EVOLVING TRENDS AND FUTURE PROSPECTS OF ADR MONITORING AND REPORTING: A LITERATURE REVIEW

Objective: Owing to the importance of safe use of medicines, adverse drug reaction (ADR) monitoring has become a fundamental component tobe performed along with other health-care services. Pharmacist being drug experts are in good position to provide professional assistance for ADRmanagement. The aim of this study is to summarize research findings from developed and developing countries as well as from Pakistan regardingevolving trends and future prospects of ADR monitoring and reporting by pharmacists. Methods: A total of 49 studies were reviewed regarding trends ofADR monitoring using different search engines including google scholar, pubmed and science direct. Results: The review highlighted that there is needto identify the barriers and gaps to further enhance the effectiveness of current ADR monitoring practices. Conclusion: Strong legislation is required inPakistan to develop and implement an effective ADR monitoring program to reinforce the conception of effective pharmacovigilance system in Pakistan.Keywords: Adverse drug reactions, Reporting, Pharmacist, Pharmacovigilance, Pakistan

The diagnostic utility of ancillary CD117 immunomarker compared with cell block cytology of thyroid lesions based on Bethesda grading system

Background: This is a cross sectional multicenter study carried out from July 2017 to December 2017. The aim of the present study is to evaluate the fine needle aspiration cytology and cell block of thyroid lesions on the basis of Bethesda grading system. Also, expression of CD117 immunostaining in thyroid lesions was evaluated. Finally, the results of cell block were compared with expression of CD117 immunomarker for diagnostic confirmation of different thyroid lesions.Methods: Total one hundred (100) patients presenting with thyroid swelling underwent fine needle aspiration, cell block preparation to diagnose and categorize thyroid lesion on the basis of Bethesda grading system and finally immunostaining with CD117 was carried out.Results: FNAC results showed 71% patients with benign thyroid morphology and about 23% cases were categorized as atypical to fairly malignant. In cell block study benign lesions diagnosed were 77%, 17% cases as suspicious and 6% were malignant thyroid nodules. Whereas expression of ancillary CD117 immunomarker, confirmed 83% as benign lesions and 17% cases as malignant. Overall ancillary CD117 immunomarker established the better diagnosis to manage and differentiate thyroid lesions.Conclusions: Cell block results are more accurate than FNAC in thyroid patients. The CD117 immunomarkers can be used as better diagnostic tool for confirmation of thyroid lesions and thus it can reduce unnecessary surgical intervention

Expression of anaplastic lymphokinase and HER2/neu immunostaining in patients with breast carcinoma

Background: The diagnosis and prognosis of breast cancer is done with various immunomarkers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2/neu), and Ki-67. The diagnostic utility of Anaplastic Lymphokinase (ALK) and HER2/neu should be explored for better management of breast carcinoma patients. So, the present study was designed to determine the expression of immunostaining with ALK and HER2/neu in patients with breast cancer and to compare the association of ALK expression and HER2/neu with clinicopathological parameters.Methods: This is a cross sectional multicenter study carried out from October 2016 to March 2017. A total of 140 subjects having breast carcinoma by using non-probability purposive sampling technique were selected. After taking informed consent, tissue samples were taken from received specimen of mastectomy for hematoxylin and eosin stain. The immunohistochemistry for ALK and HER2/neu were assessed on the paraffin blocks of the tumor.Results: Out of total 140 cases invasive ductal carcinoma (89%), invasive lobular carcinoma (8%), invasive medullary carcinoma (2.1%) and papillary carcinoma (0.7%) were seen. ALK expression was positive in 81 patients (58%) while HER2/neu expression was positive in 53 cases (38%). Significant association was observed between ALK expression with histological grade, lymph node involvement, skin involvement and necrosis. There was also a significant association was seen between HER2/neu expression with lymph node metastasis and necrosis.Conclusions: Present study shows higher expression of ALK when compared to HER2/neu expression in breast cancer patients

Congenital Aortic-Left Atrial Tunnel with Coarctation and Anomalous Left Coronary Artery from the Pulmonary Artery: A First-of-its-kind Case Report.

Aortic-left atrial (Ao-LA) tunnel is an extremely rare vascular anomaly that involves an abnormal channel originating from the sinuses of the Valsalva and terminating in the left atrium. We present an unusual case of prenatally diagnosed Ao-LA tunnel with postnatal diagnosis of coarctation of the aorta and anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)

Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p<0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77–0.93; p = 2.7×10−4). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes

Synthesis of Sheet Like Morphology of NiO for Sensitive and Selective Determination of Urea

An efficient and simple method has been demonstrated for the synthesis of nickel oxide nanostructures using urea as a capping agent. The nanosheet-like morphology was confirmed by scanning electron microscopy, crystalline nature was studied by using the X-ray diffraction (XRD) and surface area of nanomaterial was investigated by automated sorption analyzer. Then synthesized NiO nanostructures were used to fabricate the surface of glassy carbon electrode (GCE). The electrocatalytic parameters of modified NiO/GCE electrode were investigated by using various techniques such as electrochemical impedance spectroscopy (EIS), square wave voltammetry (SWV), differential pulse voltammetry (DPV), normal pulse voltammetry (NPV) and cyclic voltammetry (CV) and chronoamperometry. Various working experimental conditions were optimized in order to attain the highest sensitivity for the determination of urea and the highest peak current 1032 μA of response were obtained at 100 μM concentration of urea. A linear calibration plot was obtained for peak current versus concentration of urea in the range of 10 μM urea to 80 μM urea with a good detection limit of 2 μM. The proposed working strategy was successfully employed for the estimation of urea in human urine samples and the obtained results are found satisfactory. The newly functional urea sensor can be exploited at large scale as an alternative analytical device beside to the other reported urea sensorsValiderad;2018;Nivå 1;2018-02-12 (andbra)</p

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.The aim of this study was to inform vaccination prioritization by modelling the impact of vaccination on elective inpatient surgery. The study found that patients aged at least 70 years needing elective surgery should be prioritized alongside other high-risk groups during early vaccination programmes. Once vaccines are rolled out to younger populations, prioritizing surgical patients is advantageous

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60&nbsp;years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death.&nbsp;The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death