Probabilistic Methods of Quantitative Risk Analysis: A Case Study with Bayesian Networks and Petri Nets Approach

PresentationConventional risk assessment methods such as Bow Ties have been incapable of capturing the dynamic nature of a system and hence have failed to properly predict the time dependent failure of barriers. Modifications made to incorporate time dependencies in such methods have not found wide application yet. Rapidly changing physical parameters necessitate techniques capable of considering the dynamic aspects of a system throughout its lifetime. The present work is aimed at demonstrating the applicability of Bayesian Networks and Petri Nets to capture the time dependencies of systems to carry out a quantitative risk analysis. A case study is to be carried out using both Bayesian Network and Petri Nets to provide an insight into the pros and cons of using each method to model the system. This insight is to provide a starting point for the development of a model that will enable us to conduct a quantitative risk analysis considering all factors that can lead to an incident

Lessons from Canada’s notice of compliance with conditions policy for the life-cycle regulation of drugs

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada\u27s regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market clinical trials, finding that most NOC/c authorizations are based on one, single-arm clinical trial using a surrogate endpoint. Post-market trials are more likely to be randomized, Phase III trials but mostly use surrogate endpoints. Based on our findings, we recommend increasing decision-making transparency throughout the regulatory process, developing comprehensive eligibility criteria for selecting appropriate health technologies, modernizing pre-market evidence requirements, adopting a more active role in designing post-market trials, and utilizing automatic expiry, stronger penalties, and ongoing disclosure of the status of post-market trials to promote compliance

Genetic variation in the interleukin-28B gene is associated with spontaneous clearance and progression of hepatitis C virus in Moroccan patients

Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population. We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5' allelic discrimination assay. The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99-11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19-66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99-3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08-8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40-3.93; p = 0.0100). In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection

Preconception care: promoting reproductive planning

INTRODUCTION: Preconception care recognizes that many adolescent girls and young women will be thrust into motherhood without the knowledge, skills or support they need. Sixty million adolescents give birth each year worldwide, even though pregnancy in adolescence has mortality rates at least twice as high as pregnancy in women aged 20-29 years. Reproductive planning and contraceptive use can prevent unintended pregnancies, unsafe abortions and sexually-transmitted infections in adolescent girls and women. Smaller families also mean better nutrition and development opportunities, yet 222 million couples continue to lack access to modern contraception. METHOD: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Comprehensive interventions can prevent first pregnancy in adolescence by 15% and repeat adolescent pregnancy by 37%. Such interventions should address underlying social and community factors, include sexual and reproductive health services, contraceptive provision; personal development programs and emphasizes completion of education. Appropriate birth spacing (18-24 months from birth to next pregnancy compared to short intervals <6 months) can significantly lower maternal mortality, preterm births, stillbirths, low birth weight and early neonatal deaths. CONCLUSION: Improving adolescent health and preventing adolescent pregnancy; and promotion of birth spacing through increasing correct and consistent use of effective contraception are fundamental to preconception care. Promoting reproductive planning on a wider scale is closely interlinked with the reliable provision of effective contraception, however, innovative strategies will need to be devised, or existing strategies such as community-based health workers and peer educators may be expanded, to encourage girls and women to plan their families

Perbandingan Kandungan Gizi Ikan Nila Oreochromis Niloticus Asal Danau Mawang Kabupaten Gowa Dan Danau Universitas Hasanuddin Kota Makassar

Penelitian tentang “Perbandingan Kandungan Gizi Ikan Nila Oreochromis niloticus Asal Danau Mawang Kabupaten Gowa dan Danau Universitas Hasanuddin (Unhas) Kota Makassar” telah dilaksanakan pada bulan Maret-Juni 2016. Penelitian ini bertujuan untuk mengetahui kandungan gizi ikan nila Oreochromis niloticus yang hidup di perairan berbeda. Analisis kandungan gizi dilakukan di Balai Besar Laboratorium Kesehatan Makassar, Makassar, Sulawesi Selatan. Metoda yang digunakan untuk mengukur kandungan karbohidrat adalah Luff Schroorl; kandungan protein menggunakan metode Kjeldhal; kadar lemak menggunakan metode Soxhlet. Pengukuran penetapan kandungan mineral kalsium dan besi dengan metode AAS (Atom Absorbance System) dan fosfor dengan metode spektrofotometer UV-Vis. Hasil penelitian menunjukkan, bahwa: ikan nila Oreochromis niloticus asal danau Mawang (0,32 g) mempunyai kandungan karbohidrat ikan lebih tinggi dibanding asal Danau Unhas (0,18 g); kandungan protein ikan asal danau Mawang (12,94 g) lebih rendah dibanding ikan asal danau Unhas (16,79 g), kandungan lemak ikan asal danau Mawang (0,10 g) lebih rendah dibanding ikan asal danau Unhas (0,18 g); kandungan kalsium ikan asal danau Mawang (4,782 mg) lebih tinggi dibanding ikan asal danau Unhas (3,027 mg); kandungan fosfor ikan asal danau Mawang (360 mg) lebih rendah dibanding ikan asal danau Unhas (610 mg); dan kandungan zat besi ikan asal danau Mawang (2,756 mg) lebih rendah dibanding ikan asal danau Unhas (0,835 mg)

Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

BACKGROUND: Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear. METHODS: From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression. RESULTS: EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p  pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone

Locoregional Residual Esophageal Cancer after Neo-adjuvant Chemoradiotherapy and Surgery Regarding Anatomic Site and Radiation Target Fields A Histopathologic Evaluation Study:A Histopathologic Evaluation Study

OBJECTIVE: Neoadjuvant chemoradiotherapy followed by surgery establishes a considerable pathologic complete response (pCR) in EC. The aim was to determine site of residual tumor and its prognostic impact. SUMMARY BACKGROUND DATA: High rates of residual tumor in the adventitial region even inside the radiation fields will influence current decision-making. METHODS: We evaluated resection specimens with marked target fields from 151 consecutive EC patients treated with carboplatin/paclitaxel and 41.4Gy between 2009 and 2018. RESULTS: In radically resected (R0) specimens 19.8% (27/136) had a pCR (ypT0N0) and 14% nearly no response (tumor regression grade: tumor regression grade 4-5). Residual tumor commonly extended in or restricted to the adventitia (43.1%; 47/109), whereas 7.3% was in the mucosa (ypT1a), 16.5% in the submucosa (ypT1b) and 6.4% only in lymph nodes (ypT0N+). Macroscopic residues in R0-specimens of partial responders (tumor regression grade 2-3: N = 90) were found in- and outside the gross tumor volume (GTV) in 33.3% and 8.9%, and only microscopic in- and outside the clinical target volume in 58.9% and 1.1%, respectively. Residual nodal disease was observed proximally and distally to the clinical target volume in 2 and 5 patients, respectively. Disease Free Survival decreased significantly if macroscopic tumor was outside the GTV and in ypT2-4aN+. CONCLUSIONS: After neoadjuvant chemoradiotherapy, pCR and ypT1aN0 were seen in a limited number of R0 resected specimens (19.8% and 7.3%, respectively), whereas 6.4% had only nodal disease (yT0N+). Disease Free Survival decreased significantly if macroscopic residue was outside the GTV and in responders with only nodal disease. Therefore, we should be cautious in applying wait and see strategies

Clinical Determinants and Prognostic Implications of Renin and Aldosterone in Patients with Symptomatic Heart Failure

Aims Activation of the renin-angiotensin-aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF. Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT-CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all-cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT-CHF study, median renin and aldosterone levels were 85.3 (percentile(25-75) = 28-247) mu IU/mL and 9.4 (percentile(25-75) = 4.4-19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted-HR (95% CI) = 1.47 (1.16-1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted-HR (95% CI) = 1.16 (0.93-1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT-CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies. Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the "point" measurement of renin and aldosterone in HF is of limited clinical utility