The central policy unit in the governance of Hong Kong : a study of institutional dynamics

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Incorporating Breastfeeding-Related Variability with Physiologically Based Pharmacokinetic Modeling to Predict Infant Exposure to Maternal Medication Through Breast Milk: a Workflow Applied to Lamotrigine

The version of record of this article, first published in The American Association of Pharmaceutical Scientists Journal (The AAPS Journal), is available online at Publisher’s website: http://dx.doi.org/10.1208/s12248-021-00599-5Current methods to assess risk in infants exposed to maternal medication through breast milk do not specifically account for infants most vulnerable to high drug exposure. A workflow applied to lamotrigine incorporated variability in infant anatomy and physiology, milk intake volume, and milk concentration to predict infant exposure. An adult physiologically based pharmacokinetic model of lamotrigine was developed and evaluated. The model was scaled to account for growth and maturation of a virtual infant population (n=100). Daily infant doses were simulated using milk intake volume and concentration models described by a nonlinear equation of weight-normalized intake across infant age and a linear function on the relationship of observed milk concentrations and maternal doses, respectively. Average infant plasma concentration at steady state was obtained through simulation. Models were evaluated by comparing observed to simulated infant plasma concentrations from breastfeeding infants based on a 90% prediction interval (PI). Upper AUC ratio (UAR) was defined as a novel risk metric. Twenty-five paired (milk concentrations measured) and 18 unpaired (milk concentrations unknown) infant plasma samples were retrieved from the literature. Forty-four percent and 11% of the paired and unpaired infant plasma concentrations were outside of the 90% PI, respectively. Over all ages (0–7 months), unpaired predictions captured more observed infant plasma concentrations within 90% PI than paired. UAR was 0.18–0.44 when mothers received 200 mg lamotrigine, suggesting that infants can receive 18–44% of the exposure per dose as compared to adults. UARs determined for further medications could reveal trends to better classify at-risk mother-infant pairs.Canadian Institutes of Health Research (CIHR); Project Grant; Award Number: PJT-159782 || Canadian Institutes of Health Research (CIHR); Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (CGS-D), a Canada Graduate Scholarship to Honour Nelson Mandela; Award Number: DF2-17144

Examining trends in the incidence of HIV infection among people with a history of drug use to inform an outbreak investigation and response: a retrospective cohort study

Background: In the context of an outbreak of HIV among people who inject drugs in Glasgow, Scotland, identified in 2015, our objectives were to: (1) develop epidemiological methods to estimate HIV incidence using data linkage, and (2) examine temporal changes in HIV incidence to inform public health responses. Methods: This was a retrospective cohort study involving data linkage of laboratory HIV testing data to identify individuals with a history of drug use. Person-years (PY) and Poisson regression were used to estimate incidence by time period (pre-outbreak: 2000–2010 and 2011–2013; early outbreak: 2014–2016; ongoing outbreak: 2017–2019). Results: Among 13 484 individuals tested for HIV, 144 incident HIV infections were observed from 2000 to 2019. Incidence rates increased from pre-outbreak periods (1.00/1000 PY (95% confidence interval, CI: 0.60–1.65) in 2000–2010 and 1.70/1000 PY (95% CI: 1.14–2.54) in 2011–2013) to 3.02/1000 PY (95% CI: 2.36–3.86) early outbreak (2014–2016) and 2.35 (95% CI 1.74–3.18) during the ongoing outbreak period (2017–2019). Compared with the pre-outbreak period (2000–2010), the incidence rates were significantly elevated during both the early outbreak (2014–16) (adjusted incidence rate ratio (aIRR) = 2.87, 95% CI: 1.62–5.09, p &lt; 0.001) and the ongoing outbreak periods (2017–19) (aIRR = 2.12, 95% CI: 1.16–3.90, p = 0.015). Conclusions: Public health responses helped to curb the rising incidence of HIV infection among people with a history of drug use in Glasgow, but further efforts are needed to reduce it to levels observed prior to the outbreak. Data linkage of routine diagnostic test data to assess and monitor incidence of HIV infection provided enhanced surveillance, which is important to inform outbreak investigations and guide national strategies on elimination of HIV transmission.</p

Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study):multicentre randomised controlled trial

OBJECTIVE: To evaluate whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with post-covid-19 condition (long covid).DESIGN: Pragmatic, multicentre, parallel group, superiority randomised controlled trial.SETTING: England and Wales, with home based interventions delivered remotely online from a single trial hub.PARTICIPANTS: 585 adults (26-86 years) discharged from NHS hospitals at least three months previously after covid-19 and with ongoing physical and/or mental health sequelae (post-covid-19 condition), randomised (1:1.03) to receive the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) intervention (n=298) or usual care (n=287).INTERVENTIONS: Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions.MAIN OUTCOME MEASURES: The primary outcome was health related quality of life using the patient reported outcomes measurement information system (PROMIS) preference (PROPr) score at three months. Secondary outcomes, measured at three, six, and 12 months, included PROMIS subscores (depression, fatigue, sleep disturbance, pain interference, physical function, social roles/activities, and cognitive function), severity of post-traumatic stress disorder, general health, and adverse events.RESULTS: Between January 2021 and July 2022, 39 697 people were invited to take part in the study and 725 were contacted and eligible. 585 participants were randomised. Mean age was 56 (standard deviation (SD) 12) years, 52% were female participants, mean health related quality of life PROMIS-PROPr score was 0.20 (SD 0.17), and mean time from hospital discharge was 323 (SD 144) days. Compared with usual care, the REGAIN intervention led to improvements in health related quality of life (adjusted mean difference in PROPr score 0.03 (95% confidence interval 0.01 to 0.05), P=0.02) at three months, driven predominantly by greater improvements in the PROMIS subscores for depression (1.39 (0.06 to 2.71), P=0.04), fatigue (2.50 (1.19 to 3.81), P&lt;0.001), and pain interference (1.80 (0.50 to 3.11), P=0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P=0.02). Of 21 serious adverse events, only one was possibly related to the REGAIN intervention. In the intervention group, 141 (47%) participants fully adhered to the programme, 117 (39%) partially adhered, and 40 (13%) did not receive the intervention.CONCLUSIONS: In adults with post-covid-19 condition, an online, home based, supervised, group physical and mental health rehabilitation programme was clinically effective at improving health related quality of life at three and 12 months compared with usual care.TRIAL REGISTRATION: ISRCTN registry ISRCTN11466448.</p

Development of an online intervention for the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) trial [version 2; peer review: 2 approved]

Background: Up to half of people hospitalised with COVID-19 report diverse and persistent symptoms affecting quality of life for months and sometimes years after discharge (long-COVID). We describe the development of an online group exercise and behavioural support intervention for people who continue to experience such physical and/or emotional health problems more than three months after hospital discharge.  Methods: Intervention development was informed by the Medical Research Council framework for complex interventions. Our multidisciplinary team of academics, clinicians, and people with long-COVID, had collective expertise in the development and testing of complex interventions. We integrated a bio-psycho-social model of care drawing on rehabilitation literature for long-term health conditions and experiences from our pre-pilot study. Multiple stakeholder meetings were held to refine the intervention which was designed to be deliverable within the UK National Health Service. We adhere to TIDieR guidance for transparent and explicit reporting of telehealth interventions.  Results: The final REGAIN online exercise and behavioural support intervention consisted of an initial 1:1 consultation with a trained practitioner, followed by eight online group exercise, and six group support, sessions delivered over eight weeks. Participants could also access an online library of on-demand exercise and support videos. Conclusions: The final REGAIN intervention, combining exercise and behavioural support, is fully manualised with clear pathways to delivery and implementation. It is currently being tested in a randomised controlled trial. The intervention, developed with extensive patient and stakeholder engagement, could be incorporated into existing NHS rehabilitation programmes, should it prove to be clinically and cost-effective for people with long-COVID. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 11466448: Rehabilitation exercise and psychological support after COVID-19 infection: REGAIN

Study protocol for a peer-led web-based intervention to promote safe usage of dating applications among young adults: a cluster randomized controlled trial.

BACKGROUND: Dating applications are a popular platform to meet new people. At the same time, they have been associated with risks such as unsafe sexual behavior and privacy concerns in young adults. This paper presents a study protocol of a cluster randomized controlled trial (RCT) to evaluate the effectiveness of a peer-led web-based intervention to promote its safe usage in young adults. METHODS: The study design is an open-labeled cluster RCT with an intervention and a placebo control arm. The intervention group will receive a web-based intervention developed through focus group discussions, a crowdsourcing contest, and a Peer-Vetted Creative Production (PVCP) workshop. The control group will receive a web-based resource on health and exercise. We aim to recruit approximately 338 young adults aged 17-27 years from three tertiary educational institutions in Hong Kong with the class as the cluster unit. Based on the Information, Motivation, and Behavioral Skills (IMB) model, the primary outcome of this study is self-efficacy in using dating applications measured by the General Self Efficacy Scale. Secondary outcomes include change in risk perception measured by the Risk Propensity Scale and a Risk Assessment Tool. Questionnaires will be administered before the intervention, after the intervention, and at one-month follow-up. Intention-to-treat analysis and multilevel regression modeling will be used to evaluate differences in outcomes between groups and the factors affecting these outcomes, respectively. DISCUSSION: Dating application usage presents opportunities as well as challenges to young adults meeting new friends. Innovative and relatable interventions are needed to promote the safe usage of dating applications to this population. Practical knowledge gained from the development process may be helpful for future intervention utilizing the peer-led approach. If effective, the intervention will be disseminated to non-governmental organizations and educational institutions to be used as a teaching resource. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03685643 . Registered on 26 September 2018. University of Hong Kong Clinical Trials Registry, HKUCTR-2512

Population pharmacokinetics of artesunate and amodiaquine in African children

<p>Abstract</p> <p>Background</p> <p>Pharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this study was to evaluate the PK properties of a newly developed and registered fixed dose combination (FDC) of artesunate and amodiaquine.</p> <p>Methods</p> <p>A prospective population pharmacokinetic study of AS and AQ was conducted in children aged six months to five years. Participants were randomized to receive the new artesunate and amodiaquine FDC or the same drugs given in separate tablets. Children were divided into two groups of 70 (35 in each treatment arm) to evaluate the pharmacokinetic properties of AS and AQ, respectively. Population pharmacokinetic models for dihydroartemisinin (DHA) and desethylamodiaquine (DeAq), the principal pharmacologically active metabolites of AS and AQ, respectively, and total artemisinin anti-malarial activity, defined as the sum of the molar equivalent plasma concentrations of DHA and artesunate, were constructed using the non-linear mixed effects approach. Relative bioavailability between products was compared by estimating the ratios (and 95% CI) between the areas under the plasma concentration-time curves (AUC).</p> <p>Results</p> <p>The two regimens had similar PK properties in young children with acute malaria. The ratio of loose formulation to fixed co-formulation AUCs, was estimated as 1.043 (95% CI: 0.956 to 1.138) for DeAq. For DHA and total anti-malarial activity AUCs were estimated to be the same. Artesunate was rapidly absorbed, hydrolysed to DHA, and eliminated. Plasma concentrations were significantly higher following the first dose, when patients were acutely ill, than after subsequent doses when patients were usually afebrile and clinically improved. Amodiaquine was converted rapidly to DeAq, which was then eliminated with an estimated median (range) elimination half-life of 9 (7 to 12) days. Efficacy was similar in the two treatments groups, with cure rates of 0.946 (95% CI: 0.840–0.982) in the AS+AQ group and 0.892 (95% CI: 0.787 – 0.947) in the AS/AQ group. Four out of five patients with PCR confirmed recrudescences received AQ doses < 10 mg/kg. Both regimens were well tolerated. No child developed severe, post treatment neutropaenia (<1,000/μL). There was no evidence of AQ dose related hepatotoxicity, but one patient developed an asymptomatic rise in liver enzymes that was resolving by Day-28.</p> <p>Conclusion</p> <p>The bioavailability of the co-formulated AS-AQ FDC was similar to that of the separate tablets for desethylamodiaquine, DHA and the total anti-malarial activity. These data support the use this new AS-AQ FDC in children with acute uncomplicated falciparum malaria.</p

Reactive, self-administered malaria treatment against asymptomatic malaria infection: results of a cluster randomized controlled trial in The Gambia.

BACKGROUND: Selectively targeting and treating malaria-infected individuals may further decrease parasite carriage in low-burden settings. Using a trans-disciplinary approach, a reactive treatment strategy to reduce Plasmodium falciparum prevalence in participating communities was co-developed and tested. METHODS: This is a 2-arm, open-label, cluster-randomized trial involving villages in Central Gambia during the 2017 and 2018 malaria transmission season. Villages were randomized in a 1:1 ratio using a minimizing algorithm. In the intervention arm, trained village health workers delivered a full course of pre-packed dihydroartemisinin-piperaquine to all residents of compounds where clinical cases were reported while in the control arm, compound residents were screened for infection at the time of the index case reporting. All index cases were treated following national guidelines. The primary endpoint was malaria prevalence, determined by molecular methods, at the end of the intervention period. RESULTS: The trial was carried out in 50 villages: 34 in 2017 and 16 additional villages in 2018. At the end of the 2018 transmission season, malaria prevalence was 0.8% (16/1924, range 0-4%) and 1.1% (20/1814, range 0-17%) in the intervention and control arms, respectively. The odds of malaria infection were 29% lower in the intervention than in the control arm after adjustment for age (OR 0.71, 95% CI 0.27-1.84, p = 0.48). Adherence to treatment was high, with 98% (964/979) of those treated completing the 3-day treatment. Over the course of the study, only 37 villages, 20 in the intervention and 17 in the control arm, reported at least one clinical case. The distribution of clinical cases by month in both transmission seasons was similar and the odds of new clinical malaria cases during the trial period did not vary between arms (OR 1.04, 95% CI 0.57-1.91, p = 0.893). All adverse events were classified as mild to moderate and resolved completely. CONCLUSION: The systematic and timely administration of an anti-malarial treatment to residents of compounds with confirmed malaria cases did not significantly decrease malaria prevalence and incidence in communities where malaria prevalence was already low. Treatment coverage and adherence was very high. Results were strongly influenced by the lower-than-expected malaria prevalence, and by no clinical cases in villages with asymptomatic malaria-infected individuals. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT02878200. Registered 25 August 2016. https://clinicaltrials.gov/ct2/show/NCT02878200

The estimated prevalence of exposure to asthmagens in the Australian workforce

Background: There is very little information available on a national level as to the number of people exposed to specific asthmagens in workplaces. Methods: We conducted a national telephone survey in Australia to investigate the prevalence of current occupational exposure to 277 asthmagens, assembled into 27 groups. Demographic and current job information were obtained. A web-based tool, OccIDEAS, was used to collect job task information and assign exposure to each asthmagen group. Results: In the Australian Workplace Exposure Study – Asthma (AWES- Asthma) we interviewed 4878 participants (2441 male and 2437 female). Exposure to at least one asthmagen was more common among men (47 %) than women (40 %). Extrapolated to the Australian population, approximately 2.8 million men and 1.7 million women were estimated to be exposed. Among men, the most common exposures were bioaerosols (29 %) and metals (27 %), whilst the most common exposures among women were latex (25 %) and industrial cleaning and sterilising agents (20 %). Conclusions: This study provides information about the prevalence of exposure to asthmagens in Australian workplaces which will be useful in setting priorities for control and prevention of occupational asthma

Reactive community-based self-administered treatment against residual malaria transmission: study protocol for a randomized controlled trial

Background: Systematic treatment of all individuals living in the same compound of a clinical malaria case may clear asymptomatic infections and possibly reduce malaria transmission, where this is focal. High and sustained coverage is extremely important and requires active community engagement. This study explores a communitybased approach to treating malaria case contacts. Methods/design: This is a cluster-randomized trial to determine whether, in low-transmission areas, treating individuals living in the same compound of a clinical malaria case with dihydroartemisinin-piperaquine can reduce parasite carriage and thus residual malaria transmission. Treatment will be administered through the local health system with the approach of encouraging community participation designed and monitored through formative research. The trial goal is to show that this approach can reduce in intervention villages the prevalence of Plasmodium falciparum infection toward the end of the malaria transmission season. Discussion: Adherence and cooperation of the local communities are critical for the success of mass treatment campaigns aimed at reducing malaria transmission. By exploring community perceptions of the changing trends in malaria burden, existing health systems, and reaction to self-administered treatment, this study will develop and adapt a model for community engagement toward malaria elimination that is cost-effective and fits within the existing health system. Trial registration: Clinical trials.gov, NCT02878200. Registered on 25 August 2016