Discovering novel cancer bio-markers in acquired lapatinib resistance using Bayesian methods.

Signalling transduction pathways (STPs) are commonly hijacked by many cancers for their growth and malignancy, but demystifying their underlying mechanisms is difficult. Here, we developed methodologies with a fully Bayesian approach in discovering novel driver bio-markers in aberrant STPs given high-throughput gene expression (GE) data. This project, namely 'PathTurbEr' (Pathway Perturbation Driver) uses the GE dataset derived from the lapatinib (an EGFR/HER dual inhibitor) sensitive and resistant samples from breast cancer cell lines (SKBR3). Differential expression analysis revealed 512 differentially expressed genes (DEGs) and their pathway enrichment revealed 13 highly perturbed singalling pathways in lapatinib resistance, including PI3K-AKT, Chemokine, Hippo and TGF-$\beta$ singalling pathways. Next, the aberration in TGF-$\beta$ STP was modelled as a causal Bayesian network (BN) using three MCMC sampling methods, i.e. Neighbourhood sampler (NS) and Hit-and-Run (HAR) sampler that potentially yield robust inference with lower chances of getting stuck at local optima and faster convergence compared to other state-of-art methods. Next, we examined the structural features of the optimal BN as a statistical process that generates the global structure using $p_1$-model, a special class of Exponential Random Graph Models (ERGMs), and MCMC methods for their hyper-parameter sampling. This step enabled key drivers identification that drive the aberration within the perturbed BN structure of STP, and yielded 34, 34 and 23 perturbation driver genes out of 80 constituent genes of three perturbed STP models of TGF-$\beta$ signalling inferred by NS, HAR and MH sampling methods, respectively. Functional-relevance and disease-relevance analyses suggested their significant associations with breast cancer progression/resistance

Clinically Applicable Machine Learning Approaches to Identify Attributes of Chronic Kidney Disease (CKD) for Use in Low-Cost Diagnostic Screening.

OBJECTIVE: Chronic kidney disease (CKD) is a major public health concern worldwide. High costs of late-stage diagnosis and insufficient testing facilities can contribute to high morbidity and mortality rates in CKD patients, particularly in less developed countries. Thus, early diagnosis aided by vital parameter analytics using affordable computer-aided diagnosis could not only reduce diagnosis costs but improve patient management and outcomes. METHODS: In this study, we developed machine learning models using selective key pathological categories to identify clinical test attributes that will aid in accurate early diagnosis of CKD. Such an approach will save time and costs for diagnostic screening. We have also evaluated the performance of several classifiers with k-fold cross-validation on optimized datasets derived using these selected clinical test attributes. RESULTS: Our results suggest that the optimized datasets with important attributes perform well in diagnosis of CKD using our proposed machine learning models. Furthermore, we evaluated clinical test attributes based on urine and blood tests along with clinical parameters that have low costs of acquisition. The predictive models with the optimized and pathologically categorized attributes set yielded high levels of CKD diagnosis accuracy with random forest (RF) classifier being the best performing. CONCLUSIONS: Our machine learning approach has yielded effective predictive analytics for CKD screening which can be developed as a resource to facilitate improved CKD screening for enhanced and timely treatment plans

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Prevalence and Knowledge of Respiratory Symptoms Among the General Public in the Southern Area of Najran, Saudi Arabia: A Cross-Sectional Health Survey Study

Mohammad H Alyami,1 Abdallah Y Naser,2 Hamad S Alyami,1 Thamer S Algahtani,1 Abdullah H Alyami,3 Saleh A Alsalem,3 Abdullah H Almansour,3 Hadi S Alswar,3 Ali M Al Alhareth3 1Department of Pharmaceutics, College of Pharmacy, Najran University, Najran, Saudi Arabia; 2Department of Applied Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman, Jordan; 3Directorate of Health Affairs Najran, Ministry of Health, Najran, Saudi ArabiaCorrespondence: Mohammad H Alyami, Department of Pharmaceutics, College of Pharmacy, Najran University, Najran, 11001, Saudi Arabia, Tel +966 565022774, Email [email protected] Abdallah Y Naser, Department of Applied Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman, Jordan, Tel +962 795285555, Email [email protected]: To investigate the knowledge, prevalence of chronic respiratory disorders, and utilization of their medications among the adults at Najran region, Saudi Arabia.Methods: An online cross-sectional survey was carried out in Najran region, Saudi Arabia. A self-administered questionnaire was distributed among a random sample of the general population, aged 18 or above between March and December 2022. The survey instrument included questions regarding history and exposure, physician diagnosed-disorders, respiratory symptoms, allergy, use of medications and possible risk-related factors.Results: This research had a total of 712 individuals. Nearly one-third of the participants in the survey (n = 218; 30.6%) said that they or a member of their family suffer from respiratory ailments. The majority of research participants (n = 167; 76.8%) identified asthma as their primary respiratory condition. A total of 32.0% of participants (n = 70) reported dealing with dust or chemicals such as paints, fertilizers, and cleaning products on a daily basis at work or at home. Around 62.0% of the participants (n = 134) said that exposure to gases, fragrances, and other such substances negatively impacts their health. Almost 78.0% (n = 169) of them indicated that summer weather affects their health, whereas 63.0% (n = 138) reported that winter cold affects their health. Participants aged 41– 50 years were 38.0% less likely to have CRDs compared to others (p < 0.05).Conclusion: This study is among the first few studies that explored the knowledge, prevalence of chronic respiratory disorders, and utilization of their medications among the adults at Najran region, Saudi Arabia. In the southern area of Najran, respiratory symptoms are frequent among the inhabitants of Saudi Arabia. More research is required to discover avoidable risk factors and create countermeasures for them. It is recommended that healthcare personnel increase their efforts to educate their patients about respiratory illness prevention methods.Keywords: diseases, respiratory, Saudi Arabia, symptom

Trends of Over-the-Counter and Prescribed Medication Use During Pregnancy: A Cross-Sectional Study

Amal A Alyami,1 Manal M Alem,2 Shereen R Dorgham,3 Sahar A Alshamandy4 1Obstetrics & Gynecology Hospital, King Saud Medical City, Riyadh, Saudi Arabia; 2Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Department of Nursing Education, College of Nursing, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Obstetrics and Women’s Health Nursing Department, College of Nursing, Minia University, Minya, EgyptCorrespondence: Manal M Alem, Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, PO Box 1982, Dammam, 31441, Saudi Arabia, Email [email protected]: Globally, unjustified medication use during pregnancy, a critical phase in human life, is a threat that compromises the safety of both, the mother and the child. We aim to investigate the prevalence of over-the-counter (OTC) or non-prescription and prescription medication use during pregnancy in women from the city of Riyadh, Saudi Arabia, the level of prior knowledge, and the sources of their information about medication hazard/safety.Methods: A cross-sectional study was performed using a self-administered questionnaire for 287 pregnant women visiting King Saud Medical City (KSMC) – outpatient departments for routine antenatal care during 3 months (1st Mar– 31st May 2021). The questionnaire was developed by Navaro et al with 4 sections: socio-demographic data, medication use during pregnancy, level of knowledge, and relevant sources of information.Results: The participants had a mean age of 32.21 years ± 6.41 (SD), and gestational age of 23.67 weeks ± 8.47. About 76.66% of them reported using medication during their current pregnancy: predominantly prescribed (86.36%). Women who used medication during pregnancy were slightly older; the mean difference was 1.97 years (95% CI 0.23– 3.71) (P=0.027). Women living in an urban environment as compared with rural had a higher prevalence of medication use (79.01% vs 52%) (P=0.002). Overall, 58.19% reported using non-prescribed medications during pregnancy, with analgesics as the most frequently used class (70.30%). The mild nature of the illnesses and availability of an old prescription and information from pharmacists were the main reasons for self-medication. About 40.77% denied receiving any information about medication use during pregnancy.Conclusion: The prevalence of the medication use during pregnancy in our population is alarmingly high. Analgesics were the most frequently used. Lack of adequate information from treating physicians appears to be contributory to self-medication during this critical time.Keywords: nursing, antenatal care, pregnancy care, prescription medication, non-prescription medications, over-the-counter, fetal health and development, self-medicatio