Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P < 0.05). Organ injury was present at 96 h in the I.P. LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the I.P. LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-I.N. LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn’s, P < 0.01). At 24 h in the post-I.N. LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of I.N. LPS in mice produced lung injury but did not produce sepsis. Higher doses of I.P. LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

Background and Objectives: The Philippine Department of Health (DOH) is mandated by law to, among others, develop capacities and accredit physicians and rehabilitation practitioners across the country on the assessment and management of drug dependence. This paper describes the design and presents the outputs of an advanced course on screening and assessment of drug dependence developed by DOH in partnership with the College of Public Health of the University of the Philippines Manila, Philippine College of Addiction Medicine, and the Group for Addiction Psychiatry of the Philippines.

Methodology: Review, abstraction and synthesis of data from training-related documents and records for the training activities implemented in 2014.

Results: The Level 2a course is a five-day program that focuses on enhancing the skills of physicians and rehabilitation practitioners on the screening and assessment of drug dependence using team-based and practical learning approaches, and builds on learnings from the basic accreditation course. A total of 36 participants from ten Drug Abuse Treatment and Rehabilitation Centers (DATRCs) in nine regions completed the pilot implementation of the course in 2014. In general, the overall participant feedback on the training was mainly favorable based on data from 47% of participants who agreed or strongly agreed to statements on the relevance and attainment of the course aims (mean rating of 1.10±0.31, 1 = Strongly agree, 5 = Strongly disagree), and the appropriateness of its content (1.24±0.43) and design (1.18±0.39). A paired-samples t-test comparing scores for 44% of participants showed that there was a highly statistically significant difference in the pre-test (54%±13%) and post-test scores (69%±10%); t(16)=6.4240, p <0.0001.

Conclusion: Development and design of capability-building initiatives in the field of drug rehabilitation will necessitate alignment with practice standards, grounding in the real-world setting in which professionals work, and orientation towards practical learning.

Objective: This study evaluated the validity of self-reported smartphone usage data against objectively-measured smartphone usage data by directly tracking the activities in the participants’ smartphone among Chinese adolescents and young adults in Hong Kong. Methods: A total of 187 participants were recruited (mean age 19.4, 71.7% female) between 2017 and 2018. A smartphone usage tracking app was installed on all participants’ smartphone for 7 consecutive days. After the 7-day monitoring period, they completed a selfadministered questionnaire on smartphone usage habits. Results: Although the correlation between self-reported and objectively-measured total smartphone usage time was insignificant (ρ=-0.10, p=0.18), in three out of the four usage domains were positively and significantly correlated, namely social network (ρ=0.21, p=0.005), instant messaging (ρ=0.27, p<0.001), and games (ρ=0.64, p<0.001). Participants’ self-report of the total time spent on smartphones exceeded the objective data by around 760 min per week (self-reported 1,930.3 min/wk vs. objectively-measured 1,170.7 min/wk, p<0.001). Most of the over-reporting was contributed by the web browsing domain (self-reported 447.8 min/wk vs. objectively-measured 33.3 min/wk, p<0.001). Conclusion Our results showed large discrepancies between self-reported smartphone and objectively-measured smartphone usage except for self-reported usage on game apps.

High-risk human papillomaviruses (HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α (TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase (hTERT)-immortalized cells. TNFα treatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as (1) calcium resistance, (2) anchorage independence, and (3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in hTERT-immortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated hTERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting microRNAs miR-203 and miR-200c. Overexpression of miR-203 and miR-200c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.

High-quality data are the foundation to monitor the progress and evaluate the effects of road traffic injury prevention measures. Unfortunately, official road traffic injury statistics delivered by governments worldwide, are often believed somewhat unreliable and invalid. We summarized the reported problems concerning the road traffic injury statistics through systematically searching and reviewing the literature. The problems include absence of regular data, under-reporting, low specificity, distorted cause spectrum of road traffic injury, inconsistency, inaccessibility, and delay of data release. We also explored the mechanisms behind the problematic data and proposed the solutions to the addressed challenges for road traffic statistics.
Accidental Injuries ; epidemiology ; prevention & control ; Accidents, Traffic ; prevention & control ; statistics & numerical data ; Global Health ; Humans

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment. Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”) were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged 70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged 80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged 80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.
Age Factors ; Aged ; Aged, 80 and over ; Databases, Factual ; Humans ; Kaplan-Meier Estimate ; Lower Urinary Tract Symptoms ; Male ; Middle Aged ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Transurethral Resection of Prostate/methods* ; Urinary Retention/surgery*