Incident Reporting Systems: How did we get here and where should we go? a narrative review

Since the authoring of the seminal report by the Institute of Medicine (IOM) “To Err is Human: Building a Safer Health System” in 2000, there has been an increased focus on patient safety and the responsibility born by the healthcare system to reduce what are known as adverse events (AE). One of the recommendations of the IOM report was the establishment and development of Incident Reporting System (IRS) that would track AE resulting in serious injury and death. The Joint Commission in the USA similarly requires all hospitals have and use an IRS. The objective of this review is to explore barriers and feature of IRS and patient safety.    &nbsp

CLINICAL PROFILE AND THE OUTCOME OF COVID-19 IN PATIENTS WITH HEMATOLOGICAL MALIGNANCY: A SINGLE CENTRE EXPERIENCE

Objective: In the present study, we are reporting the clinical profile; and outcomes of COVID-19 in patients with hematological malignancy at tertiary care hospitals. Methods: Data from laboratory-confirmed 40 COVID-19 patients diagnosed between January 1, 2021 and July 31, 2021, were analyzed retrospectively. All COVID-19 patients with hematological malignancy (n=40) were included in the study. Results: In the present study, a total of 40 patients were included. Of 40, 25 (62.5%) were males, and 15 (37.5%) were females. The median age in this study was 43 years (Range, 8–70). Of these 40 patients, acute myeloid leukemia was the most common malignancy 11 (27.5%), followed by acute lymphoblastic leukemia 9 (22.5%) than non-Hodgkin lymphoma 5 (12.5%), plasma cell dyscrasia 4 (10%), chronic myeloid leukemia 4 (10%), chronic lymphocytic leukemia 3 (7.5%), acute promyelocytic leukemia 2 (5%), chronic myelomonocytic leukemia 2 (5%). Mean hemoglobin was (8.04 g/dl), white blood cell count was (10.14×109/l), platelet count was (77.7×109/l) creatinine was (0.86 mg/dl), bilirubin was (1.24 mg/dl). The overall case-fatality rate was 8 (22.5%). Conclusion: Patients with hematological malignancy are immunocompromised, and our study reveals that there is an increased case fatality rate among these patients. Hence, physicians should be aggressive in the management of COVID‐19 patients with hematological malignancy

Public Disclosure on Social Media of Identifiable Patient Information by Health Professionals: Content Analysis of Twitter Data

Background: Respecting patient privacy and confidentiality is critical for doctor-patient relationships and public trust in medical professionals. The frequency of potentially identifiable disclosures online during periods of active engagement is unknown. Objective: The objective of this study was to quantify potentially identifiable content shared on social media by physicians and other health care providers using the hashtag #ShareAStoryInOneTweet. Methods: We accessed and searched Twitter’s API using Symplur software for tweets that included the hashtag #ShareAStoryInOneTweet. We identified 1206 tweets by doctors, nurses, and other health professionals out of 43,374 tweets shared in May 2018. Tweet content was evaluated in January 2019 to determine the incidence of instances where names or potentially identifiable information about patients were shared; content analysis of tweets in which information about others had been disclosed was performed. The study also evaluated whether participants raised concerns about privacy breaches and estimated the frequency of deleted tweets. The study used dual, blinded coding for a 10% sample to estimate intercoder reliability using Cohen κ statistic for identifying the potential identifiability of tweet content. Results: Health care professionals (n=656) disclosing information about others included 486 doctors (74.1%) and 98 nurses (14.9%). Health care professionals sharing stories about patient care disclosed the time frame in 95 tweets (95/754, 12.6%) and included patient names in 15 tweets (15/754, 2.0%). It is estimated that friends or families could likely identify the clinical scenario described in 242 of the 754 tweets (32.1%). Among 348 tweets about potentially living patients, it was estimated that 162 (46.6%) were likely identifiable by patients. Intercoder reliability in rating the potential identifiability demonstrated 86.8% agreement, with a Cohen κ of 0.8 suggesting substantial agreement. We also identified 78 out of 754 tweets (6.5%) that had been deleted on the website but were still viewable in the analytics software data set. Conclusions: During periods of active sharing online, nurses, physicians, and other health professionals may sometimes share more information than patients or families might expect. More study is needed to determine whether similar events arise frequently and to understand how to best ensure that patients’ rights are adequately respected

Analyzing Tobin’s Q Ratio of Banking Industry of Bangladesh: A Comprehensive Guideline for Investors

Due to the share market crash in 2010-2011, the investors have lost confidence regarding the share market till now. Therefore, this study is an endeavor to giveaway to rethink about the share market of Bangladesh and to increase the confidence of the investors. For that, Tobin’s Q ratio used to analyze the share market in this study. Tobin’s Q represents the ratio of the market value of a firm's share capital to the replacement cost of the firm's share capital. Tobin’s Q is greater than one means stock is overvalued. Tobin’s Q is less than one means stock is undervalued. Again, Tobin’s Q is equal to one means stock is fairly valued. The study found that, the value of Tobin’s Q of the all sampling banks is gradually decreasing means moving the value of the stock from overvalued to undervalue. The value of Tobin’s Q of the all sampling banks is less than one in the year 2014 except Dutch Bangla Bank Limited (DBBL). The average value of Tobin’s Q of the banking industry is also decreasing and the average value of Tobin’s Q of the banking industry is less than one in the year 2014. Thus, the average stock value of the banking industry is moving from overvalued to undervalue gradually. Again, the value of Tobin’s Q of all sampling banks fell down drastically from the year 2010 to the year 2011 as share market has been crashed in those years. As a result, the average value of Tobin’s Q of banking industry also fell down drastically from the year 2010 to the year 2011. Therefore, the value of the share slopes down drastically from the year 2010 to the year 2011

Comparative transcriptome profiling reveals differential defense responses among Alternaria brassicicola resistant Sinapis alba and susceptible Brassica rapa

Alternaria blight is a devastating disease that causes significant crop losses in oilseed Brassicas every year. Adoption of conventional breeding to generate disease-resistant varieties has so far been unsuccessful due to the lack of suitable resistant source germplasms of cultivated Brassica spp. A thorough understanding of the molecular basis of resistance, as well as the identification of defense-related genes involved in resistance responses in closely related wild germplasms, would substantially aid in disease management. In the current study, a comparative transcriptome profiling was performed using Illumina based RNA-seq to detect differentially expressed genes (DEGs) specifically modulated in response to Alternaria brassicicola infection in resistant Sinapis alba, a close relative of Brassicas, and the highly susceptible Brassica rapa. The analysis revealed that, at 48 hpi (hours post inoculation), 3396 genes were upregulated and 23239 were downregulated, whereas at 72 hpi, 4023 genes were upregulated and 21116 were downregulated. Furthermore, a large number of defense response genes were detected to be specifically regulated as a result of Alternaria infection. The transcriptome data was validated using qPCR-based expression profiling for selected defense-related DEGs, that revealed significantly higher fold change in gene expression in S. alba when compared to B. rapa. Expression of most of the selected genes was elevated across all the time points under study with significantly higher expression towards the later time point of 72 hpi in the resistant germplasm. S. alba activates a stronger defense response reaction against the disease by deploying an array of genes and transcription factors involved in a wide range of biological processes such as pathogen recognition, signal transduction, cell wall modification, antioxidation, transcription regulation, etc. Overall, the study provides new insights on resistance of S. alba against A. brassicicola, which will aid in devising strategies for breeding resistant varieties of oilseed Brassica

Somatostatin secretion by Na+-dependent Ca2+-induced Ca2+ release in pancreatic delta-cells.

Pancreatic islets are complex micro-organs consisting of at least three different cell types: glucagon-secreting α-, insulin-producing β- and somatostatin-releasing δ-cells1. Somatostatin is a powerful paracrine inhibitor of insulin and glucagon secretion2. In diabetes, increased somatostatinergic signalling leads to defective counter-regulatory glucagon secretion3. This increases the risk of severe hypoglycaemia, a dangerous complication of insulin therapy4. The regulation of somatostatin secretion involves both intrinsic and paracrine mechanisms5 but their relative contributions and whether they interact remains unclear. Here we show that dapagliflozin-sensitive glucose- and insulin-dependent sodium uptake stimulates somatostatin secretion by elevating the cytoplasmic Na+ concentration ([Na+]i) and promoting intracellular Ca2+-induced Ca2+ release (CICR). This mechanism also becomes activated when [Na+]i is elevated following the inhibition of the plasmalemmal Na+-K+ pump by reductions of the extracellular K+ concentration emulating those produced by exogenous insulin in vivo6. Islets from some donors with type-2 diabetes hypersecrete somatostatin, leading to suppression of glucagon secretion that can be alleviated by a somatostatin receptor antagonist. Our data highlight the role of Na+ as an intracellular second messenger, illustrate the significance of the intraislet paracrine network and provide a mechanistic framework for pharmacological correction of the hormone secretion defects associated with diabetes that selectively target the δ-cells

Voltage Gated Calcium Channels Negatively Regulate Protective Immunity to Mycobacterium tuberculosis

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity

Scleroderma and related disorders: 223. Long Term Outcome in a Contemporary Systemic Sclerosis Cohort

Background: We have previously compared outcome in two groups of systemic sclerosis (SSc) patients with disease onset a decade apart and we reported data on 5 year survival and cumulative incidence of organ disease in a contemporary SSc cohort. The present study examines longer term outcome in an additional cohort of SSc followed for 10 years. Methods: We have examined patients with disease onset between years 1995 and 1999 allowing for at least 10 years of follow-up in a group that has characteristics representative for the patients we see in contemporary clinical practice. Results: Of the 398 patients included in the study, 252 (63.3%) had limited cutaneous (lc) SSc and 146 (36.7%) had diffuse cutaneous (dc) SSc. The proportion of male patients was higher among the dcSSc group (17.1% v 9.9%, p = 0.037) while the mean age of onset was significantly higher among lcSSc patients (50 ± 13 v 46 ± 13 years ± SD, p = 0.003). During a 10 year follow-up from disease onset, 45% of the dcSSc and 21% of the lcSSc subjects developed clinically significant pulmonary fibrosis, p < 0.001. Among them approximately half reached the endpoint within the first 3 years (23% of dcSSc and 10% of lcSSc) and over three quarters within the first 5 years (34% and 16% respectively). There was a similar incidence of pulmonary hypertension (PH) in the two subsets with a steady rate of increase over time. At 10 years 13% of dcSSc and 15% of lcSSc subjects had developed PH (p=0.558), with the earliest cases observed within the first 2 years of disease. Comparison between subjects who developed PH in the first and second 5 years from disease onset demonstrated no difference in demographic or clinical characteristics, but 5-year survival from PH onset was better among those who developed this complication later in their disease (49% v 24%), with a strong trend towards statistical significance (p = 0.058). Incidence of SSc renal crisis (SRC) was significantly higher among the dcSSc patients (12% v 4% in lcSSc, p = 0.002). As previously observed, the rate of development of SRC was highest in the first 3 years of disease- 10% in dcSSc and 3% in lcSSc. All incidences of clinically important cardiac disease developed in the first 5 years from disease onset (7% in dcSSc v 1% in lcSSc, p < 0.001) and remained unchanged at 10 years. As expected, 10-year survival among lcSSc subjects was significantly higher (81%) compared to that of dcSSc patients (70%, p = 0.006). Interestingly, although over the first 5 years the death rate was much higher in the dcSSc cohort (16% v 6% in lcSSc), over the following years it became very similar for both subsets (14% and 13% between years 5 and 10, and 18% and 17% between years 10 and 15 for dcSSc and lcSSc respectively). Conclusions: Even though dcSSc patients have higher incidence for most organ complications compared to lcSSc subjects, the worse survival among them is mainly due to higher early mortality rate. Mortality rate after first 5 years of disease becomes comparable in the two disease subsets. Disclosure statement: The authors have declared no conflicts of interes

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes