Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention.

PURPOSE: Patients with coronary artery disease have increased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dual anti-platelet therapy (DAPT). METHODS: We identified all adults who underwent first-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong. Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes of interest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for MOF associated with ticagrelor versus clopidogrel use. RESULTS: 3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained MOF (annualized fracture risks: 0.34% and 0.56%, respectively). Ticagrelor use was associated with lower risks of MOF (HR 0.60, 95%CI 0.44-0.83; p = 0.002). Consistent HRs were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history. CONCLUSION: Among adults who underwent first-ever PCI for ACS, ticagrelor use in the DAPT was associated with a lower risk of MOF compared with clopidogrel. Our results support the use of ticagrelor in the DAPT from the perspective of bone health.

Ten-year territory-wide trends in the utilisation and clinical outcomes of extracorporeal membrane oxygenation in Hong Kong.

INTRODUCTION: The utilisation of extracorporeal membrane oxygenation (ECMO) has been rapidly increasing in Hong Kong. This study examined 10-year trends in the utilisation and clinical outcomes of ECMO in Hong Kong. METHODS: We retrospectively reviewed the records of all adult patients receiving ECMO who were admitted to the intensive care units (ICUs) of public hospitals in Hong Kong between 2010 and 2019. Temporal trends across years were assessed using the Mann-Kendall test. Observed hospital mortality was compared with the Acute Physiology and Chronic Health Evaluation (APACHE) IV-predicted mortality. RESULTS: The annual number of patients receiving ECMO increased from 18 to 171 over 10 years. In total, 911 patients received ECMO during the study period: 297 (32.6%) received veno-arterial ECMO, 450 (49.4%) received veno-venous ECMO, and 164 (18.0%) received extracorporeal cardiopulmonary resuscitation. The annual number of patients aged ≥65 years increased from 0 to 47 (27.5%) [P for trend=0.001]. The median (interquartile range) Charlson Comorbidity Index increased from 1 (0-1) to 2 (1-3) [P for trend<0.001] while the median (interquartile range) APACHE IV score increased from 90 (57-112) to 105 (77-137) [P for trend=0.003]. The overall standardised mortality ratio comparing hospital mortality with APACHE IV-predicted mortality was 1.11 (95% confidence interval=1.01-1.22). Hospital and ICU length of stay both significantly decreased (P for trend=0.011 and <0.001, respectively). CONCLUSION: As ECMO utilisation increased in Hong Kong, patients put on ECMO were older, more critically ill, and had more co-morbidities. It is important to combine service expansion with adequate resource allocation and training to maintain quality of care.

Young people's perceptions of acne and acne treatments: secondary analysis of qualitative interview data.

BACKGROUND: Acne vulgaris is a common skin condition affecting approximately 95% of adolescents to some extent. First-line treatments are topical preparations but nonadherence is common. A substantial proportion of patients take long courses of oral antibiotics, associated with antibiotic resistance. OBJECTIVES: This study aimed to explore young people's views and experiences of acne and its treatments. METHODS: We report a secondary thematic analysis of interview data collected by researchers in the Health Experiences Research Group (HERG), University of Oxford. A total of 25 transcripts from young people aged 13-24 years with acne were included. RESULTS: Acne is often perceived as a short-term self-limiting condition of adolescence and this appears to have implications for seeking treatment or advice. Participants widely perceived topical treatments as being ineffective, which seemed related to unrealistic expectations around speed of onset of action. Many participants felt they had tried all available topical treatments, although were unsure what was in them or unaware of differences between cosmetic and pharmaceutical treatments. They had concerns around how to use topicals 'properly' and how to avoid side-effects. They were also concerned about the side-effects or necessity of oral treatments, although few seemed aware of antibiotic resistance. CONCLUSIONS: People with acne need support to manage their condition effectively, particularly a better understanding of different topicals, how to use them and how to avoid side-effects. Unrealistic expectations about the onset of action of treatments appears to be a common cause of frustration and nonadherence. Directing people towards accessible evidence-based information is crucial. What's already known about this topic? There is a common perception that acne is a short-term condition that will resolve without treatment. Previous research has shown that nonadherence to topical treatments is common and that oral antibiotics are the most commonly prescribed treatment for acne in the U.K. Further research is needed to understand how young people perceive acne treatments and the implications of this for treatment adherence and self-management. What does this study add? People often said they had tried all available topical preparations for acne, but seemed confused between cosmetic and pharmaceutical treatments. People seemed unsure how to use topical treatments 'properly' or how to avoid side-effects. This was rarely discussed with health professionals. People's perception of acne as a short-term condition appeared to influence their expectations around onset of action of treatment and their views about its effectiveness and necessity. What are the clinical implications of the work? The perception of acne as a short-term condition has implications for self-management and motivation to seek and adhere to treatments. Providing advice about onset of action of treatments and how to prevent side-effects is crucial, including directing people towards accessible, written, evidence-based information. People's confusion about the different topical treatments available may be alleviated by such information, or by encouraging photos or other recordings of treatments tried and for how long. Linked Comment: Prior. Br J Dermatol 2020; 183:208-209. Plain language summary available online.

Dynamic Trap Formation and Elimination in Colloidal Quantum Dots.

Using first-principles simulations on PbS and CdSe colloidal quantum dots, we find that surface defects form in response to electronic doping and charging of the nanoparticles. We show that electronic trap states in nanocrystals are dynamic entities, in contrast with the conventional picture wherein traps are viewed as stable electronic states that can be filled or emptied, but not created or destroyed. These traps arise from the formation or breaking of atomic dimers at the nanoparticle surface. The dimers' energy levels can reside within the bandgap, in which case a trap is formed. Fortunately, we are also able to identify a number of shallow-electron-affinity cations that stabilize the surface, working to counter dynamic trap formation and allowing for trap-free doping.

Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis.

Four women and three men after allogeneic (n=4) and autologous (n=3) haematopoietic SCT (HSCT) were observed to have an increase in T-cell large granular lymphocytes (T-LGLs) of CD3+CD8+ phenotype for a median of 41 (15-118) months. Clonal rearrangement of the T-cell receptor gene was verified by two PCR techniques and direct DNA sequencing, confirming that the cases were neoplastic and therefore classifiable as T-LGL leukaemia. In the allogeneic HSCT cases, T-LGL leukaemia was derived from donor T cells in three patients, as shown by DNA chimerism analysis, and recipient T cells in one patient who had graft failure previously. None of the patients showed cytopenia, autoimmune phenomenon or organ infiltration, which were features typical of de novo T-LGL leukaemia. Six patients had remained asymptomatic with stable large granular lymphocyte counts. One patient died from cerebral relapse of the original lymphoma. T-LGL leukaemias occurring post-HSCT are distinct from de novo T-LGL leukaemia and may have a different pathogenesis and clinical course. Patients did not require specific treatment, and the disease remained stable for long periods.

Reactive Black dye adsorption/desorption onto different adsorbents: effect of salt, surface chemistry, pore size and surface area.

The adsorption of a large reactive dye, Reactive Black 5 dye, onto two bamboo based active carbons using phosphoric acid in a two stage activation process and three conventional adsorbents, carbon F400, bone char and peat, has been studied. The monolayer saturation adsorption capacities for Reactive Black 5 were determined by the Langmuir isotherm analysis and are: 176, 157, 7, 447 and 545 mg dye/g adsorbent for active carbon F400, bone char, peat, bamboo carbon (2123 m(2)/g) and bamboo carbon (1400 m(2)/g), respectively. The equilibrium experiments were analysed using three isotherms, Langmuir, Freundlich and Redlich-Peterson and the based on the lowest SSE values, the Redlich-Peterson was the best fit correlation. The effect of adding salt, in the form of sodium phosphate, on the adsorption capacities has been studied and was found to increase the adsorption capacities of both bamboo carbons to over 900 mg/g.

Production and comparison of high surface area bamboo derived active carbons.

High surface area activated carbons have been produced from the natural biomaterial bamboo, using phosphoric acid as the activating agent. The effects of phosphoric acid impregnation ratio, activation temperature, heating rate on the carbon surface area, porosity and mass yield are presented. Three of these bamboo derived active carbons, surface areas 1337, 1628 and 2123m(2)/g were assessed for their ability to adsorb Acid Red 18 dye from aqueous solution; these results were compared with three conventional adsorbents: activated carbon F400, bone char and peat. Isotherm data were analysed using Langmuir, Freundlich, Redlich-Peterson and Langmuir-Freundlich isotherms. Different isotherms provided the best fit correlations to the adsorption experimental data but the Langmuir-Freundlich equation provided the best overall correlation of data. The adsorption capacities of two of the selected bamboo derived carbons were much greater than the capacities of the other three adsorbents.

Identifying the psychosocial correlates of condom use by female sex workers in Hong Kong.

This study examined factors affecting condom use by Hong Kong female sex workers when they have sex with their clients and steady partners. Our respondents consisted of 109 active female sex workers, mainly streetwalkers or sex workers who worked in villas. During a 30-minute interview, respondents were interviewed individually and were asked questions regarding their condom use practice. These questions were designed to measure various factors affecting their condom use practice, including attitudes toward condom use, normative pressure, perceived behavioural control, perceived AIDS risks, past condom use behaviour, and future condom use intentions with respect to the two types of partners. Multiple regression analyses reveal that perceived behavioural control is the most important factor associated with these respondents' future condom use across the two types of partners. Perceived AIDS risk is the additional predictor for condom use with clients, while normative pressure is the additional predictor for condom use with steady partners. Past condom use behaviour also provided significant additional prediction for both types of partners, implying the habitual nature of condom use among our respondents. These results have significant implications for designing intervention programmes targeting at increasing condom use by female sex workers in Hong Kong.

Immunolocalization of ion-transport proteins to branchial epithelium mitochondria-rich cells in the mudskipper (Periophthalmodon schlosseri).

The branchial epithelium of the mudskipper Periophthalmodon schlosseri is densely packed with mitochondria-rich (MR) cells. This species of mudskipper is also able to eliminate ammonia against large inward gradients and to tolerate extremely high environmental ammonia concentrations. To test whether these branchial MR cells are the sites of active ammonia elimination, we used an immunological approach to localize ion-transport proteins that have been shown pharmacologically to be involved in the elimination of NH(4)(+) (Na(+)/NH(4)(+) exchanger and Na(+)/NH(4)(+)-ATPase). We also investigated the role of carbonic anhydrase and boundary-layer pH effects in ammonia elimination by using the carbonic anhydrase inhibitor acetazolamide and by buffering the bath water with Hepes, respectively. In the branchial epithelium, Na(+)/H(+) exchangers (both NHE2- and NHE3-like isoforms), a cystic fibrosis transmembrane regulator (CFTR)-like anion channel, a vacuolar-type H(+)-ATPase (V-ATPase) and carbonic anhydrase immunoreactivity are associated with the apical crypt region of MR cells. Associated with the MR cell basolateral membrane and tubular system are the Na(+)/K(+)-ATPase and a Na(+)/K(+)/2Cl(-) cotransporter. A proportion of the ammonia eliminated by P. schlosseri involves carbonic anhydrase activity and is not dependent on boundary-layer pH effects. The apical CFTR-like anion channel may be serving as a HCO(3)(-) channel accounting for the acid-base neutral effects observed with net ammonia efflux inhibition.

Treatment of palmar hyperhidrosis using tap water iontophoresis: local experience.

To evaluate the efficacy and safety of tap water iontophoresis in the treatment of severe idiopathic palmar hyperhidrosis, nine Chinese patients with severe palmar hyperhidrosis that had failed to respond to topical aluminium chloride were given 6 weeks' treatment with tap water iontophoresis at the Social Hygiene Service, Department of Health, Hong Kong. The reduction in sweat output was assessed objectively and subjectively. The mean objective reduction in sweat output was 49%, 51%, 26%, and 22% at week 3, 6, 10, and 12, respectively, since the start of treatment with tap water iontophoresis The mean subjective improvements were 43%, 59%, 30%, and 12% at week 3, 6,10, and 12, respectively. The side effects reported were all mild and transient. We conclude that tap water iontophoresis is a safe and useful treatment modality for palmar hyperhidrosis.

Stability of recombinant consensus interferon to air-jet and ultrasonic nebulization.

The stability of recombinant consensus alpha-interferon (rConIFN) to air-jet and ultrasonic nebulization was evaluated. Volumes of 10 mL of 0.5 mg/mL rConIFN in phosphate-buffered saline (PBS) at pH 6.3 were nebulized with a Collison three-jet nebulizer at 40 psig (10 L/min) for up to 25 min. The effects of pH (3.0, 6.3, and 9.0), additive (0.1% w/v Tween 80, 0.1% w/v Tween 20, and 1% w/v PEG 8000), and ionic strength (0, 0.25, and 1.0) were examined. The effects of ultrasonic nebulization were studied using three devices (DeVilbiss "Aerosonic"; Mountain Medical "Microstat", and Medix "Easimist"). Stability of rConIFN was assessed by size exclusion chromatography and native and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). Structural effects were examined by circular dichroism spectroscopy and bioactivity was assessed by an in vitro mitogenic inhibition bioassay. rConIFN is destabilized by air-jet nebulization. Insoluble noncovalent aggregates are produced rapidly, and only approximately 25% of the initial monomeric protein remains after 25 min of nebulization. This correlates with a decrease in in vitro bioactivity. Aggregation during nebulization is influenced by pH (9.0 < 6.3 < 3.0) but even at the highest pH, > 25% aggregation is observed. Ionic strength does not appear to influence aggregation. rConIFN is also seen to adhere to glass after nebulization. Samples from a rinse of the emptied reservoir with 0.1% w/v SDS, after thorough rinsing with water (three times), show a strong rConIFN band on SDS-PAGE gels. The use of PEG 8000 and Tween mitigate aggregate formation and adhesion (< 20%). The cumulative output collected as a wet or dry aerosol is not aggregated to the same extent as the residual protein remaining in the nebulizer. Ultrasonic nebulization also results in aggregation, but the extent of denaturation is dependent upon the nebulizer used and is related to the heating of nebulizer solutions. Cooling of the nebulizer solution during operation (< 30 degrees C) minimizes aggregation (< 5%), and bioactivity is retained.

The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF.

PURPOSE: The objective of this study was to highlight differences in the pulmonary absorption of a monoPEGylated rhG-CSF and rhG-CSF after intratracheal instillation and aerosol delivery. METHODS: Male Sprague Dawley rats (250 g) were anesthetized and intratracheally instilled (IT) with protein solution or were endotracheally intubated and administered aerosol for 20 min via a Harvard small animal ventilator. A DeVilbiss "Aerosonic" nebulizer containing 5 ml of protein solution at approximately 3 mg/ml was used to generate aerosol. The volume of protein solution deposited in the lung lobes was estimated to be approximately 13 microliters after delivery of Tc-99m HSA solutions. The PEGylated proteins consisted of a 6 kDa (P6) or 12 kDa PEG (P12) linked to the N-terminus of rhG-CSF. rhG-CSF also was administered IT in buffers at pH 4 and pH 7 and in dosing volumes ranging from 100 to 400 microliters. Blood samples were removed at intervals after dosing and the total white blood cell counts (WBC) were determined. Plasma was assayed for proteins by an enzyme immuno assay. RESULTS: The plasma protein concentration v. time profiles were strikingly different for aerosol v. IT delivery. The Cmax values for rhG-CSF and P12 after aerosol delivery were greater than found after IT (Aerosol: 598 +/- 135 (ng/ml) rhG-CSF; 182 +/- 14 P12 v. IT: 105 +/- 12 rhG-CSF; 65.9 +/- 5 P12). Similarly, Tmax was reached much earlier after aerosol administration (Aerosol: 21.7 +/- 4.8 (min) rhG-CSF; 168 +/- 31 P12 v. IT: 100 +/- 17 rhG-CSF; 310 +/- 121 P12). Estimated bioavailabilities (F(lung)%) were significantly greater via aerosol delivery than those obtained after IT (Aerosol: 66 +/- 14 rhG-CSF; 12.3 +/- 1.9 P12 v. IT: 11.9 +/- 1.5 rhG-CSF; 1.6 +/- 0.1 P12). An increase in circulating WBC counts was induced by all proteins delivered to the lungs. The rate and extent of absorption of rhG-CSF was not influenced by the pH employed nor the instilled volume. CONCLUSIONS: Estimates of bioavailability are dependent upon the technique employed to administer drug to the lungs. Aerosol administration provides a better estimate of the systemic absorption of macromolecules.

Some factors associated with the ultrasonic nebulization of proteins.

Ultrasonic nebulization of lactate dehydrogenase (LDH) was investigated using a DeVilbiss "Aerosonic" nebulizer. The enzyme (8ml, 0.025 mg/ml Na2HPO4, pH 7.0) was completely inactivated after 20 minutes of operation. However, the inactivation profile observed during ultrasonic nebulization was different from that previously observed using air-jet nebulization. At least two mechanisms are involved, one associated with heating and the other with aerosol production. By preventing heating of the nebulizer fluid during operation, the denaturation profile was dramatically altered. By additionally including 0.01% w/v Tween 80 or 1% w/v PEG 8000, almost all activity was retained. Similar results were obtained by preventing aerosol production and heating. However, 100% of activity was lost when heating was allowed to occur without aerosol formation. The results demonstrate that cooling in conjunction with a surfactant is one approach that could be used to stabilize proteins to ultrasonic nebulization. However, cooling also significantly reduced solute output from the nebulizer. When operated at 10 degrees C output was negligible. At 50 degrees C the output was 5x greater than that found at room temperature. The median droplet size (micron(s)) was not significantly influenced by the operating temperature of the nebulizer fluid (3.6 +/- 0.4, 21 degrees C; 3.9 +/- 0.2, 50 degrees C, p = NS (n = 6)) although the size distribution was noted to increase at the higher temperature.

Pulmonary delivery of powders and solutions containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the rabbit.

Two powder formulations (MMAD < 4 microns) containing rhG-CSF were insufflated (IF) via an endotracheal tube at doses of 5, 75 or 500 micrograms/kg to New Zealand white rabbits. Doses of 5 and 500 micrograms/kg of solutions were administered by intratracheal instillation (IT), subcutaneous (SC) injection in the thigh and intravenous injection (i.v.) via the marginal ear vein. Blood samples were removed at regular intervals from an indwelling jugular catheter. Blood was analyzed directly for total white blood cell counts (WBC). Plasma was assayed for rhG-CSF by a specific ELISA. The distribution of radioactive dose in lung tissue was found after administering Tc99m HSA in solution or when incorporated into powders. The pharmacokinetics and pharmacodynamics were determined for all routes of administration. High dose IV concentration vs. time profiles declined biexponentially (t1/2 alpha = 0.6 +/- 0.2 hrs, t 1/2 beta = 4.6 +/- 0.2 hrs, n = 8). Clearance was does dependent (11.6 +/- 2.6 [500 micrograms/kg, n = 8] vs; 21.8 +/- 3.3 ml/hr/kg [5 micrograms/kg, n = 5]). A normal systemic response was obtained after IF, indicating that rhG-CSF retains activity in the solid state. Dissolution and absorption of rhG-CSF from the powders were not rate limiting. The plasma concentration vs. time profiles peaked at similar times to those after IT (Tmax 1-2 hrs) but were earlier than obtained after SC (Tmax 6-10 hrs). Powders were less efficiently dosed to the lung lobes after insufflation compared with instillates (14.7 +/- 10.5 vs. 60.1 +/- 10.6%), resulting in bioavailabilities ranging from 5 to 33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction and experimental determination of solute output from a Collison nebulizer.

The total output from a nebulizer is made up of aqueous droplets containing solute and a significant component of water vapor. The solvent loss is reflected in an increase in the nebulizer solution concentration over time and this has been described mathematically. This theory, originally described by Mercer et al., was modified to describe the solute output from a three-jet Collison nebulizer. The influence of concentration, air flow (air pressure), volume, and temperature on the output parameters were then studied. Inlet air pressures were 10 (4.1), 20 (6.4), and 40 (10.0) psig (L/min), starting concentrations were 0.1, 2, and 5% (w/w) and initial solution volumes were 10 and 20 mL. To study temperature effects, solutions were nebulized at fixed temperatures ranging from 4 to 50 degrees C. This was achieved by water-jacketing the nebulizer flask. Test solutions consisted of mannitol and a fixed concentration of 11.1 micrograms/mL carboxyfluorescein. Nebulization was carried out for up to 30 min using dry, filtered air at ambient temperature. Total output was determined gravimetrically while solute output was determined by fluorimetry (495-nm excitation, 515-nm emission). Solution concentration changes were also monitored over time by fluorimetry. The results show that the solution and solvent output parameters are independent of concentration, volume, and air flow within the ranges studied but that solvent output, in particular, is highly dependent upon temperature.

Quality monitoring of haemapheresis platelet concentrates: sampling in EDTA helps with the standardization and improves the consistency.

At the North London Blood Transfusion Centre, all haemapheresis platelet concentrates (PC) are tested in duplicate by a Technicon H-1 analyser to provide accurate information on the cell separator performance and on the cellular content of packs before issue. Repeated counting on fresh samples (within 4 h) reveals spontaneous aggregation (SA), which causes inconsistency in the estimated platelet yields and invalidates the cellular indices. Preliminary work showed that sampling into EDTA eliminated SA. Further studies on the effect of EDTA were undertaken as follows: (i) using the same PCS preparations (n = 7) stored conventionally and sampled daily in tubes with and without EDTA, and (ii) using fresh V50 and CS3000 PC to assess the difference on samples routinely collected in EDTA tubes for 2 months compared to those collected without EDTA in the previous 2 months. EDTA improved concordance of duplicate counts in fresh products. The increase in platelet yield in V50 and CS3000 preparations (12-22% respectively) was associated with a concomitant decrease (60-74%) in erythrocyte contamination. The variation in leucocyte count (3-5%) was less pronounced but the percentage differential was affected. There was also a systematic increase (8-11%) in mean platelet volume (MPV) due to EDTA. In PCS preparations the EDTA-induced variation in the cellular indices remained essentially in the same order (2-6%), while the MPV decreased progressively on storage. The difference in MPV can be used to assess the storage stability of various PC preparations. The implication of a double sampling technique (CPDA-1 and EDTA/CPDA-1) in the quality monitoring of haemapheresis procedures is substantial.

Characteristics of platelet concentrates, with particular reference to Autopheresis C Plateletcell: correlation between dMPV and other tests for platelet function.

The quality of platelet concentrates (PC) collected by the Autopheresis C cell separator was assessed in two Regional Transfusion Centres taking part in a multicentre study. This study also enabled the assessment of a new simple, rapid test of platelet function and comparison with more established tests, such as aggregation to adenosine diphosphate, as a tool for the quality testing of PC. The new test, based upon the measurement of mean platelet volume using automated haematological cell analysers, is rapid and uses the same samples as those used to estimate the platelet and leucocyte content of the concentrates. The high correlation between this test and the other tests of platelet function used in the study suggests that it is an ideal tool in the quality testing of platelet concentrates.