Polarised radiative transfer, rotation measure fluctuations and large-scale magnetic fields

Faraday rotation measure at radio wavelengths is commonly used to diagnose large-scale magnetic fields. It is argued that the length-scales on which magnetic fields vary in large-scale diffuse astrophysical media can be inferred from correlations in the observed RM. RM is a variable which can be derived from the polarised radiative transfer equations in restrictive conditions. This paper assesses the usage of RMF (rotation measure fluctuation) analyses for magnetic field diagnostics in the framework of polarised radiative transfer. We use models of various magnetic field configurations and electron density distributions to show how density fluctuations could affect the correlation length of the magnetic fields inferred from the conventional RMF analyses. We caution against interpretations of RMF analyses when a characteristic density is ill-defined, e.g. in cases of log-normal distributed and fractal-like density structures. As the spatial correlations are generally not the same in the line-of-sight longitudinal direction and the sky plane direction, one also needs to clarify the context of RMF when inferring from observational data. In complex situations, a covariant polarised radiative transfer calculation is essential to capture all aspects of radiative and transport processes, which would otherwise ambiguate the interpretations of magnetism in galaxy clusters and larger-scale cosmological structures

Polarized radiative transfer, rotation measure fluctuations, and large-scale magnetic fields

Faraday rotation measure (RM) at radio wavelengths is commonly used to diagnose large-scale magnetic fields. It is argued that the length-scales on which magnetic fields vary in large-scale diffuse astrophysical media can be inferred from correlations in the observed RM. RM is a variable which can be derived from the polarized radiative transfer equations in restrictive conditions. This paper assesses the usage of rotation measure fluctuation (RMF) analyses for magnetic field diagnostics in the framework of polarized radiative transfer. We use models of various magnetic field configurations and electron density distributions to show how density fluctuations could affect the correlation length of the magnetic fields inferred from the conventional RMF analyses. We caution against interpretations of RMF analyses when a characteristic density is ill defined, e.g. in cases of lognormal-distributed and fractal-like density structures. As the spatial correlations are generally not the same in the line-of-sight longitudinal direction and the sky plane direction, one also needs to clarify the context of RMF when inferring from observational data. In complex situations, a covariant polarized radiative transfer calculation is essential to capture all aspects of radiative and transport processes, which would otherwise ambiguate the interpretations of magnetism in galaxy clusters and larger scale cosmological structures

Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice

Background: Assessing pain in infants, children and young people with life-limiting conditions remains a challenge due to diverse patient conditions, types of pain and often a reduced ability or inability of patients to communicate verbally. Aim: To systematically identify pain assessment tools that are currently used in paediatric palliative care and examine their psychometric properties and feasibility and make recommendations for clinical practice. Design: A systematic literature review and evaluation of psychometric properties of pain assessment tools of original peer-reviewed research published from inception of data sources to April 2021. Data sources: PsycINFO via ProQuest, Web of Science Core, Medline via Ovid, EMBASE, BIOSIS and CINAHL were searched from inception to April 2021. Hand searches of reference lists of included studies and relevant reviews were performed. Results: From 1168 articles identified, 201 papers were selected for full-text assessment. Thirty-four articles met the eligibility criteria and we examined the psychometric properties of 22 pain assessment tools. Overall, the Faces Pain Scale-Revised (FPS-R) had high cross-cultural validity, construct validity (hypothesis testing) and responsiveness; while the Faces, Legs, Activity, Cry and Consolability (FLACC) scale and Paediatric Pain Profile (PPP) had high internal consistency, criterion validity, reliability and responsiveness. The number of studies per psychometric property of each pain assessment tool was limited and the methodological quality of included studies was low. Conclusion: Balancing aspects of feasibility and psychometric properties, the FPS-R is recommended for self-assessment, and the FLACC scale/FLACC Revised and PPP are the recommended observational tools in their respective age groups

Associations between prenatal exposure to antipsychotics and attention-deficit/hyperactivity disorder, autism spectrum disorder, preterm birth and small for gestational age: a population-based cohort study

Importance: The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear. / Objective: To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems. / Design, Setting, Participants: This population-based cohort study included children born between 2001–2015 with follow-up to 2019, identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestational-exposed and gestational non-exposed with propensity score fine-stratification. Additional analyses included gestational-exposed versus past-exposed and sibling-matched analysis to evaluate the effect of confounding by indication. / Exposures: Prenatal antipsychotic exposure. Main outcomes and measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. / Results: The cohorts included 333,749 mother-child pairs for ADHD and 411,251 pairs for ASD/preterm birth/small for gestational age analyses. There were 13,196 children (3.95%) diagnosed with ADHD, 8,715 (2.12%) with ASD, 33,891 (8.24%) preterm, and 7,009 (1.70%) small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% confidence interval [CI]=0.83-1.61) for ADHD and 1.06 (95%CI=0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95%CI=1.13-1.75) for preterm birth and 1.36 (95%CI=0.86-2.14) for small for gestational age, when comparing gestational-exposed to gestational non-exposed. Additional analyses showed no association when comparing gestational-exposed to past-exposed (ADHD: wHR=0.99, 95%CI=0.60-1.61); ASD: wHR=1.10, 95%CI=0.58-2.08; preterm birth: wOR=0.93, 95%CI=0.70-1.24; small for gestational age: wOR=1.21, 95%CI=0.66-2.20), and in sibling-matched analysis (ADHD: wHR=0.41, 95%CI=0.04-4.93; ASD: wHR=0.90, 95%CI=0.40-2.01; preterm birth: wOR=1.25, 95%CI=0.85-1.82; small for gestational age: wOR=0.86, 95%CI=0.32-2.31). / Conclusions and Relevance: We found no evidence that prenatal antipsychotics exposure increased the risk of ADHD, ASD or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestational-exposed to past-exposed and comparing gestational exposed to gestational non-exposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to stop their regular antipsychotic treatment during pregnancy

Linking cohort-based data with electronic health records: a proof-of-concept methodological study in Hong Kong.

OBJECTIVES: Data linkage of cohort-based data and electronic health records (EHRs) has been practised in many countries, but in Hong Kong there is still a lack of such research. To expand the use of multisource data, we aimed to identify a feasible way of linking two cohorts with EHRs in Hong Kong. METHODS: Participants in the 'Children of 1997' birth cohort and the Chinese Early Development Instrument (CEDI) cohort were separated into several batches. The Hong Kong Identity Card Numbers (HKIDs) of each batch were then uploaded to the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to retrieve EHRs. Within the same batch, each participant has a unique combination of date of birth and sex which can then be used for exact matching, as no HKID will be returned from CDARS. Raw data collected for the two cohorts were checked for the mismatched cases. After the matching, we conducted a simple descriptive analysis of attention deficit hyperactivity disorder (ADHD) information collected in the CEDI cohort via the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour Scale (SWAN) and EHRs. RESULTS: In total, 3473 and 910 HKIDs in the birth cohort and CEDI cohort were separated into 44 and 5 batches, respectively, and then submitted to the CDARS, with 100% and 97% being valid HKIDs respectively. The match rates were confirmed to be 100% and 99.75% after checking the cohort data. From our illustration using the ADHD information in the CEDI cohort, 36 (4.47%) individuals had ADHD-Combined score over the clinical cut-off in the SWAN survey, and 68 (8.31%) individuals had ADHD records in EHRs. CONCLUSIONS: Using date of birth and sex as identifiable variables, we were able to link the cohort data and EHRs with high match rates. This method will assist in the generation of databases for future multidisciplinary research using both cohort data and EHRs

Access and Unmet Needs of Orphan Drugs in 194 Countries and Six Areas: a Global Policy Review with Content Analysis

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs$3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001). Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs

Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery

published_or_final_versio

Attention-Deficit/Hyperactivity Disorder medication consumption in 64 countries and regions from 2015 to 2019: a longitudinal study

Background: Timely recognition and appropriate treatment of attention-deficit/hyperactivity disorder (ADHD) are essential to enhance long-term outcomes of individuals with ADHD. This study aimed to evaluate the multinational trends and patterns of ADHD medication consumption. Methods: In this longitudinal trend study, we used pharmaceutical sales data of ADHD medication from the IQVIA-Multinational Integrated Data Analysis System between 2015 and 2019, covering 64 countries across the world. Consumption rates of ADHD medication were expressed as defined daily dose per 1000 child and adolescent inhabitants (aged 5–19) per day (DDD/TID). Linear mixed models were used to estimate the multinational, regional, and income level trend changes. Findings: The results showed that multinational ADHD medication consumption increased by +9.72% (95% confidence interval [CI], +6.25%, +13.31%) per year, from 1.19 DDD/TID in 2015 to 1.43 DDD/TID in 2019 across the 64 countries with marked differences between geographical locations. When stratified by countries’ income levels, increases in ADHD medication consumption were observed in high-income countries but not in middle-income countries. In 2019, the pooled consumption rates of ADHD medication were 6.39 DDD/TID (95% CI, 4.63, 8.84) in high-income countries, 0.37 DDD/TID (95% CI, 0.23, 0.58) in upper-middle-income countries and 0.02 DDD/TID (95% CI, 0.01, 0.05) in lower-middle-income countries. Interpretation: Current ADHD prevalence estimates and rates of ADHD medication consumption in most middle-income countries are lower than the global epidemiological prevalence. It is therefore imperative to evaluate the potential barriers to diagnosis and treatment in these countries to minimise the risk of negative outcomes from undiagnosed and untreated ADHD. Funding: This project was funded by a grant from the Hong Kong Research Grants Council Collaborative Research Fund (project number C7009-19G)

Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study

BACKGROUND: Bell's palsy is a rare adverse event reported in clinical trials of COVID-19 vaccines. However, to our knowledge no population-based study has assessed the association between the inactivated SARS-CoV-2 vaccines and Bell's palsy. The aim of this study was to evaluate the risk of Bell's palsy after BNT162b2 and CoronaVac vaccination. METHODS: In this case series and nested case-control study done in Hong Kong, we assessed the risk of Bell's palsy within 42 days following vaccination with BNT162b2 (Fosun–BioNTech [equivalent to Pfizer–BioNTech]) or CoronaVac (from Sinovac Biotech, Hong Kong) using data from voluntary surveillance reporting with the Hospital Authority, the COVID-19 Vaccine Adverse Event Online Reporting system for all health-care professionals, and the Hospital Authority's territory-wide electronic health records from the Clinical Data Analysis and Reporting System. We described reported cases of Bell's palsy among vaccine recipients (aged 18–110 years for CoronaVac and aged 16–110 years for BNT162b2). We compared the estimated age-standardised incidence of clinically confirmed cases among individuals who had received the CoronaVac or BNT162b2 vaccination (up to 42 days before presentation) with the background incidence in the population. A nested case-control study was also done using conditional logistic regression to estimate the odds ratio (OR) for risk of Bell's palsy and vaccination. Cases and controls were matched (1:4) by age, sex, admission setting, and admission date. FINDINGS: Between February 23 and May 4, 2021, 451 939 individuals received the first dose of CoronaVac and 537 205 individuals received the first dose of BNT162b2. 28 clinically confirmed cases of Bell's palsy were reported following CoronaVac and 16 cases were reported following BNT162b2. The age-standardised incidence of clinically confirmed Bell's palsy was 66·9 cases per 100 000 person-years (95% CI 37·2 to 96·6) following CoronaVac vaccination and 42·8 per 100 000 person-years (19·4 to 66·1) for BNT162b2 vaccination. The age-standardised difference for the incidence compared with the background population was 41·5 (95% CI 11·7 to 71·4) for CoronaVac and 17·0 (−6·6 to 40·6) for BNT162b2, equivalent to an additional 4·8 cases per 100 000 people vaccinated for CoronaVac and 2·0 cases per 100 000 people vaccinated for BNT162b2. In the nested case-control analysis, 298 cases were matched to 1181 controls, and the adjusted ORs were 2·385 (95% CI 1·415 to 4·022) for CoronaVac and 1·755 (0·886 to 3·477) for BNT162b2. INTERPRETATION: Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings. FUNDING: The Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section

Global, regional, and national trends in opioid analgesic consumption from 2015 to 2019: a longitudinal study.

BACKGROUND: Previous studies have reported an extremely unbalanced global access to opioid analgesics. We aimed to determine contemporary trends and patterns of opioid analgesic consumption at the global, regional, and national levels. METHODS: We analysed the global pharmaceutical sales data of 66 countries or regions from the IQVIA-Multinational Integrated Data Analysis System database on opioid analgesics between 2015 and 2019. Opioid analgesic consumption was measured in milligram morphine equivalent per 1000 inhabitants per day (MME per 1000/day). The global, regional, and national trend changes were estimated using linear regressions. Factors associated with consumption patterns and trend changes were explored in multivariable linear regression analyses. FINDINGS: Overall opioid analgesic sales in the 66 countries or regions increased from 27·52 MME per 1000/day (16·63-45·54) in 2015 to 29·51 MME per 1000/day (17·85-48·79) in 2019 (difference per year 3·96%, 95% CI 0·26 to 7·80). Sales reduced yearly in North America (-12·84%; 95% CI -15·34 to -10·27) and Oceania (-2·96%; -4·20 to -1·70); increased in South America (28·69%; 7·18 to 54·53), eastern Europe (7·68%; 3·99 to 11·49), Asia (5·74%; 0·61 to 11·14), and western and central Europe (1·64%; 0·52 to 2·78); and did not differ in Africa or central America and the Caribbean. The global opioid consumption patterns were associated with country-level Human Development Index (p=0·040), cancer death rate excluding leukaemia (p=0·0072), and geographical location (p<0·0001). In 2019, opioid analgesic consumption ranged from 0·01 MME per 1000/day to 5·40 MME per 1000/day in the 17 countries and regions in the lowest consumption quartile, despite high income levels and cancer death rates in some of them. INTERPRETATION: Global opioid analgesic consumption increased from 2015 to 2019. The trend changes were distinctive across regions, which could reflect the different actions in response to known issues of opioid use and misuse. Disparities in opioid analgesic consumption remained, indicating potential inadequate access to essential pain relief in countries with low consumption. FUNDING: None