Cardiovascular outcomes associated with use of clarithromycin: population based study

Study question What is the association between clarithromycin use and cardiovascular outcomes? Methods In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke. Study answer and limitations The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients. What this study adds Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population

A Comparison Between Chinese Children Infected with Coronavirus Disease-2019 and with Severe Acute Respiratory Syndrome 2003

OBJECTIVES: To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in two Chinese pediatric cohorts, given that the causative pathogens and are biologically similar. , STUDY DESIGN: This is a cross-sectional study reviewing paediatric patients with SARS (n = 43) and COVID-19 (n=244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children's Hospital in Wuhan, respectively. Demographics, hospital length of stay, clinical and laboratory features were compared RESULTS: Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiological associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients COVID-19. No SARS patients were asymptomatic at the time of admission. 29.1% and 20.9% COVID-19 patients were asymptomatic on admission and throughout their hospital stay, respectively. More SARS patients required oxygen supplementation than COVID-19 patients (18.6 vs. 4.7%, P = 004). Only 1.6% COVID-19 and 2.3% SARS patients required mechanical ventilation. Leukopenia (37.2% vs. 18.6%, p=0.008), lymphopenia (95.4% versus 32.6%, p<0.01), and thrombocytopenia (41.9% vs 3.8%, p<0.001) were significantly more common in SARS than COVID-19 patients. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in COVID-19 patients regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding. CONCLUSIONS: Children with COVID-19 were less symptomatic and had more favorable hematological findings than children with SARS

Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study

Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12–18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization’s Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14–73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04–217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01–4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed (P = 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A study on the solid state characteristics of spray-congealed glyceryl dibehenate solid lipid microparticles containing ibuprofen

<p><i>Objective</i>: To study the solid state modifications of ibuprofen (IBU)-loaded spray-congealed glyceryl dibehenate (GB) solid lipid microparticles (SLMs) and the influence of polymeric additives using a combination of calorimetric and spectroscopic techniques.</p> <p><i>Materials and methods</i>: IBU-loaded SLMs were produced by spray congealing with GB as the matrix material. Polyvinyl-2-pyrrolidone-vinyl-acetate (PVP/VA) and ethylcellulose (EC) were employed as additives. Of particular interest in this study were the solid state modifications of the drug and GB matrix induced by spray congealing and the effects of aging, as well as drug–matrix interactions. Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, differential scanning calorimetry, hot stage microscopy and powder X-ray diffraction provided complementary analyses in understanding drug and lipid matrix polymorphism and interaction. The yield, morphology, drug content and encapsulation efficiencies of SLMs were also investigated.</p> <p><i>Results and discussion</i>: Drug encapsulation efficiencies and yields of spray congealed SLMs were consistently high for all formulations. GB congealed as an unstable α-polymorph which reverted to the stable β′-polymorph within a few weeks. PVP/VA accelerated the polymorphic conversion in less than a week, while EC took about a year. IBU formed a solid solution with GB regardless of the GB polymorphic form.</p> <p><i>Conclusions</i>: Spray congealing is efficient for producing drug-loaded SLMs. It induces polymorphic changes in GB. The latter incorporated 20%, w/w IBU as a solid solution and polymeric additives exerted contrasting effects on the GB polymorphic conversion.</p

Development and validation of risk prediction model for recurrent cardiovascular events among Chinese: the Personalized CARdiovascular DIsease risk Assessment for Chinese model

Aims: Cardiovascular disease (CVD) is a leading cause of mortality, especially in developing countries. This study aimed to develop and validate a CVD risk prediction model, Personalized CARdiovascular DIsease risk Assessment for Chinese (P-CARDIAC), for recurrent cardiovascular events using machine learning technique. Methods and results: Three cohorts of Chinese patients with established CVD were included if they had used any of the public healthcare services provided by the Hong Kong Hospital Authority (HA) since 2004 and categorized by their geographical locations. The 10-year CVD outcome was a composite of diagnostic or procedure codes with specific International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariate imputation with chained equations and XGBoost were applied for the model development. The comparison with Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2°P) and Secondary Manifestations of ARTerial disease (SMART2) used the validation cohorts with 1000 bootstrap replicates. A total of 48 799, 119 672 and 140 533 patients were included in the derivation and validation cohorts, respectively. A list of 125 risk variables were used to make predictions on CVD risk, of which 8 classes of CVD-related drugs were considered interactive covariates. Model performance in the derivation cohort showed satisfying discrimination and calibration with a C statistic of 0.69. Internal validation showed good discrimination and calibration performance with C statistic over 0.6. The P-CARDIAC also showed better performance than TRS-2°P and SMART2. Conclusion: Compared with other risk scores, the P-CARDIAC enables to identify unique patterns of Chinese patients with established CVD. We anticipate that the P-CARDIAC can be applied in various settings to prevent recurrent CVD events, thus reducing the related healthcare burden

Safety of Nurse-administered Propofol Sedation Using PCA Pump for Outpatient Colonoscopy in Chinese Patients: A Pilot Study

To determine the safety and effectiveness of nurse-administered propofol sedation using patient-controlled analgesia (PCA) pump in outpatient colonoscopy in a Chinese population. METHODS: From April to June 2005, 50 consecutive ASA class I or II patients aged 18–65 undergoing outpatient colonoscopy in an endoscopy centre of a regional hospital were prospectively recruited in this study. After a loading dose of 40–60 mg intravenous propofol, a mixture containing 14.3 mg propofol and 35μg alfentanil were delivered via a patient-controlled syringe pump as bolus dose by an endoscopy nurse under the supervision of an endoscopist during the procedure. Lockout time was set to be zero. We aimed to achieve conscious sedation, with an Observer's Scale for Sedation and Alertness (OSSA) score of 3. The primary outcome measure was complications from sedation, which included hypotension, bradycardia and desaturation. Other outcome measures included onset time, patients' pain score, endoscopists' and nurses' satisfaction on the level of sedation, patients' satisfaction regarding the procedure (measured by 10 cm visual analogue scale), and their willingness to repeat the procedure. RESULTS: The mean lowest systolic blood pressure and mean arterial pressure (MAP) were 103.2 ± 12.4 mmHg and 78.3 ± 11.0 mmHg, respectively. The mean percentage drop in MAP was 15.7 ± 11.9%. Six patients (12.2%) developed transient hypotension. Three patients (6.1%) had bradycardia. There was no episode of desaturation. The median onset time to reach OSSA score of 3 was 1 minute (range, 0.5–20.5). The OSSA score of 3 could be maintained throughout the procedure. The mean loading dose of propofol was 48.9 ± 6.7 mg. The mean total dosages of propofol and alfentanil given were 124.2 ± 38.1 mg and 184.3 ± 93.7μg, respectively. Endoscopists, endoscopy nurses and patients were highly satisfied with the sedation. The median pain score was 1 (range, 0–10; 0 = no pain, 10 = very painful), and the mean recovery time was 2.8 ± 2.8 minutes. Most patients (93.9%) were willing to repeat the procedure. CONCLUSION: Nurse-administered propofol sedation using PCA pump is safe and effective in sedation and pain control in outpatient colonoscopy in a healthy Chinese population