Descriptive analysis of poisoning cases involving attention deficit hyperactivity disorder medications in Hong Kong.

INTRODUCTION: The number of poisoning cases involving attention deficit hyperactivity disorder (ADHD) medications has reportedly risen with their increased use. However, there is limited relevant evidence from Asia. We analysed the characteristics of poisoning events involving these medications in Hong Kong. METHODS: We retrieved data regarding ADHD medication-related poisoning cases from the Hong Kong Poison Information Centre and conducted a descriptive analysis of the demographic information and poisoning information including sources of cases, exposure reason, exposure location, and outcome. The HKPIC data were linked with the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) via de-identified Accident and Emergency numbers of public hospitals to investigate clinical characteristics. We also retrieved ADHD medication prescription records from the CDARS, then compared trends between poisoning cases and ADHD medication use. RESULTS: We identified 72 poisoning cases involving ADHD medications between 2009 and 2019, of which approximately 70% occurred in the affected individual's residence; most were intentional poisoning events (65.3%). No statistically significant association was observed between ADHD medication prescription trends and poisoning events involving ADHD medications. Of the 66 cases (91.7%) successfully linked to CDARS, 40 (60.6%) occurred in individuals with ADHD (median age: 14 years); 26 (39.4%) occurred in individuals who lacked ADHD (median age: 33 years) but displayed higher rates of other mental disorders including depression and anxiety. CONCLUSION: No significant correlation was evident between ADHD medication prescriptions and poisoning events involving ADHD medications. However, medication management and caregiver education must be emphasised to prevent potential poisoning events.

Budget impact of introducing tofacitinib to the public hospital formulary in Hong Kong, 2017-2021.

INTRODUCTION: As the first approved oral kinase inhibitor, tofacitinib is effective and well-tolerated, but more expensive than conventional treatments for uncontrolled rheumatoid arthritis. Public formulary listing typically exerts a positive impact on the uptake of new drugs. We aimed to assess the budgetary impact of introducing tofacitinib into the Hospital Authority Drug Formulary as a fully subsidised drug in Hong Kong. METHODS: We applied a population-based budget impact model to trace the number of eligible patients receiving biologics or tofacitinib treatment, then estimated the 5-year healthcare expenditure on rheumatoid arthritis treatments, with or without tofacitinib (2017-2021). We used linear regression to estimate the number of target patients and compound annual growth rate to estimate market share. Competing treatments included abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and tofacitinib. Retail price was used for drug costs, valued in Hong Kong dollars (HK$) in 2017 and discounted at 4% per year. RESULTS: The annual treatment cost of tofacitinib was HK$74 214 per patient, and the costs of biologics ranged from HK$64 350 to HK$115 700. Without tofacitinib, the annual government health expenditures for rheumatoid arthritis treatment were estimated to increase from HK$147.9 million (2017) to HK$190.6 million (2021). The introduction of tofacitinib to the formulary would reduce healthcare expenditures by 17.3% to 20.3% per year, with cumulative savings of HK$192.8 million; this change was estimated to provide consistent savings (HK$66.4 million to HK$196.8 million) in all tested scenarios. CONCLUSION: Introduction of tofacitinib to the formulary will provide 5-year savings, given the current drug price and patient volume.

Budget impact and cost-effectiveness analyses of direct-acting antivirals for chronic hepatitis C virus infection in Hong Kong.

The purpose of this investigation was to evaluate the budget impact and cost-effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection in Hong Kong. A decision analytic model was developed to compare short-term costs and health outcomes of patients with chronic HCV genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based treatments (sofosbuvir or ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171 per course while improving the rate of sustained virologic response (SVR) from 59-66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments ranged from $9724 to $29,189 per treatment success, which were all below the cost-effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection management over 5 years. A 50% change in DAA medication costs reflected a change in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs to the public hospital formulary yields a considerable budget increase but is still economically favorable to the local government.

Improving medication safety and diabetes management in Hong Kong: a multidisciplinary approach.

INTRODUCTION: Patients with diabetes often require complex medication regimens. The positive impact of pharmacists on improving diabetes management or its co-morbidities has been recognised worldwide. This study aimed to characterise drug-related problems among diabetic patients in Hong Kong and their clinical significance, and to explore the role of pharmacists in the multidisciplinary diabetes management team by evaluating the outcome of their clinical interventions. METHODS: An observational study was conducted at the Diabetes Clinic of a public hospital in Hong Kong from October 2012 to March 2014. Following weekly screening, and prior to the doctor's consultation, selected high-risk patients were interviewed by a pharmacist for medication reconciliation and review. Drug-related problems were identified and documented by the pharmacist who presented clinical recommendations to doctors to optimise a patient's drug regimen and resolve or prevent potential drug-related problems. RESULTS: A total of 522 patients were analysed and 417 drug-related problems were identified. The incidence of patients with drug-related problems was 62.8% with a mean of 0.9 (standard deviation, 0.6) drug-related problems per patient. The most common categories of drug-related problems were associated with dosing (43.9%), drug choice (17.3%), and non-allergic adverse reactions (15.6%). Drugs most frequently involved targeted the endocrine or cardiovascular system. The majority (71.9%) of drug-related problems were of moderate clinical significance and 28.1% were considered minor problems. Drug-related problems were totally solved (50.1%) and partially solved (11.0%) by doctors' acceptance of pharmacist recommendations, or received acknowledgement from doctors (5.5%). CONCLUSIONS: Pharmacists, in collaboration with the multidisciplinary team, demonstrated a positive impact by identifying, resolving, and preventing drug-related problems in patients with diabetes. Further plans for sustaining pharmacy service in the Diabetes Clinic would enable further studies to explore the long-term impact of pharmacists in improving patients' clinical outcomes in diabetes management.

Elevated risk of multimorbidity post-COVID-19 infection: protective effect of vaccination.

BACKGROUND: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association. AIM: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination. DESIGN: Nested case-control study. METHODS: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity. RESULTS: In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger. CONCLUSIONS: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.

Scleral-fixated intraocular lens implants-evolution of surgical techniques and future developments.

Varied options are available for the implantation of secondary intraocular lens implants in the absence of zonular or capsular support. Loss of the capsule can occur in the context of complicated cataract surgery, trauma or inherited conditions such as Marfan syndrome or pseudoexfoliation. Approaches to overcome this include optical measures such as the use of spectacles or contact lenses, and surgical therapy incorporating the use of anterior chamber, iris-fixated or scleral-fixated lenses. Surgical techniques to implant scleral-fixated lenses have undergone various modifications, since the first publication of sutured intrascleral fixation described in the 1980s. However, despite the advances in surgical techniques, studies are limited either by their retrospective nature, small sample size and most importantly small duration of follow-up. This comprehensive review aims to amalgamate the evolution of various surgical techniques with regards to intrascleral lens fixation and suggests areas for future development.

SGLT2i as fourth-line therapy and risk of mortality, end-stage renal diseases and cardiovascular diseases in patients with type 2 diabetes mellitus.

AIM: Current guideline recommends insulin as fourth-line glucose-lowering medications. However, treatment effects of sodium glucose co-transporter-2 inhibitors (SGLT2i) on the risk of complications are uncertain. This study examines risks of all-cause mortality, cardiovascular diseases (CVD) and end-stage renal diseases (ESRD) in type 2 diabetes mellitus (T2DM) patients on triple oral glucose-lowering medications initiating SGLT2i, insulin or other oral medications. METHODS: A population-based retrospective cohort of patients with T2DM between 2006-2017 was extracted from Hong Kong Hospital Authority database. Patients who were initiated a fourth-line therapy with SGLT2i, insulin or other oral medications were included. Hazard ratios (HRs) for all-cause mortality, CVD and ESRD were assessed using Cox proportional hazard models. RESULTS: Over a median follow-up period of 18.5 months with 63,122 person-years, SGLT2i and insulin group had the lowest and highest incidence rate of all-cause mortality, CVD and ESRD (1.06, 0.65 and 0.61 vs 4.25, 5.58 and 4.39/100 person-years), respectively. Initiating SGLT2i as fourth-line medication had more benefits on CVD, in particular coronary heart disease and stroke. Insulin users had higher risks of CVD (HR=8.04, 95%CI=3.06-21.12) than SGLT2i users. SGLT2i was associated with insignificant reduction in ESRD (HR=4.62, 95%CI=0.73-29.09) and all-cause mortality (HR=3.06, 95%CI=0.75-12.45), and HF (HR=2.99, 95%CI=0.37-24.42) among patients without established HF. CONCLUSION: Among T2DM patients initiating fourth-line therapy, SGLT2i users had significant benefits in lowering risk of CVD, and potential benefits in lowering risks of ESRD and all-cause mortality. SGLT2i was the preferred fourth-line glucose-lowering medication least likely to be associated with complication risks.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Decoupling of normal CD40/interleukin-4 immunoglobulin heavy chain switch signal leads to genomic instability in SGH-MM5 and RPMI 8226 multiple myeloma cell lines.

The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines that are optimally triggered via CD40 and/or IL-4 demonstrate abnormal decoupling of IL-4 signal transduction from CD40. Specifically, CD40 alone was sufficient to trigger maximal growth of tumor cells. We further demonstrate that CD40 triggering induced both DNA DSBs as well as newly acquired karyotypic abnormalities in MM cell lines. Importantly, these observations were accompanied by induction of activation induced cytidine deaminase expression, but not gross apoptosis. These data support the role of abnormal CD40 signal transduction in mediating genomic instability, suggesting a role for the CD40 pathway and intermediates in myelomagenesis and clonal evolution in vivo.

Light rare earth element depletion during Deepwater Horizon blowout methanotrophy.

Rare earth elements have generally not been thought to have a biological role. However, recent work has demonstrated that the light REEs (LREEs: La, Ce, Pr, and Nd) are essential for at least some methanotrophs, being co-factors in the XoxF type of methanol dehydrogenase (MDH). We show here that dissolved LREEs were significantly removed in a submerged plume of methane-rich water during the Deepwater Horizon (DWH) well blowout. Furthermore, incubation experiments conducted with naturally methane-enriched waters from hydrocarbon seeps in the vicinity of the DWH wellhead also showed LREE removal concurrent with methane consumption. Metagenomic sequencing of incubation samples revealed that LREE-containing MDHs were present. Our field and laboratory observations provide further insight into the biochemical pathways of methanotrophy during the DWH blowout. Additionally, our results are the first observations of direct biological alteration of REE distributions in oceanic systems. In view of the ubiquity of LREE-containing MDHs in oceanic systems, our results suggest that biological uptake of LREEs is an overlooked aspect of the oceanic geochemistry of this group of elements previously thought to be biologically inactive and an unresolved factor in the flux of methane, a potent greenhouse gas, from the ocean.

Bleeding-related hospital admissions and 30-day readmissions in patients with non-valvular atrial fibrillation treated with dabigatran versus warfarin.

Essentials Bleeding is a common cause of hospital admission and readmission in oral anticoagulant users. Patients with dabigatran and warfarin were included to assess hospital admission risk. Dabigatran users had a higher risk of 30-day readmission with bleeding than warfarin users. Close monitoring following hospital discharge for dabigatran-related bleeding is warranted. SUMMARY: Background Reducing 30-day hospital readmission is a policy priority worldwide. Warfarin-related bleeding is among the most common cause of hospital admissions as a result of adverse drug events. Compared with warfarin, dabigatran achieves a full anticoagulation effect more quickly following its initiation; hence it may lead to early-onset bleeds. Objectives To compare the incidence of bleeding-related hospital admissions and 30-day readmissions with dabigatran vs. warfarin in patients with non-valvular atrial fibrillation (NVAF). Methods This was a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through to 2014 and prescribed dabigatran or warfarin were 1:1 matched by propensity score. The incidence rate of hospital admission with bleeding (a composite of gastrointestinal bleeding, intracranial hemorrhage and bleeding at other sites) was assessed. Results Among the 51 946 patients with NVAF, 8309 users of dabigatran or warfarin were identified, with 5160 patients matched by propensity score. The incidence of first hospitalized bleeding did not differ significantly between groups (incidence rate ratio, 0.92; 95% confidence interval [CI], 0.66-1.28). Among patients who were continuously prescribed their initial anticoagulants upon discharge, dabigatran use was associated with a higher risk of 30-day readmission with bleeding over warfarin (adjusted hazard ratio, 2.87; 95%CI, 1.10-7.43). Conclusion When compared with warfarin, dabigatran was associated with a comparable incidence of first hospital admission but a higher risk of 30-day redmission with respect to bleeding. Close early monitoring of patients initiated on dabigatran following hospital discharge for bleeding is warranted.

Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system.

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined, and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20,586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10,000 patient-years. No increased risk was found during MPH-exposed compared with non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment.

Effects of polyethylene glycol on reverse transcriptase and other polymerase activities.

Polyethylene glycol enhances reverse transcription, augmenting both the rate and duration of polymerization. The effective mean molecular weight of polyethylene glycol is 6000 and the optimal concentration is 12% (w/w). Polyethylene glycol is effective on the reverse transcriptase reaction of all ten type B, C, and D viruses tested under a variety of exogenous, endogenous, and reconstitution assay systems, including the highly efficient conditions involving calf thymus DNA oligonucleotide primers. By three methods of synthesis, polyethylene glycol increased the yields of complementary [3H]DNA by a factor of 1.8--6.5. Polyethylene glycol does not alter the divalent cation requirements of the specificities of the enzyme. Complementary [3H]DNAs made in the presence of polyethylene glycol are indistinguishable in terms of size and sequence complementarity from those made in the absence of the polymer. The stimulatory effect was partly due to the ability of polyethylene glycol to stabilize reverse transcriptase. Preliminary tests indicate that polyethylene glycol also stimulates other nucleotide polymerases, such as the DNA-dependent DNA and RNA polymerases of Escherichia coli and the terminal transferase of calf thymus.

Systematic review with meta-analysis: the association between the use of calcium channel blockers and gastrointestinal bleeding.

BACKGROUND: Due to their potential anti-platelet effect, it is suggested that calcium channel blockers (CCBs) are associated with gastrointestinal bleeding (GIB). However, results from previous studies are conflicting. AIM: To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies to clarify the association between CCBs and GIB. METHODS: We conducted a systematic search of PubMed, EMBASE, Cochrane library and Trial Register databases up to January 2015. Studies that evaluated exposure to CCBs reporting GIB outcomes were included in the meta-analysis. The inverse variance method with random effects model was used to calculate the pooled estimates. RESULTS: Seventeen studies (four RCTs, eleven case-control and two cohort studies) were included in the meta-analysis. The summary risk ratio (RR) for GIB was 1.17 (95% CI 1.01-1.36) for CCB users vs. non-users. Subgroup analysis showed that CCB use was associated with a moderately higher risk of lower GIB (RR = 1.83, 95% CI 1.17-2.84) but not upper GIB. However, data from four RCTs did not support association between CCBs and GIB (RR = 0.93, 95% CI 0.82-1.05). Subgroup analyses further showed that the increased risk of GIB among CCB users was only observed in studies that failed to adjust for prior history of GIB (RR = 1.67, 95% CI 1.34-2.08) or use of anti-ulcer drugs (RR = 1.40, 95% CI 1.19-1.65). CONCLUSION: Our meta-analysis showed a marginal association between calcium channel blocker use and the risk of gastrointestinal bleeding. This association is of dubious clinical significance, as the effects of different comparators or adjustment for confounding factors render this association nonsignificant.

Triptolide induced cytotoxic effects on human promyelocytic leukemia, T cell lymphoma and human hepatocellular carcinoma cell lines.

Triptolide, a traditional Chinese medicine, has been reported to be effective in the treatment of auto-immune diseases, and it can also induce anti-neoplastic activity on several human tumor cell lines. This study investigates the cytotoxic function and the functional mechanism of triptolide on tumor cells. Promyelocytic leukemia, (HL-60), T cell lymphoma (Jurkat), and human hepatocelluar carcinoma (SMMC-7721) cells were subjected to triptolide treatment, and cell growth inhibition was examined by XTT cell viability assay. Cell death mechanism (apoptosis) was confirmed through DNA fragmentation and DAPI staining. Triptolide inhibited 50% of cell growth (IC(50)) on HL-60 cells at 7.5 nM, Jurkat cells at 27.5 nM and SMMC cells at 32 nM. Characteristic apoptotic features including internucleosomal DNA fragmentation and chromatin condensation were observed in triptolide treated cells. Data from the study indicates that triptolide could induce apoptosis in human tumor cell lines and it may be applicable as a potential chemotherapeutic agent for cancer treatment.