increased N.A. when the baseline scores were high. More in-depth research is needed to explore the W.A.R.A. technique and the extent of confounding variables such as the placebo effect.
Conclusions: The findings suggest that W.A.R.A. may be an effective, accessible, and brief intervention reducing negative affect. Although premature, these first results are encouraging.
Fulltext Impact of a training program on disaster preparedness among paramedic students of a tertiary care hospital of North India: A single-group, before-after intervention study

Bhattacharya S, Singh A, Semwal J, Marzo RR, Sharma N, Goyal M, et al.

J Educ Health Promot, 2020;9:5.
PMID: 32154300 DOI: 10.4103/jehp.jehp_423_19

INTRODUCTION: Disaster can occur at any time any place. Disaster preparedness plays an important role to reduce the loss of a community/country. The aim of this interventional study was to ascertain the impact of a video-based educational intervention program on improvement in knowledge and attitude of paramedical students in a hospital.
MATERIALS AND METHODS: A pre-post study (interventional study design) was conducted on paramedic students. Our study period was 6 months which was divided into Phases I, II, and III. For administrative purpose, we included all paramedical students, and our sample size was 119. The baseline assessment of knowledge and attitude of paramedic students was done by a pretested questionnaire (Observation 1) with having a baseline scoring. After that, intervention Phase 1 was implemented, and later, end line observation (Observation 2) was made. Changes in knowledge and attitude were observed by the score difference (Observation 2-Observation 1). Descriptive statistics were calculated, and the mean of cumulative score was compared using the Wilcoxon signed-rank test. We applied Mann-Whitney U-test for finding associations between dependent variables with an independent variable using SPSS version 22 (IBM, Chicago, USA) software.
RESULTS: Our baseline results showed that most of our participants had average knowledge (54.6%), followed by poor knowledge (24.4%). Approximately one-fifth (21.0%) of the participants had good knowledge regarding disaster preparedness. A significant improvement was observed in cumulative score (P < 0.005). A significant difference was observed in knowledge and attitude with respect to age and courses (P < 0.05). Forty percent of the students responded that they would like to get trained by that mock drill, and 26.1% were interested in disaster preparedness workshops in the future.
CONCLUSION: Our present study results indicate that the overall knowledge and attitude level of the students was average and required improvement. A similar result was reported in some studies conducted globally for the same purpose. All of our students perceived that training for disaster preparedness is necessary for all health facilities, and it is important to have an emergency plan and disaster management committee. Regarding training methods, most of our students liked our interactive audiovisual method. However, their preferred methods were mock drill and workshops. It can be arranged in the future for them.
Fulltext Improving PM2.5 prediction in New Delhi using a hybrid extreme learning machine coupled with snake optimization algorithm

Masood A, Hameed MM, Srivastava A, Pham QB, Ahmad K, Razali SFM, et al.

Sci Rep, 2023 Nov 29;13(1):21057.
PMID: 38030733 DOI: 10.1038/s41598-023-47492-z

Fine particulate matter (PM2.5) is a significant air pollutant that drives the most chronic health problems and premature mortality in big metropolitans such as Delhi. In such a context, accurate prediction of PM2.5 concentration is critical for raising public awareness, allowing sensitive populations to plan ahead, and providing governments with information for public health alerts. This study applies a novel hybridization of extreme learning machine (ELM) with a snake optimization algorithm called the ELM-SO model to forecast PM2.5 concentrations. The model has been developed on air quality inputs and meteorological parameters. Furthermore, the ELM-SO hybrid model is compared with individual machine learning models, such as Support Vector Regression (SVR), Random Forest (RF), Extreme Learning Machines (ELM), Gradient Boosting Regressor (GBR), XGBoost, and a deep learning model known as Long Short-Term Memory networks (LSTM), in forecasting PM2.5 concentrations. The study results suggested that ELM-SO exhibited the highest level of predictive performance among the five models, with a testing value of squared correlation coefficient (R2) of 0.928, and root mean square error of 30.325 µg/m3. The study's findings suggest that the ELM-SO technique is a valuable tool for accurately forecasting PM2.5 concentrations and could help advance the field of air quality forecasting. By developing state-of-the-art air pollution prediction models that incorporate ELM-SO, it may be possible to understand better and anticipate the effects of air pollution on human health and the environment.
Fulltext Narrative Review of the Evolution of COVID-19 Vaccination Recommendations in Countries in Latin America, Africa and the Middle East, and Asia

Spinardi J, Dantas AC, Carballo C, Thakkar K, Akoury NA, Kyaw MH, et al.

Infect Dis Ther, 2023 May;12(5):1237-1264.
PMID: 37097556 DOI: 10.1007/s40121-023-00804-2

The rapid rollout of vaccines to combat the coronavirus disease 2019 (COVID-19) pandemic over the past 2 years has resulted in the use of various vaccine platforms and regional differences in COVID-19 vaccine implementation strategies. The aim of this narrative review was to summarize evolving COVID-19 vaccine recommendations in countries in Latin America, Asia, and Africa and the Middle East across various vaccine platforms, age groups, and specific subpopulations. Nuances in primary and booster vaccination schedules were evaluated, and the preliminary impact of such diverse vaccination strategies are discussed, including key vaccine effectiveness data in the era of Omicron-lineage variants. Primary vaccination rates for included Latin American countries were 71-94% for adults and between 41% and 98% for adolescents and children; rates for first booster in adults were 36-85%. Primary vaccination rates for adults in the included Asian countries ranged from 64% in the Philippines to 98% in Malaysia, with corresponding booster rates varying from 9% in India to 78% in Singapore; for adolescents and children, primary vaccination rates ranged from 29% in the Philippines to 93% in Malaysia. Across included African and Middle Eastern countries, primary vaccination rates in adults varied widely from 32% in South Africa to 99% in the United Arab Emirates; booster rates ranged from 5% in South Africa to 60% in Bahrain. Evidence from the regions studied indicates preference of using an mRNA vaccine as a booster on the basis of safety and effectiveness of observed real-world data, especially during circulation of Omicron lineages. Vaccination against COVID-19 remains of paramount importance to reduce the burden of disease; strategies to overcome vaccine inequity, fatigue, hesitancy, and misinformation and to ensure adequate access and supply are also important.
Management and monitoring of pediatric inflammatory bowel disease in the Asia-Pacific region: A position paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group: Surgical management, disease monitoring, and special considerations

Lee WS, Arai K, Alex G, Treepongkaruna S, Kim KM, Choong CL, et al.

J Gastroenterol Hepatol, 2023 Apr;38(4):510-522.
PMID: 36508314 DOI: 10.1111/jgh.16084

Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia-Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia-Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia-Pacific region.
Optimizing hybrid vigor: a comprehensive analysis of genetic distance and heterosis in eggplant landraces

Rajan N, Debnath S, Perveen K, Khan F, Pandey B, Srivastava A, et al.

Front Plant Sci, 2023;14:1238870.
PMID: 37719210 DOI: 10.3389/fpls.2023.1238870

INTRODUCTION: This study explored the molecular characterization of 14 eggplant (brinjal) genotypes to evaluate their genetic diversity and the impact of heterosis. As eggplant is a vital horticultural crop with substantial economic and nutritional value, a comprehensive understanding of its genetic makeup and heterosis effects is essential for effective breeding strategies. Our aim was not only to dissect the genetic diversity among these genotypes but also to determine how genetic distance impacts heterotic patterns, which could ultimately help improve hybrid breeding programs.
METHODS: Genetic diversity was assessed using 20 SSR markers, and the parental lines were grouped into five clusters based on the Unweighted Pair Group Method of Arithmetic Means (UPGMA). Heterosis was examined through yield and yield-related traits among parents and hybrids.
RESULTS: Polymorphisms were detected in eight out of the twenty SSR markers across the parental lines. Notably, a high genetic distance was observed between some parents. The analysis of yield and yield-related traits demonstrated significant heterosis over mid, superior, and standard parents, particularly in fruit yield per plant. Two crosses (RKML-26 X PPC and RKML1 X PPC) displayed substantial heterosis over mid and better parents, respectively. However, the positive correlation between genetic distance and heterosis was only up to a certain threshold; moderate genetic distance often resulted in higher heterosis compared to very high genetic distance.
DISCUSSION: These findings emphasize the critical role of parental selection in hybrid breeding programs. The results contribute to the understanding of the relationship between genetic distance and heterosis, and it is suggested that future research should delve into the genetic mechanisms that drive heterosis and the effect of genetic distance variance on heterosis. The insights drawn from this study can be harnessed to enhance crop yield and economic value in breeding programs.
Fulltext Challenges in Global Access to CAR-T cells: an Asian Perspective

Hwang WY, Takahashi S, Choi B, Huang H, Kawamata S, Ng SC, et al.

Blood Cell Ther, 2024 Feb 25;7(1):10-13.
PMID: 38486827 DOI: 10.31547/bct-2023-023

The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.
Fulltext Comparison of Non-Operative Mesotherapy and Surgery in the Management of Superficial Lipomas

Kataria K, Venkatesh M, Chumber S, Rathore Y, Srivastava A, Dhar A, et al.

Malays J Med Sci, 2021 Feb;28(1):51-58.
PMID: 33679220 DOI: 10.21315/mjms2021.28.1.7

Background: Lipomas are benign adipocytic tumours. Surgical excision is the gold standard for treating such lipomas, but it results in unaesthetic scarring.
Methods: A total of 126 patients were randomised into two groups. The patients in Group A underwent mesotherapy (n = 66) and those in Group B underwent surgery (n = 60). The patients in Group A group received six sessions of mesotherapy treatment at 2-week intervals. Both groups were followed up for 12 weeks, during which they were assessed for complications arising from treatment, reduction of the size of the lipoma and cosmetic outcomes.
Results: The overall mean age of the patients was 32.93 (± 10.1) years old and the mean volume of the lipomas was 2.29 (± 3.8) mL. A 55.86% (P = 0.0032) mean reduction in the volume of lipomas was noted in the patients who received mesotherapy, while one patient showed a gain of 16% by volume. The patients in Group A (cosmetic score ≥ 4: 63%) were happier with the treatment than those in Group B (cosmetic score ≥ 4: 21%).
Conclusion: Our findings indicate that mesotherapy modestly reduces the volume of lipomas with very few and minor complications and excellent cosmetic outcomes.
Smart Adsorbents for Aquatic Environmental Remediation

Nazarzadeh Zare E, Mudhoo A, Ali Khan M, Otero M, Bundhoo ZMA, Patel M, et al.

Small, 2021 Aug;17(34):e2007840.
PMID: 33899324 DOI: 10.1002/smll.202007840

A noticeable interest and steady rise in research studies reporting the design and assessment of smart adsorbents for sequestering aqueous metal ions and xenobiotics has occurred in the last decade. This motivates compiling and reviewing the characteristics, potentials, and performances of this new adsorbent generation's metal ion and xenobiotics sequestration. Herein, stimuli-responsive adsorbents that respond to its media (as internal triggers; e.g., pH and temperature) or external triggers (e.g., magnetic field and light) are highlighted. Readers are then introduced to selective adsorbents that selectively capture materials of interest. This is followed by a discussion of self-healing and self-cleaning adsorbents. Finally, the review ends with research gaps in material designs.
Valorization of renewable resources to functional oligosaccharides: Recent trends and future prospective

Narisetty V, Parhi P, Mohan B, Hakkim Hazeena S, Naresh Kumar A, Gullón B, et al.

Bioresour Technol, 2022 Feb;346:126590.
PMID: 34953996 DOI: 10.1016/j.biortech.2021.126590

Lignocellulosic wastes have the ability to be transformed into oligosaccharides and other value-added products. The synthesis of oligosaccharides from renewable sources bestow to growing bioeconomies. Oligosaccharides are synthesized chemically or biologically from agricultural residues. These oligosaccharides are functional food supplements that have a positive impact on humans and livestock. Non-digestible oligosaccharides, refered as prebiotics are beneficial for the colonic microbiota inhabiting the f the digestive system. These microbiota plays a crucial role in stimulating the host immune system and other physiological responses. The commonly known prebiotics, galactooligosaccharides (GOS), xylooligosaccharides (XOS), fructooligosaccharides (FOS), mannanooligosaccharides (MOS), and isomaltooligosaccharides (IOS) are synthesized either through enzymatic or whole cell-mediated approaches using natural or agricultural waste substrates. This review focusses on recent advancements in biological processes, for the synthesis of oligosaccharides using renewable resources (lignocellulosic substrates) for sustainable circular bioeconomy. The work also addresses the limitations associated with the processes and commercialization of the products.
Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial

Young G, Srivastava A, Kavakli K, Ross C, Sathar J, You CW, et al.

Lancet, 2023 Mar 29.
PMID: 37003287 DOI: 10.1016/S0140-6736(23)00284-2

BACKGROUND: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors.
METHODS: This multicentre, randomised, open-label phase 3 study was done at 26 sites (primarily secondary or tertiary centres) in 12 countries. Men, boys, and young adults aged 12 years or older with severe haemophilia A or haemophilia B with inhibitors previously treated with on-demand bypassing agents were randomly assigned (2:1) to receive once-a-month 80 mg subcutaneous fitusiran prophylaxis (fitusiran prophylaxis group) or to continue with bypassing agents on-demand (bypassing agents on-demand group) for 9 months. The primary endpoint was mean annualised bleeding rate during the efficacy period in the intention-to-treat population estimated by negative binomial model. Safety was assessed as a secondary endpoint in the safety population. This trial is complete and is registered with ClinicalTrials.gov, NCT03417102.
FINDINGS: Between Feb 14, 2018, and June 23, 2021, 85 participants were screened for inclusion, of whom 57 (67%; 57 [100%] men; median age 27·0 years [IQR 19·5-33·5]) were randomly assigned: 19 (33%) participants to the bypassing agent on-demand group and 38 (67%) participants to the fitusiran prophylaxis. Negative binomial model-based mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (1·7 [95% CI 1·0-2·7]) than in the bypassing agents on-demand group (18·1 [10·6-30·8]), corresponding to a 90·8% (95% CI 80·8-95·6) reduction in annualised bleeding rate in favour of fitusiran prophylaxis (p<0·0001). 25 (66%) participants had zero treated bleeds in the fitusiran prophylaxis group versus one (5%) in the bypassing agents on-demand group. The most frequent treatment-emergent adverse event in the fitusiran prophylaxis group was increased alanine aminotransferase in 13 (32%) of 41 participants in the safety population; there were no increased alanine aminotransferase treatment-emergent adverse events in the bypassing agents on-demand group. Suspected or confirmed thromboembolic events were reported in two (5%) participants in the fitusiran prophylaxis group. No deaths were reported.
INTERPRETATION: Subcutaneous fitusiran prophylaxis resulted in statistically significant reductions in annualised bleeding rate in participants with haemophilia A or haemophilia B with inhibitors, with two-thirds of participants having zero bleeds. Fitusiran prophylaxis might show haemostatic efficacy in participants with haemophilia A or haemophilia B with inhibitors; therefore, the therapeutic might have the potential to improve the management of people with haemophilia.
FUNDING: Sanofi.
Fulltext Incidence and outcome of SARS-CoV-2 reinfection in the pre-Omicron era: A global systematic review and meta-analysis

Ismail NF, Rahman AE, Kulkarni D, Zhu F, Wang X, Del Carmen Morales G, et al.

J Glob Health, 2023 Nov 24;13:06051.
PMID: 37994839 DOI: 10.7189/jogh.13.06051

BACKGROUND: With the emergence of new variants and sub-lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reinfections can significantly impact herd immunity, vaccination policies, and decisions on other public health measures. We conducted a systematic review and meta-analysis to synthesise the global evidence on SARS-CoV-2 reinfections in the pre-Omicron era.
METHODS: We searched five global databases (MEDLINE, Embase, CINAHL Plus, Global Health, WHO COVID-19) on 12 May 2022 and 28 July 2023 and three Chinese databases (CNKI, Wanfang, CQvip) on 16 October 2022 for articles reporting incidence and outcomes of SARS-CoV-2 reinfection before the period of Omicron (B.1.1.529) predominance. We assessed risk of bias using Joanna Briggs Institute critical appraisal tools and conducted meta-analyses with random effects models to estimate the proportion of SARS-CoV-2 reinfection among initially infected cases and hospitalisation and mortality proportions among reinfected ones.
RESULTS: We identified 7593 studies and extracted data from 64 included ones representing 21 countries. The proportion of SARS-CoV-2 reinfection was 1.16% (95% confidence interval (CI) = 1.01-1.33) based on 11 639 247 initially infected cases, with ≥45 days between the two infections. Healthcare providers (2.28%; 95% CI = 1.37-3.40) had a significantly higher risk of reinfection than the general population (1.00%; 95% CI = 0.81-1.20), while young adults aged 18 to 35 years (1.01%; 95% CI = 0.8-1.25) had a higher reinfection burden than other age groups (children <18 years old: 0.57%; 95% CI = 0.39-0.79, older adults aged 36-65 years old: 0.53%; 95% CI = 0.41-0.65, elderly >65 years old: 0.37%; 95% CI = 0.15-0.66). Among the reinfected cases, 8.12% (95% CI = 5.30-11.39) were hospitalised, 1.31% (95% CI = 0.29-2.83) were admitted to the intensive care unit, and 0.71% (95% CI = 0.02-2.01) died.
CONCLUSIONS: Our data suggest a relatively low risk of SARS-CoV-2 reinfection in the pre-Omicron era, but the risk of hospitalisation was relatively high among the reinfected cases. Considering the possibility of underdiagnosis, the reinfection burden may be underestimated.
REGISTRATION: PROSPERO: CRD42023449712.
Fulltext Epidemiology and clinical features of SARS-CoV-2 infection in children and adolescents in the pre-Omicron era: A global systematic review and meta-analysis

Kulkarni D, Ismail NF, Zhu F, Wang X, Del Carmen Morales G, Srivastava A, et al.

J Glob Health, 2024 Mar 01;14:05003.
PMID: 38419461 DOI: 10.7189/jogh.14.05003

METHODS: We searched MEDLINE, Embase, Global Health, CINAHL, China National Knowledge Infrastructure, Wanfang, CQvip, and the World Health Organization (WHO) COVID-19 global literature databases for primary studies recruiting children aged ≤18 years with a diagnosis of SARS-CoV-2 infection confirmed either by molecular or antigen tests. We used the Joanna Briggs Institute critical appraisal tools to appraise the study quality and conducted meta-analyses using the random effects model for all outcomes except for race/ethnicity as risk factors of SARS-CoV-2 infection.
RESULTS: We included 237 studies, each reporting at least one of the study outcomes. Based on data from 117 studies, the pooled SARS-CoV-2 positivity rate was 9.30% (95% confidence interval (CI) = 7.15-11.73). Having a comorbidity was identified as a risk factor for SARS-CoV-2 infection (risk ratio (RR) = 1.33; 95% CI = 1.04-1.71) based on data from 49 studies. Most cases in this review presented with mild disease (n = 50; 52.47% (95% CI = 44.03-60.84)). However, 20.70% of paediatric SARS-CoV-2 infections were hospitalised (67 studies), 7.19% required oxygen support (57 studies), 4.26% required intensive care (93 studies), and 2.92% required assisted ventilation (63 studies). The case fatality ratio (n = 119) was 0.87% (95% CI = 0.54-1.28), which included in-hospital and out-of-hospital deaths.
CONCLUSIONS: Our data showed that children were at risk for SARS-CoV-2 infections and severe outcomes in the pre-Omicron era. These findings underscore the need for effective vaccination strategies for the paediatric population to protect against the acute and long-term sequelae of COVID-19.
REGISTRATION: PROSPERO: CRD42022327680.
Medical Management of Pediatric Inflammatory Bowel Disease (PIBD) in the Asia Pacific Region: A Position Paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group

Lee WS, Arai K, Alex G, Treepongkaruna S, Kim KM, Choong CL, et al.

J Gastroenterol Hepatol, 2022 Dec 27.
PMID: 36574956 DOI: 10.1111/jgh.16097

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialised and affluent areas in the Asia Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up-to-date, evidence-based approach to PIBD in the Asia Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine-S-methyltransferase (TPMT). The main considerations in the use of biologics in the Asia Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. Conclusion: This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia Pacific region.
Fulltext Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015

Iida M, Kodera Y, Dodds A, Ho AYL, Nivison-Smith I, Akter MR, et al.

Bone Marrow Transplant, 2019 Dec;54(12):1973-1986.
PMID: 31089289 DOI: 10.1038/s41409-019-0554-9

Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center. Between 2005 and 2015, the greatest increase in the number of HSCTs was observed in Vietnam. Allogeneic HSCT was performed more frequently than autologous HSCT, and a majority of cases involved related donors. Regarding allogeneic HSCT, the use of cord blood has remained steady, especially in Japan, and the number of cases involving related HLA non-identical donors has increased rapidly, particularly in China. The incidence of hemoglobinopathy, a main indication for allogeneic HSCT in India, China, Iran, and Pakistan, increased nearly six-fold over the last decade. Among the 18 participating countries/regions, the transplant rate per population varied widely according to the absolute number of HSCTs and the national/regional population size. We believe that this report will not only benefit the AP region but will also provide information about HSCT to other regions worldwide.

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