Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma.

BACKGROUND: Treatment outcome of children with pediatric hepatocellular carcinoma (pHCC) is poor. Therefore, we evaluated the tyrosine kinase inhibitor sorafenib in a model of pHCC. METHODS: Cell viability after treatment with sorafenib was evaluated in HC-AFW1 cells (pHCC) using MTT assay and compared to an adult HCC (aHCC) and two hepatoblastoma (HB) cell lines. ERK, pERK, E-cadherin, and vimentin expression were investigated using Western Blot. Sorafenib (60 mg/kg) was administered orally to NOD.Cg-Prkdcscid-IL2rgtmWjl/Sz mice bearing subcutaneous HC-AFW1-derived tumors. Tumor progression, viability, and vascularization were monitored by tumor volume, AFP levels, and CD31 immunostaining, respectively. Sensitization to sorafenib was evaluated using the ß-catenin inhibitor ICG001. RESULTS: Sorafenib reduced cell viability in HC-AFW1 (IC50: 8 µM), comparable to HB cells, however less pronounced in aHCC cells (IC50: 23 µM). Sorafenib inhibited ERK signaling in both, HC-AFW1 cells and -xenografts. In vivo, sorafenib treatment only led to a moderate tumor growth inhibition, although significant reduction of vascularization and tumor growth kinetics was observed. Long-term treatment with sorafenib decreased E-cadherin, but showed no induction of vimentin expression. Combining sorafenib with a ß-catenin inhibitor led to an additional reduction of cell viability. CONCLUSION: Sorafenib together with inhibitors of the ß-catenin pathway might be an effective tool in the treatment of pediatric HCC.

Managing Adult Obese Patients at Primary Health Care Centers in Qassim Province, Saudi Arabia.

Background Overweight and obesity have become a global health problem. This study aims to reduce the same problem, primarily with all levels of physicians and the hidden responsibility of all other allied health care workers and communities, including families and individuals. Objective The objective of this study is to determine the knowledge, attitude, and practice among the physicians toward the management of adult obesity at primary health care centers (PHCCs) of Qassim Province, Saudi Arabia. Methods A cross-sectional study was conducted among the 140 physicians working at the PHCC of Qassim through a self-administered questionnaire. A simple random method was used for the PHCC selection, and all the physicians were included at the PHCC level. Data was collected, cleaned, and analyzed with IBM SPSS Statistics, version 21.0 (IBM Corp., Armonk, NY). Necessary statistical tests were applied. Results The mean age and standard deviation (SD) in the study population were 34.29 ± 9.42, and 55.7% were males. The mean knowledge score and SD of correct answers were 4.61 ± 1.31. About four or more questions were answered correctly out of six knowledge questions (80.7%, n = 113). Out of 13 questions, the mean ± SD of correct practice questions was 9.88 ± 2.02. The mean ± SD of attitude questions was 8.06 ± 1.13. About 33 (23.6%) of the study population received obesity training courses. Conclusions Based on the study results, good knowledge, practice, and attitude were observed among the PHCC physicians of Qassim. However, a smaller number of physicians received obesity training in the study.

The risk factors of biliary fistula after radical resection of perihilar cholangiocarcinoma in elderly patients and its influence on prognosis: a retrospective cohort study.

Background: Nowadays, the incidence of perihilar cholangiocarcinoma (PHCC) is increasing yearly, and biliary fistula is a common complication. However, there are few reports on the factors affecting the occurrence of biliary fistula. This study aimed to analyze the risk factors for the occurrence of biliary fistula after radical surgery for PHCC in elderly patients to provide a reference basis for improving the prognosis. Methods: From April 2016 to April 2021, we randomly included 250 elderly patients with pathologically diagnosed PHCC. Based on our established inclusion and exclusion criteria, we included 211 patients finally Bile drainage for 3 consecutive days after abdominal drainage or single bile drainage ≥100 mL/d was used as the diagnostic criteria for biliary fistula. Multiple logistic regression was used to analyze the independent risk factors for biliary fistula after radical surgery for PHCC. Besides, the Prognostic Score (PS), the Karnofsky performance score (KPS), and the quality of life (QOL) score were used to assess the patients' postoperative recovery, and survival curves were drawn to reflect their 1-year survival rate, using overall survival. Results: The statistical results showed a 36.5% incidence of biliary fistula. Our study showed that preoperative cholangitis, number of biliary anastomoses, etc. were independent risk factors for grade B and grade C biliary fistula. Besides, the presence of intraoperative hemorrhage (OR =0.223, P=0.006) and γ-glutamyl transpeptidase (γ-GT) on the first postoperative day (OR =1.011, P=0.013) were still independent risk factors for grade B biliary fistula, while C-reactive protein (CRP) (OR =1.026, P=0.011) and total bilirubin (TBil) (OR =0.003, P=1.066) on the first postoperative day and bile duct diameter (OR =0.299, P=0.020) were independent risk factors for grade C biliary fistula. Analysis of variance (ANOVA) showed statistically significant differences (P<0.05) between the three groups in terms of PS (P=0.000), KPS (P=0.001), and QOL scores (P=0.000). Conclusions: The incidence of postoperative biliary fistula remains high in elderly patients treated with radical surgery for PHCC and seriously affects their prognosis. Therefore, focusing on the clinical characteristics and risk factors of patients, improving surgical precision and enhancing postoperative patient care to reduce the likelihood of postoperative biliary fistula, thereby prolonging patient life.

Preparedness of Primary Care Centers for COVID-19 epidemic in Aseer region, KSA.

Objective: The objective of this study is to assesses the preparedness of primary care centers (PHCs) in Aseer region, KSA, for the coronavirus disease 2019 (COVID-19) pandemic. Methods: This survey was conducted during April 2020 in PHCs. The questionnaire was developed by the investigators and sent via e-mail to health care providers of primary health care centers (PHCCs). The questionnaire consisted of five parts to assesses readiness of PHCs, knowledge, attitude, and practice of health care providers (HCPs) concerning the COVID-19 pandemic. Data entry and analysis were managed by SPSS version 20. Results: Three hundred and seventy-one HCPs participated in this study. Most of them were males (58%), doctors or nurses (81%). Almost all PHCCs have adequate infection control resources, with some shortage in sterilization rooms. Most of participants received on-job training (85%) and had good knowledge about COVID-19. Attitudes of participants showed variation toward COVID-19; 74% were afraid to be infected, 54% were afraid to care for infected patients, 58% were ready for vaccination, and 80% thought that COVID-19 has a huge negative impact on the health care system. Compliance with preventive measures ranged from 66% for keeping social distance to 90% for using personal protective equipment. Most of the participants had positive contributions regarding health education of individuals and communities using different methods including the new social media (80%). Conclusion: This study revealed that PHCCs in Aseer region were well equipped and HCPs were well prepared to deal with the COVID-19 pandemic. There are some shortage in a few items of infection control at PHCCs and gaps in knowledge and practice among HCPs which need continuous assessment and monitoring to overcome such barriers.

Assessment of Indoor Air Quality of Four Primary Health Care Centers in Qatar.

Airborne bacteria pose a potential risk to human health upon inhalation in the indoor environments of health care facilities. Airborne bacteria may originate from various sources, including patients, workers, and daily visitors. Hence, this study investigates the quantity, size, and identification of airborne bacteria indoors and outdoors of four Primary Health Care Centers (PHCC) in Doha, Qatar. Air samples were collected from the lobby, triage room, and outside environment of the centers, including, Qatar University (QU-HC), Al-Rayyan (AR-HC), Umm-Ghuwailina (UG-HC), and Old Airport (OA-HC) between August 2020 and March 2021, throughout both the hot and the cold seasons. Samples were collected using an Anderson six-stage cascade impactor. The mean of the total colony-forming units was calculated per cubic meter of air (CFU/m3). QU-HC had the lowest mean of total bacterial count compared with other centers in the indoor and outdoor areas with 100.4 and 99.6 CFU/m3, respectively. In contrast, AR-HC had the highest level, with 459 CFU/m3 indoors, while OA-HC recorded the highest bacterial concentration of the outdoor areas with a total mean 377 CFU/m3. In addition, 16S rRNA sequencing was performed for genera identification. Staphylococcus, Acinetobacter, Bacillus, and Pseudomonas were the four most frequently identified bacterial genera in this study. The abundance of airborne bacteria in the four health centers was higher in the cold season. About 46% of the total airborne bacterial count for three PHCC centers exceeded 300 CFU/m3, making them uncompliant with the World Health Organization's (WHO) recommendation for indoor settings. Consequently, an IAQ standards should be shaped to establish a baseline for measuring air pollution in Qatar. Additionally, it is crucial to understand seasonal fluctuations better so that hospitals can avoid rising and spreading infection peaks.

Validation study of postoperative liver failure and mortality risk scores after liver resection for perihilar cholangiocarcinoma.

Background: Surgery for perihilar cholangiocarcinoma (PHCC) remains a challenging procedure with high morbidity and mortality. The Academic Medical Center (Amsterdam UMC) and Memorial Sloan Kettering Cancer Center proposed a postoperative mortality risk score (POMRS) and post-hepatectomy liver failure score (PHLFS) to predict patient outcomes. This study aimed to validate the POMRS and PHLFS for PHCC patients at Hokkaido University. Methods: Medical records of 260 consecutive PHCC patients who had undergone major hepatectomy with extrahepatic bile duct resection without pancreaticoduodenectomy at Hokkaido University between March 2001 and November 2018 were evaluated to validate the PHLFS and POMRS. Results: The observed risks for PHLF were 13.7%, 24.5%, and 39.8% for the low-risk, intermediate-risk, and high-risk groups, respectively, in the study cohort. A receiver-operator characteristic (ROC) analysis revealed that the PHLFS had moderate predictive value, with an analysis under the curve (AUC) value of 0.62. Mortality rates based on the POMRS were 1.7%, 5%, and 5.1% for the low-risk, intermediate-risk, and high-risk groups, respectively. The ROC analysis demonstrated an AUC value of 0.58. Conclusions: This external validation study showed that for PHLFS the threshold for discrimination in an Eastern cohort was reached (AUC >0.6), but it would require optimization of the model before use in clinical practice is acceptable. The POMRS were not applicable in the eastern cohort. Further external validation is recommended.

Cardiovascular Risks and Outcome in COVID-19 Positive Patients With Cardiovascular Disease Attending Primary Health Care Corporation in Qatar: A Retrospective Cohort Study.

Background: Coronavirus disease (COVID-19) patients with cardiovascular disease (CVD) are at a higher risk of morbidity and mortality. This study describes the risks and outcome in COVID-19 patients with CVD attending Primary Health Care Corporationsettings in Qatar. Objective: To report whether CVD increases the risk for hospitalization and further complications in COVID-19 patients. Methods: Retrospective cohort study. Results: A total of 10,178 CVD patients' data who tested positive for COVID-19 were extracted from electronic medical records on the basis of inclusion criteria and analyzed during the period of February 1, 2020 to December 31, 2020 (11 months). Among the patients included in the study, 64% (n=6527) were men and 36% (n=3651) were women; 23% (n=2299) were Qataris and 77% (n=7879) were non-Qataris. Among the selected age group of greater than 25 to less than 75 years, the median age was 50.83 years. More than half of the patients had diabetes (69.6%; n=7086) followed by hypertension (68.4%; n=6965) and dyslipidemia (45.1%; n=4590). Other comorbidities were obesity (18.3%; n=1862), kidney disease (6.5%; n=659), hematologic problems (4.2%; n=425), liver disorders (1.4%; n=142), rheumatic heart disease (1.3%; n=131) and neurologic symptoms (1.3%; n=128). Multivariate analysis for factors associated with inpatient admissions in last 28 days for patients with CVD reported that patients with age greater than 70 years are 2.8 (1.86-4.18) times higher risk of hospital admission as compared with the patients 25-30 years of age. Conclusion: The pre-existing CVD with age and other comorbidities predict the risk for hospitalization and further complications in patients with COVID-19. Further studies are needed to investigate the data from primary and secondary care about the long-term cardiovascular outcomes of patients who have survived COVID-19.

Qualitative Focus Group Study Examining Perceptions of the Community's Important Health Issues, Health Care Needs and Perceived Barriers to Access Among Arabic Speaking Primary Care Clients in the State of Qatar.

OBJECTIVE: This study is a part of the Primary Health Care Corporation's (PHCC) Health Needs Assessment (HNA) Initiative. It focuses on identifying perceptions of Arabic speaking primary care clients regarding community's major health issues, their experiences in utilizing health services, and the barriers that limit their access to health care in the State of Qatar. STUDY SETTING AND DESIGN: A total of 10 focus groups sessions were conducted at different PHCC's health centers between October of 2019 and March of 2020. Sessions were distributed to cover all PHCC's three geographical regions. Data were analyzed using thematic analysis. PARTICIPANTS: A total of 89 adult Arabic speaking individuals were recruited. Participants included were in the age groups (18-69), native Arabic speaker, and registered at one of the PHCC's health centers with a valid health card at time of recruitment. RESULTS: Areas investigated included perceptions of the community's health issues, needed health services, and perceived barriers to health care. Priority health issues identified were chronic non-communicable diseases, mental health, timely access to care, cultural competency of delivered services, and integration and coordination across health care settings and sectors. Participants were able to identify socioeconomic and environmental factors such as the need for health and wellness interventions at schools that affects the health of the individual and the community. The importance of raising the community's awareness about health-related issues and availability of health services was highlighted by study participants. CONCLUSION: Collecting qualitative data provides an opportunity to examine people's perceptions, and motivations and engage the whole community. This process is very important for strategic planning of health services. The study attempts to fill the knowledge gap and should be linked to health policy and the development of socially and culturally appropriate health programs.

Qatar's Primary Health Care Medication Home Delivery Service: A Response Toward COVID-19.

The COVID-19 pandemic has strained health care systems around the world. Pharmacists have made substantial contributions to the health care operations during the COVID-19 response. The Pharmacy Department at Qatar Primary Health Care Corporation (PHCC) acted proactively to ensure that all patients received their medications and their refilled prescriptions in time and without any disruption. The Medication Home Delivery Service was introduced and implemented for all Qatar residents to prevent unnecessary visits to health centers, minimize the spread of COVID-19 to vulnerable populations, especially those with multiple comorbidities, and protect health care workers from exposure to the virus. Moreover, several other precautionary measures were taken by the PHCC to ensure uninterrupted access to health care, including moving to a virtual health care delivery model. As of September 2020, the service had served around 64,213 patients since its launch in March 2020. In total, 70,357 medications were delivered and 69,092 (98.2%) medication packages were delivered successfully to patients, with an average of 450.8 medication packages delivered per month. Despite various challenges, the PHCC is considering continuing the Medication Home Delivery Service in the long term to continue with a more effective and efficient service for patients during the coming months and years.

Development and validation of a risk score for predicting mortality after resection of primary hepatocellular carcinoma.

BACKGROUND: Primary hepatocellular carcinoma (PHCC) has a poor prognosis and high short-term mortality rate, even after resection. Thus, early diagnosis in PHCC cases can help improve quality of life via personalized management strategies. RESULTS: The risk score system (RSS) were classified as low risk (<5 points), medium risk (5-10 points), or high risk (>10 points). The areas under the receiver operating characteristic curves were 0.80 in the training cohort and 0.69 in the validation cohort, which indicated satisfactory prognostic performance. The Hosmer-Lemeshow goodness of fit test (P>0.05) revealed consistent performance in both groups. The concordance index (C-index: 0.663, 95% CI: 0.618-0.708) revealed excellent discrimination and good calibration in the validation cohort. CONCLUSIONS: This simple RSS, which is based on clinical and laboratory data from patients undergoing resection of PHCC, might allow clinicians and medical staff to better manage PHCC. MATERIALS AND METHODS: A total of 672 PHCC cases were retrospectively obtained from the First Affiliated Hospital of Wenzhou Medical University between January 2007 and February 2015. Cox proportional hazard models were used to identify independent predictors of mortality. Kaplan-Meier curves and the log-rank test were used to examine the relationships between the prognostic factors and overall mortality.

A sample model established by S-index predicting overall survival after curative resection of primary hepatocellular carcinoma.

PURPOSE: Prognostic prediction after curative resection of primary hepatocellular carcinoma (PHCC) remains an arduous task. The S-index calculated from γ-glutamyl transpeptidase, albumin, and platelets is reported to predict the severity of liver fibrosis. We constructed a nomogram for predicting the survival probability of PHCC based on a new indicator, the S-index, combined with other routine clinical parameters. PATIENTS AND METHODS: We selected 490 patients with PHCC postradical surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2007 and January 2014. The subjects were randomly allocated into the training cohort and the validation cohort in the ratio 7:3 by the digital method. Important variables screened by univariate analysis were included in multivariate analysis to obtain independent risk factors for predicting the prognosis of PHCC. The construction of the nomogram was based on Cox proportional hazard regression models. The concordance index (C-index) was used in the nomogram for evaluating the model performance for prognosis. We drew time-dependent receiver operating characteristic curves to compare our model with other staging systems. RESULTS: The nomogram based on six independent risk factors after multivariate analyses had good predictive power after radical surgery of PHCC. In the training and validation groups, the C-index of the nomogram was highly consistent for evaluating survival from PHCC. Compared with the traditional scoring system, the areas under time-dependent receiver operating characteristic curves were 0.7382, 0.7293, and 0.7520 for 1-, 3-, and 5-year overall survival, respectively. In summary, the nomogram showed excellent results in terms of prognosis of PHCC. CONCLUSION: Based on the S-index and the other clinical indicators, we developed a precise nomogram that predicts the survival probability of patients with PHCC after radical surgery. This tool can provide effective information for surgeons and patients.

Integrating immunisation services into nutrition sites to improve immunisation status of internally displaced persons' children living in Bentiu protection of civilian site, South Sudan.

INTRODUCTION: The protracted war in South Sudan has led to severe humanitarian crisis with high level of malnutrition and disruption of the health systems with continuous displacement of the population and low immunization coverage predisposing the population to vaccine preventable diseases. The study aimed at evaluating the effect of integrating immunization services with already established nutrition services on immunization coverage in resource-constrained humanitarian response. METHODS: A community and health facility based interventional study involving integration of immunization into nutrition services in two Outpatient Therapeutic Program(OTP)centers in Bentiu PoC between January-December 2017. The main hypothesis was that inclusion of immunization services during nutrition services both at the OTP and community outreaches be an effective strategy for reducing missed opportunity for immunizing all eligible children accessing nutrition services. Data analyzed using STATA version 15 and bivariate analysis using logistic regression was conducted to identify predictor of missed vaccinations. RESULTS: Integration of immunization into the nutrition services through the OTP centres increased the number of children immunized with various antigens and the dropout rate was much lower and statistically significant among children who received immunization at the OTP centers than those in the Primary Health Care Centers (PHC Centers) in the study sites. Children who were vaccinated at the OTP centre in sector 2 were 45% less likely to miss vaccination than those vaccinated at the PHCC (OR: 0.45; 95%CI:0.36- 0.55), p<0.05 while those vaccinated at the OTP sector in sector 5 were 27% less likely to miss vaccination than those vaccinated at the PHCC (OR: 0.27; 95%CI: 0.20 -0.35) p<0.05). CONCLUSION: This study indicated that immunization coverage improved effectively with integration with nutrition services as a model of an integrated immunization programme for child health in line with the Integrated Management of Childhood Illnesses (IMCI) and the Global Immunization Vision and Strategy (GIV).

Primary Health Care Center (PHCC) Location-Allocation with Multi-Objective Modelling: A Case Study in Idleb, Syria.

The Syrian crisis began on 15 March 2011. It is one of the bloodiest and complicated conflicts in the world today. Although almost eight years have passed over this tragedy, civilians continue to suffer from conflicts and destructions in the area. As a result, this situation disregards human life and the number of people in need increases day by day. Particularly, people who have to live in the conflict area encounter troubles with regard to health, shelter, food and other needs. Thus, we have focused on identifying the Primary Health Care Center (PHCC) locations within Idleb Governorate in Syria. Data is extracted from a sample containing 23 sub-districts in the governorate and a total of 338 communities. We have formulated a mixed integer-weighted goal programming model and combined it with a Geographic Information System-GIS (ArcMap). The model is solved via an optimization package and moreover, sensitivity analyses are conducted to achieve a more in-depth study. Our aim was to have 60 PHCCs out of 77 available candidate PHCCs and the model located 42 PHCCs in total, by allocating 379,080 people, with a total cost of USD 1,000,353 and a cash for work amounting to USD 163,549. Accordingly, the model's outputs and sensitivity analyses are expected to help decision-makers in case of such disasters.

The family role in children׳s sleep disturbances: Results from a cross-sectional study in a Portuguese Urban pediatric population.

BACKGROUND: Sleep Disorders (SlD) are frequently undervalued complaints in childhood. Several factors influence sleep, particularly socio-cultural environment and medical conditions such as breathing disorders. Poor sleep hygiene has physical, educational and social consequences. In Portugal, there are few published studies about children׳s sleep habits and rarely based on validated questionnaires. AIM: To study the prevalence of SlD and associated factors, in an outpatient pediatric population of a Primary Health Care Center (PHCC). METHODS: Cross-sectional study of children admitted to a PHCC on a suburban area of Lisbon. Children Sleep Habits Questionnaire, validated for the Portuguese population (CSHQ-PT) for the screening of SlD (cut-off=44), was applied to parents, as well as a demographic inquiry. Body mass index z-score was evaluated. Children scoring 44 or above were sent to Pediatric Sleep Disorders consultation (PSDC). Parametric and non-parametric tests were used whenever appropriate. RESULTS: From 128 children, 57.8% were male; the median age was 6.0 years (P 25=5.0; P 75=8.0). The median of cohabitants per family was 4.0 (P 25=3.0; P 75=5.0); 21.1% lived in a single-parent family. From CSHQ-PT, 59.4% (76) scored above the cut-off. Data showed that children from a single-parent family have more SlD (p=0.048), particularly parasomnia (p=0.019). Children with sleep disordered breathing (SDB) suffer more daytime sleepiness (p=0.034). From 63 children sent to PSDC, 33 attended. Regarding these children, a difference was found between BMI z-scores of those with and without SDB (p=0.06). CONCLUSION: Family structure plays a non-negligible role in children's sleep habits. Daily performance of children with SDB may become compromised.