Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.

Adipokines and the risk of active TB: a nested case-control study.

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.

Tobacco use and other aspects related to smoking among school-going adolescents aged 13-15 years in Malaysia: Analysis of three cross-sectional nationally representative surveys in 2003, 2009 and 2016.

INTRODUCTION: Periodic surveys on tobacco use patterns and other aspects of tobacco use among school-going adolescents in Malaysia provide information on the effectiveness of anti-smoking measures implemented. However, such information is limited in Malaysia. We investigated the prevalence of smoking and other related aspects among middle-secondary school students in Malaysia from the years 2003-2016 to fill this gap. METHODS: We analyzed data from the Global Youth Tobacco Survey (GYTS) 2003, GYTS 2009, and the Tobacco and Electronic Cigarette Survey among Malaysia Adolescents (TECMA) 2016. The surveys employed multistage sampling to select representative samples of adolescents attending secondary school in Malaysia. Data were collected using a pre-validated self-administered anonymous questionnaire adopted from the GYTS. RESULTS: Between 2003 and 2016, major changes occurred in which there were reductions in the prevalence of ever smoking, current smoking, and susceptibility to smoking. Reductions were also observed in exposure to SHS in public places and in the home. The proportion of school-going adolescents who support a ban on smoking in public places increased between 2013 to 2016, and there was a significant reduction in the proportion of respondents that were offered 'free' cigarettes by tobacco company representatives. However, there was no difference in the proportion of adolescents who initiated smoking before the age of 10 years and current smokers seeking advice to quit smoking across the time period. CONCLUSIONS: Our study indicates that the smoking policies and measures have been effective in reducing smoking prevalence, secondhand smoke exposure, and access to cigarettes, among school-going adolescents in Malaysia. However, measures to reduce smoking initiation and increase smoking cessation need to be strengthened to reduce the burden of smoking-related diseases in Malaysia in the long-term.

Malaysian adolescents' exposure to secondhand smoke in the car of their parents/guardians: A nationwide cross-sectional school-based study.

INTRODUCTION: We investigated the prevalence of children's exposure to secondhand smoke (SHS) in the car of their parents/guardians and the associated factors. METHODS: A self-administered validated questionnaire was used to obtain data from the nationally representative samples of school-going adolescents aged 11-19 years in Malaysia. Prevalence rates were computed and chi-squared tests and multiple logistic regression were conducted. RESULTS: Of the participants, 23.3% reported exposure to SHS at least once in the car of their parents/guardians during the last 7 days before the survey. The prevalence and likelihood of SHS exposure were significantly higher in Malays, descendants of natives of Sabah and Sarawak, schools in rural areas, females, and current smokers. However, age group and knowledge on the harmful effects of SHS were not significant after adjusting for confounding effects. CONCLUSIONS: A substantial proportion of school-going adolescents were exposed to secondhand smoke in the car of their parents/guardians. This highlights the need for effective tobacco control measures to include health promotion and smoke-free car regulations to be introduced to prevent severe health hazards and to reduce smoking initiation among non-smoking adolescents.

Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

BACKGROUND: Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors. PATIENTS AND METHODS: This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21 days on, 7 days off. Atezolizumab was dosed at 800 mg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival. RESULTS: Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n = 84), melanoma (n = 22), non-small-cell lung cancer (NSCLC; n = 28), and other solid tumors (n = 16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases. CONCLUSIONS: Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study. CLINICALTRIALS.GOV IDENTIFIER: NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix, available at Annals of Oncology online).

MRI Features of Aquaporin-4 Antibody-Positive Longitudinally Extensive Transverse Myelitis: Insights into the Diagnosis of Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND PURPOSE: Longitudinally extensive transverse myelitis is a well-documented spinal manifestation of neuromyelitis optica spectrum disorders, however, other forms of nontumorous myelopathy can also manifest as longitudinally extensive transverse myelitis. Our aim was to evaluate the MR imaging features of aquaporin-4 antibody-positive longitudinally extensive transverse myelitis, which is strongly associated with neuromyelitis optica spectrum disorders. MATERIALS AND METHODS: We evaluated cervicomedullary junction involvement, cord expansion ratios, bright spotty lesions, the number of involved segments, skipped lesions, enhancement patterns, and axial distribution patterns using spinal MR imaging of 41 patients with longitudinally extensive transverse myelitis who underwent aquaporin-4 antibody testing. Univariate logistic regression analysis was performed to identify factors associated with aquaporin-4 antibody seropositivity, which were then used to develop a scoring system for diagnosing aquaporin-4 antibody-positive longitudinally extensive transverse myelitis. Interrater reliability for cord expansion ratio measurement and bright spotty lesions was determined using intraclass correlation coefficients and κ values, respectively. RESULTS: Fifteen patients with longitudinally extensive transverse myelitis were aquaporin-4 antibody-positive. Sex (female), cervicomedullary junction involvement, a cord expansion ratio of >1.4, and bright spotty lesions were significantly associated with aquaporin-4 antibody seropositivity. The sensitivity and specificity of the scoring system were 73.3% and 96.2%, respectively. The interclass correlation value for the cord expansion ratio was 0.78, and the κ value for bright spotty lesions was 0.61. CONCLUSIONS: Our scoring system, based on cervicomedullary junction involvement, higher cord expansion ratio, bright spotty lesions, and female sex, can facilitate the timely diagnosis of neuromyelitis optica spectrum disorders.

Prevalence and factors associated with smoking among adults in Malaysia: Findings from the National Health and Morbidity Survey (NHMS) 2015.

INTRODUCTION: The continuous monitoring of smoking prevalence and its associated factors is an integral part of anti-smoking programmes and valuable for the evaluation of the effectiveness of anti-smoking measures and policies. This study aimed at determining prevalence of smoking and identifying socio-demographic factors associated with smoking among adults in Malaysia aged 15 years and over. METHODS: This is a cross-sectional study with a representative sample of 21 445 adults in Malaysia, aged 15 years and over, selected via a stratified, two-stage proportionate-to-size sampling method. Data were obtained from face-to-face interviews by trained research assistants, using a standard validated questionnaire. Multivariable logistic regression was performed to determine socio-demographic factors associated with smoking among Malaysians. RESULTS: The overall prevalence of smoking was 22.8% (95% CI: 21.9-23.8%), with males having a significantly higher prevalence compared to females (43.0%, 95% CI: 41.1-44.6 vs 1.4%, 95% CI: 1.1-1.7). The highest smoking prevalence was observed among other ethnicities (35.7%), those aged 25-44 years (59.3%), and low educational attainment (25.2%). Males, those with lower educational attainment and Malays were significantly associated with smoking. CONCLUSIONS: The prevalence of smoking among Malaysians, aged 15 years and over, remains high despite the implementation of several anti-smoking measures over the past decades. Specially tailored anti-smoking policies or measures, particularly targeting males, the Malays, younger adults and those with lower educational attainment, are greatly warranted to reduce the prevalence of smoking in Malaysia.

[The psychiatric hospital discharge database (RIM-P): An essential tool for the surveillance of hospitalization after a suicide attempt]. / Le Recueil d'information médicalisé en psychiatrie (RIM-P) : un outil nécessaire pour la surveillance des hospitalisations suite à une tentative de suicide.

BACKGROUND: Epidemiological surveillance of suicide attempts is essential for monitoring indicator trends in the evaluation of prevention actions. As part of this surveillance, analysis of data from hospitalization for suicide attempts is particularly useful. METHODS: For the first time, data from two national hospital discharge databases, the "Programme de médicalisation des systèmes d'information en médecine, chirurgie, obstétrique" (PMSI-MCO) and the " Recueil d'information médicalisé en psychiatrie" (RIM-P) have been analyzed jointly. All patients aged 10 or more hospitalized in 2012 in medicine, surgery or psychiatry departments in metropolitan France have were included. RESULTS: Through 2012, 89,072 patients (62% females and 38% males) totalized 134,051 hospital stays following a suicide attempt, with 93.4% (n=83,196) in medicine or surgery wards and 32.1% (n=28,594) in psychiatry wards (solely or transferred after a stay in medicine or surgery). However, among the patients transferred to psychiatry after hospitalization in medicine or surgery for suicide attempt, 82.4% had no suicide attempt code noted at their discharge from psychiatry. One or more psychiatric diagnoses were observed in 75% of the patients hospitalized for suicide attempt. The most common diagnoses in men and in women were mood disorders (46%), particularly depression (42%; 44% in women and 38% in men). Mental disorders related to alcohol use were noted in more than a quarter of the patients, more frequently in men (37%) than in women (21%). Some diagnoses were rarely noted in medicine or surgery, such as anxiety disorders and disorders of adult personality and behavior. CONCLUSION: Improvement of the epidemiological surveillance of suicide attempts requires a systematic coding of hospitalizations in psychiatry as well as in medicine and surgery. Data from hospitalization in psychiatry yield a more precise identification of psychiatric co-morbidities associated with suicide attempts. The frequent presence of mental problems associated with suicide attempts should encourage clinicians to search for these symptoms systematically as soon as possible after admission of the patient.